O75563 (SKAP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Src kinase-associated phosphoprotein 2

Alternative name(s):
Pyk2/RAFTK-associated protein
Retinoic acid-induced protein 70
SKAP55 homolog
Short name=SKAP-55HOM
Short name=SKAP-HOM
Src family-associated phosphoprotein 2
Src kinase-associated phosphoprotein 55-related protein
Src-associated adapter protein with PH and SH3 domains

Gene names

Name:	SKAP2
Synonyms:	PRAP, RA70, SAPS, SCAP2, SKAP55R

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	May be involved in B-cell and macrophage adhesion processes. In B-cells, may act by coupling the B-cell receptor (BCR) to integrin activation. May play a role in src signaling pathway. Ref.1 Ref.4
Subunit structure	Homodimer By similarity. Interacts with PTPNS1. Part of a complex consisting of SKAP2, FYB and PTPNS1. Part of a complex consisting of SKAP2, FYB and LILRB3. May interact with actin By similarity. Interacts with FYB, which is required for SKAP2 protein stability. Interacts with LAT, GRB2, PTK2B and PRAM1. May interact with FYN, HCK and LYN. Interacts with FASLG. Ref.1 Ref.2 Ref.3 Ref.4 Ref.12 Ref.13 Ref.15
Subcellular location	Cytoplasm Ref.4.
Tissue specificity	Ubiquitously expressed. Present in platelets (at protein level). Ref.1 Ref.2 Ref.12
Induction	By retinoic acid. Ref.1 Ref.13
Domain	The SH3 domain interacts with FYB and PTK2B.
Post-translational modification	Phosphorylated in resting platelets. Phosphorylated by FYN on Tyr-261 upon T-cell activation Probable. Dephosphorylated on Tyr-75 by PTPN22. Ref.2 Ref.3 Ref.4 Ref.12 Ref.16
Sequence similarities	Belongs to the SKAP family. Contains 1 PH domain. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	B-cell activation
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell activation Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara protein complex assembly Traceable author statement Ref.3. Source: ProtInc signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome plasma membrane Inferred from direct assay PubMed 11390434. Source: MGI
Molecular_function	SH3/SH2 adaptor activity Traceable author statement Ref.3. Source: ProtInc phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 359	359	Src kinase-associated phosphoprotein 2		PRO_0000270179
Regions
	Domain	116 – 219	104	PH
	Domain	297 – 358	62	SH3
	Region	14 – 64	51	Homodimerization By similarity
Amino acid modifications
	Modified residue	75	1	Phosphotyrosine Ref.16
	Modified residue	151	1	Phosphotyrosine By similarity
	Modified residue	197	1	Phosphotyrosine By similarity
	Modified residue	261	1	Phosphotyrosine By similarity
Natural variations
	Natural variant	202	1	A → S. Ref.1 Ref.2 Ref.5 Corresponds to variant rs1129771 [ dbSNP | Ensembl ].		VAR_029812
	Natural variant	253	1	S → T. Corresponds to variant rs17154402 [ dbSNP | Ensembl ].		VAR_029813
Experimental info
	Sequence conflict	6	1	S → C in BAA36194. Ref.1
	Sequence conflict	352	1	Y → H in BAD96605. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	O75563 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 65F266535A89281E	FASTA	359	41,217
	10 20 30 40 50 60 MPNPSSTSSP YPLPEEIRNL LADVETFVAD ILKGENLSKK AKEKRESLIK KIKDVKSIYL 70 80 90 100 110 120 QEFQDKGDAE DGEEYDDPFA GPPDTISLAS ERYDKDDEAP SDGAQFPPIA AQDLPFVLKA 130 140 150 160 170 180 GYLEKRRKDH SFLGFEWQKR WCALSKTVFY YYGSDKDKQQ KGEFAIDGYS VRMNNTLRKD 190 200 210 220 230 240 GKKDCCFEIS APDKRIYQFT AASPKDAEEW VQQLKFVLQD MESDIIPEDY DERGELYDDV 250 260 270 280 290 300 DHPLPISNPL TSSQPIDDEI YEELPEEEED SAPVKVEEQR KMSQDSVHHT SGDKSTDYAN 310 320 330 340 350 FYQGLWDCTG AFSDELSFKR GDVIYILSKE YNRYGWWVGE MKGAIGLVPK AYIMEMYDI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"RA70 is a src kinase-associated protein expressed ubiquitously." Kouroku Y., Soyama A., Fujita E., Urase K., Tsukahara T., Momoi T. Biochem. Biophys. Res. Commun. 252:738-742(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION, POSSIBLE INTERACTION WITH FYN; HCK AND LYN, FUNCTION, VARIANT SER-202. Tissue: Testis.
[2]	"SKAP-HOM, a novel adaptor protein homologous to the FYN-associated protein SKAP55." Marie-Cardine A., Verhagen A.M., Eckerskorn C., Schraven B. FEBS Lett. 435:55-60(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, PHOSPHORYLATION, INTERACTION WITH FYB, VARIANT SER-202. Tissue: Leukocyte.
[3]	"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: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH FYB, PHOSPHORYLATION. Tissue: Lymphocyte.
[4]	"Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation." Takahashi T., Yamashita H., Nagano Y., Nakamura T., Ohmori H., Avraham H., Avraham S., Yasuda M., Matsumoto M. J. Biol. Chem. 278:42225-42233(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH PTK2B, PHOSPHORYLATION, SUBCELLULAR LOCATION, FUNCTION. Tissue: Hippocampus.
[5]	"Src-associated adaptor protein with PH and SH3 domain." Lee J.-S., Suh K.S., Burr J.G. Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-202. Tissue: Pancreas.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[8]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	"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]. Tissue: Lung and Testis.
[12]	"Interaction of linker for activation of T cells with multiple adapter proteins in platelets activated by the glycoprotein VI-selective ligand, convulxin." Asazuma N., Wilde J.I., Berlanga O., Leduc M., Leo A., Schweighoffer E., Tybulewicz V., Bon C., Liu S.K., McGlade C.J., Schraven B., Watson S.P. J. Biol. Chem. 275:33427-33434(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH FYB; LAT AND GRB2, TISSUE SPECIFICITY.
[13]	"PRAM-1 is a novel adaptor protein regulated by retinoic acid (RA) and promyelocytic leukemia (PML)-RA receptor alpha in acute promyelocytic leukemia cells." Moog-Lutz C., Peterson E.J., Lutz P.G., Eliason S., Cave-Riant F., Singer A., Di Gioia Y., Dmovski S., Kamens J., Cayre Y.E., Koretzky G. J. Biol. Chem. 276:22375-22381(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION, INTERACTION WITH PRAM1.
[14]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[15]	"Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening." Voss M., Lettau M., Janssen O. BMC Immunol. 10:53-53(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FASLG.
[16]	"Substrate specificity of lymphoid-specific tyrosine phosphatase (Lyp) and identification of Src kinase-associated protein of 55 kDa homolog (SKAP-HOM) as a Lyp substrate." Yu X., Chen M., Zhang S., Yu Z.H., Sun J.P., Wang L., Liu S., Imasaki T., Takagi Y., Zhang Z.Y. J. Biol. Chem. 286:30526-30534(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 71-79 IN COMPLEX WITH PTPN22, PHOSPHORYLATION AT TYR-75.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB014486 mRNA. Translation: BAA36194.1.
AJ004886 mRNA. Translation: CAA06193.1.
AF072166 mRNA. Translation: AAC39924.1.
AF051323 mRNA. Translation: AAC99296.1.
AK313209 mRNA. Translation: BAG36025.1.
AK222885 mRNA. Translation: BAD96605.1.
AC003999 Genomic DNA. Translation: AAS02033.1.
AC011299 Genomic DNA. Translation: AAS07536.1.
CH236948 Genomic DNA. Translation: EAL24231.1.
CH471073 Genomic DNA. Translation: EAW93859.1.
BC002893 mRNA. Translation: AAH02893.1.
BC036044 mRNA. Translation: AAH36044.1.

IPI

IPI00022508.

RefSeq

NP_003921.2. NM_003930.3.

UniGene

Hs.200770.
Hs.610137.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3OMH	X-ray	2.90	E/F/G/H	71-79	[»]

ProteinModelPortal

O75563.

ModBase

Search...

Protein-protein interaction databases

IntAct

O75563. 3 interactions.

STRING

9606.ENSP00000005587.

PTM databases

PhosphoSite

O75563.

2D gel databases

OGP

O75563.

Proteomic databases

PaxDb

O75563.

PRIDE

O75563.

Protocols and materials databases

DNASU

8935.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000345317; ENSP00000005587; ENSG00000005020.

GeneID

8935.

KEGG

hsa:8935.

UCSC

uc003syc.3. human.

Organism-specific databases

CTD

8935.

GeneCards

GC07M026706.

H-InvDB

HIX0025350.

HGNC

HGNC:15687. SKAP2.

HPA

HPA005560.
HPA024045.

MIM

605215. gene.

neXtProt

NX_O75563.

PharmGKB

PA162403393.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG46742.

HOGENOM

HOG000231109.

HOVERGEN

HBG052827.

InParanoid

O75563.

OMA

ETFVADT.

OrthoDB

EOG4ZKJMX.

PhylomeDB

O75563.

Enzyme and pathway databases

Reactome

REACT_111155. Cell-Cell communication.

Gene expression databases

ArrayExpress

O75563.

Bgee

O75563.

CleanEx

HS_SKAP2.

Genevestigator

O75563.

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

ChiTaRS

SKAP2. human.

GenomeRNAi

8935.

NextBio

33596.

SOURCE

Search...

Entry information

Entry name

SKAP2_HUMAN

Accession

Primary (citable) accession number: O75563
Secondary accession number(s): A4D173 , Q53GP6, Q75MK6, Q75MZ4, Q9UBZ3, Q9UED8

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 9, 2007
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 103 of the entry and version 1 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.