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Protein

Src kinase-associated phosphoprotein 1

Gene

SKAP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 kinase binding Source: UniProtKB
  • protein phosphatase binding Source: UniProtKB
  • SH2 domain binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: UniProtKB
  • 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 from RNA polymerase II promoter Source: UniProtKB
  • protein localization to plasma membrane Source: Ensembl
  • T cell receptor signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Adaptive 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

HGNCiHGNC:15605. SKAP1.

Subcellular locationi

GO - Cellular componenti

  • cell-cell junction Source: Ensembl
  • cytoplasm Source: UniProtKB
  • cytosol Source: Ensembl
  • nucleus Source: HPA
  • plasma membrane Source: UniProtKB
  • T cell receptor complex Source: Ensembl
Complete GO annotation...

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 FYB-dependent activation of ITGAL clustering. 1 Publication1
Mutagenesisi298Y → F: Impairs interaction with FYB. 1 Publication1
Mutagenesisi333W → R: Abolishes homodimerization, interaction with FYB 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 FYB. Tyr-232 is dephosphorylated by PTPRC (Probable).4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ86WV1.
PaxDbiQ86WV1.
PeptideAtlasiQ86WV1.
PRIDEiQ86WV1.

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 and PTPRC. Interacts with GRB2 when phosphorylated on Tyr-271. Interacts with FYB, which is required for SKAP2 protein stability. Part of a complex consisting of SKAP1, FYB and CLNK. Interacts with RASGRP1.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BLCAPP629523EBI-2477305,EBI-3895726
FAM102AQ5T9C23EBI-2477305,EBI-10246318
FYBO151176EBI-2477305,EBI-1753267
PRAM1Q96QH23EBI-2477305,EBI-2860740
SH2D4AQ9H7883EBI-2477305,EBI-747035
SH2D4AQ9H788-23EBI-2477305,EBI-10308083

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi114184. 97 interactors.
IntActiQ86WV1. 7 interactors.
MINTiMINT-6939971.
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 FYB6

Compositional bias

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

Domaini

The SH3 domain interacts with FYB.

Sequence similaritiesi

Belongs to the SKAP family.Curated
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3 domain

Phylogenomic databases

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

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
SMARTiSM00233. PH. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

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 → S.1 PublicationCorresponds to variant rs2278868dbSNPEnsembl.1
Natural variantiVAR_035343242S → G.Corresponds to variant rs35288886dbSNPEnsembl.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

Cross-referencesi

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.

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...

Protein-protein interaction databases

BioGridi114184. 97 interactors.
IntActiQ86WV1. 7 interactors.
MINTiMINT-6939971.
STRINGi9606.ENSP00000338171.

PTM databases

iPTMnetiQ86WV1.
PhosphoSitePlusiQ86WV1.

Polymorphism and mutation databases

BioMutaiSKAP1.
DMDMi269849660.

Proteomic databases

MaxQBiQ86WV1.
PaxDbiQ86WV1.
PeptideAtlasiQ86WV1.
PRIDEiQ86WV1.

Protocols and materials databases

DNASUi8631.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8631.
DisGeNETi8631.
GeneCardsiSKAP1.
HGNCiHGNC:15605. SKAP1.
HPAiCAB025882.
CAB055513.
HPA002969.
MIMi604969. gene.
neXtProtiNX_Q86WV1.
OpenTargetsiENSG00000141293.
PharmGKBiPA162403362.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

SignaLinkiQ86WV1.
SIGNORiQ86WV1.

Miscellaneous databases

ChiTaRSiSKAP1. human.
EvolutionaryTraceiQ86WV1.
GeneWikiiSKAP1.
GenomeRNAii8631.
PROiQ86WV1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141293.
CleanExiHS_SKAP1.
ExpressionAtlasiQ86WV1. baseline and differential.
GenevisibleiQ86WV1. HS.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
SMARTiSM00233. PH. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSKAP1_HUMAN
AccessioniPrimary (citable) accession number: Q86WV1
Secondary accession number(s): D3DTV1, O15268
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 9, 2007
Last sequence update: November 24, 2009
Last modified: November 2, 2016
This is version 120 of the entry and version 3 of the sequence. [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

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.