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Protein

SH2B adapter protein 2

Gene

SH2B2

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

  • JAK pathway signal transduction adaptor activity Source: UniProtKB
  • SH3/SH2 adaptor activity Source: UniProtKB

GO - Biological processi

  • blood coagulation Source: Reactome
  • insulin receptor signaling pathway Source: BHF-UCL
  • intracellular signal transduction Source: UniProtKB
  • signal transduction Source: ProtInc

Enzyme and pathway databases

ReactomeiR-HSA-1433559 Regulation of KIT signaling
R-HSA-983231 Factors involved in megakaryocyte development and platelet production
SignaLinkiO14492
SIGNORiO14492

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
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000160999.10
HGNCiHGNC:17381 SH2B2
MIMi605300 gene
neXtProtiNX_O14492

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

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi10603
OpenTargetsiENSG00000160999
PharmGKBiPA145148106

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000646471 – 632SH2B adapter protein 2Add BLAST632

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52PhosphotyrosineBy similarity1
Modified residuei141PhosphoserineBy similarity1
Modified residuei310PhosphoserineBy similarity1
Modified residuei629Phosphotyrosine1 Publication1

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

EPDiO14492
MaxQBiO14492
PeptideAtlasiO14492
PRIDEiO14492
ProteomicsDBi48035

PTM databases

iPTMnetiO14492
PhosphoSitePlusiO14492

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

BgeeiENSG00000160999
CleanExiHS_SH2B2

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

GO - Molecular functioni

  • JAK pathway signal transduction adaptor activity Source: UniProtKB
  • SH3/SH2 adaptor activity Source: UniProtKB

Protein-protein interaction databases

BioGridi115850, 15 interactors
IntActiO14492, 22 interactors
MINTiO14492

Structurei

Secondary structure

1632
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi23 – 48Combined sources26
Helixi50 – 52Combined sources3
Helixi57 – 82Combined sources26

3D structure databases

ProteinModelPortaliO14492
SMRiO14492
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14492

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini193 – 306PHPROSITE-ProRule annotationCuratedAdd BLAST114
Domaini417 – 515SH2PROSITE-ProRule annotationCuratedAdd BLAST99

Sequence similaritiesi

Belongs to the SH2B adapter family.Curated

Keywords - Domaini

SH2 domain

Phylogenomic databases

GeneTreeiENSGT00530000063355
HOGENOMiHOG000047355
HOVERGENiHBG006707
InParanoidiO14492
KOiK07193
OMAiYDTEFFR
PhylomeDBiO14492

Family and domain databases

CDDicd10411 SH2_SH2B2, 1 hit
Gene3Di2.30.29.30, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR015012 Phe_ZIP
IPR036290 Phe_ZIP_sf
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR030523 SH2B
IPR030520 SH2B2
IPR035058 SH2B2_SH2
PANTHERiPTHR10872 PTHR10872, 1 hit
PTHR10872:SF4 PTHR10872:SF4, 1 hit
PfamiView protein in Pfam
PF00169 PH, 1 hit
PF08916 Phe_ZIP, 1 hit
PF00017 SH2, 1 hit
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00252 SH2, 1 hit
SUPFAMiSSF109805 SSF109805, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50003 PH_DOMAIN, 1 hit
PS50001 SH2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O14492-1) [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
MNGAGPGPAA AAPVPVPVPV PDWRQFCELH AQAAAVDFAH KFCRFLRDNP
60 70 80 90 100
AYDTPDAGAS FSRHFAANFL DVFGEEVRRV LVAGPTTRGA AVSAEAMEPE
110 120 130 140 150
LADTSALKAA PYGHSRSSED VSTHAATKAR VRKGFSLRNM SLCVVDGVRD
160 170 180 190 200
MWHRRASPEP DAAAAPRTAE PRDKWTRRLR LSRTLAAKVE LVDIQREGAL
210 220 230 240 250
RFMVADDAAA GSGGSAQWQK CRLLLRRAVA EERFRLEFFV PPKASRPKVS
260 270 280 290 300
IPLSAIIEVR TTMPLEMPEK DNTFVLKVEN GAEYILETID SLQKHSWVAD
310 320 330 340 350
IQGCVDPGDS EEDTELSCTR GGCLASRVAS CSCELLTDAV DLPRPPETTA
360 370 380 390 400
VGAVVTAPHS RGRDAVRESL IHVPLETFLQ TLESPGGSGS DSNNTGEQGA
410 420 430 440 450
ETDPEAEPEL ELSDYPWFHG TLSRVKAAQL VLAGGPRNHG LFVIRQSETR
460 470 480 490 500
PGEYVLTFNF QGKAKHLRLS LNGHGQCHVQ HLWFQSVLDM LRHFHTHPIP
510 520 530 540 550
LESGGSADIT LRSYVRAQDP PPEPGPTPPA APASPACWSD SPGQHYFSSL
560 570 580 590 600
AAAACPPASP SDAAGASSSS ASSSSAASGP APPRPVEGQL SARSRSNSAE
610 620 630
RLLEAVAATA AEEPPEAAPG RARAVENQYS FY
Length:632
Mass (Da):67,738
Last modified:September 23, 2008 - v2
Checksum:i823DF1699D404227
GO
Isoform 2 (identifier: O14492-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MDPSYCPAHGFPSQDPLWPLSSQQWSSAHYSEPAAGGCDGTEAM

Show »
Length:675
Mass (Da):72,287
Checksum:iDEB36A673870EB15
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti111P → S in BAA22514 (PubMed:9233773).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0593581M → MDPSYCPAHGFPSQDPLWPL SSQQWSSAHYSEPAAGGCDG TEAM in isoform 2. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000520 mRNA Translation: BAA22514.1
AC005088 Genomic DNA No translation available.
AC091390 Genomic DNA No translation available.
CH471197 Genomic DNA Translation: EAW50232.1
CCDSiCCDS78264.1 [O14492-2]
RefSeqiNP_066189.3, NM_020979.4 [O14492-2]
XP_005277034.1, XM_005276977.4
XP_005277036.1, XM_005276979.3
UniGeneiHs.489448

Genome annotation databases

EnsembliENST00000536178; ENSP00000440273; ENSG00000160999
GeneIDi10603
KEGGihsa:10603

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSH2B2_HUMAN
AccessioniPrimary (citable) accession number: O14492
Secondary accession number(s): A0A0A0MTI2, A6ND74
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: September 23, 2008
Last modified: July 18, 2018
This is version 154 of the entry and version 2 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

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

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