STC2

Stanniocalcin-2 is a protein that in humans is encoded by the STC2 gene.[5][6][7]

STC2
Identifiers
Aliases	STC2, STC-2, STCRP, stanniocalcin 2
External IDs	OMIM: 603665 MGI: 1316731 HomoloGene: 2753 GeneCards: STC2
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q35.2 Start 173,314,723 bp[1] End 173,328,447 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 A4 Start 31,307,307 bp[2] End 31,320,074 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium tibia lactiferous duct body of pancreas Achilles tendon upper lobe of left lung placenta gallbladder smooth muscle tissue spleen Top expressed in aortic valve ascending aorta submandibular gland epithelium of stomach pharynx epididymis intercostal muscle cheek otic placode white adipose tissue 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 [3] [4]
Wikidata
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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]