SWP70_HUMAN
ID SWP70_HUMAN Reviewed; 585 AA.
AC Q9UH65; D3DQV1; O75135; Q7LCY6; Q9P061; Q9P0Z8;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Switch-associated protein 70;
DE Short=SWAP-70;
GN Name=SWAP70; Synonyms=KIAA0640; ORFNames=HSPC321;
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], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, PHOSPHORYLATION, AND MUTAGENESIS OF TRP-297.
RX PubMed=10681448; DOI=10.1073/pnas.040374497;
RA Masat L., Caldwell J., Armstrong R., Khoshnevisan H., Jessberger R.,
RA Herndier B., Wabl M., Ferrick D.;
RT "Association of SWAP-70 with the B cell antigen receptor complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:2180-2184(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-505.
RX PubMed=11726218; DOI=10.1006/clim.2001.5116;
RA Rapalus L., Minegishi Y., Lavoie A., Cunningham-Rundles C., Conley M.E.;
RT "Analysis of SWAP-70 as a candidate gene for non-X-linked hyper IgM
RT syndrome and common variable immunodeficiency.";
RL Clin. Immunol. 101:270-275(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLU-505.
RA Monz D.W., Comtesse N.E., Heckel D.;
RT "Human SWAP-70 homolog.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-505.
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-505.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 355-543.
RC TISSUE=Umbilical cord blood;
RA Ye M., Zhang Q.-H., Zhou J., Shen Y., Wu X.-Y., Guan Z.Q., Wang L.,
RA Fan H.-Y., Mao Y.-F., Dai M., Huang Q.-H., Chen S.-J., Chen Z.;
RT "Human partial CDS from CD34+ stem cells.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP 223-ARG-ARG-224; ARG-230 AND 526-MET--GLU-585.
RX PubMed=12925760; DOI=10.1091/mbc.e03-01-0043;
RA Hilpelae P., Oberbanscheidt P., Hahne P., Hund M., Kalhammer G.,
RA Small J.V., Baehler M.;
RT "SWAP-70 identifies a transitional subset of actin filaments in motile
RT cells.";
RL Mol. Biol. Cell 14:3242-3253(2003).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP STRUCTURE BY NMR OF 211-312.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the PH domain of KIAA0640 protein from human.";
RL Submitted (OCT-2006) to the PDB data bank.
CC -!- FUNCTION: Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine
CC nucleotide exchange factor (GEF) which, independently of RAS,
CC transduces signals from tyrosine kinase receptors to RAC. It also
CC mediates signaling of membrane ruffling. Regulates the actin
CC cytoskeleton as an effector or adapter protein in response to agonist
CC stimulated phosphatidylinositol (3,4)-bisphosphate production and cell
CC protrusion (By similarity). {ECO:0000250, ECO:0000269|PubMed:10681448,
CC ECO:0000269|PubMed:12925760}.
CC -!- SUBUNIT: The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70.
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q9UH65; Q8WZA2: RAPGEF4; NbExp=4; IntAct=EBI-310749, EBI-948476;
CC Q9UH65; P49591: SARS1; NbExp=3; IntAct=EBI-310749, EBI-1053431;
CC Q9UH65; P53985-2: SLC16A1; NbExp=3; IntAct=EBI-310749, EBI-25891616;
CC Q9UH65; O15062: ZBTB5; NbExp=3; IntAct=EBI-310749, EBI-722671;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10681448}. Cell
CC membrane. Nucleus {ECO:0000269|PubMed:10681448}. Cell projection,
CC lamellipodium {ECO:0000269|PubMed:12925760}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:12925760}. Note=In resting B-cells it is localized
CC mainly in the cytoplasm and upon cell activation it is recruited to the
CC plasma membrane and then translocates to the nucleus (PubMed:10681448).
CC In activated, class-switching B-cells it is associated with membrane
CC IgG but not IgM (PubMed:10681448). Localized to loose actin filament
CC arrays located behind actively extending lamellipodia
CC (PubMed:12925760). {ECO:0000269|PubMed:10681448,
CC ECO:0000269|PubMed:12925760}.
CC -!- TISSUE SPECIFICITY: Expressed only in mature B-cells including those
CC associated with mucosa-associated tissue and bronchus-associated tissue
CC (PubMed:10681448). Widely expressed. Abundant in spleen, and fairly
CC abundant in kidney, lung and liver. Also found in monocytes and
CC macrophages (PubMed:12925760). {ECO:0000269|PubMed:10681448,
CC ECO:0000269|PubMed:12925760}.
CC -!- DOMAIN: The PH domain is essential for phosphatidylinositol 3,4,5-
CC trisphosphate binding.
CC -!- PTM: Tyrosine-phosphorylated. {ECO:0000269|PubMed:10681448}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF28999.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA31615.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF210818; AAF24486.1; -; mRNA.
DR EMBL; AF134894; AAF61403.1; -; mRNA.
DR EMBL; AB014540; BAA31615.1; ALT_INIT; mRNA.
DR EMBL; CH471064; EAW68582.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68583.1; -; Genomic_DNA.
DR EMBL; BC000616; AAH00616.1; -; mRNA.
DR EMBL; AF161439; AAF28999.1; ALT_FRAME; mRNA.
DR CCDS; CCDS31426.1; -.
DR PIR; T00379; T00379.
DR RefSeq; NP_001284643.1; NM_001297714.1.
DR RefSeq; NP_055870.2; NM_015055.3.
DR PDB; 2DN6; NMR; -; A=211-312.
DR PDBsum; 2DN6; -.
DR AlphaFoldDB; Q9UH65; -.
DR BMRB; Q9UH65; -.
DR SMR; Q9UH65; -.
DR BioGRID; 116707; 52.
DR IntAct; Q9UH65; 13.
DR MINT; Q9UH65; -.
DR STRING; 9606.ENSP00000315630; -.
DR iPTMnet; Q9UH65; -.
DR MetOSite; Q9UH65; -.
DR PhosphoSitePlus; Q9UH65; -.
DR BioMuta; SWAP70; -.
DR DMDM; 74753323; -.
DR EPD; Q9UH65; -.
DR jPOST; Q9UH65; -.
DR MassIVE; Q9UH65; -.
DR MaxQB; Q9UH65; -.
DR PaxDb; Q9UH65; -.
DR PeptideAtlas; Q9UH65; -.
DR PRIDE; Q9UH65; -.
DR ProteomicsDB; 84279; -.
DR Antibodypedia; 1856; 412 antibodies from 36 providers.
DR DNASU; 23075; -.
DR Ensembl; ENST00000318950.11; ENSP00000315630.6; ENSG00000133789.15.
DR GeneID; 23075; -.
DR KEGG; hsa:23075; -.
DR MANE-Select; ENST00000318950.11; ENSP00000315630.6; NM_015055.4; NP_055870.2.
DR UCSC; uc001mhw.4; human.
DR CTD; 23075; -.
DR DisGeNET; 23075; -.
DR GeneCards; SWAP70; -.
DR HGNC; HGNC:17070; SWAP70.
DR HPA; ENSG00000133789; Low tissue specificity.
DR MIM; 604762; gene.
DR neXtProt; NX_Q9UH65; -.
DR OpenTargets; ENSG00000133789; -.
DR PharmGKB; PA165543694; -.
DR VEuPathDB; HostDB:ENSG00000133789; -.
DR eggNOG; ENOG502QSXX; Eukaryota.
DR GeneTree; ENSGT00950000183017; -.
DR HOGENOM; CLU_029358_1_0_1; -.
DR InParanoid; Q9UH65; -.
DR OMA; DYKVNFD; -.
DR OrthoDB; 1185498at2759; -.
DR PhylomeDB; Q9UH65; -.
DR TreeFam; TF333160; -.
DR PathwayCommons; Q9UH65; -.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR SignaLink; Q9UH65; -.
DR BioGRID-ORCS; 23075; 9 hits in 1086 CRISPR screens.
DR ChiTaRS; SWAP70; human.
DR EvolutionaryTrace; Q9UH65; -.
DR GeneWiki; SWAP70; -.
DR GenomeRNAi; 23075; -.
DR Pharos; Q9UH65; Tbio.
DR PRO; PR:Q9UH65; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9UH65; protein.
DR Bgee; ENSG00000133789; Expressed in calcaneal tendon and 209 other tissues.
DR ExpressionAtlas; Q9UH65; baseline and differential.
DR Genevisible; Q9UH65; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:Ensembl.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; TAS:Reactome.
DR GO; GO:0051017; P:actin filament bundle assembly; IEA:Ensembl.
DR GO; GO:0045190; P:isotype switching; IEA:Ensembl.
DR GO; GO:0030835; P:negative regulation of actin filament depolymerization; IEA:Ensembl.
DR GO; GO:0033633; P:negative regulation of cell-cell adhesion mediated by integrin; IEA:Ensembl.
DR GO; GO:1902309; P:negative regulation of peptidyl-serine dephosphorylation; IEA:Ensembl.
DR GO; GO:0032233; P:positive regulation of actin filament bundle assembly; IEA:Ensembl.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:0060754; P:positive regulation of mast cell chemotaxis; IEA:Ensembl.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00233; PH; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cell projection; Coiled coil; Cytoplasm;
KW Cytoskeleton; DNA-binding; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..585
FT /note="Switch-associated protein 70"
FT /id="PRO_0000240280"
FT DOMAIN 210..306
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT COILED 316..539
FT /evidence="ECO:0000255"
FT VARIANT 230
FT /note="R -> G (in dbSNP:rs397686)"
FT /id="VAR_059548"
FT VARIANT 505
FT /note="Q -> E (in dbSNP:rs415895)"
FT /evidence="ECO:0000269|PubMed:11726218,
FT ECO:0000269|PubMed:9734811, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.5"
FT /id="VAR_026717"
FT MUTAGEN 223..224
FT /note="RR->EE: Abolishes binding to phosphatidylinositol
FT 3,4-bisphosphate and phosphatidic acid and the localization
FT to the loose actin filament arrays."
FT /evidence="ECO:0000269|PubMed:12925760"
FT MUTAGEN 230
FT /note="R->C: Reduced binding to phosphatidylinositol 3,4-
FT bisphosphate and reduced association with actin filament."
FT /evidence="ECO:0000269|PubMed:12925760"
FT MUTAGEN 297
FT /note="W->A: Abolishes binding to plasma membrane."
FT /evidence="ECO:0000269|PubMed:10681448"
FT MUTAGEN 526..585
FT /note="Missing: Affects targeting to loose actin filament
FT arrays."
FT /evidence="ECO:0000269|PubMed:12925760"
FT CONFLICT 385
FT /note="A -> S (in Ref. 7)"
FT /evidence="ECO:0000305"
FT STRAND 212..220
FT /evidence="ECO:0007829|PDB:2DN6"
FT STRAND 227..234
FT /evidence="ECO:0007829|PDB:2DN6"
FT STRAND 239..244
FT /evidence="ECO:0007829|PDB:2DN6"
FT STRAND 248..254
FT /evidence="ECO:0007829|PDB:2DN6"
FT STRAND 261..265
FT /evidence="ECO:0007829|PDB:2DN6"
FT STRAND 273..278
FT /evidence="ECO:0007829|PDB:2DN6"
FT STRAND 283..287
FT /evidence="ECO:0007829|PDB:2DN6"
FT HELIX 291..310
FT /evidence="ECO:0007829|PDB:2DN6"
SQ SEQUENCE 585 AA; 68998 MW; B42B63CF033E612F CRC64;
MGSLKEELLK AIWHAFTALD QDHSGKVSKS QLKVLSHNLC TVLKVPHDPV ALEEHFRDDD
EGPVSNQGYM PYLNRFILEK VQDNFDKIEF NRMCWTLCVK KNLTKNPLLI TEEDAFKIWV
IFNFLSEDKY PLIIVSEEIE YLLKKLTEAM GGGWQQEQFE HYKINFDDSK NGLSAWELIE
LIGNGQFSKG MDRQTVSMAI NEVFNELILD VLKQGYMMKK GHRRKNWTER WFVLKPNIIS
YYVSEDLKDK KGDILLDENC CVESLPDKDG KKCLFLVKCF DKTFEISASD KKKKQEWIQA
IHSTIHLLKL GSPPPHKEAR QRRKELRKKQ LAEQEELERQ MKELQAANES KQQELEAVRK
KLEEAASRAA EEEKKRLQTQ VELQARFSTE LEREKLIRQQ MEEQVAQKSS ELEQYLQRVR
ELEDMYLKLQ EALEDERQAR QDEETVRKLQ ARLLEEESSK RAELEKWHLE QQQAIQTTEA
EKQELENQRV LKEQALQEAM EQLEQLELER KQALEQYEEV KKKLEMATNK TKSWKDKVAH
HEGLIRLIEP GSKNPHLITN WGPAAFTEAE LEEREKNWKE KKTTE
