The NACHT domain consists of seven distinct conserved motifs, including the ATP/GTPase specific P-loop, the Mg2+-binding site (Walker A and B motifs, respectively) and five more specific motifs

The NACHT domain is an evolutionarily conserved protein domain. This NTPase domain is found in apoptosis proteins as well as those involved in MHC transcription. Its name reflects some of the proteins that contain it: NAIP (NLP family apoptosis inhibitor protein), CIITA (that is, C2TA or MHC class II transcription activator), HET-E (incompatibility locus protein from Podospora anserina) and TEP1 (that is, TP1 or telomerase-associated protein).

• Baculoviral IAP repeat-containing protein 1 is a protein that in humans is encoded by the NAIP gene. This gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. This copy of the gene is full length; additional copies with truncations and internal deletions are also present in this region of chromosome 5q13. It is thought that this gene is a modifier of spinal muscular atrophy caused by mutations in a neighboring gene, SMN1. The protein encoded by this gene contains regions of homology to two baculovirus inhibitor of apoptosis proteins, and it is able to suppress apoptosis induced by various signals. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.
  • Roy N, Mahadevan MS, McLean M, Shutler G, Yaraghi Z, Farahani R, Baird S, Besner-Johnston A, Lefebvre C, Kang X, et al. (Feb 1995). “The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy”. Cell. 80 (1): 167–78. doi:10.1016/0092-8674(95)90461-1. PMID 7813013. S2CID 15141092.
  • “Entrez Gene: NAIP NLR family, apoptosis inhibitory protein”
• Survival of motor neuron 1 (SMN1), also known as component of gems 1 or GEMIN1, is a gene that encodes the SMN protein in humans. SMN1 is the telomeric copy of the gene encoding the SMN protein; the centromeric copy is termed SMN2. SMN1 and SMN2 are part of a 500 kbp inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. SMN1 and SMN2 are nearly identical and encode the same protein. The critical sequence difference between the two is a single nucleotide in exon 7 which is thought to be an exon splice enhancer. It is thought that gene conversion events may involve the two genes, leading to varying copy numbers of each gene. Mutations in SMN1 are associated with spinal muscular atrophy. Mutations in SMN2 alone do not lead to disease, although mutations in both SMN1 and SMN2 result in embryonic death.^{[citation needed]}
  • Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M (January 1995). “Identification and characterization of a spinal muscular atrophy-determining gene”. Cell. 80 (1): 155–65. doi:10.1016/0092-8674(95)90460-3. PMID 7813012.
  • “Entrez Gene: SMN1 survival of motor neuron 1, telomeric”.
• Baculoviridae is a family of viruses. The earliest records of baculoviruses can be found in the literature from as early as the 16th century in reports of “wilting disease” infecting silkworm larvae. Starting in the 1940s, the viruses were used and studied widely as biopesticides in crop fields. Since the 1990s, they have been employed to produce complex eukaryotic proteins in insect cell cultures (see Sf21, High Five cells). These recombinant proteins have been used in research and as vaccines in both human and veterinary medical treatments (for example, the most widely used vaccine for prevention of H5N1 avian influenza in chickens was produced in a baculovirus expression vector). More recently, baculoviruses were found to transduce mammalian cells with a suitable promoter.
  • baculovirus.com
  • Lackner, A; Genta, K; Koppensteiner, H; Herbacek, I; Holzmann, K; Spiegl-Kreinecker, S; Berger, W; Grusch, M (2008). “A bicistronic baculovirus vector for transient and stable protein expression in mammalian cells”. Analytical Biochemistry. 380 (1): 146–8. doi:10.1016/j.ab.2008.05.020. PMID 18541133.
• When infecting a caterpillar, the advanced stages of infection cause the host to feed without resting, and then to climb to the higher parts of trees, including exposed places they would normally avoid due to the risk of predators. This is an advantage for the virus since (when the host dissolves) it can drip down onto leaves, which will be consumed by new hosts.
  • Zimmer, Carl (November 2014). “Mindsuckers – Meet Nature’s Nightmare”. National Geographic. Archived from the original on 18 October 2014.
• The virus is unable to infect humans in the way it does insects, because human stomachs are acid-based and NPV requires an alkaline digestive system in order to replicate. It is possible for the virus crystals to enter human cells, but not to replicate to the point of causing illness.
  • Chiu, E; Coulibaly, F; Metcalf, P (2012). “Insect virus polyhedra, infectious protein crystals that contain virus particles”. Curr Opin Struct Biol. 22 (2): 234–40. doi:10.1016/j.sbi.2012.02.003. PMID 22475077.
• The name of this family has been derived from the Latin word baculus, meaning “stick”. The family has been divided into four genera: Alphabaculovirus (lepidopteran-specific nucleopolyhedroviruses), Betabaculovirus (lepidopteran-specific granuloviruses), Gammabaculovirus (hymenopteran-specific nucleopolyhedroviruses), and Deltabaculovirus (dipteran-specific nucleopolyhedroviruses).
  • Jehle, JA; Blissard, GW; Bonning, BC; Cory, JS; Herniou, EA; Rohrmann, GF; Theilmann, DA; Thiem, SM; Vlak, JM; et al. (2006). “On the classification and nomenclature of baculoviruses: a proposal for revision”. Arch Virol. 151 (7): 1257–1266. doi:10.1007/s00705-006-0763-6. PMID 16648963. S2CID 6293565.
• Baculoviruses are thought to have evolved from the Nudiviridae family of viruses 310 million years ago.
  • Theze, J.; Bezier, A.; Periquet, G.; Drezen, J.-M.; Herniou, E. A. (2011). “Paleozoic origin of insect large dsDNA viruses”. Proceedings of the National Academy of Sciences. 108 (38): 15931–5. Bibcode:2011PNAS..10815931T. doi:10.1073/pnas.1105580108. PMC 3179036. PMID 21911395.
    • Nudiviruses are a family of animal viruses that constitute the family Nudiviridae. Insects and marine crustaceans serve as natural hosts. There are 11 species in this family, assigned to 4 genera. Diseases associated with this family include: death in larvae, chronic disease in adults.
      • Harrison, RL; Herniou, EA; Bézier, A; Jehle, JA; Burand, JP; Theilmann, DA; Krell, PJ; van Oers, MM; Nakai, M; ICTV Report Consortium (January 2020). “ICTV Virus Taxonomy Profile: Nudiviridae”. The Journal of General Virology. 101 (1): 3–4. doi:10.1099/jgv.0.001381. PMC 7414434. PMID 31935180.
      • “ICTV Report Nudiviridae”. Retrieved 3 February 2021.
      • “Viral Zone”. ExPASy. Retrieved 13 August 2015.
      • “Virus Taxonomy: 2020 Release”. International Committee on Taxonomy of Viruses (ICTV). March 2021. Retrieved 12 May 2021.
    • Nudiviruses are characterized by rod-shaped and enveloped nucleocapsids and they replicate in the nucleus of infected host cells. In some parasitoid wasp species, a nudivirus genome, in proviral form, is integrated into the wasp genome and produces virus like particles called polydnaviruses that are injected into lepidopteran larvae and are thought to facilitate parasitization of the larvae. Nudiviruses infect only insects and marine crustaceans.
      • “Viral Zone”. ExPASy. Retrieved 13 August 2015.
    • Transmission of nudiviruses occurs generally by feeding or mating. Infections can be lethal for the larvae and can possibly reduce the fitness of the host by reducing offspring production and survival among adults.
      • Unckless RL. (2011) A DNA Virus of Drosophila. Published online 2011 October 28
    • The word “nudivirus” comes from the Latin nudus, which means naked and virus, poison. Naked refers to the fact that most do not have the dense protein bodies which surround baculoviruses. However occluded nudiviruses, with such protein bodies, such as those of Tipula oleracea and Penaeus monodon have been characterized.
      • Moscardi, Flávio (1999). “Assessment of the Application of Baculoviruses for Control of Lepidoptera”. Annual Review of Entomology. Annual Reviews. 44 (1): 257–289. doi:10.1146/annurev.ento.44.1.257. ISSN 0066-4170. PMID 15012374. p. 260, “This strategy has been successful with the non-occluded virus of the rhinoceros beetle, Oryctes rhinoceros, in coconut palms (183).”
      • Bézier A, Thézé J, Gavory F, Gaillard J, Poulain J, Drezen JM, Herniou EA (March 2015). “The genome of the nucleopolyhedrosis-causing virus from Tipula oleracea sheds new light on the Nudiviridae family”. J. Virol. 89 (6): 3008–25. doi:10.1128/JVI.02884-14. PMC 4337555. PMID 25540386

• CIITA is a human gene which encodes a protein called the class II, major histocompatibility complex, transactivator. Mutations in this gene are responsible for the bare lymphocyte syndrome in which the immune system is severely compromised and cannot effectively fight infection. Chromosomal rearrangement of CIITA is involved in the pathogenesis of Hodgkin lymphoma and primary mediastinal B cell lymphoma.
  • Steimle V, Otten LA, Zufferey M, Mach B (Oct 1993). “Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome)”. Cell. 75 (1): 135–46. doi:10.1016/S0092-8674(05)80090-X. PMID 8402893. S2CID 30276144.
  • Steidl C, Shah SP, Woolcock BW, Rui L, Kawahara M, Farinha P, Johnson NA, Zhao Y, Telenius A, Neriah SB, McPherson A, Meissner B, Okoye UC, Diepstra A, van den Berg A, Sun M, Leung G, Jones SJ, Connors JM, Huntsman DG, Savage KJ, Rimsza LM, Horsman DE, Staudt LM, Steidl U, Marra MA, Gascoyne RD (Mar 2011). “MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers”. Nature. 471 (7338): 377–81. Bibcode:2011Natur.471..377S. doi:10.1038/nature09754. PMC 3902849. PMID 21368758.
• CIITA mRNA can only be detected in human leukocyte antigen (HLA) system class II-positive cell lines and tissues. This highly restricted tissue distribution suggests that expression of HLA class II genes is to a large extent under the control of CIITA. However, CIITA does not appear to directly bind to DNA. Instead CIITA functions through activation of the transcription factor RFX5. Hence CIITA is classified as a transcriptional coactivator.
  • Mach B, Steimle V, Reith W (Apr 1994). “MHC class II-deficient combined immunodeficiency: a disease of gene regulation”. Immunological Reviews. 138 (1): 207–21. doi:10.1111/j.1600-065X.1994.tb00853.x. PMID 8070816. S2CID 28869787.
  • Scholl T, Mahanta SK, Strominger JL (Jun 1997). “Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5”. Proceedings of the National Academy of Sciences of the United States of America. 94 (12): 6330–4. Bibcode:1997PNAS…94.6330S. doi:10.1073/pnas.94.12.6330. PMC 21049. PMID 9177217.
• The CIITA protein contains an acidic transcriptional activation domain, 4 LRRs (leucine-rich repeats) and a GTP binding domain. The protein uses GTP binding to facilitate its own transport into the nucleus. Once in the nucleus, the protein acts as a positive regulator of class II major histocompatibility complex gene transcription, and is often referred to as the “master control factor” for the expression of these genes.
  • Raval A, Howcroft TK, Weissman JD, Kirshner S, Zhu XS, Yokoyama K, Ting J, Singer DS (Jan 2001). “Transcriptional coactivator, CIITA, is an acetyltransferase that bypasses a promoter requirement for TAF(II)250”. Molecular Cell. 7 (1): 105–15. doi:10.1016/S1097-2765(01)00159-9. PMID 11172716.
  • Harton JA, Cressman DE, Chin KC, Der CJ, Ting JP (Aug 1999). “GTP binding by class II transactivator: role in nuclear import”. Science. 285 (5432): 1402–5. doi:10.1126/science.285.5432.1402. PMID 10464099.
  • Harton JA, Ting JP (Sep 2000). “Class II transactivator: mastering the art of major histocompatibility complex expression”. Molecular and Cellular Biology. 20 (17): 6185–94. doi:10.1128/MCB.20.17.6185-6194.2000. PMC 86093. PMID 10938095.
  • LeibundGut-Landmann S, Waldburger JM, Krawczyk M, Otten LA, Suter T, Fontana A, Acha-Orbea H, Reith W (Jun 2004). “Mini-review: Specificity and expression of CIITA, the master regulator of MHC class II genes”. European Journal of Immunology. 34 (6): 1513–25. doi:10.1002/eji.200424964. PMID 15162420. S2CID 21226976.
• CIITA expression is induced by interferon gamma, possibly assisted by other signals. MHC II expression in intestinal epithelial cells is upregulated under inflammation.
  • Heuberger C, Pott J, Maloy KJ (2021). “Why do intestinal epithelial cells express MHC class II?”. Immunology. 162 (4): 357–367. doi:10.1111/imm.13270. PMC 7968399. PMID 32966619.
• CIITA has been shown to interact with:
  • MAPK1,
  • Nuclear receptor coactivator 1,
  • RFX5,
  • RFXANK,
  • XPO1, and
  • ZXDC.

• MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating immune responses.
• The antigens presented by class II peptides are derived from extracellular proteins (not cytosolic as in MHC class I).
• Loading of a MHC class II molecule occurs by phagocytosis; extracellular proteins are endocytosed, digested in lysosomes, and the resulting epitopic peptide fragments are loaded onto MHC class II molecules prior to their migration to the cell surface.
• In humans, the MHC class II protein complex is encoded by the human leukocyte antigen gene complex (HLA). HLAs corresponding to MHC class II are HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, and HLA-DR.
• Mutations in the HLA gene complex can lead to bare lymphocyte syndrome (BLS), which is a type of MHC class II deficiency.

• The het-e-1 gene of the fungus Podospora anserina is responsible for vegetative incompatibility through specific interactions with different alleles of the unlinked gene, het-c. Coexpression of two incompatible genes triggers a cell death reaction that prevents heterokaryon formation.
  • Saupe S, Turcq B, Bégueret J. A gene responsible for vegetative incompatibility in the fungus Podospora anserina encodes a protein with a GTP-binding motif and G beta homologous domain. Gene. 1995 Aug 30;162(1):135-9. doi: 10.1016/0378-1119(95)00272-8. PMID: 7557402.
• The het-elA gene encodes a polypeptide that contains a putative GTP-binding site and WD40 repeats. An in vitro assay confirmed that the first domain is functional and can bind GTP and not ATP, suggesting that GTP-binding is essential for triggering the incompatibility reaction. The relationship between the number of WD40 repeats and the reactivity of the protein in incompatibility was investigated by estimating this number in different wild-type and mutant het-e alleles. It was deduced that reactive alleles contain a minimal number of ten WD40 repeats. These results demonstrate that the reactivity of the HET-E protein depends on two functional elements, a GTP-binding domain and several WD40 repeats. These motifs are present in separate polypeptides in trimeric G proteins, suggesting that HET-E polypeptides are also involved in signal transduction. Disruption of the het-e locus does not impair the phenotype of strains but DNA hybridization analyses revealed that het-e may belong to a multigenic family.
  • Espagne E, Balhadère P, Bégueret J, Turcq B. Reactivity in vegetative incompatibility of the HET-E protein of the fungus Podospora anserina is dependent on GTP-binding activity and a WD40 repeated domain. Mol Gen Genet. 1997 Nov;256(6):620-7. doi: 10.1007/s004380050610. PMID: 9435787.

• Telomerase protein component 1 is an enzyme that in humans is encoded by the TEP1 gene. This gene product is a component of the ribonucleoprotein complex responsible for telomerase activity which catalyzes the addition of new telomeres on the chromosome ends. The telomerase-associated proteins are conserved from ciliates to humans. It is also a minor vault protein.
  • Saito T, Matsuda Y, Suzuki T, Hayashi A, Yuan X, Saito M, Nakayama J, Hori T, Ishikawa F (November 1997). “Comparative gene mapping of the human and mouse TEP1 genes, which encode one protein component of telomerases”. Genomics. 46 (1): 46–50. doi:10.1006/geno.1997.5005. PMID 9403057.
  • “Entrez Gene: TEP1 telomerase-associated protein 1”

The NACHT domain contains 300 to 400 amino acids. It is a predicted nucleoside-triphosphatase (NTPase) domain, which is found in animal, fungal and bacterial proteins. It is found in association with other domains, such as the CARD domain (InterPro: IPR001315), the pyrin domain (InterPro: IPR004020), the HEAT repeat domain (InterPro: IPR004155), the WD40 repeat (InterPro: IPR001680), the leucine-rich repeat (LRR) or the BIR repeat (InterPro: IPR001370).

The NACHT domain consists of seven distinct conserved motifs, including the ATP/GTPase specific P-loop, the Mg²⁺-binding site (Walker A and B motifs, respectively) and five more specific motifs. The unique features of the NACHT domain include the prevalence of ‘tiny’ residues (glycine, alanine or serine) directly C-terminal of the Mg²⁺-coordinating aspartate in the Walker B motif, in place of a second acidic residue prevalent in other NTPases. A second acidic residue is typically found in the NACHT-containing proteins two positions downstream. Furthermore, the distal motif VII contains a conserved pattern of polar, aromatic and hydrophobic residues that is not seen in any other NTPase family.

• Koonin EV, Aravind L (May 2000). “The NACHT family – a new group of predicted NTPases implicated in apoptosis and MHC transcription activation”. Trends in Biochemical Sciences. 25 (5): 223–4. doi:10.1016/S0968-0004(00)01577-2. PMID

Examples

Human proteins containing this domain include:

• CIITA
• NAIP
• NLRC3, NLRC4, NLRC5
• NLRP1, NLRP2, NLRP3, NLRP4, NLRP5, NLRP6, NLRP7, NLRP8, NLRP9, NLRP10, NLRP11, NLRP12, NLRP13, NLRP14, NLRX1
• NOD1, NOD2
• NWD1
• TEP1

• The Walker A and Walker B motifs are protein sequence motifs, known to have highly conserved three-dimensional structures. These were first reported in ATP-binding proteins by Walker and co-workers in 1982.
  • Walker JE, Saraste M, Runswick MJ, Gay NJ (1982). “Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold”. The EMBO Journal. 1 (8): 945–951. doi:10.1002/j.1460-2075.1982.tb01276.x. PMC 553140. PMID 6329717.
• Of the two motifs, the A motif is the main “P-loop” responsible for binding phosphate, while the B motif is a much less conserved downstream region. The P-loop is best known for its presence in ATP- and GTP-binding proteins, and is also found in a variety of proteins with phosphorylated substrates. Major lineages include:
  • RecA and rotor ATP synthase / ATPases (α and β subunits).
  • Nucleic acid-dependent ATPases: helicases, Swi2, and PhoH (InterPro: IPR003714)
  • AAA proteins
  • STAND NTPases including MJ, PH, AP, and NACHT ATPases
  • ABC–PilT ATPases
  • Nucleotide kinases (InterPro: IPR000850)
  • G domain proteins: G-proteins (transducin), myosin.
    • Leipe DD, Wolf YI, Koonin EV, Aravind L (March 2002). “Classification and evolution of P-loop GTPases and related ATPases”. Journal of Molecular Biology. 317 (1): 41–72. doi:10.1006/jmbi.2001.5378. PMID 11916378.
    • Stryer L, Berg JM, Tymoczko JL (2002). Biochemistry. San Francisco: W.H. Freeman. ISBN 0-7167-4684-0.
    • Ramakrishnan C, Dani VS, Ramasarma T (October 2002). “A conformational analysis of Walker motif A [GXXXXGKT (S)] in nucleotide-binding and other proteins”. Protein Engineering. 15 (10): 783–798. doi:10.1093/protein/15.10.783. PMID 12468712.
    • Saraste M, Sibbald PR, Wittinghofer A (November 1990). “The P-loop–a common motif in ATP- and GTP-binding proteins”. Trends in Biochemical Sciences. 15 (11): 430–434. doi:10.1016/0968-0004(90)90281-f. PMID 2126155.
• Walker A motif, also known as the Walker loop, or P-loop, or phosphate-binding loop, is a motif in proteins that is associated with phosphate binding. The motif has the pattern G-x(4)-GK-[TS], where G, K, T and S denote glycine, lysine, threonine and serine residues respectively, and x denotes any amino acid. It is present in many ATP or GTP utilizing proteins; it is the β phosphate of the nucleotide that is bound. The lysine (K) residue in the Walker A motif, together with the main chain NH atoms, are crucial for nucleotide-binding. It is a glycine-rich loop preceded by a beta strand and followed by an alpha helix; these features are typically part of an α/β domain with four strands sandwiched between two helices on each side. The phosphate groups of the nucleotide are also coordinated to a divalent cation such as a magnesium, calcium, or manganese(II) ion.
  • Hanson PI, Whiteheart SW (July 2005). “AAA+ proteins: have engine, will work”. Nature Reviews. Molecular Cell Biology. 6 (7): 519–529. doi:10.1038/nrm1684. PMID 16072036. S2CID 27830342.
  • Bugreev DV, Mazin AV (July 2004). “Ca2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity”. Proceedings of the National Academy of Sciences of the United States of America. 101 (27): 9988–9993. Bibcode:2004PNAS..101.9988B. doi:10.1073/pnas.0402105101. PMC 454202. PMID 15226506.
• Apart from the conserved lysine, a feature of the P-loop used in phosphate binding is a compound LRLR nest comprising the four residues xxGK, as above, whose main chain atoms form a phosphate-sized concavity with the NH groups pointing inwards. The synthetic hexapeptide SGAGKT has been shown to bind inorganic phosphate strongly; since such a short peptide does not form an alpha helix, this suggests that it is the nest, rather than being at the N-terminus of a helix, that is the main phosphate binding feature.
  • Watson JD, Milner-White EJ (January 2002). “A novel main-chain anion-binding site in proteins: the nest. A particular combination of phi,psi values in successive residues gives rise to anion-binding sites that occur commonly and are found often at functionally important regions”. Journal of Molecular Biology. 315 (2): 171–182. doi:10.1006/jmbi.2001.5227. PMID 11779237.
  • Bianchi A, Giorgi C, Ruzza P, Toniolo C, Milner-White EJ (May 2012). “A synthetic hexapeptide designed to resemble a proteinaceous P-loop nest is shown to bind inorganic phosphate”. Proteins. 80 (5): 1418–1424. doi:10.1002/prot.24038. PMID 22275093. S2CID 5401588.
• Upon nucleotide hydrolysis the loop does not significantly change the protein conformation, but stays bound to the remaining phosphate groups. Walker motif A-binding has been shown to cause structural changes in the bound nucleotide, along the line of the induced fit model of enzyme binding.^{[citation needed]}
• Similar folds
  • PTPs (protein tyrosine phosphatases) that catalyse the hydrolysis of an inorganic phosphate from a phosphotyrosine residue (the reverse of a tyrosine kinase reaction) contain a motif which folds into a P-loop-like structure with an arginine in the place of the conserved lysine. The conserved sequence of this motif is C-x(5)-R-[ST], where C and R denote cysteine and arginine residues respectively.
    • Zhang M, Stauffacher CV, Lin D, Van Etten RL (August 1998). “Crystal structure of a human low molecular weight phosphotyrosyl phosphatase. Implications for substrate specificity”. The Journal of Biological Chemistry. 273 (34): 21714–21720. doi:10.1074/jbc.273.34.21714. PMID 9705307.
  • Pyridoxal phosphate (PLP) utilizing enzymes such as cysteine synthase have also been said to resemble a P-loop.
• A-loop
  • The A-loop (aromatic residue interacting with the adenine ring of ATP) refers to conserved aromatic amino acids, essential for ATP-binding, found in about 25 amino acids upstream of the Walker A motif in a subset of P-loop proteins.
    • Ambudkar SV, Kim IW, Xia D, Sauna ZE (February 2006). “The A-loop, a novel conserved aromatic acid subdomain upstream of the Walker A motif in ABC transporters, is critical for ATP binding”. FEBS Letters. 580 (4): 1049–1055. doi:10.1016/j.febslet.2005.12.051. PMID 16412422.
• Walker B motif
  • Walker B motif is a motif in most P-loop proteins situated well downstream of the A-motif. The consensus sequence of this motif was reported to be [RK]-x(3)-G-x(3)-LhhhD, where R, K, G, L and D denote arginine, lysine, glycine, leucine and aspartic acid residues respectively, x represents any of the 20 standard amino acids and h denotes a hydrophobic amino acid. This motif was changed to be hhhhDE, where E denotes a glutamate residue. The aspartate and glutamate also form a part of the DEAD/DEAH motifs found in helicases. The aspartate residue co-ordinates magnesium ions, and the glutamate is essential for ATP hydrolysis. There is considerable variability in the sequence of this motif, with the only invariant features being a negatively charged residue following a stretch of bulky, hydrophobic amino acids.
    • Walker JE, Saraste M, Runswick MJ, Gay NJ (1982). “Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold”. The EMBO Journal. 1 (8): 945–951. doi:10.1002/j.1460-2075.1982.tb01276.x. PMC 553140. PMID 6329717.
    • Hanson PI, Whiteheart SW (July 2005). “AAA+ proteins: have engine, will work”. Nature Reviews. Molecular Cell Biology. 6 (7): 519–529. doi:10.1038/nrm1684. PMID 16072036. S2CID 27830342.
    • Koonin EV (June 1993). “A common set of conserved motifs in a vast variety of putative nucleic acid-dependent ATPases including MCM proteins involved in the initiation of eukaryotic DNA replication”. Nucleic Acids Research. 21 (11): 2541–2547. doi:10.1093/nar/21.11.2541. PMC 309579. PMID 8332451.
      • DEAD box proteins are involved in an assortment of metabolic processes that typically involve RNAs, but in some cases also other nucleic acids. They are highly conserved in nine motifs and can be found in most prokaryotes and eukaryotes, but not all. Many organisms, including humans, contain DEAD-box (SF2) helicases, which are involved in RNA metabolism.
        • Takashi Kikuma; Masaya Ohtsu; Takahiko Utsugi; Shoko Koga; Kohji Okuhara; Toshihiko Eki; Fumihiro Fujimori; Yasufumi Murakami (March 2004). “Dbp9p, a Member of the DEAD Box Protein Family, Exhibits DNA Helicase Activity”. J. Biol. Chem. 279 (20): 20692–20698. doi:10.1074/jbc.M400231200. PMID 15028736.
        • Heung LJ, Del Poeta M (March 2005). “Unlocking the DEAD-box: a key to cryptococcal virulence?”. J. Clin. Invest. 115 (3): 593–5. doi:10.1172/JCI24508. PMC 1052016. PMID 15765144.
      • DEAD box proteins were first brought to attention in the late 1980s in a study that looked at a group of NTP binding sites that were similar in sequence to the eIF4A RNA helicase sequence. The results of this study showed that these proteins (p68, SrmB, MSS116, vasa, PL10, mammalian eIF4A, yeast eIF4A) involved in RNA metabolism had several common elements. There were nine common sequences found to be conserved amongst the studied species, which is an important criterion of the DEAD box family.
        • Gorbalenya AE, Koonin EV, Donchenko AP, Blinov VM (June 1989). “Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes”. Nucleic Acids Res. 17 (12): 4713–30. doi:10.1093/nar/17.12.4713. PMC 318027. PMID 2546125.
        • Linder, P.; Lasko, P. F.; Ashburner, M.; Leroy, P.; Nielsen, P. J.; Nishi, K.; Schnier, J.; Slonimski, P. P. (1989). “Birth of the D-E-A-D box”. Nature. 337 (6203): 121–122. Bibcode:1989Natur.337..121L. doi:10.1038/337121a0. PMID 2563148. S2CID 13529955.
      • The nine conserved motif from the N-terminal to the C-terminal are named as follows: Q-motif, motif 1, motif 1a, motif 1b, motif II, motif III, motif IV, motif V, and motif VI, as shown in the figure. Motif II is also known as the Walker B motif and contains the amino acid sequence D-E-A-D (asp-glu-ala-asp), which gave this family of proteins the name “DEAD box”. Motif 1, motif II, the Q motif, and motif VI are all needed for ATP binding and hydrolysis, while motifs, 1a, 1b, III, IV, and V may be involved in intramolecular rearrangements and RNA interaction.
        • Linder, P.; Lasko, P. F.; Ashburner, M.; Leroy, P.; Nielsen, P. J.; Nishi, K.; Schnier, J.; Slonimski, P. P. (1989). “Birth of the D-E-A-D box”. Nature. 337 (6203): 121–122. Bibcode:1989Natur.337..121L. doi:10.1038/337121a0. PMID 2563148. S2CID 13529955.
        • Tanner NK, Cordin O, Banroques J, Doère M, Linder P (January 2003). “The Q motif: a newly identified motif in DEAD box helicases may regulate ATP binding and hydrolysis”. Mol. Cell. 11 (1): 127–38. doi:10.1016/S1097-2765(03)00006-6. PMID 12535527.
      • The DEAH and SKI2 families have had proteins that have been identified to be related to the DEAD box family. These two relatives have a few particularly unique motifs^[which?] that are conserved within their own family. DEAD box, DEAH, and the SKI2 families are collectively referred to as DExD/H proteins. It is thought that each family has a specific role in RNA metabolism, for example both DEAD box and DEAH box proteins NTPase activities become stimulated by RNA, but DEAD box proteins use ATP and DEAH does not.
        • Tanner NK, Cordin O, Banroques J, Doère M, Linder P (January 2003). “The Q motif: a newly identified motif in DEAD box helicases may regulate ATP binding and hydrolysis”. Mol. Cell. 11 (1): 127–38. doi:10.1016/S1097-2765(03)00006-6. PMID 12535527.
        • Tanaka N, Schwer B (July 2005). “Characterization of the NTPase, RNA-binding, and RNA helicase activities of the DEAH-box splicing factor Prp22”. Biochemistry. 44 (28): 9795–803. doi:10.1021/bi050407m. PMID 16008364.
        • Xu J, Wu H, Zhang C, Cao Y, Wang L, Zeng L, Ye X, Wu Q, Dai J, Xie Y, Mao Y (2002). “Identification of a novel human DDX40gene, a new member of the DEAH-box protein family”. J. Hum. Genet. 47 (12): 681–3. doi:10.1007/s100380200104. PMID 12522690.
        • Wang L, Lewis MS, Johnson AW (August 2005). “Domain interactions within the Ski2/3/8 complex and between the Ski complex and Ski7p”. RNA. 11 (8): 1291–302. doi:10.1261/rna.2060405. PMC 1370812. PMID 16043509.
        • de la Cruz J, Kressler D, Linder P (May 1999). “Unwinding RNA in Saccharomyces cerevisiae: DEAD-box proteins and related families”. Trends Biochem. Sci. 24 (5): 192–8. doi:10.1016/S0968-0004(99)01376-6. PMID 10322435.
      • Biological functions
      • DEAD box proteins are considered to be RNA helicases and many have been found to be required in cellular processes such as RNA metabolism, including nuclear transcription, pre mRNA splicing, ribosome biogenesis, nucleocytoplasmic transport, translation, RNA decay and organellar gene expression.
        • de la Cruz J, Kressler D, Linder P (May 1999). “Unwinding RNA in Saccharomyces cerevisiae: DEAD-box proteins and related families”. Trends Biochem. Sci. 24 (5): 192–8. doi:10.1016/S0968-0004(99)01376-6. PMID 10322435.
        • Aubourg S, Kreis M, Lecharny A (January 1999). “The DEAD box RNA helicase family in Arabidopsis thaliana”. Nucleic Acids Res. 27 (2): 628–36. doi:10.1093/nar/27.2.628. PMC 148225. PMID 9862990.
        • Staley JP, Guthrie C (February 1998). “Mechanical devices of the spliceosome: motors, clocks, springs, and things”. Cell. 92 (3): 315–26. doi:10.1016/S0092-8674(00)80925-3. PMID 9476892. S2CID 6208113.
      • Pre-mRNA splicing
      • Pre-mRNA splicing requires rearrangements of five large RNP complexes, which are snRNPs U1, U2, U4, U5, and U6. DEAD box proteins are helicases that perform unwinding in an energy dependent approach and are able to perform these snRNP rearrangements in a quick and efficient manner. There are three DEAD box proteins in the yeast system, Sub2, Prp28, and Prp5, and have been proven to be required for in vivo splicing. Prp5 has been shown to assist in a conformational rearrangement of U2 snRNA, which makes the branch point recognition sequence of U2 available to bind the branch point sequence. Prp28 may have a role in recognizing the 5’ splice site and does not display RNA helicase activity, suggesting that other factors must be present in order to activate Prp28. DExD/H proteins have also been found to be required components in pre- mRNA splicing, in particular the DEAH proteins, Prp2, Prp16, Prp22, Prp43, and Brr213. As shown in the figure, DEAD box proteins are needed in the initial steps of spliceosome formation, while DEAH box proteins are indirectly required for the transesterifications, release of the mRNA, and recycling of the spliceosome complex9.
        • Linder P (2006). “Dead-box proteins: a family affair—active and passive players in RNP-remodeling”. Nucleic Acids Res. 34 (15): 4168–80. doi:10.1093/nar/gkl468. PMC 1616962. PMID 16936318.
        • Ghetti A, Company M, Abelson J (April 1995). “Specificity of Prp24 binding to RNA: a role for Prp24 in the dynamic interaction of U4 and U6 snRNAs”. RNA. 1 (2): 132–45. PMC 1369067. PMID 7585243.
        • Strauss EJ, Guthrie C (August 1994). “PRP28, a ‘DEAD-box’ protein, is required for the first step of mRNA splicing in vitro”. Nucleic Acids Res. 22 (15): 3187–93. doi:10.1093/nar/22.15.3187. PMC 310295. PMID 7520570.
        • Silverman E, Edwalds-Gilbert G, Lin RJ (July 2003). “DExD/H-box proteins and their partners: helping RNA helicases unwind”. Gene. 312: 1–16. doi:10.1016/S0378-1119(03)00626-7. PMID 12909336.
      • Translation initiation
      • The eIF4A translation initiation factor was the first DEAD box protein found to have a RNA dependent ATPase activity. It has been proposed that this abundant protein helps in unwinding the secondary structure in the 5′-untranslated region. This can inhibit the scanning process of the small ribosomal subunit, if not unwound. Ded1 is another DEAD box protein that is also needed for translation initiation, but its exact role in this process is still obscure. Vasa, a DEAD box protein highly related to Ded1 plays a part in translation initiation by interacting with eukaryotic initiation factor 2 (eIF2).
        • Sonenberg N (1988). Cap-binding proteins of eukaryotic messenger RNA: functions in initiation and control of translation. Progress in Nucleic Acid Research and Molecular Biology. Vol. 35. pp. 173–207. doi:10.1016/S0079-6603(08)60614-5. ISBN 978-0-12-540035-0. PMID 3065823
        • Berthelot K, Muldoon M, Rajkowitsch L, Hughes J, McCarthy JE (February 2004). “Dynamics and processivity of 40S ribosome scanning on mRNA in yeast”. Mol. Microbiol. 51 (4): 987–1001. doi:10.1046/j.1365-2958.2003.03898.x. PMID 14763975.
        • Carrera P, Johnstone O, Nakamura A, Casanova J, Jäckle H, Lasko P (January 2000). “VASA mediates translation through interaction with a Drosophila yIF2 homolog”. Mol. Cell. 5 (1): 181–7. doi:10.1016/S1097-2765(00)80414-1. hdl:11858/00-001M-0000-0012-F80E-6. PMID 10678180.
• Evolutionary connections
  • There is a hypothesis that the Walker A phosphate binding motif can be evolutionarily related to Rossman‘s fold phosphate binding motif because of the shared principles in the location of the binding loop between the first β-strand and α-helix in the αβα sandwich fold and positioning of the functionally important aspartate on the tip of the second β-strand. 
    • Longo LM, Jabłońska J, Vyas P, Kanade M, Kolodny R, Ben-Tal N, Tawfik DS (December 2020). Deane CM, Boudker O (eds.). “On the emergence of P-Loop NTPase and Rossmann enzymes from a Beta-Alpha-Beta ancestral fragment”. eLife. 9: e64415. doi:10.7554/eLife.64415. PMC 7758060. PMID 33295875.
      • The Rossmann fold is a tertiary fold found in proteins that bind nucleotides, such as enzyme cofactorsFAD, NAD⁺, and NADP⁺. This fold is composed of alternating beta strands and alpha helical segments where the beta strands are hydrogen bonded to each other forming an extended beta sheet and the alpha helices surround both faces of the sheet to produce a three-layered sandwich. The classical Rossmann fold contains six beta strands whereas Rossmann-like folds, sometimes referred to as Rossmannoid folds, contain only five strands. The initial beta-alpha-beta (bab) fold is the most conserved segment of the Rossmann fold.
        • Hanukoglu I (2015). “Proteopedia: Rossmann fold: A beta-alpha-beta fold at dinucleotide binding sites”. Biochemistry and Molecular Biology Education. 43 (3): 206–9. doi:10.1002/bmb.20849. PMID 25704928.
        • Cox MM, Nelson DL (2013). Lehninger Principles of Biochemistry (6th ed.). New York: W.H. Freeman. ISBN 978-1-4292-3414-6.
      • The Rossmann fold was first described by Dr. Michael Rossmann and coworkers in 1974. He was the first to deduce the structure of lactate dehydrogenase and characterized the structural motif within this enzyme which would later be called the Rossmann fold. It was subsequently found that most dehydrogenases that utilize NAD or NADP contain this same structurally conserved Rossmann fold motif.
        • Kessel A (2010). Introduction to Proteins: Structure, Function, and Motion. Florida: CRC Press. p. 143. ISBN 978-1-4398-1071-2.
        • Rao ST, Rossmann MG (May 1973). “Comparison of super-secondary structures in proteins”. Journal of Molecular Biology. 76 (2): 241–56. doi:10.1016/0022-2836(73)90388-4. PMID 4737475.
          • Michael G. Rossmann was a German-American physicist, microbiologist, and Hanley Distinguished Professor of Biological Sciences at Purdue University who led a team of researchers to be the first to map the structure of a human common cold virus to an atomic level. He also discovered the Rossmann fold protein motif. His most well recognised contribution to structural biology is the development of a phasing technique named molecular replacement, which has led to about three quarters of depositions in the Protein Data Bank.
            • Rossmann MG, Blow DM (10 January 1962). “The detection of sub-units within the crystallographic asymmetric unit” (PDF). Acta Crystallographica. 15: 24–31. CiteSeerX 10.1.1.319.3019. doi:10.1107/s0365110x62000067.
      • In 1989, Israel Hanukoglu from the Weizmann Institute of Science discovered that the consensus sequence for NADP⁺ binding site in some enzymes that utilize NADP⁺ differs from the NAD⁺ binding motif. This discovery was used to re-engineer coenzyme specificities of enzymes.
        • Hanukoglu I, Gutfinger T (March 1989). “cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases”. European Journal of Biochemistry. 180 (2): 479–84. doi:10.1111/j.1432-1033.1989.tb14671.x. PMID 2924777.
        • Scrutton NS, Berry A, Perham RN (January 1990). “Redesign of the coenzyme specificity of a dehydrogenase by protein engineering”. Nature. 343 (6253): 38–43. Bibcode:1990Natur.343…38S. doi:10.1038/343038a0. PMID 2296288. S2CID 1580419.
      • The Rossmann fold is composed of six parallel beta strands that form an extended beta sheet. The first three strands are connected by α- helices resulting in a beta-alpha-beta-alpha-beta structure. This pattern is duplicated once to produce an inverted tandem repeat containing six strands. Overall, the strands are arranged in the order of 321456 (1 = N-terminal, 6 = C-terminal). Five stranded Rossmann-like folds are arranged in the order 32145. The overall tertiary structure of the fold resembles a three-layered sandwich wherein the filling is composed of an extended beta sheet and the two slices of bread are formed by the connecting parallel alpha-helices.One of the features of the Rossmann fold is its co-factor binding specificity. Through the analysis of four NADH-binding enzymes, it was found that in all four enzymes the nucleotide co-factor entailed the same conformation and orientation with respect to the polypeptide chain.
        • Ziegler GA, Vonrhein C, Hanukoglu I, Schulz GE (Jun 1999). “The structure of adrenodoxin reductase of mitochondrial P450 systems: electron transfer for steroid biosynthesis”. Journal of Molecular Biology. 289 (4): 981–90. doi:10.1006/jmbi.1999.2807. PMID 10369776.
        • Ziegler GA, Schulz GE (2000). “Crystal structures of adrenodoxin reductase in complex with NADP+ and NADPH suggesting a mechanism for the electron transfer of an enzyme family”. Biochemistry. 39 (36): 10986–95. doi:10.1021/bi000079k. PMID 10998235.
        • GRCh38: Ensembl release 89: ENSG00000161513 – Ensembl, May 2017
      • The fold may contain additional strands joined by short helices or coils. The most conserved segment of Rossmann folds is the first beta-alpha-beta segment. Phosphate-binding loop is located between the first beta-strand and alpha-helix. On the tip of the second beta-strand, there is a conserved aspartate residue that is involved in ribose binding. Since this segment is in contact with the ADP portion of dinucleotides such as FAD, NAD and NADP it is also called as an “ADP-binding beta-beta fold.
        • GRCh38: Ensembl release 89: ENSG00000161513 – Ensembl, May 2017
        • Aliverti A, Pandini V, Pennati A, de Rosa M, Zanetti G (June 2008). “Structural and functional diversity of ferredoxin-NADP(+) reductases”. Archives of Biochemistry and Biophysics. 474 (2): 283–91. doi:10.1016/j.abb.2008.02.014. hdl:2434/41439. PMID 18307973.
      • The function of the Rossmann fold in enzymes is to bind nucleotide cofactors. It also often contributes to substrate binding.
      • Metabolic enzymes normally have one specific function, and in the case of UDP-glucose 6-dehydrogenase, the primary function is to catalyze the two step NAD(+)-dependent oxidation of UDP-glucose into UDP-glucuronic acid. The N- and C-terminal domains of UgdG share structural features with ancient mitochondrial ribonucleases named MAR. MARs are present in lower eukaryotic microorganisms, have a Rossmannoid-fold and belong to the isochorismatase superfamily. This observation reinforces that the Rossmann structural motifs found in NAD(+)-dependent dehydrogenases can have a dual function working as a nucleotide cofactor binding domain and as a ribonuclease.
        • Spaans SK, Weusthuis RA, van der Oost J, Kengen SW (2015). “NADPH-generating systems in bacteria and archaea”. Frontiers in Microbiology. 6: 742. doi:10.3389/fmicb.2015.00742. PMC 4518329. PMID 26284036.
      • Rossman and Rossmannoids
      • The evolutionary relationship between the Rossmann fold and Rossmann-like folds is unclear. These folds are referred to as Rossmannoids. It has been hypothesized that all these folds, including a Rossmann fold originated from a single common ancestral fold, that had nucleotide binding capabilities, in addition to non-specific catalytic activity.
        • Omura T, Sanders E, Estabrook RW, Cooper DY, Rosenthal O (December 1966). “Isolation from adrenal cortex of a nonheme iron protein and a flavoprotein functional as a reduced triphosphopyridine nucleotide-cytochrome P-450 reductase”. Archives of Biochemistry and Biophysics. 117 (3): 660–673. doi:10.1016/0003-9861(66)90108-1.
      • However, an analysis of the PDB finds evidence of convergent evolution with 156 separate H-groups of demonstrable homology, from which 123 X-groups of probable homology can be found. The groups have been integrated into ECOD.
        • “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
        • “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
      • Conventional Rossman group
      • Phylogenetic analysis of the NADP binding enzyme adrenodoxin reductase revealed that from prokaryotes, through metazoa and up to primates the sequence motif difference from that of most FAD and NAD-binding sites is strictly conserved.
        • Lambeth JD, Kamin H (Jul 1976). “Adrenodoxin reductase. Properties of the complexes of reduced enzyme with NADP+ and NADPH”. The Journal of Biological Chemistry. 251 (14): 4299–306. doi:10.1016/S0021-9258(17)33296-9. PMID 6475.
          • Adrenodoxin reductase (Enzyme Nomenclature name: adrenodoxin-NADP+ reductase, EC 1.18.1.6), was first isolated from bovine adrenal cortex where it functions as the first enzyme in the mitochondrial P450 systems that catalyze essential steps in steroid hormone biosynthesis. Examination of complete genome sequences revealed that adrenodoxin reductase gene is present in most metazoans and prokaryotes.
            • Omura T, Sanders E, Estabrook RW, Cooper DY, Rosenthal O (December 1966). “Isolation from adrenal cortex of a nonheme iron protein and a flavoprotein functional as a reduced triphosphopyridine nucleotide-cytochrome P-450 reductase”. Archives of Biochemistry and Biophysics. 117 (3): 660–673. doi:10.1016/0003-9861(66)90108-1.
            • Hanukoglu I (Dec 1992). “Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis”. The Journal of Steroid Biochemistry and Molecular Biology. 43 (8): 779–804. doi:10.1016/0960-0760(92)90307-5. PMID 22217824. S2CID 112729.
            • Hanukoglu I (2017). “Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme”. Journal of Molecular Evolution. 85 (5): 205–218. Bibcode:2017JMolE..85..205H. doi:10.1007/s00239-017-9821-9. PMID 29177972. S2CID 7120148.
          • The name of the enzyme was coined based on its function to reduce a [2Fe-2S] (2 iron, 2 sulfur) electron-transfer protein that was named adrenodoxin. Later, in some studies, the enzyme was also referred to as a “ferredoxin reductase”, as adrenodoxin is a ferredoxin. In the human gene nomenclature, the standard name is ferredoxin reductase and the symbol is FDXR, with ADXR specified as a synonym.
          • The assignment of the name “ferredoxin reductase” has been criticized as a misnomer because determination of the structure of adrenodoxin reductase revealed that it is completely different from that of plant ferredoxin reductase and there is no homology between these two enzymes. With more proteins with a ferroxodin-reducing activity discovered in both families as well as novel families, this enzyme activity is now seen as an example of convergent evolution.
            • Hanukoglu I (1996). “Electron transfer proteins of cytochrome P450 systems”. Physiological Functions of Cytochrome P450 in Relation to Structure and Regulation (PDF). Advances in Molecular and Cell Biology. Vol. 14. pp. 29–55. doi:10.1016/S1569-2558(08)60339-2. ISBN 9780762301133. 
            • Ziegler GA, Vonrhein C, Hanukoglu I, Schulz GE (Jun 1999). “The structure of adrenodoxin reductase of mitochondrial P450 systems: electron transfer for steroid biosynthesis”. Journal of Molecular Biology. 289 (4): 981–90. doi:10.1006/jmbi.1999.2807. PMID 10369776.
            • Ziegler GA, Schulz GE (2000). “Crystal structures of adrenodoxin reductase in complex with NADP+ and NADPH suggesting a mechanism for the electron transfer of an enzyme family”. Biochemistry. 39 (36): 10986–95. doi:10.1021/bi000079k. PMID 10998235.
            • Aliverti A, Pandini V, Pennati A, de Rosa M, Zanetti G (June 2008). “Structural and functional diversity of ferredoxin-NADP(+) reductases”. Archives of Biochemistry and Biophysics. 474 (2): 283–91. doi:10.1016/j.abb.2008.02.014. hdl:2434/41439. PMID 18307973.
            • Spaans SK, Weusthuis RA, van der Oost J, Kengen SW (2015). “NADPH-generating systems in bacteria and archaea”. Frontiers in Microbiology. 6: 742. doi:10.3389/fmicb.2015.00742. PMC 4518329. PMID 26284036
          • Adrenodoxin reductase is a flavoprotein as it carries a FAD type coenzyme. The enzyme functions as the first electron transfer protein of mitochondrial P450 systems such as P450scc. The FAD coenzyme receives two electrons from NADPH and transfers them one at a time to the electron transfer protein adrenodoxin. Adrenodoxin functions as a mobile shuttle that transfers electrons between ADXR and mitochondrial P450s.
            • Lambeth JD, Kamin H (Jul 1976). “Adrenodoxin reductase. Properties of the complexes of reduced enzyme with NADP+ and NADPH”. The Journal of Biological Chemistry. 251 (14): 4299–306. doi:10.1016/S0021-9258(17)33296-9. PMID 6475.
            • Hanukoglu I, Jefcoate CR (Apr 1980). “Mitochondrial cytochrome P-450scc. Mechanism of electron transport by adrenodoxin” (PDF). The Journal of Biological Chemistry. 255 (7): 3057–61. doi:10.1016/S0021-9258(19)85851-9. PMID 6766943.
            • Hanukoglu I (Dec 1992). “Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis”. The Journal of Steroid Biochemistry and Molecular Biology. 43 (8): 779–804. doi:10.1016/0960-0760(92)90307-5. PMID 22217824. S2CID 112729.
          • The cDNA for adrenodoxin reductase was first cloned in 1987. In both bovine and human genomes there is only a single copy of the gene.
            • Hanukoglu I, Gutfinger T, Haniu M, Shively JE (Dec 1987). “Isolation of a cDNA for adrenodoxin reductase (ferredoxin-NADP+ reductase). Implications for mitochondrial cytochrome P-450 systems”. European Journal of Biochemistry. 169 (3): 449–455. doi:10.1111/j.1432-1033.1987.tb13632.x. PMID 3691502.
            • Solish SB, Picado-Leonard J, Morel Y, Kuhn RW, Mohandas TK, Hanukoglu I, Miller WL (Oct 1988). “Human adrenodoxin reductase: two mRNAs encoded by a single gene on chromosome 17cen—-q25 are expressed in steroidogenic tissues”. Proceedings of the National Academy of Sciences of the United States of America. 85 (19): 7104–7108. Bibcode:1988PNAS…85.7104S. doi:10.1073/pnas.85.19.7104. PMC 282132. PMID 2845396.
          • ADXR gene is expressed in all tissues that have mitochondrial P450s. The highest levels of the enzyme are found in the adrenal cortex, granulosa cells of the ovary and leydig cells of the testis that specialize in steroid hormone synthesis. Immmunofluorescent staining shows that enzyme is localized in mitochondria. The enzyme is also expressed in the liver, the kidney and the placenta.
            • Hanukoglu I (Dec 1992). “Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis”. The Journal of Steroid Biochemistry and Molecular Biology. 43 (8): 779–804. doi:10.1016/0960-0760(92)90307-5. PMID 22217824. S2CID 112729
            • Hanukoglu I, Hanukoglu Z (May 1986). “Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for membrane organization and gene regulation”. European Journal of Biochemistry. 157 (1): 27–31. doi:10.1111/j.1432-1033.1986.tb09633.x. PMID 3011431.
            • Hanukoglu I, Suh BS, Himmelhoch S, Amsterdam A (October 1990). “Induction and mitochondrial localization of cytochrome P450scc system enzymes in normal and transformed ovarian granulosa cells”. The Journal of Cell Biology. 111 (4): 1373–81. doi:10.1083/jcb.111.4.1373. PMC 2116250. PMID 2170421.
          • Adrenodoxin reductase has two domains that bind NADPH and FAD separately. The FAD and NADP binding sites of the enzyme were predicted by sequence analysis of the enzyme.
            • Hanukoglu I (2017). “Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme”. Journal of Molecular Evolution. 85 (5): 205–218. Bibcode:2017JMolE..85..205H. doi:10.1007/s00239-017-9821-9. PMID 29177972. S2CID 7120148.
            • Hanukoglu I, Gutfinger T (Mar 1989). “cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases”. European Journal of Biochemistry. 180 (2): 479–84. doi:10.1111/j.1432-1033.1989.tb14671.x. PMID 2924777.
          • While the FAD-binding site has a consensus sequence (Gly-x-Gly-x-x-Gly) that is similar to other Rossmann folds in FAD and NAD binding sites, the NADPH binding site consensus sequence differs from the FAD-binding site by the substitution of an alanine instead of the last Gly (Gly-x-Gly-x-x-Ala). The location of these FAD and NADP binding sites were confirmed by the crystal structure of the enzyme.
            • Hanukoglu I (2015). “Proteopedia: Rossmann fold: A beta-alpha-beta fold at dinucleotide binding sites”. Biochem Mol Biol Educ. 43 (3): 206–209. doi:10.1002/bmb.20849. PMID 25704928. S2CID 11857160.
            • Hanukoglu I, Gutfinger T (Mar 1989). “cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases”. European Journal of Biochemistry. 180 (2): 479–84. doi:10.1111/j.1432-1033.1989.tb14671.x. PMID 2924777.
            • Hanukoglu I (2017). “Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme”. Journal of Molecular Evolution. 85 (5): 205–218. Bibcode:2017JMolE..85..205H. doi:10.1007/s00239-017-9821-9. PMID 29177972. S2CID 7120148.
            • Ziegler GA, Schulz GE (2000). “Crystal structures of adrenodoxin reductase in complex with NADP+ and NADPH suggesting a mechanism for the electron transfer of an enzyme family”. Biochemistry. 39 (36): 10986–95. doi:10.1021/bi000079k. PMID 10998235.
        • In many articles and textbooks, a Rossmann fold is defined as a strict repeated series of βαβ structure. Yet, comprehensive examination of the Rossmann folds in many NAD(P) and FAD binding sites revealed that only the first βα structure is strictly conserved. In some enzymes, there may be many loops and several helices (i.e., not a single helix) between the beta strands that form the beta-sheet. These enzymes have a common origin indicated by conserved sequence and structural features, according to Hanukoglu.
          • Hanukoglu I (2015). “Proteopedia: Rossmann fold: A beta-alpha-beta fold at dinucleotide binding sites”. Biochemistry and Molecular Biology Education. 43 (3): 206–9. doi:10.1002/bmb.20849. PMID 25704928.
          • Hanukoglu I (2017). “Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme”. Journal of Molecular Evolution. 85 (5): 205–218. Bibcode:2017JMolE..85..205H. doi:10.1007/s00239-017-9821-9. PMID 29177972. S2CID 7120148.
        • The result by Hanukoglu (2017) is corroborated by Medvedev et al. (2020), in the form of an ECOD “H-group” called “Rossmann-related“. Even within this group, ECOD describes a wide range of non-nucleotide activities.
          • Medvedev KE, Kinch LN, Dustin Schaeffer R, Pei J, Grishin NV (February 2021). “A Fifth of the Protein World: Rossmann-like Proteins as an Evolutionarily Successful Structural unit”. Journal of Molecular Biology. 433 (4): 166788. doi:10.1016/j.jmb.2020.166788. PMC7870570. PMID33387532.
            • Medvedev KE, et al. “Rossmann-fold project”. Grishin Lab. UT Southwestern Medical Center.

See also

• Activation loop
• Autophosphorylation
• Ca²⁺/calmodulin-dependent protein kinase
• Cell signaling
• Cyclin-dependent kinase
• G protein-coupled receptor
• Nucleoside-diphosphate kinase
• Phosphatase
• Phosphatidylinositol phosphate kinases
• Phospholipid
• Phosphoprotein
• Phosphorylation
• Phosphotransferase
• Signal transduction
• Thymidine kinase
• Thymidine kinase in clinical chemistry
• Thymidylate kinase
• Wall-associated kinase
• DDX3X
• DEAD/DEAH box helicase
• RNA helicase
• Walker A motif
• Cypovirus
• BacMam
• The Cobra Event
• Pancrustacea – clade including natural hosts of the viruses
• Early 35 kDa protein
• Polyhedrosis (disambiguation)

References

1. Koonin EV, Aravind L (May 2000). “The NACHT family – a new group of predicted NTPases implicated in apoptosis and MHC transcription activation”. Trends in Biochemical Sciences. 25 (5): 223–4. doi:10.1016/S0968-0004(00)01577-2. PMID 10782090.

Further reading

• van der Steege G, Draaijers TG, Grootscholten PM, et al. (1995). “A provisional transcript map of the spinal muscular atrophy (SMA) critical region”. Eur. J. Hum. Genet. 3 (2): 87–95. doi:10.1159/000472281. PMID 7552146. S2CID 46083524.
• Liston P, Roy N, Tamai K, et al. (1996). “Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes”. Nature. 379 (6563): 349–53. Bibcode:1996Natur.379..349L. doi:10.1038/379349a0. PMID 8552191. S2CID 4305853.
• Chen Q, Baird SD, Mahadevan M, et al. (1998). “Sequence of a 131-kb region of 5q13.1 containing the spinal muscular atrophy candidate genes SMN and NAIP”. Genomics. 48 (1): 121–7. doi:10.1006/geno.1997.5141. PMID 9503025.
• Monani UR, Lorson CL, Parsons DW, et al. (1999). “A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2”. Hum. Mol. Genet. 8 (7): 1177–83. doi:10.1093/hmg/8.7.1177. PMID 10369862.
• Yamamoto K, Sakai H, Hadano S, et al. (1999). “Identification of two distinct transcripts for the neuronal apoptosis inhibitory protein gene”. Biochem. Biophys. Res. Commun. 264 (3): 998–1006. doi:10.1006/bbrc.1999.1615. PMID 10544044.
• Mercer EA, Korhonen L, Skoglösa Y, et al. (2000). “NAIP interacts with hippocalcin and protects neurons against calcium-induced cell death through caspase-3-dependent and -independent pathways”. EMBO J. 19 (14): 3597–607. doi:10.1093/emboj/19.14.3597. PMC 313967. PMID 10899114.
• Sanna MG, da Silva Correia J, Ducrey O, et al. (2002). “IAP suppression of apoptosis involves distinct mechanisms: the TAK1/JNK1 signaling cascade and caspase inhibition”. Mol. Cell. Biol. 22 (6): 1754–66. doi:10.1128/MCB.22.6.1754-1766.2002. PMC 135597. PMID 11865055.
• Akutsu T, Nishio H, Sumino K, et al. (2002). “Molecular genetics of spinal muscular atrophy: contribution of the NAIP gene to clinical severity”. Kobe Journal of Medical Sciences. 48 (1–2): 25–31. PMID 11912351.
• Xu M, Okada T, Sakai H, et al. (2002). “Functional human NAIP promoter transcription regulatory elements for the NAIP and PsiNAIP genes”. Biochim. Biophys. Acta. 1574 (1): 35–50. doi:10.1016/S0167-4781(01)00343-8. PMID 11955612.
• Notarbartolo M, Cervello M, Dusonchet L, D’Alessandro N (2002). “NAIP-deltaEx10-11: a novel splice variant of the apoptosis inhibitor NAIP differently expressed in drug-sensitive and multidrug-resistant HL60 leukemia cells”. Leuk. Res. 26 (9): 857–62. doi:10.1016/S0145-2126(02)00016-4. PMID 12127562.
• Lindholm D, Mercer EA, Yu LY, et al. (2002). “Neuronal apoptosis inhibitory protein: Structural requirements for hippocalcin binding and effects on survival of NGF-dependent sympathetic neurons”. Biochim. Biophys. Acta. 1600 (1–2): 138–47. doi:10.1016/S1570-9639(02)00454-5. PMID 12445469.
• Damiano JS, Oliveira V, Welsh K, Reed JC (2004). “Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses”. Biochem. J. 381 (Pt 1): 213–9. doi:10.1042/BJ20031506. PMC 1133779. PMID 15107016.
• Davoodi J, Lin L, Kelly J, et al. (2004). “Neuronal apoptosis-inhibitory protein does not interact with Smac and requires ATP to bind caspase-9”. J. Biol. Chem. 279 (39): 40622–8. doi:10.1074/jbc.M405963200. PMID 15280366.
• Aubin D, Gagnon A, Grunder L, et al. (2004). “Adipogenic and antiapoptotic protein levels in human adipose stromal cells after weight loss”. Obes. Res. 12 (8): 1231–4. doi:10.1038/oby.2004.156. PMID 15340105.
• Schmutz J, Martin J, Terry A, et al. (2004). “The DNA sequence and comparative analysis of human chromosome 5”. Nature. 431 (7006): 268–74. Bibcode:2004Natur.431..268S. doi:10.1038/nature02919. PMID 15372022.
• Romanish MT, Lock WM, van de Lagemaat LN, et al. (2007). “Repeated recruitment of LTR retrotransposons as promoters by the anti-apoptotic locus NAIP during mammalian evolution”. PLOS Genet. 3 (1): e10. doi:10.1371/journal.pgen.0030010. PMC 1781489. PMID 17222062.
• Maier JK, Balabanian S, Coffill CR, et al. (2007). “Distribution of neuronal apoptosis inhibitory protein in human tissues”. J. Histochem. Cytochem. 55 (9): 911–23. doi:10.1369/jhc.6A7144.2007. PMID 17510375.
• Hausmanowa-Petrusewicz I, Jedrzejowska M (2002). “Spinal muscular atrophy of childhood at the edge of the centuries”. Functional Neurology. 16 (4 Suppl): 247–53. PMID 11996521.
• Paushkin S, Gubitz AK, Massenet S, Dreyfuss G (June 2002). “The SMN complex, an assemblyosome of ribonucleoproteins”. Current Opinion in Cell Biology. 14 (3): 305–12. doi:10.1016/S0955-0674(02)00332-0. PMID 12067652.
• van der Steege G, Draaijers TG, Grootscholten PM, Osinga J, Anzevino R, Velonà I, Den Dunnen JT, Scheffer H, Brahe C, van Ommen GJ (1995). “A provisional transcript map of the spinal muscular atrophy (SMA) critical region”. European Journal of Human Genetics. 3 (2): 87–95. doi:10.1159/000472281. PMID 7552146. S2CID 46083524.
• Bussaglia E, Clermont O, Tizzano E, Lefebvre S, Bürglen L, Cruaud C, Urtizberea JA, Colomer J, Munnich A, Baiget M (November 1995). “A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients”. Nature Genetics. 11 (3): 335–7. doi:10.1038/ng1195-335. PMID 7581461. S2CID 10588736.
• Gennarelli M, Lucarelli M, Capon F, Pizzuti A, Merlini L, Angelini C, Novelli G, Dallapiccola B (August 1995). “Survival motor neuron gene transcript analysis in muscles from spinal muscular atrophy patients”. Biochemical and Biophysical Research Communications. 213 (1): 342–8. doi:10.1006/bbrc.1995.2135. PMID 7639755.
• Liu Q, Dreyfuss G (July 1996). “A novel nuclear structure containing the survival of motor neurons protein”. The EMBO Journal. 15 (14): 3555–65. doi:10.1002/j.1460-2075.1996.tb00725.x. PMC 451956. PMID 8670859.
• van der Steege G, Grootscholten PM, Cobben JM, Zappata S, Scheffer H, den Dunnen JT, van Ommen GJ, Brahe C, Buys CH (October 1996). “Apparent gene conversions involving the SMN gene in the region of the spinal muscular atrophy locus on chromosome 5”. American Journal of Human Genetics. 59 (4): 834–8. PMC 1914786. PMID 8808598.
• Bürglen L, Lefebvre S, Clermont O, Burlet P, Viollet L, Cruaud C, Munnich A, Melki J (March 1996). “Structure and organization of the human survival motor neurone (SMN) gene”. Genomics. 32 (3): 479–82. doi:10.1006/geno.1996.0147. PMID 8838816.
• Parsons DW, McAndrew PE, Monani UR, Mendell JR, Burghes AH, Prior TW (November 1996). “An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene”. Human Molecular Genetics. 5 (11): 1727–32. doi:10.1093/hmg/5.11.1727. PMID 8922999.
• Talbot K, Ponting CP, Theodosiou AM, Rodrigues NR, Surtees R, Mountford R, Davies KE (March 1997). “Missense mutation clustering in the survival motor neuron gene: a role for a conserved tyrosine and glycine rich region of the protein in RNA metabolism?”. Human Molecular Genetics. 6 (3): 497–500. doi:10.1093/hmg/6.3.497. PMID 9147655.
• Hahnen E, Schönling J, Rudnik-Schöneborn S, Raschke H, Zerres K, Wirth B (May 1997). “Missense mutations in exon 6 of the survival motor neuron gene in patients with spinal muscular atrophy (SMA)”. Human Molecular Genetics. 6 (5): 821–5. doi:10.1093/hmg/6.5.821. PMID 9158159.
• Coovert DD, Le TT, McAndrew PE, Strasswimmer J, Crawford TO, Mendell JR, Coulson SE, Androphy EJ, Prior TW, Burghes AH (August 1997). “The survival motor neuron protein in spinal muscular atrophy”. Human Molecular Genetics. 6 (8): 1205–14. doi:10.1093/hmg/6.8.1205. PMID 9259265.
• Battaglia G, Princivalle A, Forti F, Lizier C, Zeviani M (October 1997). “Expression of the SMN gene, the spinal muscular atrophy determining gene, in the mammalian central nervous system”. Human Molecular Genetics. 6 (11): 1961–71. doi:10.1093/hmg/6.11.1961. PMID 9302277.
• Liu Q, Fischer U, Wang F, Dreyfuss G (September 1997). “The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins”. Cell. 90 (6): 1013–21. doi:10.1016/S0092-8674(00)80367-0. PMID 9323129.
• Iwahashi H, Eguchi Y, Yasuhara N, Hanafusa T, Matsuzawa Y, Tsujimoto Y (November 1997). “Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy”. Nature. 390 (6658): 413–7. Bibcode:1997Natur.390..413I. doi:10.1038/37144. PMID 9389483. S2CID 1936633.
• Chen Q, Baird SD, Mahadevan M, Besner-Johnston A, Farahani R, Xuan J, Kang X, Lefebvre C, Ikeda JE, Korneluk RG, MacKenzie AE (February 1998). “Sequence of a 131-kb region of 5q13.1 containing the spinal muscular atrophy candidate genes SMN and NAIP”. Genomics. 48 (1): 121–7. doi:10.1006/geno.1997.5141. PMID 9503025.
• Francis JW, Sandrock AW, Bhide PG, Vonsattel JP, Brown RH (May 1998). “Heterogeneity of subcellular localization and electrophoretic mobility of survival motor neuron (SMN) protein in mammalian neural cells and tissues”. Proceedings of the National Academy of Sciences of the United States of America. 95 (11): 6492–7. Bibcode:1998PNAS…95.6492F. doi:10.1073/pnas.95.11.6492. PMC 27826. PMID 9600994.
• Gambardella A, Mazzei R, Toscano A, Annesi G, Pasqua A, Annesi F, Quattrone F, Oliveri RL, Valentino P, Bono F, Aguglia U, Zappia M, Vita G, Quattrone A (November 1998). “Spinal muscular atrophy due to an isolated deletion of exon 8 of the telomeric survival motor neuron gene”. Annals of Neurology. 44 (5): 836–9. doi:10.1002/ana.410440522. PMID 9818944. S2CID 22595601.
• Parsons DW, McAndrew PE, Iannaccone ST, Mendell JR, Burghes AH, Prior TW (December 1998). “Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number”. American Journal of Human Genetics. 63 (6): 1712–23. doi:10.1086/302160. PMC 1377643. PMID 9837824.
• Sparkes RS, Klisak I, Miller WL (Jun 1991). “Regional mapping of genes encoding human steroidogenic enzymes: P450scc to 15q23-q24, adrenodoxin to 11q22; adrenodoxin reductase to 17q24-q25; and P450c17 to 10q24-q25”. DNA and Cell Biology. 10 (5): 359–65. doi:10.1089/dna.1991.10.359. PMID 1863359.
• Coghlan VM, Vickery LE (Oct 1991). “Site-specific mutations in human ferredoxin that affect binding to ferredoxin reductase and cytochrome P450scc”. The Journal of Biological Chemistry. 266 (28): 18606–12. doi:10.1016/S0021-9258(18)55106-1. PMID 1917982.
• Lin D, Shi YF, Miller WL (Nov 1990). “Cloning and sequence of the human adrenodoxin reductase gene”. Proceedings of the National Academy of Sciences of the United States of America. 87 (21): 8516–20. Bibcode:1990PNAS…87.8516L. doi:10.1073/pnas.87.21.8516. PMC 54987. PMID 2236061.
• Usanov SA, Chernogolov AA, Honkakoski P, Lang M, Passanen M, Raunio H, Pelkonen O (May 1990). “[Cholesterol-hydroxylating cytochrome P-450 from bovine adrenal cortex mitochondria and human placenta: immunochemical properties and structural characteristics]”. Biokhimiya. 55 (5): 865–77. PMID 2393675.
• Sasano H, Sasano N, Okamoto M, Nonaka Y (May 1989). “Immunohistochemical demonstration of adrenodoxin reductase in bovine and human adrenals”. Pathology, Research and Practice. 184 (5): 473–9. doi:10.1016/s0344-0338(89)80137-2. PMID 2748461.
• Usanov SA, Honkakoski P, Lang MA, Pasanen M, Pelkonen O, Raunio H (Oct 1989). “Comparison of the immunochemical properties of human placental and bovine adrenal cholesterol side-chain cleavage enzyme complex”. Biochimica et Biophysica Acta (BBA) – Protein Structure and Molecular Enzymology. 998 (2): 189–95. doi:10.1016/0167-4838(89)90272-0. PMID 2790061.
• Maruyama K, Sugano S (Jan 1994). “Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides”. Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). “Construction and characterization of a full length-enriched and a 5′-end-enriched cDNA library”. Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Müller JJ, Lapko A, Bourenkov G, Ruckpaul K, Heinemann U (Jan 2001). “Adrenodoxin reductase-adrenodoxin complex structure suggests electron transfer path in steroid biosynthesis”. The Journal of Biological Chemistry. 276 (4): 2786–9. doi:10.1074/jbc.M008501200. PMID 11053423.
• Gonzalez MI, Robins DM (Mar 2001). “Oct-1 preferentially interacts with androgen receptor in a DNA-dependent manner that facilitates recruitment of SRC-1”. The Journal of Biological Chemistry. 276 (9): 6420–8. doi:10.1074/jbc.M008689200. PMID 11096094.
• Tuckey RC, Headlam MJ (Jun 2002). “Placental cytochrome P450scc (CYP11A1): comparison of catalytic properties between conditions of limiting and saturating adrenodoxin reductase”. The Journal of Steroid Biochemistry and Molecular Biology. 81 (2): 153–8. doi:10.1016/S0960-0760(02)00058-4. PMID 12137805. S2CID 44273641.
• Liu G, Chen X (Oct 2002). “The ferredoxin reductase gene is regulated by the p53 family and sensitizes cells to oxidative stress-induced apoptosis”. Oncogene. 21 (47): 7195–204. doi:10.1038/sj.onc.1205862. PMID 12370809.
• Araya Z, Hosseinpour F, Bodin K, Wikvall K (Jun 2003). “Metabolism of 25-hydroxyvitamin D3 by microsomal and mitochondrial vitamin D3 25-hydroxylases (CYP2D25 and CYP27A1): a novel reaction by CYP27A1”. Biochimica et Biophysica Acta (BBA) – Molecular and Cell Biology of Lipids. 1632 (1–3): 40–7. doi:10.1016/S1388-1981(03)00062-3. PMID 12782149.
• Thiboutot D, Jabara S, McAllister JM, Sivarajah A, Gilliland K, Cong Z, Clawson G (Jun 2003). “Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1)”. The Journal of Investigative Dermatology. 120 (6): 905–14. doi:10.1046/j.1523-1747.2003.12244.x. PMID 12787114.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (Jan 2006). “Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes”. Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Rohrmann, George (2019). Baculovirus Molecular Biology Fourth Edition (4th ed.). Bethesda, MD: NCBI. PMID 31294936.
• Federici, Brian A.; Granados, Robert R. (1986). The Biology of baculoviruses. Boca Raton: CRC Press. ISBN 978-0-8493-5988-0.
• Miller, Lois (1997). The baculoviruses. New York: Plenum Press. ISBN 978-0-306-45641-1.
• Joly EC, Tremblay E, Tanguay RM, Wu Y, Bibor-Hardy V (October 1994). “TRiC-P5, a novel TCP1-related protein, is localized in the cytoplasm and in the nuclear matrix”. Journal of Cell Science. 107 ( Pt 10) (10): 2851–9. doi:10.1242/jcs.107.10.2851. PMID 7876352.
• Harrington L, McPhail T, Mar V, Zhou W, Oulton R, Bass MB, Arruda I, Robinson MO (February 1997). “A mammalian telomerase-associated protein”. Science. 275 (5302): 973–7. doi:10.1126/science.275.5302.973. PMID 9020079. S2CID 21631570.
• Harrington L, Zhou W, McPhail T, Oulton R, Yeung DS, Mar V, Bass MB, Robinson MO (December 1997). “Human telomerase contains evolutionarily conserved catalytic and structural subunits”. Genes & Development. 11 (23): 3109–15. doi:10.1101/gad.11.23.3109. PMC 316744. PMID 9389643.
• Li H, Zhao L, Yang Z, Funder JW, Liu JP (December 1998). “Telomerase is controlled by protein kinase Calpha in human breast cancer cells”. The Journal of Biological Chemistry. 273 (50): 33436–42. doi:10.1074/jbc.273.50.33436. PMID 9837921.
• Kickhoefer VA, Stephen AG, Harrington L, Robinson MO, Rome LH (November 1999). “Vaults and telomerase share a common subunit, TEP1”. The Journal of Biological Chemistry. 274 (46): 32712–7. doi:10.1074/jbc.274.46.32712. PMID 10551828.
• Li H, Cao Y, Berndt MC, Funder JW, Liu JP (November 1999). “Molecular interactions between telomerase and the tumor suppressor protein p53 in vitro”. Oncogene. 18 (48): 6785–94. doi:10.1038/sj.onc.1203061. PMID 10597287.
• Koyanagi Y, Kobayashi D, Yajima T, Asanuma K, Kimura T, Sato T, Kida T, Yagihashi A, Kameshima H, Watanabe N (2000). “Telomerase activity is down regulated via decreases in hTERT mRNA but not TEP1 mRNA or hTERC during the differentiation of leukemic cells”. Anticancer Research. 20 (2A): 773–8. PMID 10810353.
• Beattie TL, Zhou W, Robinson MO, Harrington L (October 2000). “Polymerization defects within human telomerase are distinct from telomerase RNA and TEP1 binding”. Molecular Biology of the Cell. 11 (10): 3329–40. doi:10.1091/mbc.11.10.3329. PMC 14995. PMID 11029039.
• Zhang RG, Zhang RP, Wang XW, Xie H (March 2002). “Effects of cisplatin on telomerase activity and telomere length in BEL-7404 human hepatoma cells”. Cell Research. 12 (1): 55–62. doi:10.1038/sj.cr.7290110. PMID 11942411.
• Chang JT, Chen YL, Yang HT, Chen CY, Cheng AJ (July 2002). “Differential regulation of telomerase activity by six telomerase subunits”. European Journal of Biochemistry. 269 (14): 3442–50. doi:10.1046/j.1432-1033.2002.03025.x. PMID 12135483.
• Zhou JH, Zhang HM, Chen Q, Han DD, Pei F, Zhang LS, Yang DT (August 2003). “Relationship between telomerase activity and its subunit expression and inhibitory effect of antisense hTR on pancreatic carcinoma”. World Journal of Gastroenterology. 9 (8): 1808–14. doi:10.3748/wjg.v9.i8.1808. PMC 4611549. PMID 12918126.
• Li C, Wu MY, Liang YR, Wu XY (November 2003). “Correlation between expression of human telomerase subunits and telomerase activity in esophageal squamous cell carcinoma”. World Journal of Gastroenterology. 9 (11): 2395–9. doi:10.3748/wjg.v9.i11.2395. PMC 4656508. PMID 14606063.
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (May 2006). “A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration”. Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569.

Protein domains

Posttranslational modification

NOD-like receptor family

Protein tertiary structure

Baltimore (virus classification)

Transmembrane receptors: immunoglobulin superfamily immune receptors

Major histocompatibility complex classes

This article incorporates text from the public domain Pfam and InterPro: IPR007111

Categories: 

• Protein domains
• Genes on human chromosome 17
• Enzymes
• Genes on human chromosome 5
• Human proteins
• NOD-like receptors
• Transmembrane receptor stubs
• Spinal muscular atrophy
• Genes on human chromosome 16
• LRR proteins
• Genes on human chromosome 14
• Genes
• Immune system
• Glycoproteins
• MHC class II