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Protein

SH2B adapter protein 2

Gene

Sh2b2

Organism
Mus musculus (Mouse)
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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

  • actin cytoskeleton organization Source: MGI
  • antigen receptor-mediated signaling pathway Source: MGI
  • B-1 B cell homeostasis Source: MGI
  • brown fat cell differentiation Source: MGI
  • cytokine-mediated signaling pathway Source: MGI
  • glucose homeostasis Source: MGI
  • insulin receptor signaling pathway Source: MGI
  • intracellular signal transduction Source: UniProtKB
  • negative regulation of glucose import Source: MGI
  • nervous system development Source: MGI
  • regulation of immune response Source: MGI
  • regulation of metabolic process Source: MGI
  • regulation of Ras protein signal transduction Source: MGI

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
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1345171 Sh2b2

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000646481 – 621SH2B adapter protein 2Add BLAST621

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei47Phosphotyrosine1 Publication1
Modified residuei130PhosphoserineCombined sources1
Modified residuei303PhosphoserineCombined sources1
Modified residuei597PhosphoserineCombined sources1
Modified residuei618Phosphotyrosine1 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.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9JID9
PaxDbiQ9JID9
PeptideAtlasiQ9JID9
PRIDEiQ9JID9

PTM databases

iPTMnetiQ9JID9
PhosphoSitePlusiQ9JID9

Expressioni

Tissue specificityi

Strongly expressed in brain; also expressed in spleen, kidney and skeletal muscle, and at low levels in small intestine and bone marrow. Strongly expressed in B-cell lines, but not T-cell lines. Also expressed in myeloid and fibroblast cell lines.1 Publication

Gene expression databases

BgeeiENSMUSG00000005057
CleanExiMM_SH2B2
ExpressionAtlasiQ9JID9 baseline and differential
GenevisibleiQ9JID9 MM

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
Fgfr3Q618513EBI-8100899,EBI-6287052

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204795, 9 interactors
IntActiQ9JID9, 1 interactor
MINTiQ9JID9
STRINGi10090.ENSMUSP00000005188

Structurei

Secondary structure

1621
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi189 – 197Combined sources9
Beta strandi203 – 205Combined sources3
Beta strandi212 – 220Combined sources9
Beta strandi222 – 224Combined sources3
Beta strandi227 – 234Combined sources8
Beta strandi237 – 239Combined sources3
Turni246 – 248Combined sources3
Beta strandi258 – 260Combined sources3
Beta strandi276 – 280Combined sources5
Helixi284 – 299Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1V5MNMR-A177-299[»]
ProteinModelPortaliQ9JID9
SMRiQ9JID9
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9JID9

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini186 – 299PHPROSITE-ProRule annotationCuratedAdd BLAST114
Domaini409 – 507SH2PROSITE-ProRule annotationCuratedAdd BLAST99

Sequence similaritiesi

Belongs to the SH2B adapter family.Curated

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiENOG410IMWK Eukaryota
ENOG41102PH LUCA
GeneTreeiENSGT00530000063355
HOGENOMiHOG000047355
HOVERGENiHBG006707
InParanoidiQ9JID9
KOiK07193
OMAiYDTEFFR
OrthoDBiEOG091G04RI
TreeFamiTF323184

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
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

Sequencei

Sequence statusi: Complete.

Q9JID9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNGATPSSAA APAPVPDWRQ FCELHAQVAA VDFAHKFCRF LRDNPTYDTP
60 70 80 90 100
DAGTSFSRHF AANFLAVFSE EVRRVLGSAA DTMEPEPAVT SVTSALKTAT
110 120 130 140 150
YGHSRSSEDV SAHAATKARV RKGFSLRNMS LCVVDGVRDL WHRRSSPEPD
160 170 180 190 200
GGATPKAAEP ASEPRDKWTR RLRLARTLAA KVELVDIQRE GALRFMVADD
210 220 230 240 250
AASGPGGTAQ WQKCRLLLRR AVAGERFRLE FFVPPKASRP KVSIPLSAII
260 270 280 290 300
EVRTTMPLEM PEKDNTFVLK VENGAEYILE TIDSLQKHSW VADIQGCVDP
310 320 330 340 350
GDSEEDTGLS CARGGCLASR VASCSCELLT DADMPRPPET TTAVGAVVTA
360 370 380 390 400
PHGRARDTVG ESLAHVPLET FLQTLESSGG VSENNNPGDE GAELDTDAEA
410 420 430 440 450
ELELSDYPWF HGTLSRVKAA QLVLAGGPRS HGLFVIRQSE TRPGECVLTF
460 470 480 490 500
NFQGKAKHLR LSLNGHGQCH VQHLWFQSVF DMLRHFHTHP IPLESGGSAD
510 520 530 540 550
ITLRSYVRAQ GPPPDPGPAP NTAAPVPACW TEPAGQHYFS SLATATCPPA
560 570 580 590 600
SPSNGAGASS SSGSSSSATS LPPRPAEGPL SAHSRSNSTE HLLDAASGAT
610 620
EEPTEATLGR ARAVENQYSF Y
Length:621
Mass (Da):66,557
Last modified:July 27, 2011 - v2
Checksum:iDB20BD352F96D69E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti125S → W in AAF37891 (PubMed:10872802).Curated1
Sequence conflicti442R → K in AAC36336 (Ref. 4) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF234838 mRNA Translation: AAF37891.1
AK140319 mRNA Translation: BAE24331.1
AK140325 mRNA Translation: BAE24336.1
AF086810 mRNA Translation: AAC36336.1
BC057334 mRNA Translation: AAH57334.1
CCDSiCCDS39327.1
PIRiJC7278
RefSeqiNP_001289867.1, NM_001302938.1
NP_001289868.1, NM_001302939.1
NP_061295.2, NM_018825.4
XP_006504483.2, XM_006504420.3
XP_006504485.1, XM_006504422.2
UniGeneiMm.425294

Genome annotation databases

EnsembliENSMUST00000005188; ENSMUSP00000005188; ENSMUSG00000005057
ENSMUST00000196397; ENSMUSP00000142398; ENSMUSG00000005057
GeneIDi23921
KEGGimmu:23921
UCSCiuc009aag.2 mouse

Similar proteinsi

Entry informationi

Entry nameiSH2B2_MOUSE
AccessioniPrimary (citable) accession number: Q9JID9
Secondary accession number(s): O88936, Q6PG00
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: July 27, 2011
Last modified: June 20, 2018
This is version 148 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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