Q9NP31 (SH22A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
SH2 domain-containing protein 2A

Alternative name(s):
SH2 domain-containing adapter protein
T cell-specific adapter protein
Short name=TSAd
VEGF receptor-associated protein

Gene names

Name:	SH2D2A
Synonyms:	SCAP, TSAD, VRAP

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	389 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Could be a T-cell-specific adapter protein involved in the control of T-cell activation. May play a role in the CD4-p56-LCK-dependent signal transduction pathway. Could also play an important role in normal and pathological angiogenesis. Could be an adapter protein that facilitates and regulates interaction of KDR with effector proteins important to endothelial cell survival and proliferation.
Subunit structure	Interacts with KDR. Interacts with TXK and ITK By similarity. Ref.3 Ref.8
Subcellular location	Cytoplasm.
Tissue specificity	Expression limited to tissues of the immune system and, in particular, activated T-cells. Expressed in peripheral blood leukocytes, thymus and spleen. Much lower expression or undetectable, in brain, placenta, skeletal muscle, prostate, testis, ovary, small intestine, and colon. Expressed at low levels in unstimulated T-cells, but not expressed in normal resting or activated B-cells. According to Ref.3, expression is not restricted to activated T-cells, but strongly expressed in blood cell lineages, the endothelium and other cell and tissue types, such as heart, lung, and liver.
Induction	Rapidly induced after activation of T-cells. However, the gene continues to be expressed in long-term cultures of activated T-cells.
Post-translational modification	Phosphorylated on tyrosine residues.
Sequence similarities	Contains 1 SH2 domain.
Sequence caution	The sequence AAC99298.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Angiogenesis Differentiation
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH2 domain SH3-binding
Molecular function	Developmental protein
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytoplasm Traceable author statement Ref.1. Source: ProtInc
Molecular_function	SH3/SH2 adaptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: Q9NP31-1)

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 1 (identifier: Q9NP31-2)

The sequence of this isoform differs from the canonical sequence as follows:
     102-102: R → RRVRPPLSVTH

Isoform 3 (identifier: Q9NP31-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: Missing.

Isoform 4 (identifier: Q9NP31-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: MEFPLAQICPQGSHEAPIPTF → MSP

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 389	389	SH2 domain-containing protein 2A		PRO_0000097726
Regions
	Domain	95 – 186	92	SH2
	Motif	244 – 250	7	SH3-binding Potential
	Motif	272 – 278	7	SH3-binding Potential
	Compositional bias	187 – 389	203	Pro-rich
Amino acid modifications
	Modified residue	217	1	Phosphoserine Ref.9
	Modified residue	296	1	Phosphoserine Ref.9
Natural variations
	Alternative sequence	1 – 28	28	Missing in isoform 3.		VSP_003965
	Alternative sequence	1 – 21	21	MEFPL…PIPTF → MSP in isoform 4.		VSP_046378
	Alternative sequence	102	1	R → RRVRPPLSVTH in isoform 1.		VSP_003966
	Natural variant	52	1	N → S. Ref.1 Ref.2 Ref.3 Ref.4 Ref.7 Ref.10 Corresponds to variant rs926103 [ dbSNP | Ensembl ].		VAR_024349
	Natural variant	272	1	R → C. Corresponds to variant rs12072861 [ dbSNP | Ensembl ].		VAR_056986
Experimental info
	Sequence conflict	42 – 44	3	ASP → GIS in AAF69027. Ref.1
	Sequence conflict	111	1	P → S in AAV34675. Ref.2
	Sequence conflict	385	1	L → F in AAV34675. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified April 3, 2007. Version 3. Checksum: 986670BE084072CB	FASTA	389	42,934
	10 20 30 40 50 60 MEFPLAQICP QGSHEAPIPT FSTFQITDMT RRSCQNLGYT AASPQAPEAA SNTGNAERAE 70 80 90 100 110 120 EVPGEGSLFL QAETRAWFQK TQAHWLLQHG AAPAWFHGFI TRREAERLLE PKPQGCYLVR 130 140 150 160 170 180 FSESAVTFVL TYRSRTCCRH FLLAQLRDGR HVVLGEDSAH ARLQDLLLHY TAHPLSPYGE 190 200 210 220 230 240 TLTEPLARQT PEPAGLSLRT EESNFGSKSQ DPNPQYSPII KQGQAPVPMQ KEGAGEKEPS 250 260 270 280 290 300 QLLRPKPPIP AKPQLPPEVY TIPVPRHRPA PRPKPSNPIY NEPDEPIAFY AMGRGSPGEA 310 320 330 340 350 360 PSNIYVEVED EGLPATLGHP VLRKSWSRPV PGGQNTGGSQ LHSENSVIGQ GPPLPHQPPP 370 380 AWRHTLPHNL SRQVLQDRGQ AWLPLGPPQ
	Isoform 1 [UniParc]. Checksum: C3A455062629C26F	FASTA	399	44,078
	10 20 30 40 50 60 MEFPLAQICP QGSHEAPIPT FSTFQITDMT RRSCQNLGYT AASPQAPEAA SNTGNAERAE 70 80 90 100 110 120 EVPGEGSLFL QAETRAWFQK TQAHWLLQHG AAPAWFHGFI TRRVRPPLSV THREAERLLE 130 140 150 160 170 180 PKPQGCYLVR FSESAVTFVL TYRSRTCCRH FLLAQLRDGR HVVLGEDSAH ARLQDLLLHY 190 200 210 220 230 240 TAHPLSPYGE TLTEPLARQT PEPAGLSLRT EESNFGSKSQ DPNPQYSPII KQGQAPVPMQ 250 260 270 280 290 300 KEGAGEKEPS QLLRPKPPIP AKPQLPPEVY TIPVPRHRPA PRPKPSNPIY NEPDEPIAFY 310 320 330 340 350 360 AMGRGSPGEA PSNIYVEVED EGLPATLGHP VLRKSWSRPV PGGQNTGGSQ LHSENSVIGQ 370 380 390 GPPLPHQPPP AWRHTLPHNL SRQVLQDRGQ AWLPLGPPQ
	Isoform 3 [UniParc]. Checksum: 991632B13333CD4E	FASTA	361	39,846
	10 20 30 40 50 60 MTRRSCQNLG YTAASPQAPE AASNTGNAER AEEVPGEGSL FLQAETRAWF QKTQAHWLLQ 70 80 90 100 110 120 HGAAPAWFHG FITRREAERL LEPKPQGCYL VRFSESAVTF VLTYRSRTCC RHFLLAQLRD 130 140 150 160 170 180 GRHVVLGEDS AHARLQDLLL HYTAHPLSPY GETLTEPLAR QTPEPAGLSL RTEESNFGSK 190 200 210 220 230 240 SQDPNPQYSP IIKQGQAPVP MQKEGAGEKE PSQLLRPKPP IPAKPQLPPE VYTIPVPRHR 250 260 270 280 290 300 PAPRPKPSNP IYNEPDEPIA FYAMGRGSPG EAPSNIYVEV EDEGLPATLG HPVLRKSWSR 310 320 330 340 350 360 PVPGGQNTGG SQLHSENSVI GQGPPLPHQP PPAWRHTLPH NLSRQVLQDR GQAWLPLGPP Q
	Isoform 4 [UniParc]. Checksum: 02ACD0D38DA6EB22	FASTA	371	40,954
	10 20 30 40 50 60 MSPSTFQITD MTRRSCQNLG YTAASPQAPE AASNTGNAER AEEVPGEGSL FLQAETRAWF 70 80 90 100 110 120 QKTQAHWLLQ HGAAPAWFHG FITRREAERL LEPKPQGCYL VRFSESAVTF VLTYRSRTCC 130 140 150 160 170 180 RHFLLAQLRD GRHVVLGEDS AHARLQDLLL HYTAHPLSPY GETLTEPLAR QTPEPAGLSL 190 200 210 220 230 240 RTEESNFGSK SQDPNPQYSP IIKQGQAPVP MQKEGAGEKE PSQLLRPKPP IPAKPQLPPE 250 260 270 280 290 300 VYTIPVPRHR PAPRPKPSNP IYNEPDEPIA FYAMGRGSPG EAPSNIYVEV EDEGLPATLG 310 320 330 340 350 360 HPVLRKSWSR PVPGGQNTGG SQLHSENSVI GQGPPLPHQP PPAWRHTLPH NLSRQVLQDR 370 GQAWLPLGPP Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a T cell-specific adapter protein (TSAd) containing an Src homology (SH) 2 domain and putative SH3 and phosphotyrosine binding sites." Spurkland A., Brinchmann J.E., Markussen G., Pedeutour F., Munthe E., Lea T., Vartdal F., Aasheim H.-C. J. Biol. Chem. 273:4539-4546(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), VARIANT SER-52. Tissue: T-cell.
[2]	"The SH2D2A gene encoding the T-cell-specific adapter protein (TSAd) is localized centromeric to the CD1 gene cluster on human Chromosome 1." Dai K.Z., Vergnaud G., Ando A., Inoko H., Spurkland A. Immunogenetics 51:179-185(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), ALTERNATIVE SPLICING, VARIANT SER-52.
[3]	"VRAP is an adaptor protein that binds KDR, a receptor for vascular endothelial cell growth factor." Wu L.-W., Mayo L.D., Dunbar J.D., Kessler K.M., Ozes O.N., Warren R.S., Donner D.B. J. Biol. Chem. 275:6059-6062(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH KDR, VARIANT SER-52. Tissue: B-cell.
[4]	Lee J.-S., Suh K.S., Burr J.G. Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), VARIANT SER-52. Tissue: B-cell.
[5]	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: Dermoid cancer.
[6]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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), VARIANT SER-52. Tissue: Lung.
[8]	"VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis." Matsumoto T., Bohman S., Dixelius J., Berge T., Dimberg A., Magnusson P., Wang L., Wikner C., Qi J.H., Wernstedt C., Wu J., Bruheim S., Mugishima H., Mukhopadhyay D., Spurkland A., Claesson-Welsh L. EMBO J. 24:2342-2353(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KDR.
[9]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-217 AND SER-296, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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: VARIANT [LARGE SCALE ANALYSIS] SER-52, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF106072 Genomic DNA. Translation: AAF69027.1. AJ000553 mRNA. Translation: CAA04185.1. AY763100 mRNA. Translation: AAV34675.1. AF097744 mRNA. Translation: AAF43260.1. AF051325 mRNA. Translation: AAC99298.1. Different initiation. AK222737 mRNA. Translation: BAD96457.1. AL158169, AL590666 Genomic DNA. Translation: CAH70007.1. AL158169, AL590666 Genomic DNA. Translation: CAH70008.1. AL590666, AL158169 Genomic DNA. Translation: CAI16336.1. AL590666, AL158169 Genomic DNA. Translation: CAI16337.1. BC012107 mRNA. Translation: AAH12107.1.
IPI	IPI00099806. IPI00220388. IPI00220389. IPI00936634.
RefSeq	NP_001154914.1. NM_001161442.1. NP_001154916.1. NM_001161444.1. NP_003966.2. NM_003975.3.
UniGene	Hs.103527.
3D structure databases
ProteinModelPortal	Q9NP31.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NP31. 3 interactions.
MINT	MINT-1494397.
STRING	9606.ENSP00000357182.
PTM databases
PhosphoSite	Q9NP31.
Polymorphism databases
DMDM	143811460.
Proteomic databases
PaxDb	Q9NP31.
PRIDE	Q9NP31.
Protocols and materials databases
DNASU	9047.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368198; ENSP00000357181; ENSG00000027869. ENST00000368199; ENSP00000357182; ENSG00000027869. ENST00000392306; ENSP00000376123; ENSG00000027869.
GeneID	9047.
KEGG	hsa:9047.
UCSC	uc001fqc.1. human. uc009wsh.2. human.
Organism-specific databases
CTD	9047.
GeneCards	GC01M156776.
HGNC	HGNC:10821. SH2D2A.
MIM	604514. gene.
neXtProt	NX_Q9NP31.
PharmGKB	PA35729.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG82159.
HOGENOM	HOG000008700.
HOVERGEN	HBG055180.
KO	K08273.
OMA	EAPSNIY.
OrthoDB	EOG4M0F25.
PhylomeDB	Q9NP31.
Enzyme and pathway databases
Pathway_Interaction_DB	vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
Gene expression databases
ArrayExpress	Q9NP31.
Bgee	Q9NP31.
CleanEx	HS_SCAP. HS_SH2D2A.
Genevestigator	Q9NP31.
GermOnline	ENSG00000027869. Homo sapiens.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR000980. SH2. [Graphical view]
Pfam	PF00017. SH2. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN.
SMART	SM00252. SH2. 1 hit. [Graphical view]
PROSITE	PS50001. SH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	9047.
NextBio	33889.
SOURCE	Search...

Entry information

Entry name

SH22A_HUMAN

Accession

Primary (citable) accession number: Q9NP31
Secondary accession number(s): O43817 , Q5UBZ1, Q5VZS4, Q5VZS5, Q9UPA7

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	April 3, 2007
Last modified:	May 1, 2013
This is version 117 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.