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Protein

SH2B adapter protein 2

Gene

Sh2b2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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. Binds to EPOR and suppresses EPO-induced STAT5 activation, possibly through a masking effect on STAT5 docking sites in EPOR. Suppresses PDGF-induced mitogenesis (By similarity). Involved in stimulation of glucose uptake by insulin. Involved in coupling from immunoreceptor to Ras signaling. Acts as a negative regulator of cytokine signaling in collaboration with CBL. Induces cytoskeletal reorganization and neurite outgrowth in cultured neurons.By similarity4 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 12

Organism-specific databases

RGDi69284. Sh2b2.

Subcellular locationi

  • Cytoplasm
  • Membrane

  • Note: Recruited to the membrane by binding to an autophosphorylated receptor after receptor stimulation by its extracellular ligand.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi437R → A: Abolishes interaction with phosphorylated INSR. 1 Publication1
Mutagenesisi455K → A: Reduces interaction with phosphorylated INSR. 1 Publication1
Mutagenesisi457K → N: Abolishes interaction with phosphorylated INSR. 1 Publication1
Mutagenesisi618Y → F: Abolishes phosphorylation in response to insulin. 1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000646491 – 621SH2B adapter protein 2Add BLAST621

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei130PhosphoserineBy similarity1
Modified residuei303PhosphoserineBy similarity1
Modified residuei597PhosphoserineBy similarity1
Modified residuei618Phosphotyrosine1 Publication1

Post-translational modificationi

Phosphorylated on a tyrosine residue by NTRK1, NTRK2, NTRK3 and INSR after stimulation of the receptor by its extracellular ligand. 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 similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9Z200.
PRIDEiQ9Z200.

PTM databases

iPTMnetiQ9Z200.
PhosphoSitePlusiQ9Z200.

Expressioni

Tissue specificityi

Detected in embryonic brain, spinal cord and cortical neurons.1 Publication

Gene expression databases

BgeeiENSRNOG00000001425.
GenevisibleiQ9Z200. RN.

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 (By similarity). 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 similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-8562298,EBI-8562298

Protein-protein interaction databases

BioGridi250306. 1 interactor.
IntActiQ9Z200. 2 interactors.
MINTiMINT-3371223.
STRINGi10116.ENSRNOP00000001935.

Structurei

Secondary structure

1621
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi404 – 406Combined sources3
Helixi416 – 424Combined sources9
Helixi427 – 430Combined sources4
Beta strandi434 – 438Combined sources5
Beta strandi440 – 442Combined sources3
Beta strandi446 – 452Combined sources7
Beta strandi455 – 460Combined sources6
Helixi469 – 486Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1RPYX-ray2.30A/B401-510[»]
1RQQX-ray2.60C/D401-510[»]
1YVHX-ray2.05B609-621[»]
ProteinModelPortaliQ9Z200.
SMRiQ9Z200.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Z200.

Family & Domainsi

Domains and Repeats

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

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi551 – 588Ser-richAdd BLAST38

Sequence similaritiesi

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

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiENOG410IMWK. Eukaryota.
ENOG41102PH. LUCA.
GeneTreeiENSGT00530000063355.
HOGENOMiHOG000047355.
HOVERGENiHBG006707.
InParanoidiQ9Z200.
KOiK07193.
OMAiFDMLRHF.
OrthoDBiEOG091G04RI.
PhylomeDBiQ9Z200.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR015012. Phe_ZIP.
IPR000980. SH2.
IPR030523. SH2B.
IPR030520. SH2B2.
[Graphical view]
PANTHERiPTHR10872. PTHR10872. 1 hit.
PTHR10872:SF4. PTHR10872:SF4. 1 hit.
PfamiPF00169. PH. 1 hit.
PF08916. Phe_ZIP. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF109805. SSF109805. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Z200-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNGATPGSAA APAPVPDWRQ FCELHAQVAA VDFAHKFCRF LRDNPTYDTP
60 70 80 90 100
DAGTSFSRHF AANFLAVFSE EVRRVLGTAA DTMEPEPAVT SVTSALKTAT
110 120 130 140 150
YGHSRSSEDV SAHVATKARV RKGFSLRNMS LCVVDGVRDL WHRRASPEPE
160 170 180 190 200
GGATPKTTEP VSEPRDKWTR 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 VTSCSCELLT EADMPRPPET MTAVGAVVTA
360 370 380 390 400
PHGRARDTVG ESLAHVPLET FLQTLESSGG VSESNNTGDE GAELDPDAEA
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 SLATATCPPT
560 570 580 590 600
SPSNGAGASS SSGSSSSATS VPPRPAEGPL SARSRSNSTE HLLEAASGAT
610 620
EEPADATLGR ARAVENQYSF Y
Length:621
Mass (Da):66,708
Last modified:May 1, 1999 - v1
Checksum:i4E019DF3A73D5B4F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF095576 mRNA. Translation: AAC64408.1.
RefSeqiNP_446121.1. NM_053669.1.
XP_008767335.1. XM_008769113.2.
XP_017453727.1. XM_017598238.1.
XP_017453728.1. XM_017598239.1.
UniGeneiRn.163202.

Genome annotation databases

EnsembliENSRNOT00000001935; ENSRNOP00000001935; ENSRNOG00000001425.
GeneIDi114203.
KEGGirno:114203.
UCSCiRGD:69284. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF095576 mRNA. Translation: AAC64408.1.
RefSeqiNP_446121.1. NM_053669.1.
XP_008767335.1. XM_008769113.2.
XP_017453727.1. XM_017598238.1.
XP_017453728.1. XM_017598239.1.
UniGeneiRn.163202.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1RPYX-ray2.30A/B401-510[»]
1RQQX-ray2.60C/D401-510[»]
1YVHX-ray2.05B609-621[»]
ProteinModelPortaliQ9Z200.
SMRiQ9Z200.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250306. 1 interactor.
IntActiQ9Z200. 2 interactors.
MINTiMINT-3371223.
STRINGi10116.ENSRNOP00000001935.

PTM databases

iPTMnetiQ9Z200.
PhosphoSitePlusiQ9Z200.

Proteomic databases

PaxDbiQ9Z200.
PRIDEiQ9Z200.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000001935; ENSRNOP00000001935; ENSRNOG00000001425.
GeneIDi114203.
KEGGirno:114203.
UCSCiRGD:69284. rat.

Organism-specific databases

CTDi10603.
RGDi69284. Sh2b2.

Phylogenomic databases

eggNOGiENOG410IMWK. Eukaryota.
ENOG41102PH. LUCA.
GeneTreeiENSGT00530000063355.
HOGENOMiHOG000047355.
HOVERGENiHBG006707.
InParanoidiQ9Z200.
KOiK07193.
OMAiFDMLRHF.
OrthoDBiEOG091G04RI.
PhylomeDBiQ9Z200.

Miscellaneous databases

EvolutionaryTraceiQ9Z200.
PROiQ9Z200.

Gene expression databases

BgeeiENSRNOG00000001425.
GenevisibleiQ9Z200. RN.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR015012. Phe_ZIP.
IPR000980. SH2.
IPR030523. SH2B.
IPR030520. SH2B2.
[Graphical view]
PANTHERiPTHR10872. PTHR10872. 1 hit.
PTHR10872:SF4. PTHR10872:SF4. 1 hit.
PfamiPF00169. PH. 1 hit.
PF08916. Phe_ZIP. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF109805. SSF109805. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSH2B2_RAT
AccessioniPrimary (citable) accession number: Q9Z200
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: May 1, 1999
Last modified: November 30, 2016
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.