ID   TENS2_HUMAN             Reviewed;        1409 AA.
AC   Q63HR2; A2VDF2; A2VDF3; A2VDI8; A5PKY4; Q2NL80; Q76MW6; Q7Z5T9; Q8NFF9;
AC   Q8NFG0; Q96P25; Q9NT29; Q9UPS7;
DT   26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   26-JUN-2007, sequence version 2.
DT   24-JAN-2024, entry version 164.
DE   RecName: Full=Tensin-2;
DE            EC=3.1.3.48 {ECO:0000269|PubMed:23401856, ECO:0000269|PubMed:28955049, ECO:0000269|PubMed:30092354};
DE   AltName: Full=C1 domain-containing phosphatase and tensin homolog;
DE            Short=C1-TEN;
DE   AltName: Full=Tensin-like C1 domain-containing phosphatase;
GN   Name=TNS2; Synonyms=KIAA1075, TENC1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4), INTERACTION WITH AXL, AND
RP   TISSUE SPECIFICITY.
RC   TISSUE=Kidney;
RX   PubMed=12470648; DOI=10.1016/s0006-291x(02)02718-3;
RA   Hafizi S., Alindri F., Karlsson R., Dahlbaeck B.;
RT   "Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1
RT   domain-containing protein with homology to tensin.";
RL   Biochem. Biophys. Res. Commun. 299:793-800(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=11792844; DOI=10.1073/pnas.022518699;
RA   Chen H., Duncan I.C., Bozorgchami H., Lo S.H.;
RT   "Tensin1 and a previously undocumented family member, tensin2, positively
RT   regulate cell migration.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:733-738(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA   Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA   Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XIV. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 6:197-205(1999).
RN   [4]
RP   SEQUENCE REVISION.
RX   PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA   Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT   "Construction of expression-ready cDNA clones for KIAA genes: manual
RT   curation of 330 KIAA cDNA clones.";
RL   DNA Res. 9:99-106(2002).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 759-1409 (ISOFORM 6).
RC   TISSUE=Colon endothelium, and Testis;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5), AND NUCLEOTIDE
RP   SEQUENCE [LARGE SCALE MRNA] OF 364-1398 (ISOFORM 2).
RC   TISSUE=Brain, and Uterus;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   FUNCTION, AND MUTAGENESIS OF CYS-231.
RX   PubMed=15817639; DOI=10.1096/fj.04-2532fje;
RA   Hafizi S., Ibraimi F., Dahlbaeck B.;
RT   "C1-TEN is a negative regulator of the Akt/PKB signal transduction pathway
RT   and inhibits cell survival, proliferation, and migration.";
RL   FASEB J. 19:971-973(2005).
RN   [8]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=20069572; DOI=10.1002/jcb.22460;
RA   Clark K., Howe J.D., Pullar C.E., Green J.A., Artym V.V., Yamada K.M.,
RA   Critchley D.R.;
RT   "Tensin 2 modulates cell contractility in 3D collagen gels through the
RT   RhoGAP DLC1.";
RL   J. Cell. Biochem. 109:808-817(2010).
RN   [9]
RP   INTERACTION WITH SYK, AND SUBCELLULAR LOCATION.
RX   PubMed=22019427; DOI=10.1016/j.bbamcr.2011.10.001;
RA   Moon K.D., Zhang X., Zhou Q., Geahlen R.L.;
RT   "The protein-tyrosine kinase Syk interacts with the C-terminal region of
RT   tensin2.";
RL   Biochim. Biophys. Acta 1823:199-205(2012).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120; SER-835 AND SER-1003,
RP   AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [12]
RP   FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-231.
RX   PubMed=23401856; DOI=10.1128/mcb.01447-12;
RA   Koh A., Lee M.N., Yang Y.R., Jeong H., Ghim J., Noh J., Kim J., Ryu D.,
RA   Park S., Song P., Koo S.H., Leslie N.R., Berggren P.O., Choi J.H.,
RA   Suh P.G., Ryu S.H.;
RT   "C1-Ten is a protein tyrosine phosphatase of insulin receptor substrate 1
RT   (IRS-1), regulating IRS-1 stability and muscle atrophy.";
RL   Mol. Cell. Biol. 33:1608-1620(2013).
RN   [13]
RP   INTERACTION WITH SQSTM1, SUBCELLULAR LOCATION, UBIQUITINATION, AND
RP   MUTAGENESIS OF CYS-231.
RX   PubMed=25101860; DOI=10.1016/j.cellsig.2014.07.033;
RA   Koh A., Park D., Jeong H., Lee J., Lee M.N., Suh P.G., Ryu S.H.;
RT   "Regulation of C1-Ten protein tyrosine phosphatase by p62/SQSTM1-mediated
RT   sequestration and degradation.";
RL   Cell. Signal. 26:2470-2480(2014).
RN   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-91; SER-120; SER-455;
RP   TYR-456; SER-466; THR-474; SER-820; SER-825; SER-830; SER-832; SER-845;
RP   SER-931; SER-941; SER-972; THR-977; SER-991; SER-1003; THR-1182 AND
RP   SER-1247, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [15]
RP   FUNCTION.
RX   PubMed=26427649; DOI=10.1016/j.bbamcr.2015.09.028;
RA   Shih Y.P., Sun P., Wang A., Lo S.H.;
RT   "Tensin1 positively regulates RhoA activity through its interaction with
RT   DLC1.";
RL   Biochim. Biophys. Acta 1853:3258-3265(2015).
RN   [16]
RP   ERRATUM OF PUBMED:26427649.
RX   PubMed=29866430; DOI=10.1016/j.bbamcr.2018.05.016;
RA   Shih Y.P., Sun P., Wang A., Lo S.H.;
RL   Biochim. Biophys. Acta 1865:1383-1383(2018).
RN   [17]
RP   FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND MUTAGENESIS OF CYS-231.
RX   PubMed=28955049; DOI=10.1038/s41598-017-12382-8;
RA   Lee J., Koh A., Jeong H., Kim E., Ha T.S., Saleem M.A., Ryu S.H.;
RT   "C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through
RT   mTORC1 activation.";
RL   Sci. Rep. 7:12346-12346(2017).
RN   [18]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS
RP   OF LYS-1142; LYS-1155; LYS-1157; ARG-1165; LYS-1209; LYS-1212 AND LYS-1214.
RX   PubMed=30092354; DOI=10.1016/j.cellsig.2018.07.009;
RA   Kim E., Kim D.H., Singaram I., Jeong H., Koh A., Lee J., Cho W., Ryu S.H.;
RT   "Cellular phosphatase activity of C1-Ten/Tensin2 is controlled by
RT   Phosphatidylinositol-3,4,5-triphosphate binding through the C1-Ten/Tensin2
RT   SH2 domain.";
RL   Cell. Signal. 51:130-138(2018).
RN   [19]
RP   STRUCTURE BY NMR OF 1263-1409.
RG   RIKEN structural genomics initiative (RSGI);
RT   "Solution structure of the PTB domain of KIAA1075 protein from human.";
RL   Submitted (OCT-2006) to the PDB data bank.
CC   -!- FUNCTION: Tyrosine-protein phosphatase which regulates cell motility,
CC       proliferation and muscle-response to insulin (PubMed:15817639,
CC       PubMed:23401856). Phosphatase activity is mediated by binding to
CC       phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) via the SH2
CC       domain (PubMed:30092354). In muscles and under catabolic conditions,
CC       dephosphorylates IRS1 leading to its degradation and muscle atrophy
CC       (PubMed:23401856, PubMed:30092354). Negatively regulates PI3K-AKT
CC       pathway activation (PubMed:15817639, PubMed:23401856, PubMed:30092354).
CC       Dephosphorylates nephrin NPHS1 in podocytes which regulates activity of
CC       the mTORC1 complex (PubMed:28955049). Under normal glucose conditions,
CC       NPHS1 outcompetes IRS1 for binding to phosphatidylinositol 3-kinase
CC       (PI3K) which balances mTORC1 activity but high glucose conditions lead
CC       to up-regulation of TNS2, increased NPHS1 dephosphorylation and
CC       activation of mTORC1, contributing to podocyte hypertrophy and
CC       proteinuria (PubMed:28955049). Required for correct podocyte
CC       morphology, podocyte-glomerular basement membrane interaction and
CC       integrity of the glomerular filtration barrier (By similarity).
CC       Enhances RHOA activation in the presence of DLC1 (PubMed:26427649).
CC       Plays a role in promoting DLC1-dependent remodeling of the
CC       extracellular matrix (PubMed:20069572). {ECO:0000250|UniProtKB:Q8CGB6,
CC       ECO:0000269|PubMed:15817639, ECO:0000269|PubMed:20069572,
CC       ECO:0000269|PubMed:23401856, ECO:0000269|PubMed:26427649,
CC       ECO:0000269|PubMed:28955049, ECO:0000269|PubMed:30092354}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC         COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:82620; EC=3.1.3.48;
CC         Evidence={ECO:0000269|PubMed:23401856, ECO:0000269|PubMed:28955049,
CC         ECO:0000269|PubMed:30092354};
CC   -!- SUBUNIT: Interacts with AXL (PubMed:12470648). Interacts with SYK;
CC       leading to its phosphorylation (PubMed:22019427). Interacts with SQSTM1
CC       (via PB1 domain); the interaction leads to sequestration of TNS2 in
CC       cytoplasmic aggregates with SQSTM1 and promotes TNS2 ubiquitination and
CC       proteasomal degradation (PubMed:25101860).
CC       {ECO:0000269|PubMed:12470648, ECO:0000269|PubMed:22019427,
CC       ECO:0000269|PubMed:25101860}.
CC   -!- INTERACTION:
CC       Q63HR2; Q9Y4X0-3: AMMECR1; NbExp=3; IntAct=EBI-949753, EBI-12823597;
CC       Q63HR2; P29972: AQP1; NbExp=3; IntAct=EBI-949753, EBI-745213;
CC       Q63HR2; Q03989: ARID5A; NbExp=3; IntAct=EBI-949753, EBI-948603;
CC       Q63HR2; P30049: ATP5F1D; NbExp=3; IntAct=EBI-949753, EBI-1049505;
CC       Q63HR2; Q8TBE0: BAHD1; NbExp=3; IntAct=EBI-949753, EBI-742750;
CC       Q63HR2; Q9H2G9: BLZF1; NbExp=3; IntAct=EBI-949753, EBI-2548012;
CC       Q63HR2; J3KQ12: BSCL2; NbExp=3; IntAct=EBI-949753, EBI-11532900;
CC       Q63HR2; Q6NUJ2: C11orf87; NbExp=3; IntAct=EBI-949753, EBI-6660291;
CC       Q63HR2; Q6P1W5: C1orf94; NbExp=3; IntAct=EBI-949753, EBI-946029;
CC       Q63HR2; Q6P5X5: C22orf39; NbExp=3; IntAct=EBI-949753, EBI-7317823;
CC       Q63HR2; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-949753, EBI-744545;
CC       Q63HR2; Q8NE01: CNNM3; NbExp=3; IntAct=EBI-949753, EBI-741032;
CC       Q63HR2; Q8N684-3: CPSF7; NbExp=3; IntAct=EBI-949753, EBI-11523759;
CC       Q63HR2; O43186: CRX; NbExp=3; IntAct=EBI-949753, EBI-748171;
CC       Q63HR2; Q9UBR2: CTSZ; NbExp=3; IntAct=EBI-949753, EBI-8636823;
CC       Q63HR2; Q86YF9: DZIP1; NbExp=3; IntAct=EBI-949753, EBI-998108;
CC       Q63HR2; Q86Y13: DZIP3; NbExp=3; IntAct=EBI-949753, EBI-948630;
CC       Q63HR2; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-949753, EBI-744099;
CC       Q63HR2; Q9UM22: EPDR1; NbExp=3; IntAct=EBI-949753, EBI-946972;
CC       Q63HR2; P04626: ERBB2; NbExp=4; IntAct=EBI-949753, EBI-641062;
CC       Q63HR2; P21860: ERBB3; NbExp=3; IntAct=EBI-949753, EBI-720706;
CC       Q63HR2; Q8N9I5: FADS6; NbExp=3; IntAct=EBI-949753, EBI-3943864;
CC       Q63HR2; Q86W67: FAM228A; NbExp=3; IntAct=EBI-949753, EBI-12958227;
CC       Q63HR2; P48023: FASLG; NbExp=3; IntAct=EBI-949753, EBI-495538;
CC       Q63HR2; P49639: HOXA1; NbExp=3; IntAct=EBI-949753, EBI-740785;
CC       Q63HR2; P17482: HOXB9; NbExp=3; IntAct=EBI-949753, EBI-745290;
CC       Q63HR2; P31273: HOXC8; NbExp=3; IntAct=EBI-949753, EBI-1752118;
CC       Q63HR2; Q9C086: INO80B; NbExp=3; IntAct=EBI-949753, EBI-715611;
CC       Q63HR2; Q7L273: KCTD9; NbExp=3; IntAct=EBI-949753, EBI-4397613;
CC       Q63HR2; P10721: KIT; NbExp=2; IntAct=EBI-949753, EBI-1379503;
CC       Q63HR2; Q5T749: KPRP; NbExp=5; IntAct=EBI-949753, EBI-10981970;
CC       Q63HR2; Q01546: KRT76; NbExp=3; IntAct=EBI-949753, EBI-2952745;
CC       Q63HR2; Q8IUG1: KRTAP1-3; NbExp=5; IntAct=EBI-949753, EBI-11749135;
CC       Q63HR2; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-949753, EBI-10172150;
CC       Q63HR2; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-949753, EBI-10172290;
CC       Q63HR2; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-949753, EBI-10171774;
CC       Q63HR2; Q8IUC1: KRTAP11-1; NbExp=5; IntAct=EBI-949753, EBI-1052037;
CC       Q63HR2; P59991: KRTAP12-2; NbExp=6; IntAct=EBI-949753, EBI-10176379;
CC       Q63HR2; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-949753, EBI-11953334;
CC       Q63HR2; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-949753, EBI-11953846;
CC       Q63HR2; Q9BYR3: KRTAP4-4; NbExp=3; IntAct=EBI-949753, EBI-11958132;
CC       Q63HR2; Q14847-2: LASP1; NbExp=3; IntAct=EBI-949753, EBI-9088686;
CC       Q63HR2; Q8IXW0: LMNTD2; NbExp=3; IntAct=EBI-949753, EBI-12028858;
CC       Q63HR2; O60711: LPXN; NbExp=3; IntAct=EBI-949753, EBI-744222;
CC       Q63HR2; Q9P127: LUZP4; NbExp=3; IntAct=EBI-949753, EBI-10198848;
CC       Q63HR2; P08581: MET; NbExp=2; IntAct=EBI-949753, EBI-1039152;
CC       Q63HR2; Q86VE0: MYPOP; NbExp=3; IntAct=EBI-949753, EBI-2858213;
CC       Q63HR2; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-949753, EBI-22310682;
CC       Q63HR2; Q9Y5Y2: NUBP2; NbExp=3; IntAct=EBI-949753, EBI-1048886;
CC       Q63HR2; P32242: OTX1; NbExp=5; IntAct=EBI-949753, EBI-740446;
CC       Q63HR2; Q9HBE1-4: PATZ1; NbExp=3; IntAct=EBI-949753, EBI-11022007;
CC       Q63HR2; O43189: PHF1; NbExp=3; IntAct=EBI-949753, EBI-530034;
CC       Q63HR2; Q13526: PIN1; NbExp=3; IntAct=EBI-949753, EBI-714158;
CC       Q63HR2; Q13835: PKP1; NbExp=3; IntAct=EBI-949753, EBI-2513407;
CC       Q63HR2; Q9NRY6: PLSCR3; NbExp=3; IntAct=EBI-949753, EBI-750734;
CC       Q63HR2; Q9BTL3: RAMAC; NbExp=3; IntAct=EBI-949753, EBI-744023;
CC       Q63HR2; Q9NYW8: RBAK; NbExp=3; IntAct=EBI-949753, EBI-1210429;
CC       Q63HR2; Q96HR9: REEP6; NbExp=3; IntAct=EBI-949753, EBI-750345;
CC       Q63HR2; Q04864: REL; NbExp=3; IntAct=EBI-949753, EBI-307352;
CC       Q63HR2; A0A0S2Z4G9: RNF6; NbExp=3; IntAct=EBI-949753, EBI-16428950;
CC       Q63HR2; Q14140: SERTAD2; NbExp=3; IntAct=EBI-949753, EBI-2822051;
CC       Q63HR2; Q9NUL5: SHFL; NbExp=4; IntAct=EBI-949753, EBI-10313866;
CC       Q63HR2; Q6ZT89-3: SLC25A48; NbExp=3; IntAct=EBI-949753, EBI-12065614;
CC       Q63HR2; O14512: SOCS7; NbExp=3; IntAct=EBI-949753, EBI-1539606;
CC       Q63HR2; O60504: SORBS3; NbExp=3; IntAct=EBI-949753, EBI-741237;
CC       Q63HR2; Q9UGT4: SUSD2; NbExp=3; IntAct=EBI-949753, EBI-1054721;
CC       Q63HR2; Q5T7P8-2: SYT6; NbExp=3; IntAct=EBI-949753, EBI-10246152;
CC       Q63HR2; Q9BXF9: TEKT3; NbExp=3; IntAct=EBI-949753, EBI-8644516;
CC       Q63HR2; Q96M29: TEKT5; NbExp=6; IntAct=EBI-949753, EBI-10239812;
CC       Q63HR2; Q96A09: TENT5B; NbExp=3; IntAct=EBI-949753, EBI-752030;
CC       Q63HR2; Q7Z6R9: TFAP2D; NbExp=3; IntAct=EBI-949753, EBI-11952651;
CC       Q63HR2; Q63HR2: TNS2; NbExp=3; IntAct=EBI-949753, EBI-949753;
CC       Q63HR2; Q9BZR9: TRIM8; NbExp=3; IntAct=EBI-949753, EBI-2340370;
CC       Q63HR2; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-949753, EBI-11975223;
CC       Q63HR2; Q8WYQ9: ZCCHC14; NbExp=3; IntAct=EBI-949753, EBI-3937908;
CC       Q63HR2; Q9NZV7: ZIM2; NbExp=3; IntAct=EBI-949753, EBI-11962760;
CC       Q63HR2; P52741: ZNF134; NbExp=3; IntAct=EBI-949753, EBI-18054945;
CC       Q63HR2; O95201: ZNF205; NbExp=3; IntAct=EBI-949753, EBI-747343;
CC       Q63HR2; P15622-3: ZNF250; NbExp=3; IntAct=EBI-949753, EBI-10177272;
CC       Q63HR2; Q8TAU3: ZNF417; NbExp=9; IntAct=EBI-949753, EBI-740727;
CC       Q63HR2; Q6ZNH5: ZNF497; NbExp=3; IntAct=EBI-949753, EBI-10486136;
CC       Q63HR2; Q86XF7: ZNF575; NbExp=3; IntAct=EBI-949753, EBI-14069183;
CC       Q63HR2; Q96SQ5: ZNF587; NbExp=6; IntAct=EBI-949753, EBI-6427977;
CC       Q63HR2; Q5T619: ZNF648; NbExp=3; IntAct=EBI-949753, EBI-11985915;
CC       Q63HR2; A0A0S2Z5X4: ZNF688; NbExp=3; IntAct=EBI-949753, EBI-16429014;
CC       Q63HR2; Q96EG3: ZNF837; NbExp=3; IntAct=EBI-949753, EBI-11962574;
CC       Q63HR2; Q9NWL9; NbExp=3; IntAct=EBI-949753, EBI-10315054;
CC   -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion
CC       {ECO:0000269|PubMed:11792844, ECO:0000269|PubMed:20069572,
CC       ECO:0000269|PubMed:22019427}. Cell membrane
CC       {ECO:0000269|PubMed:11792844, ECO:0000269|PubMed:30092354}; Peripheral
CC       membrane protein {ECO:0000269|PubMed:11792844}; Cytoplasmic side
CC       {ECO:0000269|PubMed:11792844}. Cytoplasm {ECO:0000269|PubMed:22019427,
CC       ECO:0000269|PubMed:25101860}. Note=Detected at the end of actin stress
CC       fibers. Detected in cytoplasmic punctate bodies (PubMed:22019427,
CC       PubMed:25101860). Localizes to both focal adhesions and fibrillar
CC       adhesions but is found mainly in focal adhesions (PubMed:20069572).
CC       Enriched in dynamic focal adhesions at the leading edge of the cell and
CC       is found only rarely in fibrillar adhesions on the ventral surface of
CC       cells (PubMed:20069572). {ECO:0000269|PubMed:20069572,
CC       ECO:0000269|PubMed:22019427, ECO:0000269|PubMed:25101860}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=1;
CC         IsoId=Q63HR2-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q63HR2-2; Sequence=VSP_026460;
CC       Name=4;
CC         IsoId=Q63HR2-4; Sequence=VSP_026458;
CC       Name=5;
CC         IsoId=Q63HR2-5; Sequence=VSP_026457;
CC       Name=6;
CC         IsoId=Q63HR2-6; Sequence=VSP_026461;
CC   -!- TISSUE SPECIFICITY: Detected in heart, kidney, brain, thymus, spleen,
CC       liver, placenta, lung, skeletal muscle and small intestine.
CC       {ECO:0000269|PubMed:11792844, ECO:0000269|PubMed:12470648}.
CC   -!- INDUCTION: By high glucose levels in differentiated podocytes (at
CC       protein level). {ECO:0000269|PubMed:28955049}.
CC   -!- DOMAIN: The SH3 domain mediates binding to phosphatidylinositol-3,4,5-
CC       triphosphate (PtdIns(3,4,5)P3) (PubMed:30092354). It is also required
CC       to ensure podocyte integrity while the phosphatase domain is
CC       dispensible for podocyte maintenance (By similarity).
CC       {ECO:0000250|UniProtKB:Q8CGB6, ECO:0000269|PubMed:30092354}.
CC   -!- PTM: Ubiquitinated following sequestration in cytoplasmic aggregates
CC       with SQSTM1, leading to proteasomal degradation.
CC       {ECO:0000269|PubMed:25101860}.
CC   -!- SIMILARITY: Belongs to the PTEN phosphatase protein family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAI29829.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAI29830.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAI31504.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAA83027.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=CAH56176.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR   EMBL; AF518729; AAM74225.1; -; mRNA.
DR   EMBL; AF518728; AAN03866.1; -; mRNA.
DR   EMBL; AF417490; AAL14641.1; -; mRNA.
DR   EMBL; AB028998; BAA83027.2; ALT_INIT; mRNA.
DR   EMBL; AL137564; CAB70815.1; -; mRNA.
DR   EMBL; BX647126; CAH56176.1; ALT_SEQ; mRNA.
DR   EMBL; BC054099; AAH54099.1; -; mRNA.
DR   EMBL; BC110854; AAI10855.1; -; mRNA.
DR   EMBL; BC129828; AAI29829.1; ALT_INIT; mRNA.
DR   EMBL; BC129829; AAI29830.1; ALT_INIT; mRNA.
DR   EMBL; BC131503; AAI31504.1; ALT_INIT; mRNA.
DR   EMBL; BC142668; AAI42669.1; -; mRNA.
DR   EMBL; BC142712; AAI42713.1; -; mRNA.
DR   CCDS; CCDS8843.1; -. [Q63HR2-1]
DR   CCDS; CCDS8844.1; -. [Q63HR2-5]
DR   PIR; T46500; T46500.
DR   RefSeq; NP_056134.2; NM_015319.2.
DR   RefSeq; NP_736610.2; NM_170754.2. [Q63HR2-1]
DR   RefSeq; NP_938072.1; NM_198316.1. [Q63HR2-5]
DR   PDB; 2DKQ; NMR; -; A=1263-1409.
DR   PDB; 2KNO; NMR; -; A=1135-1249.
DR   PDB; 2L6K; NMR; -; A=1135-1248.
DR   PDB; 2LOZ; NMR; -; A=1263-1409.
DR   PDB; 3HQC; X-ray; 1.80 A; A=1264-1409.
DR   PDBsum; 2DKQ; -.
DR   PDBsum; 2KNO; -.
DR   PDBsum; 2L6K; -.
DR   PDBsum; 2LOZ; -.
DR   PDBsum; 3HQC; -.
DR   AlphaFoldDB; Q63HR2; -.
DR   BMRB; Q63HR2; -.
DR   SMR; Q63HR2; -.
DR   BioGRID; 116951; 233.
DR   IntAct; Q63HR2; 194.
DR   MINT; Q63HR2; -.
DR   STRING; 9606.ENSP00000319756; -.
DR   MoonDB; Q63HR2; Predicted.
DR   DEPOD; TNS2; -.
DR   GlyConnect; 2083; 1 N-Linked glycan (1 site).
DR   GlyCosmos; Q63HR2; 3 sites, 3 glycans.
DR   GlyGen; Q63HR2; 3 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (2 sites).
DR   iPTMnet; Q63HR2; -.
DR   PhosphoSitePlus; Q63HR2; -.
DR   BioMuta; TNS2; -.
DR   DMDM; 150416153; -.
DR   EPD; Q63HR2; -.
DR   jPOST; Q63HR2; -.
DR   MassIVE; Q63HR2; -.
DR   MaxQB; Q63HR2; -.
DR   PaxDb; 9606-ENSP00000319756; -.
DR   PeptideAtlas; Q63HR2; -.
DR   ProteomicsDB; 65895; -. [Q63HR2-1]
DR   ProteomicsDB; 65896; -. [Q63HR2-2]
DR   ProteomicsDB; 65897; -. [Q63HR2-4]
DR   ProteomicsDB; 65898; -. [Q63HR2-5]
DR   ProteomicsDB; 65899; -. [Q63HR2-6]
DR   Pumba; Q63HR2; -.
DR   Antibodypedia; 26823; 98 antibodies from 23 providers.
DR   DNASU; 23371; -.
DR   Ensembl; ENST00000314250.11; ENSP00000319684.7; ENSG00000111077.18. [Q63HR2-1]
DR   Ensembl; ENST00000314276.7; ENSP00000319756.3; ENSG00000111077.18. [Q63HR2-4]
DR   Ensembl; ENST00000379902.7; ENSP00000369232.3; ENSG00000111077.18. [Q63HR2-5]
DR   Ensembl; ENST00000546602.5; ENSP00000449363.1; ENSG00000111077.18. [Q63HR2-2]
DR   Ensembl; ENST00000552570.5; ENSP00000447021.1; ENSG00000111077.18. [Q63HR2-6]
DR   GeneID; 23371; -.
DR   KEGG; hsa:23371; -.
DR   MANE-Select; ENST00000314250.11; ENSP00000319684.7; NM_170754.4; NP_736610.2.
DR   UCSC; uc001sbl.4; human. [Q63HR2-1]
DR   AGR; HGNC:19737; -.
DR   CTD; 23371; -.
DR   DisGeNET; 23371; -.
DR   GeneCards; TNS2; -.
DR   HGNC; HGNC:19737; TNS2.
DR   HPA; ENSG00000111077; Low tissue specificity.
DR   MIM; 607717; gene.
DR   neXtProt; NX_Q63HR2; -.
DR   OpenTargets; ENSG00000111077; -.
DR   PharmGKB; PA134976096; -.
DR   VEuPathDB; HostDB:ENSG00000111077; -.
DR   eggNOG; KOG1930; Eukaryota.
DR   eggNOG; KOG2283; Eukaryota.
DR   GeneTree; ENSGT00940000161535; -.
DR   HOGENOM; CLU_002189_0_0_1; -.
DR   InParanoid; Q63HR2; -.
DR   OMA; RCKTATH; -.
DR   OrthoDB; 3439226at2759; -.
DR   PhylomeDB; Q63HR2; -.
DR   TreeFam; TF315996; -.
DR   PathwayCommons; Q63HR2; -.
DR   SignaLink; Q63HR2; -.
DR   BioGRID-ORCS; 23371; 47 hits in 1158 CRISPR screens.
DR   ChiTaRS; TNS2; human.
DR   EvolutionaryTrace; Q63HR2; -.
DR   GeneWiki; TENC1; -.
DR   GenomeRNAi; 23371; -.
DR   Pharos; Q63HR2; Tbio.
DR   PRO; PR:Q63HR2; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q63HR2; Protein.
DR   Bgee; ENSG00000111077; Expressed in apex of heart and 188 other cell types or tissues.
DR   ExpressionAtlas; Q63HR2; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR   GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB.
DR   GO; GO:0019725; P:cellular homeostasis; IEA:Ensembl.
DR   GO; GO:0032963; P:collagen metabolic process; IEA:Ensembl.
DR   GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR   GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR   GO; GO:0048871; P:multicellular organismal-level homeostasis; IEA:Ensembl.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB.
DR   GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IDA:UniProtKB.
DR   GO; GO:0014850; P:response to muscle activity; IEA:Ensembl.
DR   CDD; cd20887; C1_TNS2; 1.
DR   CDD; cd01213; PTB_tensin; 1.
DR   CDD; cd14562; PTP_tensin-2; 1.
DR   CDD; cd09927; SH2_Tensin_like; 1.
DR   Gene3D; 2.60.40.1110; -; 1.
DR   Gene3D; 3.30.60.20; -; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1.
DR   Gene3D; 3.30.505.10; SH2 domain; 1.
DR   IDEAL; IID00673; -.
DR   InterPro; IPR046349; C1-like_sf.
DR   InterPro; IPR035892; C2_domain_sf.
DR   InterPro; IPR002219; PE/DAG-bd.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR   InterPro; IPR013625; PTB.
DR   InterPro; IPR006020; PTB/PI_dom.
DR   InterPro; IPR000980; SH2.
DR   InterPro; IPR036860; SH2_dom_sf.
DR   InterPro; IPR035012; Tensin-like_SH2.
DR   InterPro; IPR014020; Tensin_C2-dom.
DR   InterPro; IPR029023; Tensin_phosphatase.
DR   InterPro; IPR033929; Tensin_PTB.
DR   PANTHER; PTHR45734; TENSIN; 1.
DR   PANTHER; PTHR45734:SF1; TENSIN-2; 1.
DR   Pfam; PF00130; C1_1; 1.
DR   Pfam; PF08416; PTB; 1.
DR   Pfam; PF10409; PTEN_C2; 1.
DR   Pfam; PF00017; SH2; 1.
DR   SMART; SM00109; C1; 1.
DR   SMART; SM00462; PTB; 1.
DR   SMART; SM01326; PTEN_C2; 1.
DR   SMART; SM00252; SH2; 1.
DR   SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1.
DR   SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1.
DR   SUPFAM; SSF57889; Cysteine-rich domain; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   SUPFAM; SSF55550; SH2 domain; 1.
DR   PROSITE; PS51182; C2_TENSIN; 1.
DR   PROSITE; PS51181; PPASE_TENSIN; 1.
DR   PROSITE; PS50001; SH2; 1.
DR   PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR   PROSITE; PS50081; ZF_DAG_PE_2; 1.
DR   Genevisible; Q63HR2; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW   Cytoplasm; Hydrolase; Lipid-binding; Membrane; Metal-binding; Methylation;
KW   Phosphoprotein; Protein phosphatase; Reference proteome; SH2 domain;
KW   Ubl conjugation; Zinc; Zinc-finger.
FT   CHAIN           1..1409
FT                   /note="Tensin-2"
FT                   /id="PRO_0000292987"
FT   DOMAIN          122..294
FT                   /note="Phosphatase tensin-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00590"
FT   DOMAIN          299..425
FT                   /note="C2 tensin-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00589"
FT   DOMAIN          1140..1247
FT                   /note="SH2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT   DOMAIN          1275..1408
FT                   /note="PTB"
FT                   /evidence="ECO:0000255"
FT   ZN_FING         31..79
FT                   /note="Phorbol-ester/DAG-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT   REGION          1..35
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          462..536
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          562..582
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          812..1098
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1111..1130
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        11..35
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        488..508
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        509..524
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        895..922
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        964..986
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1020..1034
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1041..1055
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        231
FT                   /note="Phosphocysteine intermediate"
FT                   /evidence="ECO:0000305|PubMed:23401856"
FT   MOD_RES         91
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         118
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CGB6"
FT   MOD_RES         120
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163,
FT                   ECO:0007744|PubMed:24275569"
FT   MOD_RES         455
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         456
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         466
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         474
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         481
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CGB6"
FT   MOD_RES         483
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CGB6"
FT   MOD_RES         555
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CGB6"
FT   MOD_RES         820
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         825
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         830
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         832
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         835
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         845
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         910
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CGB6"
FT   MOD_RES         931
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         941
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         972
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         977
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         991
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         1003
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163,
FT                   ECO:0007744|PubMed:24275569"
FT   MOD_RES         1182
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         1247
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   VAR_SEQ         1..124
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:11792844,
FT                   ECO:0000303|PubMed:15489334"
FT                   /id="VSP_026457"
FT   VAR_SEQ         1..25
FT                   /note="MKSSGPVERLLRALGRRDSSRAASR -> MDGGGVCVGRGDLLSSPQALGQL
FT                   LRKESRPRRAMK (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:12470648"
FT                   /id="VSP_026458"
FT   VAR_SEQ         776..872
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_026460"
FT   VAR_SEQ         1273..1274
FT                   /note="Missing (in isoform 6)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_026461"
FT   VARIANT         353
FT                   /note="S -> T (in dbSNP:rs11170389)"
FT                   /id="VAR_033043"
FT   VARIANT         670
FT                   /note="A -> T (in dbSNP:rs11558984)"
FT                   /id="VAR_052547"
FT   MUTAGEN         231
FT                   /note="C->S: Loss of tyrosine-protein phosphatase activity.
FT                   Reduced IRS1 degradation under catabolic conditions.
FT                   Abolishes inhibition of AKT1 kinase activity. Does not
FT                   affect disruption of SQSTM1-IRS1 interaction by TNS2.
FT                   Reduced mTORC1 complex activation."
FT                   /evidence="ECO:0000269|PubMed:15817639,
FT                   ECO:0000269|PubMed:23401856, ECO:0000269|PubMed:25101860,
FT                   ECO:0000269|PubMed:28955049"
FT   MUTAGEN         1142
FT                   /note="K->Q: 6-fold reduction in affinity for
FT                   PtdIns(3,4,5)P3 and reduced IRS1 dephosphorylation but does
FT                   not affect cell membrane localization or affinity for a
FT                   tyrosine-phosphorylated peptide; when associated with
FT                   Q-1155 and Q-1157."
FT                   /evidence="ECO:0000269|PubMed:30092354"
FT   MUTAGEN         1155
FT                   /note="K->Q: 6-fold reduction in affinity for
FT                   PtdIns(3,4,5)P3 and reduced IRS1 dephosphorylation but does
FT                   not affect cell membrane localization or affinity for a
FT                   tyrosine-phosphorylated peptide; when associated with
FT                   Q-1142 and Q-1157."
FT                   /evidence="ECO:0000269|PubMed:30092354"
FT   MUTAGEN         1157
FT                   /note="K->Q: 6-fold reduction in affinity for
FT                   PtdIns(3,4,5)P3 and reduced IRS1 dephosphorylation but does
FT                   not affect cell membrane localization or affinity for a
FT                   tyrosine-phosphorylated peptide; when associated with
FT                   Q-1142 and Q-1155."
FT                   /evidence="ECO:0000269|PubMed:30092354"
FT   MUTAGEN         1165
FT                   /note="R->A: Does not affect affinity for PtdIns(3,4,5)P3.
FT                   Reduced affinity for tyrosine-phosphorylated peptide."
FT                   /evidence="ECO:0000269|PubMed:30092354"
FT   MUTAGEN         1209
FT                   /note="K->Q: Does not affect affinity for PtdIns(3,4,5)P3;
FT                   when associated with Q-1212 and Q-1214."
FT                   /evidence="ECO:0000269|PubMed:30092354"
FT   MUTAGEN         1212
FT                   /note="K->Q: Does not affect affinity for PtdIns(3,4,5)P3;
FT                   when associated with Q-1209 and Q-1214."
FT                   /evidence="ECO:0000269|PubMed:30092354"
FT   MUTAGEN         1214
FT                   /note="K->Q: Does not affect affinity for PtdIns(3,4,5)P3;
FT                   when associated with Q-1209 and Q-1212."
FT                   /evidence="ECO:0000269|PubMed:30092354"
FT   CONFLICT        702
FT                   /note="A -> V (in Ref. 6; AAH54099)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        898
FT                   /note="P -> Q (in Ref. 6; AAH54099)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1036
FT                   /note="P -> L (in Ref. 5; CAB70815)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1083
FT                   /note="G -> E (in Ref. 6; AAI29830)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1119
FT                   /note="P -> S (in Ref. 6; AAH54099)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1148
FT                   /note="D -> G (in Ref. 6; AAH54099)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1236
FT                   /note="P -> L (in Ref. 5; CAH56176)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1246
FT                   /note="P -> L (in Ref. 1; AAM74225/AAN03866, 2; AAL14641
FT                   and 3; BAA83027)"
FT                   /evidence="ECO:0000305"
FT   HELIX           1137..1140
FT                   /evidence="ECO:0007829|PDB:2KNO"
FT   STRAND          1141..1144
FT                   /evidence="ECO:0007829|PDB:2L6K"
FT   HELIX           1147..1154
FT                   /evidence="ECO:0007829|PDB:2KNO"
FT   STRAND          1161..1166
FT                   /evidence="ECO:0007829|PDB:2KNO"
FT   STRAND          1168..1170
FT                   /evidence="ECO:0007829|PDB:2KNO"
FT   STRAND          1173..1179
FT                   /evidence="ECO:0007829|PDB:2KNO"
FT   STRAND          1184..1189
FT                   /evidence="ECO:0007829|PDB:2KNO"
FT   STRAND          1190..1192
FT                   /evidence="ECO:0007829|PDB:2L6K"
FT   HELIX           1194..1198
FT                   /evidence="ECO:0007829|PDB:2KNO"
FT   STRAND          1199..1205
FT                   /evidence="ECO:0007829|PDB:2KNO"
FT   STRAND          1210..1213
FT                   /evidence="ECO:0007829|PDB:2L6K"
FT   STRAND          1222..1224
FT                   /evidence="ECO:0007829|PDB:2L6K"
FT   HELIX           1225..1230
FT                   /evidence="ECO:0007829|PDB:2KNO"
FT   TURN            1231..1234
FT                   /evidence="ECO:0007829|PDB:2KNO"
FT   STRAND          1237..1241
FT                   /evidence="ECO:0007829|PDB:2L6K"
FT   HELIX           1266..1272
FT                   /evidence="ECO:0007829|PDB:3HQC"
FT   STRAND          1274..1285
FT                   /evidence="ECO:0007829|PDB:3HQC"
FT   HELIX           1291..1304
FT                   /evidence="ECO:0007829|PDB:3HQC"
FT   STRAND          1305..1307
FT                   /evidence="ECO:0007829|PDB:2DKQ"
FT   STRAND          1312..1319
FT                   /evidence="ECO:0007829|PDB:3HQC"
FT   STRAND          1322..1329
FT                   /evidence="ECO:0007829|PDB:3HQC"
FT   STRAND          1332..1339
FT                   /evidence="ECO:0007829|PDB:3HQC"
FT   HELIX           1340..1342
FT                   /evidence="ECO:0007829|PDB:3HQC"
FT   STRAND          1343..1348
FT                   /evidence="ECO:0007829|PDB:3HQC"
FT   STRAND          1350..1352
FT                   /evidence="ECO:0007829|PDB:2LOZ"
FT   STRAND          1354..1356
FT                   /evidence="ECO:0007829|PDB:3HQC"
FT   TURN            1358..1360
FT                   /evidence="ECO:0007829|PDB:2DKQ"
FT   STRAND          1362..1372
FT                   /evidence="ECO:0007829|PDB:3HQC"
FT   STRAND          1375..1385
FT                   /evidence="ECO:0007829|PDB:3HQC"
FT   STRAND          1389..1391
FT                   /evidence="ECO:0007829|PDB:2DKQ"
FT   HELIX           1393..1405
FT                   /evidence="ECO:0007829|PDB:3HQC"
SQ   SEQUENCE   1409 AA;  152580 MW;  67824299A1382140 CRC64;
     MKSSGPVERL LRALGRRDSS RAASRPRKAE PHSFREKVFR KKPPVCAVCK VTIDGTGVSC
     RVCKVATHRK CEAKVTSACQ ALPPVELRRN TAPVRRIEHL GSTKSLNHSK QRSTLPRSFS
     LDPLMERRWD LDLTYVTERI LAAAFPARPD EQRHRGHLRE LAHVLQSKHR DKYLLFNLSE
     KRHDLTRLNP KVQDFGWPEL HAPPLDKLCS ICKAMETWLS ADPQHVVVLY CKGNKGKLGV
     IVSAYMHYSK ISAGADQALA TLTMRKFCED KVATELQPSQ RRYISYFSGL LSGSIRMNSS
     PLFLHYVLIP MLPAFEPGTG FQPFLKIYQS MQLVYTSGVY HIAGPGPQQL CISLEPALLL
     KGDVMVTCYH KGGRGTDRTL VFRVQFHTCT IHGPQLTFPK DQLDEAWTDE RFPFQASVEF
     VFSSSPEKIK GSTPRNDPSV SVDYNTTEPA VRWDSYENFN QHHEDSVDGS LTHTRGPLDG
     SPYAQVQRPP RQTPPAPSPE PPPPPMLSVS SDSGHSSTLT TEPAAESPGR PPPTAAERQE
     LDRLLGGCGV ASGGRGAGRE TAILDDEEQP TVGGGPHLGV YPGHRPGLSR HCSCRQGYRE
     PCGVPNGGYY RPEGTLERRR LAYGGYEGSP QGYAEASMEK RRLCRSLSEG LYPYPPEMGK
     PATGDFGYRA PGYREVVILE DPGLPALYPC PACEEKLALP TAALYGLRLE REAGEGWASE
     AGKPLLHPVR PGHPLPLLLP ACGHHHAPMP DYSCLKPPKA GEEGHEGCSY TMCPEGRYGH
     PGYPALVTYS YGGAVPSYCP AYGRVPHSCG SPGEGRGYPS PGAHSPRAGS ISPGSPPYPQ
     SRKLSYEIPT EEGGDRYPLP GHLASAGPLA SAESLEPVSW REGPSGHSTL PRSPRDAPCS
     ASSELSGPST PLHTSSPVQG KESTRRQDTR SPTSAPTQRL SPGEALPPVS QAGTGKAPEL
     PSGSGPEPLA PSPVSPTFPP SSPSDWPQER SPGGHSDGAS PRSPVPTTLP GLRHAPWQGP
     RGPPDSPDGS PLTPVPSQMP WLVASPEPPQ SSPTPAFPLA ASYDTNGLSQ PPLPEKRHLP
     GPGQQPGPWG PEQASSPARG ISHHVTFAPL LSDNVPQTPE PPTQESQSNV KFVQDTSKFW
     YKPHLSRDQA IALLKDKDPG AFLIRDSHSF QGAYGLALKV ATPPPSAQPW KGDPVEQLVR
     HFLIETGPKG VKIKGCPSEP YFGSLSALVS QHSISPISLP CCLRIPSKDP LEETPEAPVP
     TNMSTAADLL RQGAACSVLY LTSVETESLT GPQAVARASS AALSCSPRPT PAVVHFKVSA
     QGITLTDNQR KLFFRRHYPV NSITFSSTDP QDRRWTNPDG TTSKIFGFVA KKPGSPWENV
     CHLFAELDPD QPAGAIVTFI TKVLLGQRK
//