ID SKAP1_MOUSE Reviewed; 355 AA.
AC Q3UUV5; Q3TE54; Q3UUT7; Q3UUX6;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 24-JAN-2024, entry version 138.
DE RecName: Full=Src kinase-associated phosphoprotein 1;
DE AltName: Full=Src family-associated phosphoprotein 1;
GN Name=Skap1; Synonyms=Scap1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP FUNCTION, INTERACTION WITH FYB1 AND FYN, AND IDENTIFICATION IN A COMPLEX
RP WITH FYB1 AND CLNK.
RX PubMed=12681493; DOI=10.1016/s0014-5793(03)00234-5;
RA Fujii Y., Wakahara S., Nakao T., Hara T., Ohtake H., Komurasaki T.,
RA Kitamura K., Tatsuno A., Fujiwara N., Hozumi N., Ra C., Kitamura D.,
RA Goitsuka R.;
RT "Targeting of MIST to Src-family kinases via SKAP55-SLAP-130 adaptor
RT complex in mast cells(1).";
RL FEBS Lett. 540:111-116(2003).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-142, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
CC -!- FUNCTION: Positively regulates T-cell receptor signaling by enhancing
CC the MAP kinase pathway (By similarity). Required for optimal
CC conjugation between T-cells and antigen-presenting cells by promoting
CC the clustering of integrin ITGAL on the surface of T-cells (By
CC similarity). May be involved in high affinity immunoglobulin epsilon
CC receptor signaling in mast cells (PubMed:12681493).
CC {ECO:0000250|UniProtKB:Q86WV1, ECO:0000269|PubMed:12681493}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with FYN
CC (PubMed:12681493). Interacts with PTPRC (By similarity). Interacts with
CC GRB2 when phosphorylated on Tyr-268 (By similarity). Interacts with
CC FYB1, which is required for SKAP2 protein stability (By similarity).
CC Part of a complex consisting of SKAP1, FYB1 and CLNK (PubMed:12681493).
CC Interacts with RASGRP1 (By similarity). Interacts with FYB2 (By
CC similarity). {ECO:0000250|UniProtKB:Q86WV1,
CC ECO:0000269|PubMed:12681493}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q86WV1}. Nucleus
CC {ECO:0000250|UniProtKB:Q86WV1}. Cell membrane
CC {ECO:0000250|UniProtKB:Q86WV1}. Note=Upon T-cell stimulation,
CC translocates to lipid rafts at the cell membrane.
CC {ECO:0000250|UniProtKB:Q86WV1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q3UUV5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UUV5-2; Sequence=VSP_022180, VSP_022181, VSP_022182;
CC Name=3;
CC IsoId=Q3UUV5-3; Sequence=VSP_022181, VSP_022183;
CC Name=4;
CC IsoId=Q3UUV5-4; Sequence=VSP_022181;
CC -!- DOMAIN: The SH3 domain interacts with FYB1.
CC {ECO:0000250|UniProtKB:Q86WV1}.
CC -!- PTM: Phosphorylated on tyrosines. Phosphorylation by FYN on Tyr-268 is
CC required for GRB2 interaction (By similarity). Phosphorylation by FYN
CC on Tyr-291 abolishes interaction with FYB1. Tyr-237 is dephosphorylated
CC by PTPRC (By similarity). {ECO:0000250|UniProtKB:Q86WV1}.
CC -!- SIMILARITY: Belongs to the SKAP family. {ECO:0000305}.
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DR EMBL; AK137792; BAE23497.1; -; mRNA.
DR EMBL; AK137942; BAE23518.1; -; mRNA.
DR EMBL; AK138030; BAE23537.1; -; mRNA.
DR EMBL; AK169825; BAE41394.1; -; mRNA.
DR CCDS; CCDS25301.1; -. [Q3UUV5-1]
DR CCDS; CCDS48891.1; -. [Q3UUV5-4]
DR CCDS; CCDS48892.1; -. [Q3UUV5-3]
DR RefSeq; NP_001028358.1; NM_001033186.3. [Q3UUV5-1]
DR RefSeq; NP_001171369.1; NM_001177898.1. [Q3UUV5-3]
DR RefSeq; NP_001171370.1; NM_001177899.1. [Q3UUV5-4]
DR AlphaFoldDB; Q3UUV5; -.
DR SMR; Q3UUV5; -.
DR BioGRID; 219428; 2.
DR DIP; DIP-60767N; -.
DR IntAct; Q3UUV5; 2.
DR STRING; 10090.ENSMUSP00000099443; -.
DR iPTMnet; Q3UUV5; -.
DR PhosphoSitePlus; Q3UUV5; -.
DR EPD; Q3UUV5; -.
DR jPOST; Q3UUV5; -.
DR MaxQB; Q3UUV5; -.
DR PaxDb; 10090-ENSMUSP00000099443; -.
DR ProteomicsDB; 257189; -. [Q3UUV5-1]
DR ProteomicsDB; 257190; -. [Q3UUV5-2]
DR ProteomicsDB; 257191; -. [Q3UUV5-3]
DR ProteomicsDB; 257192; -. [Q3UUV5-4]
DR Antibodypedia; 1187; 269 antibodies from 32 providers.
DR DNASU; 78473; -.
DR Ensembl; ENSMUST00000071510.14; ENSMUSP00000071445.8; ENSMUSG00000057058.17. [Q3UUV5-4]
DR Ensembl; ENSMUST00000100521.10; ENSMUSP00000098090.4; ENSMUSG00000057058.17. [Q3UUV5-3]
DR Ensembl; ENSMUST00000103154.11; ENSMUSP00000099443.5; ENSMUSG00000057058.17. [Q3UUV5-1]
DR GeneID; 78473; -.
DR KEGG; mmu:78473; -.
DR UCSC; uc007lce.2; mouse. [Q3UUV5-2]
DR UCSC; uc007lcf.2; mouse. [Q3UUV5-1]
DR UCSC; uc007lcg.2; mouse. [Q3UUV5-4]
DR UCSC; uc011ydi.1; mouse. [Q3UUV5-3]
DR AGR; MGI:1925723; -.
DR CTD; 8631; -.
DR MGI; MGI:1925723; Skap1.
DR VEuPathDB; HostDB:ENSMUSG00000057058; -.
DR eggNOG; ENOG502QSSU; Eukaryota.
DR GeneTree; ENSGT00390000017856; -.
DR HOGENOM; CLU_062032_0_0_1; -.
DR InParanoid; Q3UUV5; -.
DR OMA; NYYQGMW; -.
DR OrthoDB; 2968233at2759; -.
DR PhylomeDB; Q3UUV5; -.
DR TreeFam; TF331055; -.
DR BioGRID-ORCS; 78473; 0 hits in 75 CRISPR screens.
DR ChiTaRS; Skap1; mouse.
DR PRO; PR:Q3UUV5; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q3UUV5; Protein.
DR Bgee; ENSMUSG00000057058; Expressed in thymus and 79 other cell types or tissues.
DR ExpressionAtlas; Q3UUV5; baseline and differential.
DR Genevisible; Q3UUV5; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0001772; C:immunological synapse; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0044853; C:plasma membrane raft; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0042101; C:T cell receptor complex; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0042169; F:SH2 domain binding; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0002821; P:positive regulation of adaptive immune response; ISO:MGI.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:MGI.
DR GO; GO:0033634; P:positive regulation of cell-cell adhesion mediated by integrin; ISO:MGI.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:MGI.
DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; ISO:MGI.
DR GO; GO:0033625; P:positive regulation of integrin activation; ISO:MGI.
DR GO; GO:1903039; P:positive regulation of leukocyte cell-cell adhesion; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:MGI.
DR CDD; cd13380; PH_Skap1; 1.
DR CDD; cd12044; SH3_SKAP1; 1.
DR Gene3D; 6.10.250.220; -; 1.
DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR Gene3D; 2.30.30.40; SH3 Domains; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR035765; SKAP1_SH3.
DR InterPro; IPR037781; SKAP_fam.
DR PANTHER; PTHR15129:SF1; SRC KINASE-ASSOCIATED PHOSPHOPROTEIN 1; 1.
DR PANTHER; PTHR15129; SRC-ASSOCIATED ADAPTOR PROTEIN; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00233; PH; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50729; PH domain-like; 1.
DR SUPFAM; SSF50044; SH3-domain; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Cell membrane; Cytoplasm;
KW Immunity; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW SH3 domain.
FT CHAIN 1..355
FT /note="Src kinase-associated phosphoprotein 1"
FT /id="PRO_0000270174"
FT DOMAIN 107..210
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 290..351
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 64..83
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 219..252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 286..291
FT /note="Interaction with FYB1"
FT /evidence="ECO:0000250"
FT COMPBIAS 219..239
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 142
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 237
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q86WV1"
FT MOD_RES 268
FT /note="Phosphotyrosine; by FYN"
FT /evidence="ECO:0000250|UniProtKB:Q86WV1"
FT MOD_RES 291
FT /note="Phosphotyrosine; by FYN"
FT /evidence="ECO:0000250"
FT VAR_SEQ 95..148
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_022180"
FT VAR_SEQ 273..288
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_022181"
FT VAR_SEQ 323..355
FT /note="EYNMYGWWVGELNSVIGIVPKDYLTTAFEMEGI -> VKM (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_022182"
FT VAR_SEQ 323..355
FT /note="EYNMYGWWVGELNSVIGIVPKDYLTTAFEMEGI -> GTYSQTIRNSRPLLW
FT PWILLFPEWSQDSAASCDFKPLIR (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_022183"
FT CONFLICT 355
FT /note="I -> R (in Ref. 1; BAE41394)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 355 AA; 40962 MW; 4DFE6CC655894B66 CRC64;
MQAVALPEEI CWLLEDTEDF LAEGLQNENL SPGAQDQRAH ILRGFQQIKS RYCWDFQPQG
GDLGQDGSDD NLSGTHGPPL TSEASFWSDY QDEGIEDILR GAQELDSVIK QGYLEKKSKD
HSFFGSEWQK RWCVISRGLF LYYANEKSKQ PKGTFLIKGY SVRMAPHLRK DSKKESCFEL
ISQDRRSYEF TASSPAEARD WVDQISFLLK DLSSLTIPFE EEEEEEEEEE KEEEEMYNDV
DGFDSPRSGS QCRAMALPEP TEKEEDIYEV LPDDDDLEED TCGAHRRRVD YADYYQGLWD
CHGDQPDELS FQRGDLIRIL SKEYNMYGWW VGELNSVIGI VPKDYLTTAF EMEGI
//
