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Q9NP31

- SH22A_HUMAN

UniProt

Q9NP31 - SH22A_HUMAN

Protein

SH2 domain-containing protein 2A

Gene

SH2D2A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 130 (01 Oct 2014)
      Sequence version 3 (03 Apr 2007)
      Previous versions | rss
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    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

    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

    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.1 Publication

    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 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

    ArrayExpressiQ9NP31.
    BgeeiQ9NP31.
    CleanExiHS_SCAP.
    HS_SH2D2A.
    GenevestigatoriQ9NP31.

    Interactioni

    Subunit structurei

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

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini95 – 18692SH2PROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi244 – 2507SH3-bindingSequence Analysis
    Motifi272 – 2787SH3-bindingSequence Analysis

    Compositional bias

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

    Sequence similaritiesi

    Contains 1 SH2 domain.PROSITE-ProRule annotation

    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.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti42 – 443ASP → GIS in AAF69027. (PubMed:9468509)Curated
    Sequence conflicti111 – 1111P → S in AAV34675. (PubMed:10752626)Curated
    Sequence conflicti385 – 3851L → F in AAV34675. (PubMed:10752626)Curated

    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. 2 PublicationsVSP_003965Add
    BLAST
    Alternative sequencei1 – 2121MEFPL…PIPTF → MSP in isoform 4. 1 PublicationVSP_046378Add
    BLAST
    Alternative sequencei102 – 1021R → RRVRPPLSVTH in isoform 1. 1 PublicationVSP_003966

    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

    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: October 1, 2014
    This is version 130 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