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O14492

- SH2B2_HUMAN

UniProt

O14492 - SH2B2_HUMAN

Protein

SH2B adapter protein 2

Gene

SH2B2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 2 (23 Sep 2008)
      Previous versions | rss
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    Functioni

    Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways. May be involved in coupling from immunoreceptor to Ras signaling. Acts as a negative regulator of cytokine signaling in collaboration with CBL. Binds to EPOR and suppresses EPO-induced STAT5 activation, possibly through a masking effect on STAT5 docking sites in EPOR. Suppresses PDGF-induced mitogenesis. May induce cytoskeletal reorganization via interaction with VAV3.4 Publications

    GO - Molecular functioni

    1. JAK pathway signal transduction adaptor activity Source: UniProtKB
    2. protein binding Source: IntAct
    3. SH3/SH2 adaptor activity Source: UniProtKB
    4. signal transducer activity Source: InterPro

    GO - Biological processi

    1. blood coagulation Source: Reactome
    2. insulin receptor signaling pathway Source: BHF-UCL
    3. intracellular signal transduction Source: UniProtKB
    4. positive regulation of signal transduction Source: GOC
    5. regulation of JAK-STAT cascade Source: GOC
    6. signal transduction Source: ProtInc

    Enzyme and pathway databases

    ReactomeiREACT_111225. Regulation of KIT signaling.
    REACT_24970. Factors involved in megakaryocyte development and platelet production.
    SignaLinkiO14492.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    SH2B adapter protein 2
    Alternative name(s):
    Adapter protein with pleckstrin homology and Src homology 2 domains
    SH2 and PH domain-containing adapter protein APS
    Gene namesi
    Name:SH2B2
    Synonyms:APS
    OrganismiHomo sapiens (Human)Imported
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:17381. SH2B2.

    Subcellular locationi

    Cytoplasm 1 Publication. Cell membrane 1 Publication
    Note: Cytoplasmic before PDGF stimulation. After PDGF stimulation, localized at the cell membrane and peripheral region.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: Reactome
    3. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA145148106.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 632632SH2B adapter protein 2PRO_0000064647Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei629 – 6291Phosphotyrosine1 Publication

    Post-translational modificationi

    Tyrosine phosphorylated by JAK2, KIT and other kinases activated by B-cell receptor in response to stimulation with cytokines, IL3, IL5, PDGF, IGF1, IGF2, CSF2/GM-CSF and cross-linking of the B-cell receptor complex.By similarity3 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO14492.
    PaxDbiO14492.
    PRIDEiO14492.

    PTM databases

    PhosphoSiteiO14492.

    Expressioni

    Tissue specificityi

    Expressed in spleen, prostate, testis, uterus, small intestine and skeletal muscle. Among hematopoietic cell lines, expressed exclusively in B-cells. Not expressed in most tumor cell lines.2 Publications

    Gene expression databases

    ArrayExpressiO14492.
    BgeeiO14492.
    CleanExiHS_SH2B2.
    GenevestigatoriO14492.

    Organism-specific databases

    HPAiHPA051131.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with KIT/c-KIT, SHC1, EPOR, PDGFR, VAV1 and VAV3. Interacts (via N-terminal region) with SHC1. Interacts (via the phosphorylated C-terminus) with GRB2. Interacts (via its SH2 domain) with EPOR, INSR and KIT. Interacts with GRB2 after B-cell antigen receptor stimulation. Interacts (via PH domain) with VAV3. Interacts with NTRK1, NTRK2 and NTRK3 (phosphorylated); after stimulation of the receptor by its extracellular ligand and subsequent autophosphorylation of the receptor. Binds INSR, GRB2, ASB6 and CAP. Insulin stimulation leads to dissociation of CAP. Binds CBS only when SH2B2/APS has become phosphorylated. INSR binding does not depend on the phosphorylation of SH2B2/APS By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CBLP226817EBI-7507432,EBI-518228

    Protein-protein interaction databases

    BioGridi115850. 13 interactions.
    IntActiO14492. 5 interactions.
    MINTiMINT-1498797.
    STRINGi9606.ENSP00000304701.

    Structurei

    Secondary structure

    1
    632
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi23 – 4826
    Helixi50 – 523
    Helixi57 – 8226

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1Q2HX-ray1.70A/B/C21-85[»]
    ProteinModelPortaliO14492.
    SMRiO14492. Positions 21-83, 182-310, 410-494.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO14492.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini193 – 306114PHCuratedPROSITE-ProRule annotationAdd
    BLAST
    Domaini417 – 51599SH2CuratedPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the SH2B adapter family.Curated
    Contains 1 PH domain.CuratedPROSITE-ProRule annotation
    Contains 1 SH2 domain.CuratedPROSITE-ProRule annotation

    Keywords - Domaini

    SH2 domain

    Phylogenomic databases

    eggNOGiNOG77816.
    HOGENOMiHOG000047355.
    HOVERGENiHBG006707.
    KOiK07193.
    OMAiCVGSSQW.
    PhylomeDBiO14492.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    3.30.505.10. 1 hit.
    InterProiIPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR015012. Phe_ZIP.
    IPR000980. SH2.
    [Graphical view]
    PfamiPF00169. PH. 1 hit.
    PF08916. Phe_ZIP. 1 hit.
    PF00017. SH2. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    SMARTiSM00233. PH. 1 hit.
    SM00252. SH2. 1 hit.
    [Graphical view]
    SUPFAMiSSF109805. SSF109805. 1 hit.
    SSF55550. SSF55550. 1 hit.
    PROSITEiPS50003. PH_DOMAIN. 1 hit.
    PS50001. SH2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O14492-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNGAGPGPAA AAPVPVPVPV PDWRQFCELH AQAAAVDFAH KFCRFLRDNP    50
    AYDTPDAGAS FSRHFAANFL DVFGEEVRRV LVAGPTTRGA AVSAEAMEPE 100
    LADTSALKAA PYGHSRSSED VSTHAATKAR VRKGFSLRNM SLCVVDGVRD 150
    MWHRRASPEP DAAAAPRTAE PRDKWTRRLR LSRTLAAKVE LVDIQREGAL 200
    RFMVADDAAA GSGGSAQWQK CRLLLRRAVA EERFRLEFFV PPKASRPKVS 250
    IPLSAIIEVR TTMPLEMPEK DNTFVLKVEN GAEYILETID SLQKHSWVAD 300
    IQGCVDPGDS EEDTELSCTR GGCLASRVAS CSCELLTDAV DLPRPPETTA 350
    VGAVVTAPHS RGRDAVRESL IHVPLETFLQ TLESPGGSGS DSNNTGEQGA 400
    ETDPEAEPEL ELSDYPWFHG TLSRVKAAQL VLAGGPRNHG LFVIRQSETR 450
    PGEYVLTFNF QGKAKHLRLS LNGHGQCHVQ HLWFQSVLDM LRHFHTHPIP 500
    LESGGSADIT LRSYVRAQDP PPEPGPTPPA APASPACWSD SPGQHYFSSL 550
    AAAACPPASP SDAAGASSSS ASSSSAASGP APPRPVEGQL SARSRSNSAE 600
    RLLEAVAATA AEEPPEAAPG RARAVENQYS FY 632
    Length:632
    Mass (Da):67,738
    Last modified:September 23, 2008 - v2
    Checksum:i823DF1699D404227
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti111 – 1111P → S in BAA22514. (PubMed:9233773)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB000520 mRNA. Translation: BAA22514.1.
    AC005088 Genomic DNA. No translation available.
    RefSeqiNP_066189.3. NM_020979.4.
    XP_005277034.1. XM_005276977.2.
    XP_005277036.1. XM_005276979.1.
    UniGeneiHs.489448.

    Genome annotation databases

    EnsembliENST00000306803; ENSP00000304701; ENSG00000160999.
    GeneIDi10603.
    KEGGihsa:10603.
    UCSCiuc011kko.2. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB000520 mRNA. Translation: BAA22514.1 .
    AC005088 Genomic DNA. No translation available.
    RefSeqi NP_066189.3. NM_020979.4.
    XP_005277034.1. XM_005276977.2.
    XP_005277036.1. XM_005276979.1.
    UniGenei Hs.489448.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1Q2H X-ray 1.70 A/B/C 21-85 [» ]
    ProteinModelPortali O14492.
    SMRi O14492. Positions 21-83, 182-310, 410-494.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 115850. 13 interactions.
    IntActi O14492. 5 interactions.
    MINTi MINT-1498797.
    STRINGi 9606.ENSP00000304701.

    PTM databases

    PhosphoSitei O14492.

    Proteomic databases

    MaxQBi O14492.
    PaxDbi O14492.
    PRIDEi O14492.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000306803 ; ENSP00000304701 ; ENSG00000160999 .
    GeneIDi 10603.
    KEGGi hsa:10603.
    UCSCi uc011kko.2. human.

    Organism-specific databases

    CTDi 10603.
    GeneCardsi GC07P101928.
    HGNCi HGNC:17381. SH2B2.
    HPAi HPA051131.
    MIMi 605300. gene.
    neXtProti NX_O14492.
    PharmGKBi PA145148106.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG77816.
    HOGENOMi HOG000047355.
    HOVERGENi HBG006707.
    KOi K07193.
    OMAi CVGSSQW.
    PhylomeDBi O14492.

    Enzyme and pathway databases

    Reactomei REACT_111225. Regulation of KIT signaling.
    REACT_24970. Factors involved in megakaryocyte development and platelet production.
    SignaLinki O14492.

    Miscellaneous databases

    EvolutionaryTracei O14492.
    GeneWikii SH2B2.
    GenomeRNAii 10603.
    NextBioi 40266.
    PROi O14492.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O14492.
    Bgeei O14492.
    CleanExi HS_SH2B2.
    Genevestigatori O14492.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    3.30.505.10. 1 hit.
    InterProi IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR015012. Phe_ZIP.
    IPR000980. SH2.
    [Graphical view ]
    Pfami PF00169. PH. 1 hit.
    PF08916. Phe_ZIP. 1 hit.
    PF00017. SH2. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    SMARTi SM00233. PH. 1 hit.
    SM00252. SH2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF109805. SSF109805. 1 hit.
    SSF55550. SSF55550. 1 hit.
    PROSITEi PS50003. PH_DOMAIN. 1 hit.
    PS50001. SH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation."
      Yokouchi M., Suzuki R., Masuhara M., Komiya S., Inoue A., Yoshimura A.
      Oncogene 15:7-15(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INTERACTION WITH GRB2; KIT AND SHC1, PHOSPHORYLATION AT TYR-629.
      Tissue: B-cell1 Publication.
    2. "The DNA sequence of human chromosome 7."
      Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
      , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
      Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "APS, an adaptor protein containing pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl."
      Wakioka T., Sasaki A., Mitsui K., Yokouchi M., Inoue A., Komiya S., Yoshimura A.
      Leukemia 13:760-767(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH CBL AND EPOR.
    4. "APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis."
      Yokouchi M., Wakioka T., Sakamoto H., Yasukawa H., Ohtsuka S., Sasaki A., Ohtsubo M., Valius M., Inoue A., Komiya S., Yoshimura A.
      Oncogene 18:759-767(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH CBL AND PDGFR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    5. "Adaptor protein APS binds the NH2-terminal autoinhibitory domain of guanine nucleotide exchange factor Vav3 and augments its activity."
      Yabana N., Shibuya M.
      Oncogene 21:7720-7729(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH VAV1 AND VAV3.
    6. "Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor."
      Roskoski R. Jr.
      Biochem. Biophys. Res. Commun. 337:1-13(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON ROLE IN KIT SIGNALING.
    7. Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 21-85, FUNCTION, SUBUNIT.

    Entry informationi

    Entry nameiSH2B2_HUMAN
    AccessioniPrimary (citable) accession number: O14492
    Secondary accession number(s): A6ND74
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 15, 2003
    Last sequence update: September 23, 2008
    Last modified: October 1, 2014
    This is version 124 of the entry and version 2 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3