Protein: Tensin-3 (EC 3.1.3.-) (Tensin-like SH2 domain-containing protein 1) (Q5SSZ5)
Organism: Mus musculus (Mouse)
Function: May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in the dissociation of the integrin-tensin-actin complex (By similarity). EGF activates TNS4 and down-regulates TNS3 which results in capping the tail of ITGB1 (By similarity). Increases DOCK5 guanine nucleotide exchange activity towards Rac and plays a role in osteoclast podosome organization. Enhances RHOA activation in the presence of DLC1 (By similarity). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces TNS3 phosphorylation which changes its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex, displacing PI3K inhibitor PTEN and resulting in translocation of the TNS3-p85 complex to the leading edge of migrating cells to promote RAC1 activation (By similarity). Meanwhile, PTEN switches binding preference from p85 to DLC1 and the PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA (By similarity). Acts as an adapter protein by bridging the association of scaffolding protein PEAK1 with integrins ITGB1, ITGB3 and ITGB5 which contributes to the promotion of cell migration. Controls tonsil-derived mesenchymal stem cell proliferation and differentiation by regulating the activity of integrin ITGB1 (By similarity).
Subcellular location: Cell junction, focal adhesion {ECO:0000250|UniProtKB:Q68CZ2}. Cell projection, podosome {ECO:0000269|PubMed:27505886}. Note=Localizes to both focal and fibrillar adhesions but is mostly found in fibrillar adhesions. {ECO:0000250|UniProtKB:Q68CZ2}.
Sequence: MEDSHELDLTYVTERIIAVSFPASCSEESYLHSLQEVTRMLKCKHGDNYLVLNLSEKRYDLTKLNPKIMDVGWPELHAPPLDKMCTICKAQESWLNNDPQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFYDDKISALMEPSQKRYVQFLSGLLSGAMKMNTSPLFLHFVIMHGVPSFDTGGACRPFLKLYQAMQPVYTSGIYNVGSENPSRIRIAIEPAQLLKGDIMVKCYHKKFRSATRDVIFRLQFHTGAVQGYGLLFGKEELDSACKDDRFPDYGKIELVFSATPEKIQGSEHLYSDQGVTVDYNTADPLIRWDSYENMSADGEVLHTQGPVDGSLYAKVRKKSASDTGIPSSPQGMPATSSPDHGDHTLSVSSDSGHSTASARTDKTEERLTPGARRGLSPQEKAELDQLLSGFGLEDSASSHKDMTDMRSKYSGTRHVVPAQVHVNGDAALKDRETDILDDEMPHHDLHSVDSLGTLSSSEGPQSTHLGPFTCLKSSQNSLLSDGFGNGVAEDHNGVLSPDLGLGVDTLYDRERMCGGREQKPLQPLLRKPSAPTPVQAYGQSNYSTQTWVRQQQMVAAHQYSFASDGEARLGSRSTVDNTGLAQPPPHIPVTPNRGASSRVAVQRGISNGPNPPDTQQLCPGKALQPRFQDDRVTNGVHQEPNTGSSPGSPTLDIDQSIEQLNRLILELDPTFEPIPTHLNALGISAVCPDGVGSGLRCSGRLDSVDGPGRSPGRQGDDPIGGRLRKLSIGQYDNDAASQVTFSKCGWGKAGVDPAPSLGSFSSPEDIKETVITAYPSDLNMIDGRIPNSKESSMCLTPSFPVSPETPYVKTSPRYPPFSPPEPQLSSPASLHKGREPRGCPEIISHTVGMSESPVGPKPTMLRADMPATPNFQQVFASSCTVSSNGPGQRRESPPSAERQWVESSPKSTLTLLGNSHPSESPLGTHEFCSSGKDSPGLPCFQSSELQASFHSHELSMSEPQGALPPAGSQTFLGFNTVTTATSVLPPGEDAGTLLVNSHGTSPAPGTPLLTTGAADNGFLPHNFLTVSPGASSHHSPGLQNQNVSLPGQPPLPEKKRASEGDRSLGSVSPSSSGFSSPHSGSTMSIPFPNVLPDFCKPSEVASPLPDSPNDKLVIVKFVQDTSKFWYKADISREQAIAMLKDKAPGSFIVRDSHSFRGAYGLAMKVATPPPSVLHLNKKAGDLSNELVRHFLIECTPKGVRLKGCSNEPYFGSLTALVCQHSITPLALPCKLLIPERDPLEEIAENSPQTAANSAAELLKQGAACNVWYLNSVEMESLTGHQAVQKALSMTLVQEPPPVSTVVHFKVSAQGITLTDNQRKLFFRRHYPVSSVIFCALDPQDRKWIKDGPSSKVFGFVARKQGSATDNVCHLFAEHDPEQPASAIVNFVSKVMIGSPKKI
InterPro domains: - IPR029021: Protein-tyrosine phosphatase-like (homologous_superfamily) [6-170]
- IPR035892: C2 domain superfamily (homologous_superfamily) [173-301]
- IPR051484: Tensin Phosphatase (family) [1-1439]
- IPR000387: Tyrosine-specific protein phosphatases domain (domain) [103-142]
- IPR014020: Tensin phosphatase, C2 domain (domain) [173-301]
- IPR029023: Tensin-type phosphatase domain (domain) [1-170]
- IPR033929: Tensin, phosphotyrosine-binding domain (domain) [1303-1434]
- IPR003595: Protein-tyrosine phosphatase, catalytic (domain) [64-186]
- IPR036860: SH2 domain superfamily (homologous_superfamily) [1156-1287]
- IPR006020: PTB/PI domain (domain) [1301-1438]
- IPR035012: Tensin-like, SH2 domain (domain) [1163-1279]
- IPR013625: Tensin/EPS8 phosphotyrosine-binding domain (domain) [1305-1439]
- IPR000980: SH2 domain (domain) [1165-1277]
- IPR011993: PH-like domain superfamily (homologous_superfamily) [1291-1440]
Interaction partners: - Epidermal growth factor receptor
- Paxillin
- Breast cancer anti-estrogen resistance protein 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0009987 (cellular process), GO:0071840 (cellular component organization or biogenesis), GO:0048870 (cell motility), GO:0016043 (cellular component organization), GO:0044085 (cellular component biogenesis), GO:0016477 (cell migration), GO:0034330 (cell junction organization), GO:0001667 (ameboidal-type cell migration), GO:0022607 (cellular component assembly), GO:0010761 (fibroblast migration), GO:0150115 (cell-substrate junction organization), GO:0034329 (cell junction assembly), GO:0007044 (cell-substrate junction assembly)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0030054 (cell junction), GO:0070161 (anchoring junction), GO:0030055 (cell-substrate junction), GO:0005925 (focal adhesion)