Q3UND0 (SKAP2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Src kinase-associated phosphoprotein 2

Alternative name(s):
Pyk2/RAFTK-associated protein
SKAP55 homolog
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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	358 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.10 Ref.11
Subunit structure	Interacts with LAT, GRB2, PTK2B and PRAM1 By similarity. Homodimer. Interacts with FYB, which is required for SKAP2 protein stability. 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. May interact with FYN, HCK and LYN. Interacts with FASLG By similarity. Ref.1 Ref.7 Ref.8 Ref.10 Ref.13 Ref.15
Subcellular location	Cytoplasm. Note: Membrane ruffles of macrophages. Perikarya and dendrites from neurons. Ref.1 Ref.9 Ref.15
Tissue specificity	Expressed in kidney, lung, liver, spleen, bone marrow and testis. Present in T-cells, B-cells, and all cells of the myelomonocytic lineage. Present in all brain regions, with highest levels in neurons from the Purkinje cell layer, hippocampal gyrus, cortex and substantia nigra (at protein level). Ref.1 Ref.9 Ref.10 Ref.11
Induction	By IL-6 in myeloid cells. Ref.1
Domain	The SH3 domain interacts with FYB and PTK2B By similarity.
Post-translational modification	Dephosphorylated on Tyr-75 by PTPN22 By similarity. Phosphorylated by FYN on Tyr-260. In case of infection with Y.pseudotuberculosis, dephosphorylated by bacterial phosphatase yopH. Ref.1 Ref.7 Ref.10 Ref.12
Disruption phenotype	Mice are healthy and do not display any obvious abnormality. They have normal T-cell, platelet and macrophage function, but show reduced levels of spontaneous immunoglobulins in the serum, and defects in B-cell proliferation. Ref.11
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	Alternative splicing
Domain	SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	B cell activation Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell proliferation Inferred from mutant phenotype Ref.1. Source: MGI
Cellular_component	cytoplasm Inferred from direct assay Ref.1. Source: MGI plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q3UND0-1)

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: Q3UND0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     22-28: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 358

358

Src kinase-associated phosphoprotein 2

PRO_0000270180

Regions

Domain

116 – 219

104

PH

Domain

296 – 357

62

SH3

Region

14 – 64

51

Homodimerization

Amino acid modifications

Modified residue

75

1

Phosphotyrosine Ref.12 Ref.14

Modified residue

151

1

Phosphotyrosine Ref.14

Modified residue

197

1

Phosphotyrosine Ref.12

Modified residue

260

1

Phosphotyrosine; by FYN Ref.1 Ref.12 Ref.14

Natural variations

Alternative sequence

22 – 28

7

Missing in isoform 2.

VSP_022184

Experimental info

Mutagenesis

260

1

Y → F: Abolishes interaction with FYN, phosphorylation by FYN, and effects on cell growth. Ref.1

Sequence conflict

16

1

E → K in BAE25817. Ref.4

Sequence conflict

104

1

N → P AA sequence Ref.7

Secondary structure

1

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358

Helix Strand Turn

Details...

Helix

15 – 29

15

Turn

30 – 34

5

Helix

39 – 55

17

Helix

56 – 59

4

Helix

61 – 63

3

Helix

111 – 113

3

Beta strand

115 – 126

12

Beta strand

128 – 130

3

Turn

132 – 134

3

Beta strand

136 – 145

10

Beta strand

148 – 154

7

Beta strand

161 – 165

5

Beta strand

170 – 173

4

Helix

175 – 177

3

Helix

183 – 185

3

Beta strand

186 – 190

5

Beta strand

192 – 194

3

Beta strand

196 – 200

5

Helix

204 – 217

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 9, 2007. Version 2. Checksum: B66973A656E44E05	FASTA	358	40,712
	10 20 30 40 50 60 MPNPSCTSSP GPLPEEIRNL LADVETFVAD TLKGENLSKK AKEKRESLIK KIKDVKSVYL 70 80 90 100 110 120 QEFQDKGDAE DGDEYDDPFA GPADTISLAS ERYDKDDDGP SDGNQFPPIA AQDLPFVIKA 130 140 150 160 170 180 GYLEKRRKDH SFLGFEWQKR WCALSKTVFY YYGSDKDKQQ KGEFAIDGYD VRMNNTLRKD 190 200 210 220 230 240 GKKDCCFEIC APDKRIYQFT AASPKDAEEW VQQLKFILQD LGSDVIPEDD EERGELYDDV 250 260 270 280 290 300 DHPAAVSSPQ RSQPIDDEIY EELPEEEEDT ASVKMDEQGK GSRDSVHHTS GDKSTDYANF 310 320 330 340 350 YQGLWDCTGA LSDELSFKRG DVIYILSKEY NRYGWWVGEM KGAIGLVPKA YLMEMYDI
	Isoform 2 [UniParc]. Checksum: A6C08305272498D8	FASTA	351	39,950
	10 20 30 40 50 60 MPNPSCTSSP GPLPEEIRNL LADTLKGENL SKKAKEKRES LIKKIKDVKS VYLQEFQDKG 70 80 90 100 110 120 DAEDGDEYDD PFAGPADTIS LASERYDKDD DGPSDGNQFP PIAAQDLPFV IKAGYLEKRR 130 140 150 160 170 180 KDHSFLGFEW QKRWCALSKT VFYYYGSDKD KQQKGEFAID GYDVRMNNTL RKDGKKDCCF 190 200 210 220 230 240 EICAPDKRIY QFTAASPKDA EEWVQQLKFI LQDLGSDVIP EDDEERGELY DDVDHPAAVS 250 260 270 280 290 300 SPQRSQPIDD EIYEELPEEE EDTASVKMDE QGKGSRDSVH HTSGDKSTDY ANFYQGLWDC 310 320 330 340 350 TGALSDELSF KRGDVIYILS KEYNRYGWWV GEMKGAIGLV PKAYLMEMYD I

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Adaptor protein SKAP55R is associated with myeloid differentiation and growth arrest." Curtis D.J., Jane S.M., Hilton D.J., Dougherty L., Bodine D.M., Begley C.G. Exp. Hematol. 28:1250-1259(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INDUCTION, POSSIBLE INTERACTION WITH FYN; HCK AND LYN, PHOSPHORYLATION AT TYR-260, MUTAGENESIS OF TYR-260, FUNCTION. Tissue: Testis.
[2]	"Mouse Saps, 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] (ISOFORM 1). Tissue: Liver.
[3]	"RA70, retinoic acid responsive gene, is expressed specifically in spermatocyte in mouse testis." Momoi T., Urase K., Mukasa T., Fujita E., Kouroku Y., Miho Y., Soyama A., Momoi M.Y. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Testis.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Lymph node.
[5]	"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] (ISOFORMS 1 AND 2).
[6]	"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: PROTEIN SEQUENCE OF 1-12. Tissue: T-cell.
[7]	"The Yersinia tyrosine phosphatase YopH targets a novel adhesion-regulated signalling complex in macrophages." Black D.S., Marie-Cardine A., Schraven B., Bliska J.B. Cell. Microbiol. 2:401-414(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 93-114; 129-139 AND 147-158, PHOSPHORYLATION, INTERACTION WITH FYB, IDENTIFICATION IN A COMPLEX WITH FYB AND PTPNS1, IDENTIFICATION IN A COMPLEX WITH FYB AND LILRB3.
[8]	"SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-protein complexes in macrophages." Timms J.F., Swanson K.D., Marie-Cardine A., Raab M., Rudd C.E., Schraven B., Neel B.G. Curr. Biol. 9:927-930(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTPNS1, IDENTIFICATION IN A COMPLEX WITH FYB AND PTPNS1.
[9]	"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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[10]	"Macrophage colony-stimulating factor receptor induces tyrosine phosphorylation of SKAP55R adaptor and its association with actin." Bourette R.P., Therier J., Mouchiroud G. Cell. Signal. 17:941-949(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, PHOSPHORYLATION, INTERACTION WITH ACTIN, FUNCTION.
[11]	"Regulation of in vitro and in vivo immune functions by the cytosolic adaptor protein SKAP-HOM." Togni M., Swanson K.D., Reimann S., Kliche S., Pearce A.C., Simeoni L., Reinhold D., Wienands J., Neel B.G., Schraven B., Gerber A. Mol. Cell. Biol. 25:8052-8063(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[12]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-75; TYR-197 AND TYR-260, MASS SPECTROMETRY.
[13]	"ADAP is required for normal alphaIIb-beta3 activation by VWF/GP Ib-IX-V and other agonists." Kasirer-Friede A., Moran B., Nagrampa-Orje J., Swanson K., Ruggeri Z.M., Schraven B., Neel B.G., Koretzky G., Shattil S.J. Blood 109:1018-1025(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FYB.
[14]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-75; TYR-151 AND TYR-260, MASS SPECTROMETRY. Tissue: Mast cell.
[15]	"The Skap-hom dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch." Swanson K.D., Tang Y., Ceccarelli D.F., Poy F., Sliwa J.P., Neel B.G., Eck M.J. Mol. Cell 32:564-575(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 14-222, SUBUNIT, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF051324 mRNA. Translation: AAC99297.1.
AB014485 mRNA. Translation: BAA77253.1.
AK076000 mRNA. Translation: BAC36111.1.
AK144289 mRNA. Translation: BAE25817.1.
BC003711 mRNA. Translation: AAH03711.1.

IPI

IPI00131212.
IPI00817026.

RefSeq

NP_061243.1. NM_018773.2.

UniGene

Mm.221479.
Mm.392558.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1U5E	X-ray	2.60	A/B	14-222	[»]
1U5F	X-ray	1.90	A	111-248	[»]
1U5G	X-ray	2.10	A/B/C/D	103-222	[»]
2OTX	X-ray	2.60	A/B	14-222	[»]

ProteinModelPortal

Q3UND0.

SMR

Q3UND0. Positions 14-222, 303-358.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q3UND0. 1 interaction.

MINT

MINT-263820.

Proteomic databases

PaxDb

Q3UND0.

PRIDE

Q3UND0.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000078214; ENSMUSP00000077342; ENSMUSG00000059182.

GeneID

54353.

KEGG

mmu:54353.

UCSC

uc009bxv.1. mouse.
uc009bxw.1. mouse.

Organism-specific databases

CTD

8935.

MGI

MGI:1889206. Skap2.

Phylogenomic databases

eggNOG

NOG46742.

GeneTree

ENSGT00390000017856.

HOGENOM

HOG000231109.

HOVERGEN

HBG052827.

InParanoid

Q3UND0.

OMA

ETFVADT.

OrthoDB

EOG4ZKJMX.

Gene expression databases

Bgee

Q3UND0.

CleanEx

MM_SKAP2.

Genevestigator

Q3UND0.

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

Q3UND0.

NextBio

311138.

SOURCE

Search...

Entry information

Entry name

SKAP2_MOUSE

Accession

Primary (citable) accession number: Q3UND0
Secondary accession number(s): Q8BK74, Q9Z2K4

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 9, 2007
Last sequence update:	January 9, 2007
Last modified:	May 1, 2013
This is version 73 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program