Sterol carrier proteins (aka nonspecific lipid transfer proteins)

These proteins are different from plant nonspecific lipid transfer proteins but structurally similar to small proteins of unknown function from Thermus thermophilus.

• Thermus thermophilus is a Gram-negative bacterium used in a range of biotechnological applications, including as a model organism for genetic manipulation, structural genomics, and systems biology. The bacterium is extremely thermophilic, with an optimal growth temperature of about 65 °C (149 °F). Thermus thermophilus was originally isolated from a thermal vent within a hot spring in Izu, Japan by Tairo Oshima and Kazutomo Imahori.Oshima T, Imahori K (January 1974). “Description of Thermus thermophilus (Yoshida and Oshima) comb. nov., a nonsporulating thermophilic bacterium from a Japanese thermal spa”. International Journal of Systematic and Evolutionary Microbiology. 24 (1): 102–12. doi:10.1099/00207713-24-1-102. The organism has also been found to be important in the degradation of organic materials in the thermogenic phase of composting.Beffa T, Blanc M, Lyon PF, Vogt G, Marchiani M, Fischer JL, Aragno M (May 1996). “Isolation of Thermus strains from hot composts (60 to 80 °C)”. Applied and Environmental Microbiology. 62 (5): 1723–7. Bibcode:1996ApEnM..62.1723B. doi:10.1128/AEM.62.5.1723-1727.1996. PMC 167946. PMID 8633870. T. thermophilus is classified into several strains, of which HB8 and HB27 are the most commonly used in laboratory environments. Genome analyses of these strains were independently completed in 2004.Henne A, Brüggemann H, Raasch C, Wiezer A, Hartsch T, Liesegang H, et al. (May 2004). “The genome sequence of the extreme thermophile Thermus thermophilus”. Nature Biotechnology. 22 (5): 547–53. doi:10.1038/nbt956. PMID 15064768. S2CID 25469576. Thermus thermophilus is a Gram-negative bacterium with an outer membrane that is composed of phospholipids and lipopolysaccharides. This bacterium also has a thin peptidoglycan (also known as murein) layer, in this layer there are 29 muropeptides which account for more than 85% of the total murein layer. The presence of Ala, Glu, Gly, Orn, N-acetyl glucosamine and N-acetylmuramic were found in the murein layer of this bacterium. Another unique feature of this murein layer is that the N-terminal Gly is substituted with phenylacetic acid. This is the first instance of phenylacetic acid found in the murein of bacterial cells. The composition and peptide cross-bridges found in this murein layer are typical of Gram-positive bacterium, but the amount, the degree of the cross-linkage and length of the glycan chain gives this bacterium its Gram-negative properties.Quintela, J C; Pittenauer, E; Allmaier, G; Arán, V; de Pedro, M A (September 1995). “Structure of peptidoglycan from Thermus thermophilus HB8”. Journal of Bacteriology. 177 (17): 4947–4962. doi:10.1128/jb.177.17.4947-4962.1995. ISSN 0021-9193. PMC 177270. PMID 7665471.
  • Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most bacteria (domain Bacteria^[1]).^{[2]: 66–67} The sugar component consists of alternating residues of β-(1,4) linked N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM). Attached to the N-acetylmuramic acid is an oligopeptide chain made of three to five amino acids. The peptide chain can be cross-linked to the peptide chain of another strand forming the 3D mesh-like layer.
  • Phenylacetic acid (PAA; conjugate basephenylacetate), also known by various synonyms, is an organic compound containing a phenylfunctional group and a carboxylic acid functional group. It is a white solid with a strong honey-like odor. Endogenously, it is a catabolite of phenylalanine. As a commercial chemical, because it can be used in the illicit production of phenylacetone (used in the manufacture of substituted amphetamines), it is subject to controls in countries including the United States and China. “List of Regulated Drug Precursor Chemicals in China”. Archived from the original on 17 August 2015. Retrieved 27 April 2015. Phenylacetic acid has been found to be an active auxin (a type of plant hormone), found predominantly in fruits. Wightman, F.; Lighty, D. L. (1982). “Identification of phenylacetic acid as a natural auxin in the shoots of higher plants”. Physiologia Plantarum. 55 (1): 17–24. doi:10.1111/j.1399-3054.1982.tb00278.x However, its effect is much weaker than the effect of the basic auxin molecule indole-3-acetic acid. In addition the molecule is naturally produced by the metapleural gland of most ant species and used as an antimicrobial. It is also the oxidation product of phenethylamine in humans following metabolism by monoamine oxidase and subsequent metabolism of the intermediate product, phenylacetaldehyde, by the aldehyde dehydrogenase enzyme; these enzymes are also found in many other organisms. This compound may be prepared by the hydrolysis of benzyl cyanide: Adams R.; Thal, A. F. (1922). “Phenylacetic acid”. Organic Syntheses. 2: 59.; Collective Volume, vol. 1, p. 436 Wenner, W. (1952). “Phenylacetamide”. Organic Syntheses. 32: 92.; Collective Volume, vol. 4, p. 760 Phenylacetic acid is used in some perfumes, as it possesses a honey-like odor even in low concentrations. It is also used in penicillin G production and diclofenac production. It is also employed to treat type II hyperammonemia to help reduce the amounts of ammonia in a patient’s bloodstream by forming phenylacetyl-CoA, which then reacts with nitrogen-rich glutamine to form phenylacetylglutamine. This compound is then excreted from the patient’s body. It’s also used in the illicit production of phenylacetone, which is used in the manufacture of methamphetamine. The sodium salt of phenylacetic acid, sodium phenylacetate, is used as a pharmaceutical drug for the treatment of urea cycle disorders, including as the combination drug sodium phenylacetate/sodium benzoate (Ammonul).  “Sodium Phenylacetate and Sodium Benzoate Monograph for Professionals”. Drugs.com. Retrieved 16 November 2019. Phenylacetic acid is used in the preparation of several pharmaceutical drugs, including camylofin, bendazol, triafungin, phenacemide, lorcainide, phenindione, and cyclopentolate.^{[citation needed]} In the crime drama Breaking Bad, phenylacetic acid is featured twice as a precursor to methamphetamine, first in the episode titled “A No-Rough-Stuff-Type Deal“, then in “Salud“. In the police drama S.W.A.T S6E14, phenylacetic acid is featured as a chemical needed to process a new drug called Iso. See also Cathinone and Methyl phenylacetate Mehta A (20 March 2011). “Animation of Synthesis of Peptidoglycan Layer”. PharmaXChange.info. Peptidoglycan serves a structural role in the bacterial cell wall, giving structural strength, as well as counteracting the osmotic pressure of the cytoplasm. This repetitive linking results in a dense peptidoglycan layer which is critical for maintaining cell form and withstanding high osmotic pressures, and it is regularly replaced by peptidoglycan production. Peptidoglycan hydrolysis and synthesis are two processes that must occur in order for cells to grow and multiply, a technique carried out in three stages: clipping of current material, insertion of new material, and re-crosslinking of existing material to new material. Belgrave AM, Wolgemuth CW (June 2013). “Elasticity and biochemistry of growth relate replication rate to cell length and cross-link density in rod-shaped bacteria”. Biophysical Journal. 104 (12): 2607–2611. Bibcode:2013BpJ…104.2607B. doi:10.1016/j.bpj.2013.04.028. PMC 3686348. PMID 23790368. The peptidoglycan layer is substantially thicker in Gram-positive bacteria (20 to 80 nanometers) than in Gram-negative bacteria (7 to 8 nanometers).Purcell A (18 March 2016). “Bacteria”. Basic Biology. Depending on pH growth conditions, the peptidoglycan forms around 40 to 90% of the cell wall‘s dry weight of Gram-positive bacteria but only around 10% of Gram-negative strains. Thus, presence of high levels of peptidoglycan is the primary determinant of the characterisation of bacteria as Gram-positive.Hogan CM (12 October 2014). “Bacteria”. In Draggan S, Cleveland CJ (eds.). Encyclopedia of Earth. Washington DC: National Council for Science and the Environment. In Gram-positive strains, it is important in attachment roles and serotyping purposes.Salton MR, Kim KS (1996). “Structure”. In Baron S, et al. (eds.). Structure. In: Baron’s Medical Microbiology (4th ed.). Univ of Texas Medical Branch. ISBN 978-0-9631172-1-2. PMID 21413343. For both Gram-positive and Gram-negative bacteria, particles of approximately 2 nm can pass through the peptidoglycan. Demchick P, Koch AL (February 1996). “The permeability of the wall fabric of Escherichia coli and Bacillus subtilis”. Journal of Bacteriology. 178 (3): 768–773. doi:10.1128/jb.178.3.768-773.1996. PMC 177723. PMID 8550511. It is difficult to tell whether an organism is gram-positive or gram-negative using a microscope; gram staining, created by Hans Christian Gram in 1884, is required. The bacteria are stained with several dyes such as crystal violet, iodine alcohol, and safranin using the gram staining procedure. Gram positive cells are purple after staining, while Gram negative cells are red. Coico R (October 2005). “Gram Staining”. In Coico R, Kowalik T, Quarles J, Stevenson B (eds.). Current Protocols in Microbiology. Vol. Appendix 3. Hoboken, NJ, USA: John Wiley & Sons, Inc. pp. mca03cs00. doi:10.1002/9780471729259.mca03cs00. ISBN 978-0-471-72925-9. PMID 18770544. S2CID 32452815. Madigan, Michael T.; Martinko, John M.; Bender, Kelly S.; Buckley, Daniel H.; Stahl, David A. (2015). Brock Biology of Microorganisms (14 ed.). Boston: Pearson Education Limited. pp. 66–67. ISBN 978-1-292-01831-7.
• Thermus thermophilus was originally found within a thermal vent in Japan. These bacteria can be found in a variety of geothermal environments. These Thermophiles require a more stringent DNA repair system, as DNA becomes unstable at high temperatures. The GC content of this bacterium is about 69%, this contributes to the thermostability of this bacterium’s genome.Wang, Quanhui; Cen, Zhen; Zhao, Jingjing (2015-03-01). “The Survival Mechanisms of Thermophiles at High Temperatures: An Angle of Omics”. Physiology. 30 (2): 97–106. doi:10.1152/physiol.00066.2013. ISSN 1548-9213. PMID 25729055 The two most widely used strains in laboratory settings are HB27 and HB8. The strain HB27 is capable of living in an aerobic or anaerobic environment. It has a genome that consists of a main chromosome (1.89Mb long), as well as a megaplasmid, known as pTT27 (0.23Mb long).Ohtani, Naoto; Tomita, Masaru; Itaya, Mitsuhiro (2010-10-15). “An Extreme Thermophile, Thermus thermophilus, Is a Polyploid Bacterium”. Journal of Bacteriology. 192 (20): 5499–5505. doi:10.1128/JB.00662-10. ISSN 0021-9193. PMC 2950507. PMID 20729360. The chromosome of HB27 contains 1,968 protein coding genes, with 20% of these genes having no known function. While the megaplasmid contains 230 protein coding genes, about 39% of these genes have no known function.Carr, Jennifer F.; Danziger, Michael E.; Huang, Athena L.; Dahlberg, Albert E.; Gregory, Steven T. (2015-03-15). “Engineering the Genome of Thermus thermophilus Using a Counterselectable Marker”. Journal of Bacteriology. 197 (6): 1135–1144. doi:10.1128/JB.02384-14. ISSN 0021-9193. PMC 4336342. PMID 25605305. The strain HB8 is also an aerobic organism and is a model organism for systems biology. It has a genome consisting of a plasmid, known as pTT8 (9.3kb long), that is coupled with a chromosome (1.85Mb), as well as a megaplasmid, also known as pTT27 (0.26Mb). This strain was found to be a polyploid organism, with a chromosome and megaplasmid copy number of about four to five.Ohtani, Naoto; Tomita, Masaru; Itaya, Mitsuhiro (2010-10-15). “An Extreme Thermophile, Thermus thermophilus, Is a Polyploid Bacterium”. Journal of Bacteriology. 192 (20): 5499–5505. doi:10.1128/JB.00662-10. ISSN 0021-9193. PMC 2950507. PMID 20729360. This organism has been advantageous for industrial biotechnological fields as it is an excellent source of enzymes, more specifically thermozymes. One of these enzymes being the Tth DNA polymerase (rTth to emphasize it being recombinant). rTth DNA polymerase is a recombinant thermostable DNA polymerase derived from Thermus thermophilus HB8, with optimal activity at 70-80 °C, used in some PCR applications. The enzyme possesses efficient reverse transcriptase activity in the presence of manganese.Cai D, Behrmann O, Hufert F, Dame G, Urban G (2018-01-02). “Capacity of rTth polymerase to detect RNA in the presence of various inhibitors”. PLOS ONE. 13 (1): e0190041. Bibcode:2018PLoSO..1390041C. doi:10.1371/journal.pone.0190041. PMC 5749758. PMID 29293599. This enzyme is beneficial for amplification of GC-rich targets and for crude samples. It can be used in applications of PCR, RT-PCR and also primer extension.“rTth DNA Polymerase – TOYOBO USA”. www.toyobousa.com. Retrieved 2021-05-07. This polymerase has been shown to be resistant to DNA polymerase inhibitors present in clinical samples, it also has the capacity to detect RNA in the presence of inhibitors. Under the presence of inhibitors, it was shown to detect this RNA at a comparable level with its capacity to detect DNA.Cai D, Behrmann O, Hufert F, Dame G, Urban G (2018-01-02). “Capacity of rTth polymerase to detect RNA in the presence of various inhibitors”. PLOS ONE. 13 (1): e0190041. Bibcode:2018PLoSO..1390041C. doi:10.1371/journal.pone.0190041. PMC 5749758. PMID 29293599.

This domain is involved in binding sterols. The human sterol carrier protein 2 (SCP2) is a basic protein that is believed to participate in the intracellular transport of cholesterol and various other lipids.

• Johansson J, Wuthrich K, Szyperski T, Scheek S, Assmann G, Seedorf U (1993). “NMR determination of the secondary structure and the three-dimensional polypeptide backbone fold of the human sterol carrier protein 2”. FEBS Lett. 335 (1): 18–26. doi:10.1016/0014-5793(93)80431-S. PMID 8243660. S2CID 9969358.

Human proteins containing this domain

HSD17B4; 

D-bifunctional protein (DBP), also known as peroxisomal multifunctional enzyme type 2 (MFP-2), as well as 17β-hydroxysteroid dehydrogenase type IV (17β-HSD type IV) is a protein that in humans is encoded by the HSD17B4 gene. It’s an alcohol oxidoreductase, specifically 17β-Hydroxysteroid dehydrogenase. It is involved in fatty acid β-oxidation and steroid metabolism (cf. steroidogenesis).The HSD17B4 gene encodes an enzyme involved in peroxisomal fatty acid beta-oxidation. It was first identified as a 17-beta-estradiol dehydrogenase (Leenders et al., 1996; van Grunsven et al., 1998). Peroxisomal beta-oxidation of fatty acids, originally described by Lazarow and de Duve (1976), is catalyzed by 3 enzymes: acyl-CoA oxidase (see, e.g., ACOX1, MIM 609751); the ‘D-bifunctional enzyme,’ with enoyl-CoA hydratase and D-3-hydroxyacyl-CoA dehydrogenase activity, and 3-ketoacyl-CoA thiolase (MIM 604054). See also the L-bifunctional peroxisomal protein (EHHADH; MIM 607037). The D- and L-bifunctional proteins have different substrate specificities. The D-bifunctional protein catalyzes the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids and also acts in shortening cholesterol for bile acid formation. In contrast, the L-specific bifunctional protein does not have the latter 2 activities (Jiang et al., 1997).[supplied by OMIM] See also D-bifunctional protein deficiency and Perrault syndrome

• D-Bifunctional protein deficiency is an autosomal recessive peroxisomal fatty acid oxidation disorder. Peroxisomal disorders are usually caused by a combination of peroxisomal assembly defects or by deficiencies of specific peroxisomal enzymes. The peroxisome is an organelle in the cell similar to the lysosome that functions to detoxify the cell. Peroxisomes contain many different enzymes, such as catalase, and their main function is to neutralize free radicals and detoxify drugs. For this reason peroxisomes are ubiquitous in the liver and kidney. D-BP deficiency is the most severe peroxisomal disorder, often resembling Zellweger syndrome. Möller G, van Grunsven EG, Wanders RJ, Adamski J (January 2001). “Molecular basis of D-bifunctional protein deficiency”. Mol. Cell. Endocrinol. 171 (1–2): 61–70. doi:10.1016/s0303-7207(00)00388-9. PMID 11165012. S2CID 29712091. Itoh M, Suzuki Y, Akaboshi S, Zhang Z, Miyabara S, Takashima S (March 2000). “Developmental and pathological expression of peroxisomal enzymes: their relationship of D-bifunctional protein deficiency and Zellweger syndrome”. Brain Res. 858 (1): 40–7. doi:10.1016/S0006-8993(99)02423-3. PMID 10700594. S2CID 11224543. Characteristics of the disorder include neonatal hypotonia and seizures, occurring mostly within the first month of life, as well as visual and hearing impairment.Buoni S, Zannolli R, Waterham H, Wanders R, Fois A (January 2007). “D-bifunctional protein deficiency associated with drug resistant infantile spasms”. Brain Dev. 29 (1): 51–4. doi:10.1016/j.braindev.2006.06.004. PMID 16919904. S2CID 617635.  Other symptoms include severe craniofacial disfiguration, psychomotor delay, and neuronal migration defects. Most onsets of the disorder begin in the gestational weeks of development and most affected individuals die within the first two years of life. The most common clinical observations of patients with D-bifunctional protein deficiency include hypotonia, facial and skull dysmorphism, neonatal seizures, and neuronal demyelination. van Grunsven EG, Mooijer PA, Aubourg P, Wanders RJ (August 1999). “Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional protein deficiency”. Hum. Mol. Genet. 8 (8): 1509–16. doi:10.1093/hmg/8.8.1509. PMID 10400999. High levels of branched fatty acids, such as pristinic acid, bile acid intermediates, and other D-BP substrates are seen to exist. Reduced pristinic acid β-oxidation is a common indicator of D-BP deficiency. D-BP can be distinguished from Zellweger Syndrome by normal plasmalogen synthesis. Recent studies in D-BP knockout mice show compensatory upregulation of other peroxisomal enzymes in absence of D-BP such as palmitoyl-CoA oxidase, peroxisomal thiolase, and branched chain acyl-CoA oxidase.The D-bifunctional protein is composed of three enzymatic domains: the N-terminal short chain alcohol dehydrogenase reductase (SDR), central hydratase domain, and the C-terminal sterol carrier protein 2 (SDR).The DBP protein (79kDa) also known as “multifunctional protein 2”, “multifunctional enzyme 2”, or “D-peroxisomal bifunctional”enzyme”, catalyzes the second and third steps of peroxisomal β-oxidation of fatty acids and their derivatives .^{[citation needed]} A non-functional D-BP protein results in the abnormal accumulation of long chain fatty acids and bile acid intermediates. The D-BP protein contains a peroxisomal targeting signal 1 (PTS1) unit at the C-terminus allowing for its transport into peroxisomes by the PTS1 receptor. Inside the peroxisomes, the D-BP protein is partially cleaved exclusively between the SDR and hydratase”domains. DBP is a stereospecific enzyme; hydratase domain forms only (R)-hydroxy-acyl-CoA intermediates from trans-2-enoyl-CoAs. Ferdinandusse S, Ylianttila MS, Gloerich J, Koski MK, Oostheim W, Waterham HR, Hiltunen JK, Wanders RJ, Glumoff T (January 2006). “Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis”. Am. J. Hum. Genet. 78 (1): 112–24. doi:10.1086/498880. PMC 1380208. PMID 16385454  D-BP is expressed throughout the entire human body, with the highest mRNA levels in the liver and brain. The hydrogenase and hydratase units of DBP exist as dimers, necessary for correct folding and therefore function of the enzyme. Note as with many ‘genetic’ issues (as opposed to acquired? health issues, which they say over 65% of people suffer and for which they have developed treatments for 10% and cures for none?), they list three types.

• Some forms of XX gonadal dysgenesis occurs with sensorineural deafness. This type is also known as Perrault syndrome, an autosomal recessive disease affecting both sexes. Males present only with the deafness.Sampathkumar, G.; Veerasigamani, N. (2015). “Perrault syndrome – a rare case report”. Journal of Clinical and Diagnostic Research. 9 (3): OD01-2. doi:10.7860/JCDR/2015/10992.5641. PMC 4413102. PMID 25954653 The term “pure gonadal dysgenesis” (PGD) has been used to distinguish a group of patients from gonadal dysgenesis related to Turner syndrome. The consequences to the girl with XX gonadal dysgenesis:^{[citation needed]} 1.Her gonads cannot make estrogen, so her breasts will not develop and her uterus will not grow and menstruate until she is given estrogen. This is often given through the skin now. 2. Her gonads cannot make progesterone, so her menstrual periods will not be predictable until she is given a progestin, still usually as a pill. 3. Her gonads cannot produce eggs so she will not be able to conceive children naturally. A woman with a uterus but no ovaries may be able to become pregnant by implantation of another woman’s fertilized egg (embryo transfer). In 1951, Perrault reported the association of gonadal dysgenesis and deafness, now called Perrault syndrome..Perrault, M.; Klotz, B.; Housset, E.:Deux cas de syndrome de Turner avec surdi-mutite dans une meme fratrie. Bull. Mem. Soc. Med. Hop. Paris 16: 79-84, 1951. Note that M Perrault, the person, does not have a linking Wikipedia page which means any articles available should be looked up elsewhere. A quick search indicated they did a lot of work with B Klotz).

• GRCh38: Ensembl release 89: ENSG00000133835 – Ensembl, May 2017
• GRCm38: Ensembl release 89: ENSMUSG00000024507 – Ensembl, May 2017
• “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.
• Leenders F, Prescher G, Dolez V, Begue A, de Launoit Y, Adamski J (November 1996). “Assignment of human 17 beta-hydroxysteroid dehydrogenase IV to chromosome 5q2 by fluorescence in situ hybridization”. Genomics. 37 (3): 403–4. doi:10.1006/geno.1996.0578. PMID 8938456.
• Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jörnvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (March 2009). “The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative”. Chemico-Biological Interactions. 178 (1–3): 94–8. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.
• “Entrez Gene: HSD17B4 hydroxysteroid (17-beta) dehydrogenase 4”.
• Huyghe S, Mannaerts GP, Baes M, Van Veldhoven PP (September 2006). “Peroxisomal multifunctional protein-2: the enzyme, the patients and the knockout mouse model”. Biochimica et Biophysica Acta (BBA) – Molecular and Cell Biology of Lipids. 1761 (9): 973–94. doi:10.1016/j.bbalip.2006.04.006. PMID 16766224.

HSDL2; 

No Wikipedia page so…Lipid metabolism regulator human hydroxysteroid dehydrogenase-like 2 (HSDL2) modulates cervical cancer cell proliferation and metastasis. Knockdown of HSDL2 inhibits lung adenocarcinoma progression via down-regulating AKT2 expression. (NIH – https://www.ncbi.nlm.nih.gov/gene/84263)

The short-chain dehydrogenases/reductases family (SDR) is a very large family of enzymes, most of which are known to be NAD- or NADP-dependent oxidoreductases. As the first member of this family to be characterised was Drosophila alcohol dehydrogenase, this family used to be called ‘insect-type’, or ‘short-chain’ alcohol dehydrogenases. Most members of this family are proteins of about 250 to 300 amino acid residues. Most dehydrogenases possess at least 2 domains, the first binding the coenzyme, often NAD, and the second binding the substrate. This latter domain determines the substrate specificity and contains amino acids involved in catalysis. Little sequence similarity has been found in the coenzyme binding domain although there is a large degree of structural similarity, and it has therefore been suggested that the structure of dehydrogenases has arisen through gene fusion of a common ancestral coenzyme nucleotide sequence with various substrate specific domains. Ghosh D, Erman M, Wawrzak Z, Duax WL, Pangborn W (October 1994). “Mechanism of inhibition of 3 alpha, 20 beta-hydroxysteroid dehydrogenase by a licorice-derived steroidal inhibitor”. Structure. 2 (10): 973–80. doi:10.1016/S0969-2126(94)00099-9. PMID 7866748. Persson B, Krook M, Atrian S, Gonzalez-Duarte R, Jeffery J, Ghosh D, Jornvall H (1995). “Short-chain dehydrogenases/reductases (SDR)”. Biochemistry. 34 (18): 6003–6013. doi:10.1021/bi00039a038. PMID 7742302. Villarroya A, Juan E, Egestad B, Jornvall H (1989). “The primary structure of alcohol dehydrogenase from Drosophila lebanonensis. Extensive variation within insect ‘short-chain’ alcohol dehydrogenase lacking zinc”. Eur. J. Biochem. 180 (1): 191–197. doi:10.1111/j.1432-1033.1989.tb14632.x. PMID 2707261. Persson B, Krook M, Jornvall H (1991). “Characteristics of short-chain alcohol dehydrogenases and related enzymes”. Eur. J. Biochem. 200 (2): 537–543. doi:10.1111/j.1432-1033.1991.tb16215.x. PMID 1889416. Harayama S, Bairoch A, Hartnett C, Rekik M, Ornston LN, Neidle E (1992). “cis-diol dehydrogenases encoded by the TOL pWW0 plasmid xylL gene and the Acinetobacter calcoaceticus chromosomal benD gene are members of the short-chain alcohol dehydrogenase superfamily”. Eur. J. Biochem. 204 (1): 113–120. doi:10.1111/j.1432-1033.1992.tb16612.x. PMID 1740120. Benyajati C, Place AR, Powers DA, Sofer W (1981). “Alcohol dehydrogenase gene of Drosophila melanogaster: relationship of intervening sequences to functional domains in the protein”. Proc. Natl. Acad. Sci. U.S.A. 78 (5): 2717–2721. Bibcode:1981PNAS…78.2717B. doi:10.1073/pnas.78.5.2717. PMC 319428. PMID 6789320 Subfamilies Glucose/ribitol dehydrogenase InterPro: IPR002347 and Insect alcohol dehydrogenase family InterPro: IPR002424 and 2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase InterPro: IPR003560 Human proteins containing this domain BDH1; BDH2; CBR1; CBR3; CBR4; DCXR; DECR1; DECR2; DHRS1; DHRS10; DHRS13; DHRS2; DHRS3; DHRS4; DHRS4L2; DHRS7; DHRS7B; DHRS8; DHRS9; DHRSX; FASN; FVT1; HADH2; HPGD; HSD11B1; HSD11B2; HSD17B1; HSD17B10; HSD17B12; HSD17B13; HSD17B2; HSD17B3; HSD17B4; HSD17B6; HSD17B7; HSD17B7P2; HSD17B8; HSDL1; HSDL2; PECR; QDPR; RDH10; RDH11; RDH12; RDH13; RDH14; RDH16; RDH5; RDH8; RDHE2; RDHS; SCDR10; SPR; WWOX;

Related articles in PubMed

1. [HSDL2 overexpression promotes rectal cancer progression by regulating cancer cell cycle and promoting cell proliferation].Cheng Y, et al. Nan Fang Yi Ke Da Xue Xue Bao, 2023 Apr 20. PMID 37202189, Free PMC Article
2. Lipid metabolism regulator human hydroxysteroid dehydrogenase-like 2 (HSDL2) modulates cervical cancer cell proliferation and metastasis.Yang Y, et al. J Cell Mol Med, 2021 May. PMID 33738911, Free PMC Article
3. HSDL2 Promotes Bladder Cancer Growth In Vitro and In Vivo.Jia LH, et al. Int J Med Sci, 2019. PMID 31217732, Free PMC Article
4. Down-regulated HSDL2 expression suppresses cell proliferation and promotes apoptosis in papillary thyroid carcinoma.Zeng J, et al. Biosci Rep, 2019 Jun 28. PMID 31101684, Free PMC Article
5. Role of Hydroxysteroid Dehydrogenase-Like 2 (HSDL2) in Human Ovarian Cancer.Sun Q, et al. Med Sci Monit, 2018 Jun 12. PMID 29894468, Free PMC Article

See all (76) citations in PubMed

HIV-1 interactions

Replication interactions – Knockdown of hydroxysteroid dehydrogenase like 2 (HSDL2) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N https://pubmed.ncbi.nlm.nih.gov/22082156/

What’s a GeneRIF?

1. [HSDL2 overexpression promotes rectal cancer progression by regulating cancer cell cycle and promoting cell proliferation].
2. Lipid metabolism regulator human hydroxysteroid dehydrogenase-like 2 (HSDL2) modulates cervical cancer cell proliferation and metastasis.
3. Knockdown of HSDL2 inhibits lung adenocarcinoma progression via down-regulating AKT2 expression.
4. Hydroxysteroid dehydrogenase like 2 (HSDL2) expression was increased in papillary thyroid carcinoma (PTC) tissues and cells, which could promote tumor progression in vitro and in vivo.
5. Study reported that HSDL2 was upregulated in two human bladder cancer cell lines 5637 and T24 compared to normal human urothelial cells. Lentiviral-mediated HSDL2 knockdown inhibited the proliferation and colony formation while promoted the apoptosis of human bladder cancer T24 cells in vitro and in nude mice T24 derived xenografts in vivo. Results suggest that HSDL2 plays an oncogenic role in bladder cancer.
6. Study shows that HSDL2 upregulation is associated with ovarian cancer progression. HSDL2 knockdown inhibited cell proliferation, colony formation, motility, and tumorigenesis.
7. High expression of HSDL2 is associated with glioma.
8. Observational study of gene-disease association. (HuGE Navigator)

SCP2; 

Non-specific lipid-transfer protein also known as sterol carrier protein 2 (SCP-2) or propanoyl-CoA C-acyltransferase is a protein that in humans is encoded by the SCP2 gene. This gene encodes two proteins: sterol carrier protein X (SCPx) and sterol carrier protein 2 (SCP2), as a result of transcription initiation from 2 independently regulated promoters. The transcript initiated from the proximal promoter encodes the longer SCPx protein, and the transcript initiated from the distal promoter encodes the shorter SCP2 protein, with the 2 proteins sharing a common C-terminus. Evidence suggests that the SCPx protein is a peroxisome-associated thiolase that is involved in the oxidation of branched chain fatty acids, while the SCP2 protein is thought to be an intracellular lipid transfer protein. Alternative splicing of this gene produces multiple transcript variants, some encoding different isoforms. The full-length nature of all transcript variants has not been determined. This gene is highly expressed in organs involved in lipid metabolism, and may play a role in Zellweger syndrome, in which cells are deficient in peroxisomes and have impaired bile acid synthesis.

• Zellweger syndrome is a rare congenital disorder characterized by the reduction or absence of functional peroxisomes in the cells of an individual. Brul, S.; Westerveld, A.; Strijland, A.; Wanders, R.; Schram, A.; Heymans, H.; Schutgens, R.; Van Den Bosch, H.; Tager, J. (June 1988). “Genetic heterogeneity in the cerebrohepatorenal (Zellweger) syndrome and other inherited disorders with a generalized impairment of peroxisomal functions. A study using complementation analysis”. Journal of Clinical Investigation (Free full text). 81 (6): 1710–1715. doi:10.1172/JCI113510. PMC 442615. PMID 2454948. It is one of a family of disorders called Zellweger spectrum disorders which are leukodystrophies. Zellweger syndrome is named after Hans Zellweger (1909–1990), a Swiss-American pediatrician, a professor of pediatrics and genetics at the University of Iowa who researched this disorder. Zellweger’s syndrome at Who Named It? Wiedemann, H. R. (1991). “Hans-Ulrich Zellweger (1909-1990)”. European Journal of Pediatrics. 150 (7): 451. doi:10.1007/BF01958418. PMID 1915492. S2CID 34905299. Zellweger syndrome is one of three peroxisome biogenesis disorders which belong to the Zellweger spectrum of peroxisome biogenesis disorders (PBD-ZSD). The other two disorders are neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD).Krause, C.; Rosewich, H.; Thanos, M.; Gärtner, J. (2006). “Identification of novel mutations in PEX2, PEX6, PEX10, PEX12, and PEX13 in Zellweger spectrum patients”. Human Mutation. 27 (11): 1157. doi:10.1002/humu.9462. PMID 17041890. S2CID 9905589.  Although all have a similar molecular basis for disease, Zellweger syndrome is the most severe of these three disorders.Zellweger syndrome is associated with impaired neuronal migration, neuronal positioning, and brain development. In addition, individuals with Zellweger syndrome can show a reduction in central nervous system (CNS) myelin (particularly cerebral), which is referred to as hypomyelination. Myelin is critical for normal CNS functions, and in this regard, serves to insulate nerve fibers in the brain. Patients can also show postdevelopmental sensorineuronal degeneration that leads to a progressive loss of hearing and vision. Zellweger syndrome can also affect the function of many other organ systems. Patients can show craniofacial abnormalities (such as a high forehead, hypoplastic supraorbital ridges, epicanthal folds, midface hypoplasia, and a large fontanel), hepatomegaly (enlarged liver), chondrodysplasia punctata (punctate calcification of the cartilage in specific regions of the body), eye abnormalities, and renal cysts. Newborns may present with profound hypotonia (low muscle tone), seizures, apnea, and an inability to eat. Steinberg, S.; Dodt, G.; Raymond, G.; Braverman, N.; Moser, A.; Moser, H. (2006). “Peroxisome biogenesis disorders”. Biochimica et Biophysica Acta (BBA) – Molecular Cell Research. 1763 (12): 1733–48. doi:10.1016/j.bbamcr.2006.09.010. PMID 17055079  Raymond, G. V.; Watkins, P.; Steinberg, S.; Powers, J. (2009). “Peroxisomal Disorders”. Handbook of Neurochemistry and Molecular Neurobiology. pp. 631–670. doi:10.1007/978-0-387-30378-9_26. ISBN 978-0-387-30345-1.) SCP2 has been shown to interact with Caveolin 1 and peroxisomal receptor PEX5.

• GRCh38: Ensembl release 89: ENSG00000116171 – Ensembl, May 2017
• GRCm38: Ensembl release 89: ENSMUSG00000028603 – Ensembl, May 2017
• “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.
• Yamamoto R, Kallen CB, Babalola GO, Rennert H, Billheimer JT, Strauss JF (January 1991). “Cloning and expression of a cDNA encoding human sterol carrier protein 2”. Proc. Natl. Acad. Sci. U.S.A. 88 (2): 463–7. Bibcode:1991PNAS…88..463Y. doi:10.1073/pnas.88.2.463. PMC 50831. PMID 1703300.
• He Z, Yamamoto R, Furth EE, Schantz LJ, Naylor SL, George H, Billheimer JT, Strauss JF (October 1991). “cDNAs encoding members of a family of proteins related to human sterol carrier protein 2 and assignment of the gene to human chromosome 1 p21—-pter”. DNA Cell Biol. 10 (8): 559–69. doi:10.1089/dna.1991.10.559. PMID 1718316.
• “Entrez Gene: SCP2 sterol carrier protein 2”.
• Zhou M, Parr RD, Petrescu AD, Payne HR, Atshaves BP, Kier AB, Ball JM, Schroeder F (June 2004). “Sterol carrier protein-2 directly interacts with caveolin-1 in vitro and in vivo”. Biochemistry. 43 (23): 7288–306. doi:10.1021/bi035914n. PMID 15182174.
• Stanley WA, Filipp FV, Kursula P, Schüller N, Erdmann R, Schliebs W, Sattler M, Wilmanns M (December 2006). “Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p”. Mol. Cell. 24 (5): 653–63. doi:10.1016/j.molcel.2006.10.024. PMC 5030714. PMID 17157249.

STOML1; Stomatin-like protein 1 is a protein that in humans is encoded by the STOML1 gene.

• GRCh38: Ensembl release 89: ENSG00000067221 – Ensembl, May 2017
• GRCm38: Ensembl release 89: ENSMUSG00000032333 – Ensembl, May 2017
• “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.
• Seidel G, Prohaska R (Feb 1999). “Molecular cloning of hSLP-1, a novel human brain-specific member of the band 7/MEC-2 family similar to Caenorhabditis elegans UNC-24”. Gene. 225 (1–2): 23–9. doi:10.1016/S0378-1119(98)00532-0. PMID 9931417.
• “Entrez Gene: STOML1 stomatin (EPB72)-like 1”.

See also

• Steroidogenic acute regulatory protein and START domain

References

1. Johansson J, Wuthrich K, Szyperski T, Scheek S, Assmann G, Seedorf U (1993). “NMR determination of the secondary structure and the three-dimensional polypeptide backbone fold of the human sterol carrier protein 2”. FEBS Lett. 335 (1): 18–26. doi:10.1016/0014-5793(93)80431-S. PMID 8243660. S2CID 9969358.

External links

• Sterol carrier proteins in SCOP
• SCP-2 sterol transfer family in Pfam
• UMich Orientation of Proteins in Membranes families/superfamily-144
• sterol+carrier+proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the public domain Pfam and InterPro: IPR003033

Categories: 

• Peripheral membrane proteins
• Protein domains
• Protein families
• Water-soluble transporters
• Membrane protein stubs

Note: I tried to condense several notes into one. Not sure this is the best format.