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Q9NP31 (SH22A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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:
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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length389 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 389389SH2 domain-containing protein 2A
PRO_0000097726

Regions

Domain95 – 18692SH2
Motif244 – 2507SH3-binding Potential
Motif272 – 2787SH3-binding Potential
Compositional bias187 – 389203Pro-rich

Amino acid modifications

Modified residue2171Phosphoserine Ref.9
Modified residue2961Phosphoserine Ref.9

Natural variations

Alternative sequence1 – 2828Missing in isoform 3.
VSP_003965
Alternative sequence1 – 2121MEFPL…PIPTF → MSP in isoform 4.
VSP_046378
Alternative sequence1021R → RRVRPPLSVTH in isoform 1.
VSP_003966
Natural variant521N → S. Ref.1 Ref.2 Ref.3 Ref.4 Ref.7 Ref.10
Corresponds to variant rs926103 [ dbSNP | Ensembl ].
VAR_024349
Natural variant2721R → C.
Corresponds to variant rs12072861 [ dbSNP | Ensembl ].
VAR_056986

Experimental info

Sequence conflict42 – 443ASP → GIS in AAF69027. Ref.1
Sequence conflict1111P → S in AAV34675. Ref.2
Sequence conflict3851L → F in AAV34675. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 [UniParc].

Last modified April 3, 2007. Version 3.
Checksum: 986670BE084072CB

FASTA38942,934
        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 

« Hide

Isoform 1 [UniParc].

Checksum: C3A455062629C26F
Show »

FASTA39944,078
Isoform 3 [UniParc].

Checksum: 991632B13333CD4E
Show »

FASTA36139,846
Isoform 4 [UniParc].

Checksum: 02ACD0D38DA6EB22
Show »

FASTA37140,954

References

« Hide '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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+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.
CCDSCCDS1159.1. [Q9NP31-1]
CCDS53380.1. [Q9NP31-4]
CCDS53381.1. [Q9NP31-2]
RefSeqNP_001154914.1. NM_001161442.1. [Q9NP31-4]
NP_001154916.1. NM_001161444.1. [Q9NP31-1]
NP_003966.2. NM_003975.3. [Q9NP31-1]
UniGeneHs.103527.

3D structure databases

ProteinModelPortalQ9NP31.
SMRQ9NP31. Positions 87-214.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114509. 7 interactions.
IntActQ9NP31. 10 interactions.
MINTMINT-1494397.
STRING9606.ENSP00000357182.

PTM databases

PhosphoSiteQ9NP31.

Polymorphism databases

DMDM143811460.

Proteomic databases

MaxQBQ9NP31.
PaxDbQ9NP31.
PRIDEQ9NP31.

Protocols and materials databases

DNASU9047.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368198; ENSP00000357181; ENSG00000027869. [Q9NP31-4]
ENST00000368199; ENSP00000357182; ENSG00000027869. [Q9NP31-1]
ENST00000392306; ENSP00000376123; ENSG00000027869. [Q9NP31-2]
GeneID9047.
KEGGhsa:9047.
UCSCuc001fqc.1. human. [Q9NP31-1]
uc009wsh.2. human. [Q9NP31-2]

Organism-specific databases

CTD9047.
GeneCardsGC01M156776.
HGNCHGNC:10821. SH2D2A.
MIM604514. gene.
neXtProtNX_Q9NP31.
PharmGKBPA35729.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG82159.
HOGENOMHOG000008700.
HOVERGENHBG055180.
KOK08273.
OMARGQAWLP.
OrthoDBEOG7H793D.
PhylomeDBQ9NP31.
TreeFamTF336893.

Enzyme and pathway databases

SignaLinkQ9NP31.

Gene expression databases

ArrayExpressQ9NP31.
BgeeQ9NP31.
CleanExHS_SCAP.
HS_SH2D2A.
GenevestigatorQ9NP31.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR000980. SH2.
[Graphical view]
PfamPF00017. SH2. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
SMARTSM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSH2D2A.
GenomeRNAi9047.
NextBio33889.
PROQ9NP31.
SOURCESearch...

Entry information

Entry nameSH22A_HUMAN
AccessionPrimary (citable) accession number: Q9NP31
Secondary accession number(s): O43817 expand/collapse secondary AC list , Q5UBZ1, Q5VZS4, Q5VZS5, Q9UPA7
Entry history
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: April 3, 2007
Last modified: July 9, 2014
This is version 129 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

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 1

Human chromosome 1: entries, gene names and cross-references to MIM