ID SPD2A_HUMAN Reviewed; 1133 AA. AC Q5TCZ1; D3DR98; O43302; Q5TCZ2; Q5TDQ8; DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 29-MAY-2024, entry version 169. DE RecName: Full=SH3 and PX domain-containing protein 2A; DE AltName: Full=Adapter protein TKS5; DE AltName: Full=Five SH3 domain-containing protein; DE AltName: Full=SH3 multiple domains protein 1; DE AltName: Full=Tyrosine kinase substrate with five SH3 domains; GN Name=SH3PXD2A; Synonyms=FISH, KIAA0418, SH3MD1, TKS5; 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 [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=9455477; DOI=10.1093/dnares/4.5.307; RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. VIII. 78 RT new cDNA clones from brain which code for large proteins in vitro."; RL DNA Res. 4:307-313(1997). RN [2] RP SEQUENCE REVISION. RA Okazaki N., Kikuno R.F., Nagase T., Ohara O., Koga H.; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, INTERACTION WITH ADAM12; ADAM15 AND RP ADAM19, AND MUTAGENESIS OF ARG-42 AND ARG-93. RX PubMed=12615925; DOI=10.1074/jbc.m300267200; RA Abram C.L., Seals D.F., Pass I., Salinsky D., Maurer L., Roth T.M., RA Courtneidge S.A.; RT "The adaptor protein fish associates with members of the ADAMs family and RT localizes to podosomes of Src-transformed cells."; RL J. Biol. Chem. 278:16844-16851(2003). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND TISSUE SPECIFICITY. RX PubMed=15710328; DOI=10.1016/j.ccr.2005.01.006; RA Seals D.F., Azucena E.F. Jr., Pass I., Tesfay L., Gordon R., Woodrow M., RA Resau J.H., Courtneidge S.A.; RT "The adaptor protein Tks5/Fish is required for podosome formation and RT function, and for the protease-driven invasion of cancer cells."; RL Cancer Cell 7:155-165(2005). RN [7] RP FUNCTION, INTERACTION WITH ADAM12, AND PTM. RX PubMed=15710903; DOI=10.1073/pnas.0408237102; RA Malinin N.L., Wright S., Seubert P., Schenk D., Griswold-Prenner I.; RT "Amyloid-beta neurotoxicity is mediated by FISH adapter protein and ADAM12 RT metalloprotease activity."; RL Proc. Natl. Acad. Sci. U.S.A. 102:3058-3063(2005). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [9] RP SUBCELLULAR LOCATION. RX PubMed=18417249; DOI=10.1016/j.ejcb.2008.02.008; RA Blouw B., Seals D.F., Pass I., Diaz B., Courtneidge S.A.; RT "A role for the podosome/invadopodia scaffold protein Tks5 in tumor growth RT in vivo."; RL Eur. J. Cell Biol. 87:555-567(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421; SER-547; SER-567; RP SER-593; SER-644; THR-731; SER-1002; SER-1016; SER-1017 AND SER-1038, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [11] RP INTERACTION WITH FASLG. RX PubMed=19807924; DOI=10.1186/1471-2172-10-53; RA Voss M., Lettau M., Janssen O.; RT "Identification of SH3 domain interaction partners of human FasL (CD178) by RT phage display screening."; RL BMC Immunol. 10:53-53(2009). RN [12] RP FUNCTION, AND INTERACTION WITH NOXA1. RX PubMed=19755710; DOI=10.1126/scisignal.2000370; RA Gianni D., Diaz B., Taulet N., Fowler B., Courtneidge S.A., Bokoch G.M.; RT "Novel p47(phox)-related organizers regulate localized NADPH oxidase 1 RT (Nox1) activity."; RL Sci. Signal. 2:RA54-RA54(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1002, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [14] RP FUNCTION, AND INTERACTION WITH NOXA1 AND NOXO1. RX PubMed=20609497; DOI=10.1016/j.ejcb.2010.05.007; RA Gianni D., Dermardirossian C., Bokoch G.M.; RT "Direct interaction between Tks proteins and the N-terminal proline-rich RT region (PRR) of NoxA1 mediates Nox1-dependent ROS generation."; RL Eur. J. Cell Biol. 90:164-171(2011). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-406; SER-421; SER-547; RP SER-1002 AND SER-1038, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-547 AND SER-1038, AND RP 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 [17] RP STRUCTURE BY NMR OF 168-325 AND 1072-1133. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the SH3 domains from human KIAA0418 protein."; RL Submitted (AUG-2007) to the PDB data bank. CC -!- FUNCTION: Adapter protein involved in invadopodia and podosome CC formation, extracellular matrix degradation and invasiveness of some CC cancer cells. Binds matrix metalloproteinases (ADAMs), NADPH oxidases CC (NOXs) and phosphoinositides. Acts as an organizer protein that allows CC NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and CC ROS localization. In association with ADAM12, mediates the neurotoxic CC effect of amyloid-beta peptide. {ECO:0000269|PubMed:12615925, CC ECO:0000269|PubMed:15710328, ECO:0000269|PubMed:15710903, CC ECO:0000269|PubMed:19755710, ECO:0000269|PubMed:20609497}. CC -!- SUBUNIT: Interacts (via N-terminus) with CYBA (By similarity). CC Interacts with ADAM12, ADAM15 and ADAM19. Interacts with NOXO1. CC Interacts (via SH3 domains) with NOXA1. Interacts with FASLG. CC {ECO:0000250, ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:15710903, CC ECO:0000269|PubMed:19755710, ECO:0000269|PubMed:19807924, CC ECO:0000269|PubMed:20609497}. CC -!- INTERACTION: CC Q5TCZ1; Q13444: ADAM15; NbExp=4; IntAct=EBI-2483234, EBI-77818; CC Q5TCZ1-2; Q07889: SOS1; NbExp=5; IntAct=EBI-7014859, EBI-297487; CC Q5TCZ1-2; P21575: Dnm1; Xeno; NbExp=2; IntAct=EBI-7014859, EBI-80070; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell projection, podosome. CC Note=Cytoplasmic in normal cells and localizes to podosomes in SRC- CC transformed cells. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q5TCZ1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5TCZ1-2; Sequence=VSP_023312, VSP_023313; CC Name=3; CC IsoId=Q5TCZ1-3; Sequence=VSP_023313; CC -!- TISSUE SPECIFICITY: Found in several cancer cell lines, particularly CC invasive breast carcinomas and melanomas. CC {ECO:0000269|PubMed:15710328}. CC -!- DOMAIN: The PX domain is required for podosome localization because of CC its ability to bind phosphatidylinositol 3-phosphate (PtdIns(3)P) and CC phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and, to a lesser CC extent, phosphatidylinositol 4-phosphate (PtdIns(4)P), CC phosphatidylinositol 5-phosphate (PtdIns(5)P), and phosphatidylinositol CC 3,5-bisphosphate (PtdIns(3,5)P2). Binds to the third intramolecular SH3 CC domain (By similarity). {ECO:0000250}. CC -!- DOMAIN: The fifth SH3 domain mediates binding with ADAM12, ADAM15 and CC ADAM19. {ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:15710328}. CC -!- PTM: Tyrosine phosphorylated by SRC. Phosphorylation plays a regulatory CC role in the protein localization. The intramolecular interaction of the CC PX domain with the third SH3 domain maintains the protein in the CC cytoplasm and phosphorylation disrupts this interaction, resulting in CC the redistribution of the protein from cytoplasm to the perimembrane CC region. Phosphorylated on serine upon DNA damage, probably by ATM or CC ATR. CC -!- MISCELLANEOUS: [Isoform 3]: Gene prediction based on similarity to CC mouse ortholog and partial transcript data. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the SH3PXD2 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA24848.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB007878; BAA24848.2; ALT_INIT; mRNA. DR EMBL; AL121929; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL133355; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW49623.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49624.1; -; Genomic_DNA. DR CCDS; CCDS31278.1; -. [Q5TCZ1-3] DR CCDS; CCDS91343.1; -. [Q5TCZ1-1] DR PIR; T00056; T00056. DR RefSeq; NP_055446.2; NM_014631.2. [Q5TCZ1-3] DR RefSeq; XP_005270351.1; XM_005270294.4. DR PDB; 2DNU; NMR; -; A=268-325. DR PDB; 2EGA; NMR; -; A=168-224. DR PDB; 2EGC; NMR; -; A=1072-1133. DR PDB; 2EKH; NMR; -; A=842-908. DR PDBsum; 2DNU; -. DR PDBsum; 2EGA; -. DR PDBsum; 2EGC; -. DR PDBsum; 2EKH; -. DR AlphaFoldDB; Q5TCZ1; -. DR SMR; Q5TCZ1; -. DR BioGRID; 115002; 117. DR IntAct; Q5TCZ1; 26. DR MINT; Q5TCZ1; -. DR STRING; 9606.ENSP00000348215; -. DR GlyCosmos; Q5TCZ1; 1 site, 1 glycan. DR GlyGen; Q5TCZ1; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q5TCZ1; -. DR PhosphoSitePlus; Q5TCZ1; -. DR BioMuta; SH3PXD2A; -. DR DMDM; 74746151; -. DR EPD; Q5TCZ1; -. DR jPOST; Q5TCZ1; -. DR MassIVE; Q5TCZ1; -. DR MaxQB; Q5TCZ1; -. DR PaxDb; 9606-ENSP00000348215; -. DR PeptideAtlas; Q5TCZ1; -. DR ProteomicsDB; 64997; -. [Q5TCZ1-1] DR ProteomicsDB; 64998; -. [Q5TCZ1-2] DR ProteomicsDB; 64999; -. [Q5TCZ1-3] DR Pumba; Q5TCZ1; -. DR ABCD; Q5TCZ1; 9 sequenced antibodies. DR Antibodypedia; 46067; 214 antibodies from 32 providers. DR DNASU; 9644; -. DR Ensembl; ENST00000355946.7; ENSP00000348215.2; ENSG00000107957.17. [Q5TCZ1-3] DR Ensembl; ENST00000369774.9; ENSP00000358789.4; ENSG00000107957.17. [Q5TCZ1-1] DR GeneID; 9644; -. DR KEGG; hsa:9644; -. DR MANE-Select; ENST00000369774.9; ENSP00000358789.4; NM_001394015.1; NP_001380944.1. DR UCSC; uc001kxj.2; human. [Q5TCZ1-1] DR AGR; HGNC:23664; -. DR CTD; 9644; -. DR DisGeNET; 9644; -. DR GeneCards; SH3PXD2A; -. DR HGNC; HGNC:23664; SH3PXD2A. DR HPA; ENSG00000107957; Low tissue specificity. DR MalaCards; SH3PXD2A; -. DR MIM; 619455; gene. DR neXtProt; NX_Q5TCZ1; -. DR OpenTargets; ENSG00000107957; -. DR Orphanet; 252128; Malignant peripheral nerve sheath tumor with perineurial differentiation. DR Orphanet; 252212; Malignant triton tumor. DR PharmGKB; PA134956816; -. DR VEuPathDB; HostDB:ENSG00000107957; -. DR eggNOG; KOG0905; Eukaryota. DR GeneTree; ENSGT00940000157732; -. DR HOGENOM; CLU_013051_0_0_1; -. DR InParanoid; Q5TCZ1; -. DR OMA; ASPEWAH; -. DR OrthoDB; 2910367at2759; -. DR PhylomeDB; Q5TCZ1; -. DR TreeFam; TF329347; -. DR PathwayCommons; Q5TCZ1; -. DR Reactome; R-HSA-8941237; Invadopodia formation. DR Reactome; R-HSA-9013148; CDC42 GTPase cycle. DR SignaLink; Q5TCZ1; -. DR SIGNOR; Q5TCZ1; -. DR BioGRID-ORCS; 9644; 16 hits in 1127 CRISPR screens. DR ChiTaRS; SH3PXD2A; human. DR EvolutionaryTrace; Q5TCZ1; -. DR GeneWiki; SH3PXD2A; -. DR GenomeRNAi; 9644; -. DR Pharos; Q5TCZ1; Tbio. DR PRO; PR:Q5TCZ1; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q5TCZ1; Protein. DR Bgee; ENSG00000107957; Expressed in sural nerve and 191 other cell types or tissues. DR ExpressionAtlas; Q5TCZ1; baseline and differential. DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW. DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0002102; C:podosome; IDA:UniProtKB. DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IEA:Ensembl. DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IEA:Ensembl. DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IEA:Ensembl. DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IEA:Ensembl. DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; IEA:Ensembl. DR GO; GO:0002020; F:protease binding; IEA:Ensembl. DR GO; GO:0016176; F:superoxide-generating NADPH oxidase activator activity; IBA:GO_Central. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0072675; P:osteoclast fusion; IMP:CACAO. DR GO; GO:0042554; P:superoxide anion generation; IBA:GO_Central. DR GO; GO:0006801; P:superoxide metabolic process; IDA:UniProtKB. DR CDD; cd06888; PX_FISH; 1. DR CDD; cd12074; SH3_Tks5_1; 1. DR CDD; cd12077; SH3_Tks5_2; 1. DR CDD; cd12079; SH3_Tks5_3; 1. DR CDD; cd12019; SH3_Tks5_4; 1. DR CDD; cd12020; SH3_Tks5_5; 1. DR Gene3D; 3.30.1520.10; Phox-like domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 5. DR InterPro; IPR001683; PX_dom. DR InterPro; IPR036871; PX_dom_sf. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR037961; SH3PXD2_PX. DR InterPro; IPR035450; SH3PXD2A_SH3_1. DR InterPro; IPR035452; SH3PXD2A_SH3_2. DR InterPro; IPR035449; SH3PXD2A_SH3_3. DR InterPro; IPR035453; SH3PXD2A_SH3_4. DR InterPro; IPR035454; SH3PXD2A_SH3_5. DR PANTHER; PTHR15706:SF22; SH3 AND PX DOMAIN-CONTAINING PROTEIN 2A; 1. DR PANTHER; PTHR15706; SH3 MULTIPLE DOMAIN; 1. DR Pfam; PF00787; PX; 1. DR Pfam; PF00018; SH3_1; 3. DR Pfam; PF07653; SH3_2; 1. DR SMART; SM00312; PX; 1. DR SMART; SM00326; SH3; 5. DR SUPFAM; SSF64268; PX domain; 1. DR SUPFAM; SSF50044; SH3-domain; 5. DR PROSITE; PS50195; PX; 1. DR PROSITE; PS50002; SH3; 5. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell junction; Cell projection; KW Coiled coil; Cytoplasm; Phosphoprotein; Reference proteome; Repeat; KW SH3 domain. FT CHAIN 1..1133 FT /note="SH3 and PX domain-containing protein 2A" FT /id="PRO_0000278488" FT DOMAIN 4..128 FT /note="PX" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147" FT DOMAIN 166..225 FT /note="SH3 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 266..325 FT /note="SH3 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 448..507 FT /note="SH3 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 840..899 FT /note="SH3 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 1072..1133 FT /note="SH3 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT REGION 415..446 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 505..840 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 899..924 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 941..964 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1029..1059 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 917..946 FT /evidence="ECO:0000255" FT COMPBIAS 635..672 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 680..719 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 762..783 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 799..827 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 256 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O89032" FT MOD_RES 406 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 421 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 547 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 567 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 593 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 644 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 731 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 767 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O89032" FT MOD_RES 769 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O89032" FT MOD_RES 819 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O89032" FT MOD_RES 829 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O89032" FT MOD_RES 1002 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 1016 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1017 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1038 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT VAR_SEQ 1..165 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9455477" FT /id="VSP_023312" FT VAR_SEQ 240..267 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:9455477" FT /id="VSP_023313" FT VARIANT 659 FT /note="K -> Q (in dbSNP:rs11818820)" FT /id="VAR_030781" FT VARIANT 1035 FT /note="R -> Q (in dbSNP:rs3781365)" FT /id="VAR_030782" FT VARIANT 1073 FT /note="L -> P (in dbSNP:rs12764700)" FT /id="VAR_056993" FT MUTAGEN 42 FT /note="R->A: Loss of binding to (PtdIns(3)P) and FT (PtdIns(3,4)P2)." FT /evidence="ECO:0000269|PubMed:12615925" FT MUTAGEN 93 FT /note="R->A: Loss of binding to (PtdIns(3)P) and FT (PtdIns(3,4)P2)." FT /evidence="ECO:0000269|PubMed:12615925" FT STRAND 181..184 FT /evidence="ECO:0007829|PDB:2EGA" FT STRAND 194..198 FT /evidence="ECO:0007829|PDB:2EGA" FT STRAND 202..207 FT /evidence="ECO:0007829|PDB:2EGA" FT STRAND 212..216 FT /evidence="ECO:0007829|PDB:2EGA" FT HELIX 217..219 FT /evidence="ECO:0007829|PDB:2EGA" FT STRAND 221..223 FT /evidence="ECO:0007829|PDB:2EGA" FT STRAND 268..272 FT /evidence="ECO:0007829|PDB:2DNU" FT STRAND 292..295 FT /evidence="ECO:0007829|PDB:2DNU" FT STRAND 300..308 FT /evidence="ECO:0007829|PDB:2DNU" FT STRAND 311..316 FT /evidence="ECO:0007829|PDB:2DNU" FT HELIX 317..319 FT /evidence="ECO:0007829|PDB:2DNU" FT STRAND 843..847 FT /evidence="ECO:0007829|PDB:2EKH" FT STRAND 866..872 FT /evidence="ECO:0007829|PDB:2EKH" FT STRAND 876..882 FT /evidence="ECO:0007829|PDB:2EKH" FT STRAND 885..890 FT /evidence="ECO:0007829|PDB:2EKH" FT TURN 891..893 FT /evidence="ECO:0007829|PDB:2EKH" FT STRAND 1075..1079 FT /evidence="ECO:0007829|PDB:2EGC" FT STRAND 1087..1089 FT /evidence="ECO:0007829|PDB:2EGC" FT STRAND 1097..1100 FT /evidence="ECO:0007829|PDB:2EGC" FT STRAND 1107..1113 FT /evidence="ECO:0007829|PDB:2EGC" FT STRAND 1116..1118 FT /evidence="ECO:0007829|PDB:2EGC" FT STRAND 1120..1125 FT /evidence="ECO:0007829|PDB:2EGC" FT HELIX 1126..1128 FT /evidence="ECO:0007829|PDB:2EGC" FT STRAND 1129..1131 FT /evidence="ECO:0007829|PDB:2EGC" SQ SEQUENCE 1133 AA; 125289 MW; D485F49E9192359C CRC64; MLAYCVQDAT VVDVEKRRNP SKHYVYIINV TWSDSTSQTI YRRYSKFFDL QMQLLDKFPI EGGQKDPKQR IIPFLPGKIL FRRSHIRDVA VKRLKPIDEY CRALVRLPPH ISQCDEVFRF FEARPEDVNP PKEDYGSSKR KSVWLSSWAE SPKKDVTGAD ATAEPMILEQ YVVVSNYKKQ ENSELSLQAG EVVDVIEKNE SGWWFVSTSE EQGWVPATYL EAQNGTRDDS DINTSKTGEV SKRRKAHLRR LDRRWTLGGM VNRQHSREEK YVTVQPYTSQ SKDEIGFEKG VTVEVIRKNL EGWWYIRYLG KEGWAPASYL KKAKDDLPTR KKNLAGPVEI IGNIMEISNL LNKKASGDKE TPPAEGEGHE APIAKKEISL PILCNASNGS AVGVPDRTVS RLAQGSPAVA RIAPQRAQIS SPNLRTRPPP RRESSLGFQL PKPPEPPSVE VEYYTIAEFQ SCISDGISFR GGQKAEVIDK NSGGWWYVQI GEKEGWAPAS YIDKRKKPNL SRRTSTLTRP KVPPPAPPSK PKEAEEGPTG ASESQDSPRK LKYEEPEYDI PAFGFDSEPE LSEEPVEDRA SGERRPAQPH RPSPASSLQR ARFKVGESSE DVALEEETIY ENEGFRPYAE DTLSARGSSG DSDSPGSSSL SLTRKNSPKS GSPKSSSLLK LKAEKNAQAE MGKNHSSASF SSSITINTTC CSSSSSSSSS LSKTSGDLKP RSASDAGIRG TPKVRAKKDA DANAGLTSCP RAKPSVRPKP FLNRAESQSQ EKMDISTLRR QLRPTGQLRG GLKGSKSEDS ELPPQTASEA PSEGSRRSSS DLITLPATTP PCPTKKEWEG PATSYMTCSA YQKVQDSEIS FPAGVEVQVL EKQESGWWYV RFGELEGWAP SHYLVLDENE QPDPSGKELD TVPAKGRQNE GKSDSLEKIE RRVQALNTVN QSKKATPPIP SKPPGGFGKT SGTPAVKMRN GVRQVAVRPQ SVFVSPPPKD NNLSCALRRN ESLTATDGLR GVRRNSSFST ARSAAAEAKG RLAERAASQG SDSPLLPAQR NSIPVSPVRP KPIEKSQFIH NNLKDVYVSI ADYEGDEETA GFQEGVSMEV LERNPNGWWY CQILDGVKPF KGWVPSNYLE KKN //