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Q9NP31

- SH22A_HUMAN

UniProt

Q9NP31 - SH22A_HUMAN

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Protein

SH2 domain-containing protein 2A

Gene
SH2D2A, SCAP, TSAD, VRAP
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  1. protein binding Source: IntAct
  2. SH3/SH2 adaptor activity Source: ProtInc

GO - Biological processi

  1. angiogenesis Source: UniProtKB-KW
  2. cell differentiation Source: UniProtKB-KW
  3. cell proliferation Source: Ensembl
  4. positive regulation of signal transduction Source: GOC
  5. signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Angiogenesis, Differentiation

Enzyme and pathway databases

SignaLinkiQ9NP31.

Names & Taxonomyi

Protein namesi
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 namesi
Name:SH2D2A
Synonyms:SCAP, TSAD, VRAP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:10821. SH2D2A.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35729.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 389389SH2 domain-containing protein 2APRO_0000097726Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei217 – 2171Phosphoserine1 Publication
Modified residuei296 – 2961Phosphoserine1 Publication

Post-translational modificationi

Phosphorylated on tyrosine residues.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9NP31.
PaxDbiQ9NP31.
PRIDEiQ9NP31.

PTM databases

PhosphoSiteiQ9NP31.

Expressioni

Tissue specificityi

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 1 Publication, 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.

Inductioni

Rapidly induced after activation of T-cells. However, the gene continues to be expressed in long-term cultures of activated T-cells.

Gene expression databases

ArrayExpressiQ9NP31.
BgeeiQ9NP31.
CleanExiHS_SCAP.
HS_SH2D2A.
GenevestigatoriQ9NP31.

Interactioni

Subunit structurei

Interacts with KDR. Interacts with TXK and ITK By similarity.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARP102756EBI-490630,EBI-608057
ERBB2P046262EBI-490630,EBI-641062
GAB1Q134806EBI-490630,EBI-517684
KITP1072110EBI-490630,EBI-1379503
LCKP0623912EBI-490630,EBI-1348
METP085817EBI-490630,EBI-1039152

Protein-protein interaction databases

BioGridi114509. 7 interactions.
IntActiQ9NP31. 10 interactions.
MINTiMINT-1494397.
STRINGi9606.ENSP00000357182.

Structurei

3D structure databases

ProteinModelPortaliQ9NP31.
SMRiQ9NP31. Positions 87-214.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini95 – 18692SH2Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi244 – 2507SH3-binding Reviewed prediction
Motifi272 – 2787SH3-binding Reviewed prediction

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi187 – 389203Pro-richAdd
BLAST

Sequence similaritiesi

Contains 1 SH2 domain.

Keywords - Domaini

SH2 domain, SH3-binding

Phylogenomic databases

eggNOGiNOG82159.
HOGENOMiHOG000008700.
HOVERGENiHBG055180.
KOiK08273.
OMAiRGQAWLP.
OrthoDBiEOG7H793D.
PhylomeDBiQ9NP31.
TreeFamiTF336893.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 2 (identifier: Q9NP31-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MEFPLAQICP QGSHEAPIPT FSTFQITDMT RRSCQNLGYT AASPQAPEAA    50
SNTGNAERAE EVPGEGSLFL QAETRAWFQK TQAHWLLQHG AAPAWFHGFI 100
TRREAERLLE PKPQGCYLVR FSESAVTFVL TYRSRTCCRH FLLAQLRDGR 150
HVVLGEDSAH ARLQDLLLHY TAHPLSPYGE TLTEPLARQT PEPAGLSLRT 200
EESNFGSKSQ DPNPQYSPII KQGQAPVPMQ KEGAGEKEPS QLLRPKPPIP 250
AKPQLPPEVY TIPVPRHRPA PRPKPSNPIY NEPDEPIAFY AMGRGSPGEA 300
PSNIYVEVED EGLPATLGHP VLRKSWSRPV PGGQNTGGSQ LHSENSVIGQ 350
GPPLPHQPPP AWRHTLPHNL SRQVLQDRGQ AWLPLGPPQ 389
Length:389
Mass (Da):42,934
Last modified:April 3, 2007 - v3
Checksum:i986670BE084072CB
GO
Isoform 1 (identifier: Q9NP31-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:399
Mass (Da):44,078
Checksum:iC3A455062629C26F
GO
Isoform 3 (identifier: Q9NP31-3) [UniParc]FASTAAdd to Basket

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

Show »
Length:361
Mass (Da):39,846
Checksum:i991632B13333CD4E
GO
Isoform 4 (identifier: Q9NP31-4) [UniParc]FASTAAdd to Basket

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

Show »
Length:371
Mass (Da):40,954
Checksum:i02ACD0D38DA6EB22
GO

Sequence cautioni

The sequence AAC99298.1 differs from that shown. Reason: Erroneous initiation.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti52 – 521N → S.6 Publications
Corresponds to variant rs926103 [ dbSNP | Ensembl ].
VAR_024349
Natural varianti272 – 2721R → C.
Corresponds to variant rs12072861 [ dbSNP | Ensembl ].
VAR_056986

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2828Missing in isoform 3. VSP_003965Add
BLAST
Alternative sequencei1 – 2121MEFPL…PIPTF → MSP in isoform 4. VSP_046378Add
BLAST
Alternative sequencei102 – 1021R → RRVRPPLSVTH in isoform 1. VSP_003966

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti42 – 443ASP → GIS in AAF69027. 1 Publication
Sequence conflicti111 – 1111P → S in AAV34675. 1 Publication
Sequence conflicti385 – 3851L → F in AAV34675. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS1159.1. [Q9NP31-1]
CCDS53380.1. [Q9NP31-4]
CCDS53381.1. [Q9NP31-2]
RefSeqiNP_001154914.1. NM_001161442.1. [Q9NP31-4]
NP_001154916.1. NM_001161444.1. [Q9NP31-1]
NP_003966.2. NM_003975.3. [Q9NP31-1]
UniGeneiHs.103527.

Genome annotation databases

EnsembliENST00000368198; ENSP00000357181; ENSG00000027869. [Q9NP31-4]
ENST00000368199; ENSP00000357182; ENSG00000027869. [Q9NP31-1]
ENST00000392306; ENSP00000376123; ENSG00000027869. [Q9NP31-2]
GeneIDi9047.
KEGGihsa:9047.
UCSCiuc001fqc.1. human. [Q9NP31-1]
uc009wsh.2. human. [Q9NP31-2]

Polymorphism databases

DMDMi143811460.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS1159.1. [Q9NP31-1 ]
CCDS53380.1. [Q9NP31-4 ]
CCDS53381.1. [Q9NP31-2 ]
RefSeqi NP_001154914.1. NM_001161442.1. [Q9NP31-4 ]
NP_001154916.1. NM_001161444.1. [Q9NP31-1 ]
NP_003966.2. NM_003975.3. [Q9NP31-1 ]
UniGenei Hs.103527.

3D structure databases

ProteinModelPortali Q9NP31.
SMRi Q9NP31. Positions 87-214.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114509. 7 interactions.
IntActi Q9NP31. 10 interactions.
MINTi MINT-1494397.
STRINGi 9606.ENSP00000357182.

PTM databases

PhosphoSitei Q9NP31.

Polymorphism databases

DMDMi 143811460.

Proteomic databases

MaxQBi Q9NP31.
PaxDbi Q9NP31.
PRIDEi Q9NP31.

Protocols and materials databases

DNASUi 9047.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000368198 ; ENSP00000357181 ; ENSG00000027869 . [Q9NP31-4 ]
ENST00000368199 ; ENSP00000357182 ; ENSG00000027869 . [Q9NP31-1 ]
ENST00000392306 ; ENSP00000376123 ; ENSG00000027869 . [Q9NP31-2 ]
GeneIDi 9047.
KEGGi hsa:9047.
UCSCi uc001fqc.1. human. [Q9NP31-1 ]
uc009wsh.2. human. [Q9NP31-2 ]

Organism-specific databases

CTDi 9047.
GeneCardsi GC01M156776.
HGNCi HGNC:10821. SH2D2A.
MIMi 604514. gene.
neXtProti NX_Q9NP31.
PharmGKBi PA35729.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG82159.
HOGENOMi HOG000008700.
HOVERGENi HBG055180.
KOi K08273.
OMAi RGQAWLP.
OrthoDBi EOG7H793D.
PhylomeDBi Q9NP31.
TreeFami TF336893.

Enzyme and pathway databases

SignaLinki Q9NP31.

Miscellaneous databases

GeneWikii SH2D2A.
GenomeRNAii 9047.
NextBioi 33889.
PROi Q9NP31.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9NP31.
Bgeei Q9NP31.
CleanExi HS_SCAP.
HS_SH2D2A.
Genevestigatori Q9NP31.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR000980. SH2.
[Graphical view ]
Pfami PF00017. SH2. 1 hit.
[Graphical view ]
PRINTSi PR00401. SH2DOMAIN.
SMARTi SM00252. SH2. 1 hit.
[Graphical view ]
SUPFAMi SSF55550. SSF55550. 1 hit.
PROSITEi PS50001. SH2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: INTERACTION WITH KDR.
  9. 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].

Entry informationi

Entry nameiSH22A_HUMAN
AccessioniPrimary (citable) accession number: Q9NP31
Secondary accession number(s): O43817
, Q5UBZ1, Q5VZS4, Q5VZS5, Q9UPA7
Entry historyi
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 statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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