STC2
From Wikipedia the free encyclopedia
Stanniocalcin-2 is a protein that in humans is encoded by the STC2 gene.[5][6][7]
This gene encodes a secreted, homodimeric glycoprotein that is expressed in a wide variety of tissues and may have autocrine or paracrine functions. The encoded protein has 10 of its 15 cysteine residues conserved among stanniocalcin family members and is phosphorylated by casein kinase 2 exclusively on its serine residues.
Its C-terminus contains a cluster of histidine residues which may interact with metal ions. The protein may play a role in the regulation of renal and intestinal calcium and phosphate transport, cell metabolism, or cellular calcium/phosphate homeostasis. Constitutive overexpression of human stanniocalcin 2 in mice resulted in pre-and postnatal growth restriction, reduced bone and skeletal muscle growth, and organomegaly. Expression of this gene is induced by estrogen and altered in some breast cancers.[7]
Stanniocalcin reduces bone growth[8] by modulating the activity of IGF1. One mechanism of IGF1 regulation is through IGFBP4 binding it in an inactive state. The protease PAPPA can then cleave this complex, releasing bioactive IGF1.[9] Stanniocalcin inhibits the activity of PAPPA in releasing active IGF1[9] through itself binding PAPPA,[10] thus preventing the release of active IGF1.
Differences in stanniocalcin expression have been directly linked to changes in skeletal size in a variety of species. For example, laboratory mice lacking STC2 are 10 to 15% larger than wild-type mice,[11] while mice expressing STC2 at elevated levels are 45% smaller.[8] In humans, the largest known coding variant affecting human height is a rare mutation reducing STC2 activity, yielding a 2 cm height increase in heterozygous carriers.[12] Additionally, domestic dog size is strongly predicted by a variant immediately adjacent to STC2, with almost all small dogs carrying a derived allele at this locus.[13] A further striking example is the stickleback, different populations of which have either increased or decreased the length of their dorsal and pelvic spines through modulation of STC2 expression.[14]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000113739 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020303 – 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.
- ^ Chang AC, Reddel RR (Nov 1998). "Identification of a second stanniocalcin cDNA in mouse and human: stanniocalcin 2". Mol Cell Endocrinol. 141 (1–2): 95–9. doi:10.1016/S0303-7207(98)00097-5. PMID 9723890. S2CID 28106090.
- ^ Ishibashi K, Miyamoto K, Taketani Y, Morita K, Takeda E, Sasaki S, Imai M (Nov 1998). "Molecular cloning of a second human stanniocalcin homologue (STC2)". Biochem Biophys Res Commun. 250 (2): 252–8. doi:10.1006/bbrc.1998.9300. PMID 9753616.
- ^ a b "Entrez Gene: STC2 stanniocalcin 2".
- ^ a b Gagliardi AD, Kuo EY, Raulic S, Wagner GF, DiMattia GE (January 2005). "Human stanniocalcin-2 exhibits potent growth-suppressive properties in transgenic mice independently of growth hormone and IGFs". Am J Physiol Endocrinol Metab. 288 (1): E92–105. doi:10.1152/ajpendo.00268.2004. PMID 15367391. S2CID 14827240.
- ^ a b Jepsen MR, Kløverpris S, Mikkelsen JH, Pedersen JH, Füchtbauer EM, Laursen LS, Oxvig C (February 2015). "Stanniocalcin-2 inhibits mammalian growth by proteolytic inhibition of the insulin-like growth factor axis". J Biol Chem. 290 (6): 3430–9. doi:10.1074/jbc.M114.611665. PMC 4319012. PMID 25533459.
- ^ Kobberø SD, Gajhede M, Mirza OA, Kløverpris S, Kjær TR, Mikkelsen JH, Boesen T, Oxvig C (October 2022). "Structure of the proteolytic enzyme PAPP-A with the endogenous inhibitor stanniocalcin-2 reveals its inhibitory mechanism". Nat Commun. 13 (1): 6084. Bibcode:2022NatCo..13.6084K. doi:10.1038/s41467-022-33698-8. PMC 9579167. PMID 36257932.
- ^ Chang AC, Hook J, Lemckert FA, McDonald MM, Nguyen MA, Hardeman EC, Little DG, Gunning PW, Reddel RR (May 2008). "The murine stanniocalcin 2 gene is a negative regulator of postnatal growth". Endocrinology. 149 (5): 2403–10. doi:10.1210/en.2007-1219. PMID 18258678. S2CID 43118428.
- ^ Marouli E, et al. (February 2017). "Rare and low-frequency coding variants alter human adult height". Nature. 542 (7640): 186–190. Bibcode:2017Natur.542..186M. doi:10.1038/nature21039. PMC 5302847. PMID 28146470.
- ^ Rimbault M, Beale HC, Schoenebeck JJ, Hoopes BC, Allen JJ, Kilroy-Glynn P, Wayne RK, Sutter NB, Ostrander EA (December 2013). "Derived variants at six genes explain nearly half of size reduction in dog breeds". Genome Res. 23 (12): 1985–95. doi:10.1101/gr.157339.113. PMC 3847769. PMID 24026177.
- ^ Roberts Kingman GA, Lee D, Jones FC, Desmet D, Bell MA, Kingsley DM (August 2021). "Longer or shorter spines: Reciprocal trait evolution in stickleback via triallelic regulatory changes in Stanniocalcin2a". Proc Natl Acad Sci U S A. 118 (31). Bibcode:2021PNAS..11800694R. doi:10.1073/pnas.2100694118. PMC 8346906. PMID 34321354.
Further reading
[edit]- DiMattia GE, Varghese R, Wagner GF (1999). "Molecular cloning and characterization of stanniocalcin-related protein". Mol. Cell. Endocrinol. 146 (1–2): 137–40. doi:10.1016/S0303-7207(98)00163-4. PMID 10022771. S2CID 27861622.
- Moore EE, Kuestner RE, Conklin DC, et al. (1999). "Stanniocalcin 2: characterization of the protein and its localization to human pancreatic alpha cells". Horm. Metab. Res. 31 (7): 406–14. doi:10.1055/s-2007-978764. PMID 10450831. S2CID 40695938.
- Jellinek DA, Chang AC, Larsen MR, et al. (2001). "Stanniocalcin 1 and 2 are secreted as phosphoproteins from human fibrosarcoma cells". Biochem. J. 350 Pt 2 (2): 453–61. doi:10.1042/0264-6021:3500453. PMC 1221272. PMID 10947959.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
- Gagliardi AD, Kuo EY, Raulic S, et al. (2005). "Human stanniocalcin-2 exhibits potent growth-suppressive properties in transgenic mice independently of growth hormone and IGFs". Am. J. Physiol. Endocrinol. Metab. 288 (1): E92–105. doi:10.1152/ajpendo.00268.2004. PMID 15367391. S2CID 14827240.
- Luo CW, Pisarska MD, Hsueh AJ (2005). "Identification of a stanniocalcin paralog, stanniocalcin-2, in fish and the paracrine actions of stanniocalcin-2 in the mammalian ovary". Endocrinology. 146 (1): 469–76. doi:10.1210/en.2004-1197. PMID 15486227.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Stelzl U, Worm U, Lalowski M, et al. (2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923.
- Otsuki T, Ota T, Nishikawa T, et al. (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Res. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
- Esseghir S, Kennedy A, Seedhar P, et al. (2007). "Identification of NTN4, TRA1, and STC2 as prognostic markers in breast cancer in a screen for signal sequence encoding proteins". Clin. Cancer Res. 13 (11): 3164–73. doi:10.1158/1078-0432.CCR-07-0224. PMID 17545519. S2CID 35660629.
- Ichikawa T, Horie-Inoue K, Ikeda K, et al. (2007). "Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells". J. Mol. Endocrinol. 39 (4): 239–47. doi:10.1677/JME-07-0048. PMID 17909264.
 | This article on a gene on human chromosome 5 is a stub. You can help Wikipedia by expanding it. |