STC2

STC2
Identifiers
Aliases	STC2, STC-2, STCRP, stanniocalcin 2
External IDs	OMIM: 603665; MGI: 1316731; HomoloGene: 2753; GeneCards: STC2; OMA:STC2 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q35.2 Start 173,314,723 bp End 173,328,447 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 A4 Start 31,307,307 bp End 31,320,074 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium tibia epithelium of lactiferous gland lactiferous duct body of pancreas cartilage tissue Achilles tendon right auricle upper lobe of left lung placenta Top expressed in aortic valve ascending aorta lumbar subsegment of spinal cord tail of embryo gastrula parietal layer of glomerular capsule muscle of thigh lactiferous gland lumbar spinal ganglion submandibular gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity hormone activity heme binding enzyme binding Cellular component Golgi apparatus extracellular region endoplasmic reticulum perinuclear region of cytoplasm extracellular space endoplasmic reticulum lumen Biological process response to vitamin D calcium ion homeostasis negative regulation of multicellular organism growth response to peptide hormone cellular calcium ion homeostasis regulation of hormone biosynthetic process response to oxidative stress negative regulation of gene expression response to endoplasmic reticulum stress endoplasmic reticulum unfolded protein response decidualization regulation of store-operated calcium entry cellular response to hypoxia embryo implantation post-translational protein modification regulation of signaling receptor activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8614 20856 Ensembl ENSG00000113739 ENSMUSG00000020303 UniProt O76061 O88452 RefSeq (mRNA) NM_003714 NM_011491 RefSeq (protein) NP_003705 NP_035621 Location (UCSC) Chr 5: 173.31 – 173.33 Mb Chr 11: 31.31 – 31.32 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Stanniocalcin-2 is a protein that in humans is encoded by the STC2 gene.

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.

Stanniocalcin reduces bone growth 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. Stanniocalcin inhibits the activity of PAPPA in releasing active IGF1 through itself binding PAPPA, 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, while mice expressing STC2 at elevated levels are 45% smaller. 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. 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. 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.

Further reading

• 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.