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Protein

Src kinase-associated phosphoprotein 1

Gene

SKAP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Positively regulates T-cell receptor signaling by enhancing the MAP kinase pathway. Required for optimal conjugation between T-cells and antigen-presenting cells by promoting the clustering of integrin ITGAL on the surface of T-cells. May be involved in high affinity immunoglobulin epsilon receptor signaling in mast cells.5 Publications

GO - Molecular functioni

  • protein-containing complex binding Source: Ensembl
  • protein kinase binding Source: UniProtKB
  • protein phosphatase binding Source: UniProtKB
  • SH2 domain binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: GO_Central
  • SH3 domain binding Source: BHF-UCL

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • positive regulation of cell adhesion Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: BHF-UCL
  • protein localization to plasma membrane Source: Ensembl
  • T cell receptor signaling pathway Source: UniProtKB

Keywordsi

Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

SignaLinkiQ86WV1
SIGNORiQ86WV1

Names & Taxonomyi

Protein namesi
Recommended name:
Src kinase-associated phosphoprotein 1
Alternative name(s):
Src family-associated phosphoprotein 1
Src kinase-associated phosphoprotein of 55 kDa
Short name:
SKAP-55
Short name:
pp55
Gene namesi
Name:SKAP1
Synonyms:SCAP1, SKAP55
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000141293.15
HGNCiHGNC:15605 SKAP1
MIMi604969 gene
neXtProtiNX_Q86WV1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi219Y → F: Impairs interaction with PTPRC. No effect on interaction with FYN or GRB2. 2 Publications1
Mutagenesisi232Y → F: Abolishes interaction with PTPRC, translocation to cell membrane upon T-cell stimulation and activation of the MAP kinase pathway. No effect on interaction with FYN or GRB2. 2 Publications1
Mutagenesisi271Y → F: No effect on interaction with PTPRC and translocation to cell membrane upon T-cell stimulation. Abolishes interaction with FYN and GRB2 and activation of the MAP kinase pathway. 2 Publications1
Mutagenesisi295Y → F: Abolishes FYB1-dependent activation of ITGAL clustering. 1 Publication1
Mutagenesisi298Y → F: Impairs interaction with FYB1. 1 Publication1
Mutagenesisi333W → R: Abolishes homodimerization, interaction with FYB1 and activation of the MAP kinase pathway. 3 Publications1

Organism-specific databases

DisGeNETi8631
OpenTargetsiENSG00000141293
PharmGKBiPA162403362

Polymorphism and mutation databases

BioMutaiSKAP1
DMDMi269849660

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002701731 – 359Src kinase-associated phosphoprotein 1Add BLAST359

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei142PhosphotyrosineBy similarity1
Modified residuei219Phosphotyrosine1 Publication1
Modified residuei232Phosphotyrosine1 Publication1
Modified residuei271Phosphotyrosine; by FYNCombined sources1
Modified residuei295Phosphotyrosine; by FYNCurated1

Post-translational modificationi

Phosphorylated on tyrosines. Phosphorylation by FYN on Tyr-271 is required for GRB2 interaction. Phosphorylation by FYN on Tyr-295 abolishes interaction with FYB1. Tyr-232 is dephosphorylated by PTPRC (Probable).4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ86WV1
PaxDbiQ86WV1
PeptideAtlasiQ86WV1
PRIDEiQ86WV1
ProteomicsDBi70207
70208 [Q86WV1-2]

PTM databases

iPTMnetiQ86WV1
PhosphoSitePlusiQ86WV1

Expressioni

Tissue specificityi

Highly expressed in thymocytes and peripheral blood lymphocytes. Also expressed in spleen cells and testis. Present in T-cells (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000141293
CleanExiHS_SKAP1
ExpressionAtlasiQ86WV1 baseline and differential
GenevisibleiQ86WV1 HS

Organism-specific databases

HPAiCAB025882
CAB055513
HPA002969

Interactioni

Subunit structurei

Homodimer. Interacts with FYN (PubMed:9195899). Interacts with PTPRC (PubMed:11909961). Interacts with GRB2 when phosphorylated on Tyr-271 (PubMed:12171928). Interacts with FYB1, which is required for SKAP2 protein stability (PubMed:10856234, PubMed:27335501, PubMed:9671755, PubMed:10856234, PubMed:15849195, PubMed:16461356). Part of a complex consisting of SKAP1, FYB1 and CLNK (By similarity). Interacts with RASGRP1 (PubMed:17658605). Interacts with FYB2 (PubMed:27335501).By similarity9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB
  • protein phosphatase binding Source: UniProtKB
  • SH2 domain binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: GO_Central
  • SH3 domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi114184, 101 interactors
IntActiQ86WV1, 7 interactors
MINTiQ86WV1
STRINGi9606.ENSP00000338171

Structurei

Secondary structure

1359
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi108 – 119Combined sources12
Beta strandi121 – 124Combined sources4
Beta strandi126 – 136Combined sources11
Beta strandi139 – 145Combined sources7
Beta strandi152 – 156Combined sources5
Beta strandi161 – 164Combined sources4
Helixi166 – 168Combined sources3
Helixi172 – 176Combined sources5
Beta strandi177 – 181Combined sources5
Beta strandi183 – 185Combined sources3
Beta strandi188 – 191Combined sources4
Helixi195 – 212Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1U5DX-ray1.70A/B/C/D108-213[»]
ProteinModelPortaliQ86WV1
SMRiQ86WV1
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ86WV1

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini107 – 210PHPROSITE-ProRule annotationAdd BLAST104
Domaini294 – 355SH3PROSITE-ProRule annotationAdd BLAST62

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni290 – 295Interaction with FYB16

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi220 – 230Poly-GluAdd BLAST11

Domaini

The SH3 domain interacts with FYB1.

Sequence similaritiesi

Belongs to the SKAP family.Curated

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiENOG410IENN Eukaryota
ENOG410YF8P LUCA
GeneTreeiENSGT00390000017856
HOGENOMiHOG000231109
HOVERGENiHBG052827
InParanoidiQ86WV1
KOiK17699
OMAiHLRRDSK
OrthoDBiEOG091G0HBY
PhylomeDBiQ86WV1
TreeFamiTF331055

Family and domain databases

CDDicd12044 SH3_SKAP1, 1 hit
Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR035765 SKAP1_SH3
IPR037781 SKAP_fam
PANTHERiPTHR15129 PTHR15129, 1 hit
PfamiView protein in Pfam
PF00169 PH, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00326 SH3, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
PROSITEiView protein in PROSITE
PS50003 PH_DOMAIN, 1 hit
PS50002 SH3, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q86WV1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MQAAALPEEI RWLLEDAEEF LAEGLRNENL SAVARDHRDH ILRGFQQIKA
60 70 80 90 100
RYYWDFQPQG GDIGQDSSDD NHSGTLGLSL TSDAPFLSDY QDEGMEDIVK
110 120 130 140 150
GAQELDNVIK QGYLEKKSKD HSFFGSEWQK RWCVVSRGLF YYYANEKSKQ
160 170 180 190 200
PKGTFLIKGY GVRMAPHLRR DSKKESCFEL TSQDRRSYEF TATSPAEARD
210 220 230 240 250
WVDQISFLLK DLSSLTIPYE EDEEEEEKEE TYDDIDGFDS PSCGSQCRPT
260 270 280 290 300
ILPGSVGIKE PTEEKEEEDI YEVLPDEEHD LEEDESGTRR KGVDYASYYQ
310 320 330 340 350
GLWDCHGDQP DELSFQRGDL IRILSKEYNM YGWWVGELNS LVGIVPKEYL

TTAFEVEER
Length:359
Mass (Da):41,432
Last modified:November 24, 2009 - v3
Checksum:i630FE4C17295BD6D
GO
Isoform 2 (identifier: Q86WV1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     293-293: Missing.

Show »
Length:358
Mass (Da):41,333
Checksum:i158BBE1D48539DAC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti187S → T in CAA72101 (PubMed:9195899).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029811161G → S1 PublicationCorresponds to variant dbSNP:rs2278868Ensembl.1
Natural variantiVAR_035343242S → G. Corresponds to variant dbSNP:rs35288886Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_022179293Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y11215 mRNA Translation: CAA72101.1
AC006468 Genomic DNA No translation available.
AC027152 Genomic DNA No translation available.
AC036222 Genomic DNA No translation available.
AC090627 Genomic DNA No translation available.
CH471109 Genomic DNA Translation: EAW94749.1
CH471109 Genomic DNA Translation: EAW94750.1
BC047870 mRNA Translation: AAH47870.1
CCDSiCCDS32674.1 [Q86WV1-1]
RefSeqiNP_001068567.1, NM_001075099.1 [Q86WV1-2]
NP_003717.3, NM_003726.3 [Q86WV1-1]
UniGeneiHs.316931

Genome annotation databases

EnsembliENST00000336915; ENSP00000338171; ENSG00000141293 [Q86WV1-1]
ENST00000584924; ENSP00000464311; ENSG00000141293 [Q86WV1-1]
GeneIDi8631
KEGGihsa:8631
UCSCiuc002ini.2 human [Q86WV1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSKAP1_HUMAN
AccessioniPrimary (citable) accession number: Q86WV1
Secondary accession number(s): D3DTV1, O15268
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 9, 2007
Last sequence update: November 24, 2009
Last modified: June 20, 2018
This is version 133 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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