SPD2A_HUMAN
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 03-AUG-2022, entry version 159.
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};
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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 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; 106.
DR IntAct; Q5TCZ1; 24.
DR MINT; Q5TCZ1; -.
DR STRING; 9606.ENSP00000348215; -.
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; Q5TCZ1; -.
DR PeptideAtlas; Q5TCZ1; -.
DR PRIDE; Q5TCZ1; -.
DR ProteomicsDB; 64997; -. [Q5TCZ1-1]
DR ProteomicsDB; 64998; -. [Q5TCZ1-2]
DR ProteomicsDB; 64999; -. [Q5TCZ1-3]
DR ABCD; Q5TCZ1; 9 sequenced antibodies.
DR Antibodypedia; 46067; 180 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 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; TKEECIY; -.
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; 15 hits in 1049 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 189 other tissues.
DR ExpressionAtlas; Q5TCZ1; baseline and differential.
DR Genevisible; Q5TCZ1; HS.
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; -; 1.
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; IPR034917; SH3PXD2A.
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; PTHR15706:SF22; 1.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF00018; SH3_1; 4.
DR SMART; SM00312; PX; 1.
DR SMART; SM00326; SH3; 5.
DR SUPFAM; SSF50044; SSF50044; 5.
DR SUPFAM; SSF64268; SSF64268; 1.
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
