Protein: Tensin-2 (EC 3.1.3.48) (C1 domain-containing phosphatase and tensin homolog) (C1-TEN) (Tensin-like C1 domain-containing phosphatase) (Q63HR2)
Organism: Homo sapiens (Human)
Function: Tyrosine-protein phosphatase which regulates cell motility, proliferation and muscle-response to insulin. Phosphatase activity is mediated by binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) via the SH2 domain. In muscles and under catabolic conditions, dephosphorylates IRS1 leading to its degradation and muscle atrophy. Negatively regulates PI3K-AKT pathway activation. Dephosphorylates nephrin NPHS1 in podocytes which regulates activity of the mTORC1 complex. Under normal glucose conditions, NPHS1 outcompetes IRS1 for binding to phosphatidylinositol 3-kinase (PI3K) which balances mTORC1 activity but high glucose conditions lead to up-regulation of TNS2, increased NPHS1 dephosphorylation and activation of mTORC1, contributing to podocyte hypertrophy and proteinuria. Required for correct podocyte morphology, podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier (By similarity). Enhances RHOA activation in the presence of DLC1. Plays a role in promoting DLC1-dependent remodeling of the extracellular matrix.
Subcellular location: Cell junction, focal adhesion {ECO:0000269|PubMed:11792844, ECO:0000269|PubMed:20069572, ECO:0000269|PubMed:22019427}. Cell membrane {ECO:0000269|PubMed:11792844, ECO:0000269|PubMed:30092354}; Peripheral membrane protein {ECO:0000269|PubMed:11792844}; Cytoplasmic side {ECO:0000269|PubMed:11792844}. Cytoplasm {ECO:0000269|PubMed:22019427, ECO:0000269|PubMed:25101860}. Note=Detected at the end of actin stress fibers. Detected in cytoplasmic punctate bodies (PubMed:22019427, PubMed:25101860). Localizes to both focal adhesions and fibrillar adhesions but is found mainly in focal adhesions (PubMed:20069572). Enriched in dynamic focal adhesions at the leading edge of the cell and is found only rarely in fibrillar adhesions on the ventral surface of cells (PubMed:20069572). {ECO:0000269|PubMed:20069572, ECO:0000269|PubMed:22019427, ECO:0000269|PubMed:25101860}.
Interaction partners:
- Rho GTPase-activating protein 7
- Tyrosine-protein kinase receptor UFO
- Vinculin
- Proto-oncogene tyrosine-protein kinase Src
Sequence:
MKSSGPVERLLRALGRRDSSRAASRPRKAEPHSFREKVFRKKPPVCAVCKVTIDGTGVSCRVCKVATHRKCEAKVTSACQALPPVELRRNTAPVRRIEHLGSTKSLNHSKQRSTLPRSFSLDPLMERRWDLDLTYVTERILAAAFPARPDEQRHRGHLRELAHVLQSKHRDKYLLFNLSEKRHDLTRLNPKVQDFGWPELHAPPLDKLCSICKAMETWLSADPQHVVVLYCKGNKGKLGVIVSAYMHYSKISAGADQALATLTMRKFCEDKVATELQPSQRRYISYFSGLLSGSIRMNSSPLFLHYVLIPMLPAFEPGTGFQPFLKIYQSMQLVYTSGVYHIAGPGPQQLCISLEPALLLKGDVMVTCYHKGGRGTDRTLVFRVQFHTCTIHGPQLTFPKDQLDEAWTDERFPFQASVEFVFSSSPEKIKGSTPRNDPSVSVDYNTTEPAVRWDSYENFNQHHEDSVDGSLTHTRGPLDGSPYAQVQRPPRQTPPAPSPEPPPPPMLSVSSDSGHSSTLTTEPAAESPGRPPPTAAERQELDRLLGGCGVASGGRGAGRETAILDDEEQPTVGGGPHLGVYPGHRPGLSRHCSCRQGYREPCGVPNGGYYRPEGTLERRRLAYGGYEGSPQGYAEASMEKRRLCRSLSEGLYPYPPEMGKPATGDFGYRAPGYREVVILEDPGLPALYPCPACEEKLALPTAALYGLRLEREAGEGWASEAGKPLLHPVRPGHPLPLLLPACGHHHAPMPDYSCLKPPKAGEEGHEGCSYTMCPEGRYGHPGYPALVTYSYGGAVPSYCPAYGRVPHSCGSPGEGRGYPSPGAHSPRAGSISPGSPPYPQSRKLSYEIPTEEGGDRYPLPGHLASAGPLASAESLEPVSWREGPSGHSTLPRSPRDAPCSASSELSGPSTPLHTSSPVQGKESTRRQDTRSPTSAPTQRLSPGEALPPVSQAGTGKAPELPSGSGPEPLAPSPVSPTFPPSSPSDWPQERSPGGHSDGASPRSPVPTTLPGLRHAPWQGPRGPPDSPDGSPLTPVPSQMPWLVASPEPPQSSPTPAFPLAASYDTNGLSQPPLPEKRHLPGPGQQPGPWGPEQASSPARGISHHVTFAPLLSDNVPQTPEPPTQESQSNVKFVQDTSKFWYKPHLSRDQAIALLKDKDPGAFLIRDSHSFQGAYGLALKVATPPPSAQPWKGDPVEQLVRHFLIETGPKGVKIKGCPSEPYFGSLSALVSQHSISPISLPCCLRIPSKDPLEETPEAPVPTNMSTAADLLRQGAACSVLYLTSVETESLTGPQAVARASSAALSCSPRPTPAVVHFKVSAQGITLTDNQRKLFFRRHYPVNSITFSSTDPQDRRWTNPDGTTSKIFGFVAKKPGSPWENVCHLFAELDPDQPAGAIVTFITKVLLGQRK