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O14492

- SH2B2_HUMAN

UniProt

O14492 - SH2B2_HUMAN

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Protein
SH2B adapter protein 2
Gene
SH2B2, APS
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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. SH3/SH2 adaptor activity Source: UniProtKB
  3. protein binding Source: IntAct
  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
Complete GO annotation...

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)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:17381. SH2B2.

Subcellular locationi

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

GO - Cellular componenti

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

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 2
PRO_0000064647Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei629 – 6291Phosphotyrosine2 Publications

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.5 Publications

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

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.

Miscellaneous databases

EvolutionaryTraceiO14492.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini193 – 306114PH
Add
BLAST
Domaini417 – 51599SH2
Add
BLAST

Sequence similaritiesi

Belongs to the SH2B adapter family.
Contains 1 PH domain.
Contains 1 SH2 domain.

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti111 – 1111P → S in BAA22514. 1 Publication

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.
ENST00000563740; ENSP00000455175; ENSG00000259885.
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 .
ENST00000563740 ; ENSP00000455175 ; ENSG00000259885 .
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

« Hide 'large scale' publications
  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-cell.
  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: September 3, 2014
This is version 123 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

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