Q86WV1 (SKAP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SKAP1
Synonyms:	SCAP1, SKAP55

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	359 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	T cell receptor signaling pathway Inferred from mutant phenotype Ref.9. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype Ref.9. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.9. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay Ref.9. Source: UniProtKB
Molecular_function	SH2 domain binding Inferred from direct assay Ref.1. Source: UniProtKB SH3/SH2 adaptor activity Inferred by curator Ref.1. Source: UniProtKB antigen binding Inferred from physical interaction Ref.9. Source: UniProtKB phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FYB	O15117	2	EBI-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 359

359

Src kinase-associated phosphoprotein 1

PRO_0000270173

Regions

Domain

107 – 210

104

PH

Domain

294 – 355

62

SH3

Region

290 – 295

6

Interaction with FYB

Compositional bias

220 – 230

11

Poly-Glu

Amino acid modifications

Modified residue

142

1

Phosphotyrosine

Modified residue

219

1

Phosphotyrosine Probable

Modified residue

232

1

Phosphotyrosine Probable

Modified residue

271

1

Phosphotyrosine; by FYN Ref.16

Modified residue

295

1

Phosphotyrosine; by FYN Probable

Natural variations

Alternative sequence

293

1

Missing in isoform 2.

VSP_022179

Natural variant

161

1

G → S. Ref.1
Corresponds to variant rs2278868 [ dbSNP | Ensembl ].

VAR_029811

Natural variant

242

1

S → G.
Corresponds to variant rs35288886 [ dbSNP | Ensembl ].

VAR_035343

Experimental info

Mutagenesis

219

1

Y → F: Impairs interaction with PTPRC. No effect on interaction with FYN or GRB2. Ref.8 Ref.9

Mutagenesis

232

1

Y → 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

Mutagenesis

271

1

Y → 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

Mutagenesis

295

1

Y → F: Abolishes FYB-dependent activation of ITGAL clustering. Ref.7

Mutagenesis

298

1

Y → F: Impairs interaction with FYB. Ref.7

Mutagenesis

333

1

W → R: Abolishes homodimerization, interaction with FYB and activation of the MAP kinase pathway. Ref.5 Ref.8 Ref.11

Sequence conflict

187

1

S → T in CAA72101. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

359

Helix Strand Turn

Details...

Beta strand

108 – 119

12

Beta strand

121 – 124

4

Beta strand

126 – 136

11

Beta strand

139 – 145

7

Beta strand

152 – 156

5

Beta strand

161 – 164

4

Helix

166 – 168

3

Helix

172 – 176

5

Beta strand

177 – 181

5

Beta strand

183 – 185

3

Beta strand

188 – 191

4

Helix

195 – 212

18

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 24, 2009. Version 3. Checksum: 630FE4C17295BD6D	FASTA	359	41,432
	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
	Isoform 2 [UniParc]. Checksum: 158BBE1D48539DAC	FASTA	358	41,333
	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 KGDYASYYQG 310 320 330 340 350 LWDCHGDQPD ELSFQRGDLI RILSKEYNMY GWWVGELNSL VGIVPKEYLT TAFEVEER

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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.

IPI

IPI00289536.
IPI00793789.

RefSeq

NP_001068567.1. NM_001075099.1.
NP_003717.3. NM_003726.3.

UniGene

Hs.316931.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1U5D	X-ray	1.70	A/B/C/D	108-213	[»]

ProteinModelPortal

Q86WV1.

SMR

Q86WV1. Positions 7-213, 301-351.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q86WV1. 1 interaction.

MINT

MINT-6939971.

STRING

9606.ENSP00000338171.

PTM databases

PhosphoSite

Q86WV1.

Polymorphism databases

DMDM

269849660.

Proteomic databases

PaxDb

Q86WV1.

PRIDE

Q86WV1.

Protocols and materials databases

DNASU

8631.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000336915; ENSP00000338171; ENSG00000141293.
ENST00000584924; ENSP00000464311; ENSG00000141293.

GeneID

8631.

KEGG

hsa:8631.

UCSC

uc002ini.1. human.
uc002inj.1. human.

Organism-specific databases

CTD

8631.

GeneCards

GC17M046210.

HGNC

HGNC:15605. SKAP1.

HPA

CAB025882.
HPA002969.

MIM

604969. gene.

neXtProt

NX_Q86WV1.

PharmGKB

PA162403362.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG76786.

HOGENOM

HOG000231109.

HOVERGEN

HBG052827.

InParanoid

Q86WV1.

OMA

APHLRRD.

OrthoDB

EOG4CVG79.

PhylomeDB

Q86WV1.

Enzyme and pathway databases

SignaLink

Q86WV1.

Gene expression databases

Bgee

Q86WV1.

CleanEx

HS_SKAP1.

Genevestigator

Q86WV1.

Family and domain databases

Gene3D

2.30.29.30. 1 hit.

InterPro

IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00169. PH. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00452. SH3DOMAIN.

SMART

SM00233. PH. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF50044. SH3. 1 hit.

PROSITE

PS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q86WV1.

GenomeRNAi

8631.

NextBio

32353.

SOURCE

Search...

Entry information

Entry name

SKAP1_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 88 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.