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Protein

SH2 domain-containing protein 2A

Gene

SH2D2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

  • SH3/SH2 adaptor activity Source: ProtInc
  • SH3 domain binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processAngiogenesis, Differentiation

Enzyme and pathway databases

ReactomeiR-HSA-4420097. VEGFA-VEGFR2 Pathway.
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
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000027869.11.
HGNCiHGNC:10821. SH2D2A.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi9047.
OpenTargetsiENSG00000027869.
PharmGKBiPA35729.

Chemistry databases

ChEMBLiCHEMBL3217401.

Polymorphism and mutation databases

BioMutaiSH2D2A.
DMDMi143811460.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000977261 – 389SH2 domain-containing protein 2AAdd BLAST389

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei217PhosphoserineCombined sources1
Modified residuei296PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on tyrosine residues.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9NP31.
PaxDbiQ9NP31.
PeptideAtlasiQ9NP31.
PRIDEiQ9NP31.

PTM databases

iPTMnetiQ9NP31.
PhosphoSitePlusiQ9NP31.

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 PubMed:10692392, 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

BgeeiENSG00000027869.
CleanExiHS_SCAP.
HS_SH2D2A.
GenevisibleiQ9NP31. HS.

Interactioni

Subunit structurei

Interacts with KDR. Interacts with TXK and ITK (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

  • SH3/SH2 adaptor activity Source: ProtInc
  • SH3 domain binding Source: UniProtKB-KW

Protein-protein interaction databases

BioGridi114509. 36 interactors.
IntActiQ9NP31. 36 interactors.
MINTiMINT-1494397.
STRINGi9606.ENSP00000376123.

Structurei

3D structure databases

ProteinModelPortaliQ9NP31.
SMRiQ9NP31.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini95 – 186SH2Add BLAST92

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi244 – 250SH3-bindingSequence analysis7
Motifi272 – 278SH3-bindingSequence analysis7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi187 – 389Pro-richAdd BLAST203

Keywords - Domaini

SH2 domain, SH3-binding

Phylogenomic databases

eggNOGiENOG410IVEH. Eukaryota.
ENOG4111Y35. LUCA.
GeneTreeiENSGT00570000079047.
HOGENOMiHOG000008700.
HOVERGENiHBG055180.
InParanoidiQ9NP31.
KOiK08273.
OMAiTCCRHFL.
OrthoDBiEOG091G0FTD.
PhylomeDBiQ9NP31.
TreeFamiTF336893.

Family and domain databases

CDDicd10416. SH2_SH2D2A. 1 hit.
Gene3Di3.30.505.10. 1 hit.
InterProiView protein in InterPro
IPR000980. SH2.
IPR036860. SH2_dom_sf.
IPR035884. SH2D2A_SH2.
PfamiView protein in Pfam
PF00017. SH2. 1 hit.
PRINTSiPR00401. SH2DOMAIN.
SMARTiView protein in SMART
SM00252. SH2. 1 hit.
SUPFAMiSSF55550. SSF55550. 1 hit.
PROSITEiView protein in PROSITE
PS50001. SH2. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

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

        10         20         30         40         50
MEFPLAQICP QGSHEAPIPT FSTFQITDMT RRSCQNLGYT AASPQAPEAA
60 70 80 90 100
SNTGNAERAE EVPGEGSLFL QAETRAWFQK TQAHWLLQHG AAPAWFHGFI
110 120 130 140 150
TRREAERLLE PKPQGCYLVR FSESAVTFVL TYRSRTCCRH FLLAQLRDGR
160 170 180 190 200
HVVLGEDSAH ARLQDLLLHY TAHPLSPYGE TLTEPLARQT PEPAGLSLRT
210 220 230 240 250
EESNFGSKSQ DPNPQYSPII KQGQAPVPMQ KEGAGEKEPS QLLRPKPPIP
260 270 280 290 300
AKPQLPPEVY TIPVPRHRPA PRPKPSNPIY NEPDEPIAFY AMGRGSPGEA
310 320 330 340 350
PSNIYVEVED EGLPATLGHP VLRKSWSRPV PGGQNTGGSQ LHSENSVIGQ
360 370 380
GPPLPHQPPP AWRHTLPHNL SRQVLQDRGQ AWLPLGPPQ
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 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti42 – 44ASP → GIS in AAF69027 (PubMed:9468509).Curated3
Sequence conflicti111P → S in AAV34675 (PubMed:10752626).Curated1
Sequence conflicti385L → F in AAV34675 (PubMed:10752626).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02434952N → SCombined sources5 PublicationsCorresponds to variant dbSNP:rs926103Ensembl.1
Natural variantiVAR_056986272R → C. Corresponds to variant dbSNP:rs12072861Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0039651 – 28Missing in isoform 3. 2 PublicationsAdd BLAST28
Alternative sequenceiVSP_0463781 – 21MEFPL…PIPTF → MSP in isoform 4. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_003966102R → RRVRPPLSVTH in isoform 1. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
UCSCiuc001fqd.3. human. [Q9NP31-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSH22A_HUMAN
AccessioniPrimary (citable) accession number: Q9NP31
Secondary accession number(s): O43817
, Q5UBZ1, Q5VZS4, Q5VZS5, Q9UPA7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: April 3, 2007
Last modified: October 25, 2017
This is version 156 of the entry and version 3 of the sequence. See 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