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   02-SEP-2026, entry version 178.
DE   RecName: Full=SH3 and PX domain-containing protein 2A;
DE   AltName: Full=Adapter protein TKS5 {ECO:0000303|PubMed:15710328};
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 {ECO:0000312|HGNC:HGNC:23664};
GN   Synonyms=FISH {ECO:0000303|PubMed:15710328}, KIAA0418
GN   {ECO:0000303|Ref.18}, SH3MD1, TKS5 {ECO:0000303|PubMed:15710328};
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   FUNCTION, INTERACTION WITH RAB40B, DOMAIN, AND MUTAGENESIS OF TYR-24.
RX   PubMed=27789576; DOI=10.1242/jcs.193904;
RA   Jacob A., Linklater E., Bayless B.A., Lyons T., Prekeris R.;
RT   "The role and regulation of Rab40b-Tks5 complex during invadopodia
RT   formation and cancer cell invasion.";
RL   J. Cell Sci. 129:4341-4353(2016).
RN   [18]
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 (PubMed:27789576). Binds matrix metalloproteinases
CC       (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an
CC       organizer protein that allows NOX1- or NOX3-dependent reactive oxygen
CC       species (ROS) generation and ROS localization. In association with
CC       ADAM12, mediates the neurotoxic effect of amyloid-beta peptide.
CC       {ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:15710328,
CC       ECO:0000269|PubMed:15710903, ECO:0000269|PubMed:19755710,
CC       ECO:0000269|PubMed:20609497, ECO:0000269|PubMed:27789576}.
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. Interacts
CC       (via PX domain) with RAB40B (GTP-bound); interaction promotes
CC       invadopodia-mediated extracellular matrix degradation
CC       (PubMed:27789576). {ECO:0000250, ECO:0000269|PubMed:12615925,
CC       ECO:0000269|PubMed:15710903, ECO:0000269|PubMed:19755710,
CC       ECO:0000269|PubMed:19807924, ECO:0000269|PubMed:20609497,
CC       ECO:0000269|PubMed:27789576}.
CC   -!- INTERACTION:
CC       Q5TCZ1; Q13444: ADAM15; NbExp=4; IntAct=EBI-2483234, EBI-77818;
CC       Q5TCZ1; Q9H013: ADAM19; NbExp=2; IntAct=EBI-2483234, EBI-8567699;
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       {ECO:0000269|PubMed:12615925}. Note=Cytoplasmic in normal cells and
CC       localizes to podosomes in SRC-transformed cells.
CC       {ECO:0000269|PubMed:12615925}.
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). Required for interaction with RAB40B
CC       (PubMed:27789576). {ECO:0000250, ECO:0000269|PubMed:27789576}.
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};
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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_001380944.1; NM_001394015.1. [Q5TCZ1-1]
DR   RefSeq; NP_001380951.1; NM_001394022.1. [Q5TCZ1-2]
DR   RefSeq; NP_001380952.1; NM_001394023.1. [Q5TCZ1-2]
DR   RefSeq; NP_055446.2; NM_014631.3. [Q5TCZ1-3]
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   AlphaFoldDB; Q5TCZ1; -.
DR   SMR; Q5TCZ1; -.
DR   BioGRID; 115002; 127.
DR   FunCoup; Q5TCZ1; 529.
DR   IntAct; Q5TCZ1; 32.
DR   MINT; Q5TCZ1; -.
DR   STRING; 9606.ENSP00000348215; -.
DR   GlyCosmos; Q5TCZ1; 1 site, 1 glycan.
DR   GlyGen; Q5TCZ1; 6 sites, 4 N-linked glycans (4 sites), 1 O-linked glycan (1 site).
DR   iPTMnet; Q5TCZ1; -.
DR   PhosphoSitePlus; Q5TCZ1; -.
DR   BioMuta; SH3PXD2A; -.
DR   DMDM; 74746151; -.
DR   jPOST; Q5TCZ1; -.
DR   MassIVE; 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; 182 antibodies from 33 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   ClinPGx; PA134956816; -.
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   OpenTargets; ENSG00000107957; -.
DR   Orphanet; 252128; Malignant peripheral nerve sheath tumor with perineurial differentiation.
DR   Orphanet; 252212; Malignant triton tumor.
DR   VEuPathDB; HostDB:ENSG00000107957; -.
DR   eggNOG; KOG0905; Eukaryota.
DR   GeneTree; ENSGT00940000157732; -.
DR   HOGENOM; CLU_013051_0_0_1; -.
DR   InParanoid; Q5TCZ1; -.
DR   OMA; SHAIFYS; -.
DR   OrthoDB; 10255964at2759; -.
DR   PAN-GO; Q5TCZ1; 3 GO annotations based on evolutionary models.
DR   PhylomeDB; Q5TCZ1; -.
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   Agora; ENSG00000107957; -.
DR   BioGRID-ORCS; 9644; 16 hits in 1127 CRISPR screens.
DR   CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities.
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: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:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR   GO; GO:0016176; F:superoxide-generating NADPH oxidase activator activity; IBA:GO_Central.
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   FunFam; 2.30.30.40:FF:000020; SH3 and PX domain-containing protein 2A; 1.
DR   FunFam; 2.30.30.40:FF:000031; SH3 and PX domain-containing protein 2A; 1.
DR   FunFam; 2.30.30.40:FF:000042; SH3 and PX domain-containing protein 2A; 1.
DR   FunFam; 2.30.30.40:FF:000059; SH3 and PX domain-containing protein 2A; 1.
DR   FunFam; 3.30.1520.10:FF:000005; SH3 and PX domain-containing protein 2B; 1.
DR   FunFam; 2.30.30.40:FF:000194; SH3 and PX domains 2A; 1.
DR   Gene3D; 3.30.1520.10; Phox-like domain; 1.
DR   Gene3D; 2.30.30.40; SH3 Domains; 5.
DR   InterPro; IPR051228; NADPH_Oxidase/PX-Domain.
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:SF2; 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.
DR   PDBsum; 2DNU; -.
DR   PDBsum; 2EGA; -.
DR   PDBsum; 2EGC; -.
DR   PDBsum; 2EKH; -.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell junction; Cell projection;
KW   Coiled coil; Cytoplasm; Phosphoprotein; Proteomics identification;
KW   Reference proteome; Repeat; 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        546..555
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        567..576
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        577..586
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        608..620
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        634..652
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        658..670
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        686..715
FT                   /note="Low complexity"
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         24
FT                   /note="Y->A: Loss of interaction with RAB40B."
FT                   /evidence="ECO:0000269|PubMed:27789576"
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
//