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Q86WV1 (SKAP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SKAP1
Synonyms:SCAP1, SKAP55
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length359 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.9 Ref.10 Ref.12 Ref.14

Subunit structure

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. Ref.1 Ref.5 Ref.6 Ref.7 Ref.8 Ref.11 Ref.13 Ref.15

Subcellular location

Cytoplasm. Nucleus. Cell membrane. Note: Upon T-cell stimulation, translocates to lipid rafts at the cell membrane. Ref.6 Ref.9 Ref.10

Tissue specificity

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

Domain

The SH3 domain interacts with FYB.

Post-translational modification

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. Ref.1 Ref.8 Ref.9 Ref.13

Sequence similarities

Belongs to the SKAP family.

Contains 1 PH domain.

Contains 1 SH3 domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

FYBO151176EBI-2477305,EBI-1753267

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q86WV1-1)

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.
Isoform 2 (identifier: Q86WV1-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 359359Src kinase-associated phosphoprotein 1
PRO_0000270173

Regions

Domain107 – 210104PH
Domain294 – 35562SH3
Region290 – 2956Interaction with FYB
Compositional bias220 – 23011Poly-Glu

Amino acid modifications

Modified residue1421Phosphotyrosine By similarity
Modified residue2191Phosphotyrosine Probable
Modified residue2321Phosphotyrosine Probable
Modified residue2711Phosphotyrosine; by FYN Ref.16
Modified residue2951Phosphotyrosine; by FYN Probable

Natural variations

Alternative sequence2931Missing in isoform 2.
VSP_022179
Natural variant1611G → S. Ref.1
Corresponds to variant rs2278868 [ dbSNP | Ensembl ].
VAR_029811
Natural variant2421S → G.
Corresponds to variant rs35288886 [ dbSNP | Ensembl ].
VAR_035343

Experimental info

Mutagenesis2191Y → F: Impairs interaction with PTPRC. No effect on interaction with FYN or GRB2. Ref.8 Ref.9
Mutagenesis2321Y → 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. Ref.8 Ref.9
Mutagenesis2711Y → 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. Ref.8 Ref.9
Mutagenesis2951Y → F: Abolishes FYB-dependent activation of ITGAL clustering. Ref.7
Mutagenesis2981Y → F: Impairs interaction with FYB. Ref.7
Mutagenesis3331W → R: Abolishes homodimerization, interaction with FYB and activation of the MAP kinase pathway. Ref.5 Ref.8 Ref.11
Sequence conflict1871S → T in CAA72101. Ref.1

Secondary structure

........................ 359
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 24, 2009. Version 3.
Checksum: 630FE4C17295BD6D

FASTA35941,432
        10         20         30         40         50         60 
MQAAALPEEI RWLLEDAEEF LAEGLRNENL SAVARDHRDH ILRGFQQIKA RYYWDFQPQG 

        70         80         90        100        110        120 
GDIGQDSSDD NHSGTLGLSL TSDAPFLSDY QDEGMEDIVK GAQELDNVIK QGYLEKKSKD 

       130        140        150        160        170        180 
HSFFGSEWQK RWCVVSRGLF YYYANEKSKQ PKGTFLIKGY GVRMAPHLRR DSKKESCFEL 

       190        200        210        220        230        240 
TSQDRRSYEF TATSPAEARD WVDQISFLLK DLSSLTIPYE EDEEEEEKEE TYDDIDGFDS 

       250        260        270        280        290        300 
PSCGSQCRPT ILPGSVGIKE PTEEKEEEDI YEVLPDEEHD LEEDESGTRR KGVDYASYYQ 

       310        320        330        340        350 
GLWDCHGDQP DELSFQRGDL IRILSKEYNM YGWWVGELNS LVGIVPKEYL TTAFEVEER 

« Hide

Isoform 2 [UniParc].

Checksum: 158BBE1D48539DAC
Show »

FASTA35841,333

References

« Hide 'large scale' references
[1]"Molecular cloning of SKAP55, a novel protein that associates with p59fyn in human T-lymphocytes."
Marie-Cardine A., Bruyns E., Eckerskorn C., Kirchgessner H., Meuer S., Schraven B.
J. Biol. Chem. 272:16077-16080(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 101-110; 120-130 AND 153-158, PHOSPHORYLATION, INTERACTION WITH FYN, TISSUE SPECIFICITY, VARIANT SER-161.
Tissue: Blood.
[2]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Pancreas.
[5]"Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130."
Marie-Cardine A., Hendricks-Taylor L.R., Boerth N.J., Zhao H., Schraven B., Koretzky G.A.
J. Biol. Chem. 273:25789-25795(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FYB, MUTAGENESIS OF TRP-333.
[6]"FYB (FYN binding protein) serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells."
Liu J., Kang H., Raab M., da Silva A.J., Kraeft S.-K., Rudd C.E.
Proc. Natl. Acad. Sci. U.S.A. 95:8779-8784(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FYB, SUBCELLULAR LOCATION.
[7]"SH3 domain recognition of a proline-independent tyrosine-based RKxxYxxY motif in immune cell adaptor SKAP55."
Kang H., Freund C., Duke-Cohan J.S., Musacchio A., Wagner G., Rudd C.E.
EMBO J. 19:2889-2899(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FYB, MUTAGENESIS OF TYR-295 AND TYR-298, FUNCTION.
[8]"SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation."
Wu L., Yu Z., Shen S.-H.
J. Biol. Chem. 277:40420-40427(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: HOMODIMERIZATION, MUTAGENESIS OF TYR-219; TYR-232; TYR-271 AND TRP-333, PHOSPHORYLATION, INTERACTION WITH GRB2.
[9]"SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription."
Wu L., Fu J., Shen S.-H.
Mol. Cell. Biol. 22:2673-2686(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-219 AND TYR-232, DEPHOSPHORYLATION BY PTPRC, MUTAGENESIS OF TYR-219; TYR-232 AND TYR-271, SUBCELLULAR LOCATION, FUNCTION.
[10]"SKAP-55 regulates integrin adhesion and formation of T cell-APC conjugates."
Wang H., Moon E.-Y., Azouz A., Wu X., Smith A., Schneider H., Hogg N., Rudd C.E.
Nat. Immunol. 4:366-374(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]"Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells."
Huang Y., Norton D.D., Precht P., Martindale J.L., Burkhardt J.K., Wange R.L.
J. Biol. Chem. 280:23576-23583(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FYB, MUTAGENESIS OF TRP-333.
[12]"An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R."
Jo E.-K., Wang H., Rudd C.E.
J. Exp. Med. 201:1733-1739(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain of adhesion and degranulation-promoting adaptor protein."
Duke-Cohan J.S., Kang H., Liu H., Rudd C.E.
J. Biol. Chem. 281:13743-13750(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, INTERACTION WITH FYB.
[14]"The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1."
Kliche S., Breitling D., Togni M., Pusch R., Heuer K., Wang X., Freund C., Kasirer-Friede A., Menasche G., Koretzky G.A., Schraven B.
Mol. Cell. Biol. 26:7130-7144(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"SKAP55 modulates T cell antigen receptor-induced activation of the Ras-Erk-AP1 pathway by binding RasGRP1."
Kosco K.A., Cerignoli F., Williams S., Abraham R.T., Mustelin T.
Mol. Immunol. 45:510-522(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RASGRP1.
[16]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-271, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[17]"Structural basis for the dimerization and phosphoinositide specificity of the Src kinase-associated phosphoproteins SKAP55 and SKAP-HOM."
Tang Y., Swanson K.D., Neel B.G., Eck M.J.
Submitted (JUL-2005) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 108-213.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS32674.1. [Q86WV1-1]
RefSeqNP_001068567.1. NM_001075099.1. [Q86WV1-2]
NP_003717.3. NM_003726.3. [Q86WV1-1]
UniGeneHs.316931.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1U5DX-ray1.70A/B/C/D108-213[»]
ProteinModelPortalQ86WV1.
SMRQ86WV1. Positions 7-213, 301-351.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114184. 11 interactions.
IntActQ86WV1. 3 interactions.
MINTMINT-6939971.
STRING9606.ENSP00000338171.

PTM databases

PhosphoSiteQ86WV1.

Polymorphism databases

DMDM269849660.

Proteomic databases

MaxQBQ86WV1.
PaxDbQ86WV1.
PRIDEQ86WV1.

Protocols and materials databases

DNASU8631.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000336915; ENSP00000338171; ENSG00000141293. [Q86WV1-1]
ENST00000584924; ENSP00000464311; ENSG00000141293. [Q86WV1-1]
GeneID8631.
KEGGhsa:8631.
UCSCuc002ini.1. human. [Q86WV1-1]
uc002inj.1. human. [Q86WV1-2]

Organism-specific databases

CTD8631.
GeneCardsGC17M046210.
HGNCHGNC:15605. SKAP1.
HPACAB025882.
HPA002969.
MIM604969. gene.
neXtProtNX_Q86WV1.
PharmGKBPA162403362.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG76786.
HOGENOMHOG000231109.
HOVERGENHBG052827.
InParanoidQ86WV1.
KOK17699.
OMAHLRRDSK.
OrthoDBEOG7K6PVB.
PhylomeDBQ86WV1.
TreeFamTF331055.

Enzyme and pathway databases

SignaLinkQ86WV1.

Gene expression databases

ArrayExpressQ86WV1.
BgeeQ86WV1.
CleanExHS_SKAP1.
GenevestigatorQ86WV1.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR001452. SH3_domain.
[Graphical view]
PfamPF00169. PH. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PRINTSPR00452. SH3DOMAIN.
SMARTSM00233. PH. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
PROSITEPS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ86WV1.
GeneWikiSKAP1.
GenomeRNAi8631.
NextBio32353.
PROQ86WV1.
SOURCESearch...

Entry information

Entry nameSKAP1_HUMAN
AccessionPrimary (citable) accession number: Q86WV1
Secondary accession number(s): D3DTV1, O15268
Entry history
Integrated into UniProtKB/Swiss-Prot: January 9, 2007
Last sequence update: November 24, 2009
Last modified: July 9, 2014
This is version 99 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM