UniProtKB - Q91ZM2 (SH2B1_MOUSE)
SH2B adapter protein 1
Sh2b1
Functioni
Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways mediated by Janus kinase (JAK) and receptor tyrosine kinases, including the receptors of insulin (INS), insulin-like growth factor I (IGF1), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), platelet-derived growth factor (PDGF) and fibroblast growth factors (FGFs). In growth hormone (GH) signaling, autophosphorylated ('Tyr-813') JAK2 recruits SH2B1, which in turn is phosphorylated by JAK2 on tyrosine residues. These phosphotyrosines form potential binding sites for other signaling proteins. GH also promotes serine/threonine phosphorylation of SH2B1 and these phosphorylated residues may serve to recruit other proteins to the GHR-JAK2-SH2B1 complexes, such as RAC1. In leptin (LEP) signaling, binds to and potentiates the activation of JAK2 by globally enhancing downstream pathways. In response to leptin, binds simultaneously to both, JAK2 and IRS1 or IRS2, thus mediating formation of a complex of JAK2, SH2B1 and IRS1 or IRS2. Mediates tyrosine phosphorylation of IRS1 and IRS2, resulting in activation of the PI 3-kinase pathway. Acts as positive regulator of NGF-mediated activation of the Akt/Forkhead pathway; prolongs NGF-induced phosphorylation of AKT1 on 'Ser-473' and AKT1 enzymatic activity. Enhances the kinase activity of the cytokine receptor-associated tyrosine kinase JAK2 and of other receptor tyrosine kinases, such as FGFR3 and NTRK1. For JAK2, the mechanism seems to involve dimerization of both, SH2B1 and JAK2. Enhances RET phosphorylation and kinase activity (By similarity).
Isoforms seem to be differentially involved in IGF-I and PDGF-induced mitogenesis, according the order: isoform 3 > isoform 4 > isoform 1 > isoform 2.
By similarity4 PublicationsGO - Molecular functioni
- transmembrane receptor protein tyrosine kinase adaptor activity Source: GO_Central
GO - Biological processi
- intracellular signal transduction Source: GO_Central
- lamellipodium assembly Source: MGI
- positive regulation of mitotic nuclear division Source: UniProtKB
- regulation of DNA biosynthetic process Source: UniProtKB
Enzyme and pathway databases
Reactomei | R-MMU-1170546, Prolactin receptor signaling R-MMU-982772, Growth hormone receptor signaling R-MMU-983231, Factors involved in megakaryocyte development and platelet production |
Names & Taxonomyi
Protein namesi | Recommended name: SH2B adapter protein 1Alternative name(s): Pro-rich, PH and SH2 domain-containing signaling mediator Short name: PSM SH2 domain-containing protein 1B SH2-B PH domain-containing signaling mediator 1 |
Gene namesi | Name:Sh2b1 Synonyms:Sh2bpsm1 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1201407, Sh2b1 |
VEuPathDBi | HostDB:ENSMUSG00000030733 |
Subcellular locationi
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleus Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: GO_Central
Other locations
- ruffle Source: MGI
Keywords - Cellular componenti
Cytoplasm, Membrane, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000323594 | 1 – 756 | SH2B adapter protein 1Add BLAST | 756 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 88 | PhosphoserineCombined sources | 1 | |
Modified residuei | 96 | PhosphoserineCombined sources | 1 | |
Modified residuei | 270 | Omega-N-methylarginineCombined sources | 1 | |
Modified residuei | 417 | PhosphoserineCombined sources | 1 | |
Modified residuei | 420 | PhosphoserineCombined sources | 1 | |
Modified residuei | 439 | Phosphotyrosine; by JAK1, JAK2 and PDGFRBy similarity | 1 | |
Modified residuei | 494 | Phosphotyrosine; by JAK1, JAK2By similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Methylation, PhosphoproteinProteomic databases
EPDi | Q91ZM2 |
jPOSTi | Q91ZM2 |
MaxQBi | Q91ZM2 |
PaxDbi | Q91ZM2 |
PeptideAtlasi | Q91ZM2 |
PRIDEi | Q91ZM2 |
ProteomicsDBi | 257132 [Q91ZM2-1] 257133 [Q91ZM2-2] 257134 [Q91ZM2-3] 257135 [Q91ZM2-4] 257136 [Q91ZM2-5] 257137 [Q91ZM2-6] |
PTM databases
iPTMneti | Q91ZM2 |
PhosphoSitePlusi | Q91ZM2 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSMUSG00000030733, Expressed in retinal neural layer and 307 other tissues |
Genevisiblei | Q91ZM2, MM |
Interactioni
Subunit structurei
Self-associates. Homopentamer (By similarity).
Forms a heteromultimeric complex with SH2B2 (By similarity).
Interacts with SH2B2. Isoform 1 interacts via its SH2 domain with JAK2. Isoform 2 interacts via its SH2 domain and its N-terminus with JAK2; the SH2 domain is required for the major interaction with JAK2 phosphorylated on tyrosine residues; the N-terminus provides a low-affinity binding to JAK2 independent of JAK2 phosphorylation. Isoform 3 interacts via its SH2 domain with JAK2. Isoform 1 interacts via its SH2 domain with INSR; the interaction requires receptor activation. Isoform 3 interacts via its SH2 domain with INSR; the interaction requires receptor activation and requires INSR phosphorylation at 'Tyr-1175'.
Isoform 1 interacts with IGF1R; the interaction requires receptor activation. Isoform 2 interacts via its SH2 domain with FGFR3; the interaction requires FGFR3 'Tyr-719' and 'Tyr-755'.
Isoform 2 interacts with RET; the interaction requires RET kinase activity and RET 'Tyr-982'.
Isoform 2 interacts with RAC1.
Isoform 2 interacts with PDGFRA and/or PDGFRB; the interaction requires receptor activation.
Interacts with ISR1 and ISR2. Isoform 3 is probably part of a complex consisting of INSR, ISR1 and SH2B1. Probably part of a ternary complex consisting of SH2B1, JAK2 and ISR1 or ISR2. May interact with FCER1G (By similarity).
Interacts (via SH2 domain) with NTRK1 (phosphorylated) (By similarity).
By similarityBinary interactionsi
Q91ZM2
With | #Exp. | IntAct |
---|---|---|
Jak2 [Q62120] | 3 | EBI-7178606,EBI-646604 |
GO - Molecular functioni
- transmembrane receptor protein tyrosine kinase adaptor activity Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 203201, 3 interactors |
IntActi | Q91ZM2, 4 interactors |
MINTi | Q91ZM2 |
STRINGi | 10090.ENSMUSP00000032978 |
Miscellaneous databases
RNActi | Q91ZM2, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q91ZM2 |
SMRi | Q91ZM2 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q91ZM2 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 267 – 376 | PHAdd BLAST | 110 | |
Domaini | 527 – 625 | SH2PROSITE-ProRule annotationAdd BLAST | 99 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 555 | Interaction with JAK2 (low-affinity binding; independent of JAK2 phosphorylation)By similarityAdd BLAST | 555 | |
Regioni | 1 – 27 | DisorderedSequence analysisAdd BLAST | 27 | |
Regioni | 24 – 85 | Required for self-associationBy similarityAdd BLAST | 62 | |
Regioni | 85 – 196 | Interaction with RAC1By similarityAdd BLAST | 112 | |
Regioni | 100 – 243 | Required for NGF signalingBy similarityAdd BLAST | 144 | |
Regioni | 123 – 152 | DisorderedSequence analysisAdd BLAST | 30 | |
Regioni | 173 – 224 | DisorderedSequence analysisAdd BLAST | 52 | |
Regioni | 224 – 233 | Required for nuclear localizationBy similarity | 10 | |
Regioni | 263 – 284 | DisorderedSequence analysisAdd BLAST | 22 | |
Regioni | 418 – 455 | DisorderedSequence analysisAdd BLAST | 38 | |
Regioni | 468 – 503 | DisorderedSequence analysisAdd BLAST | 36 | |
Regioni | 626 – 664 | DisorderedSequence analysisAdd BLAST | 39 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 9 – 27 | Pro residuesSequence analysisAdd BLAST | 19 | |
Compositional biasi | 130 – 148 | Polar residuesSequence analysisAdd BLAST | 19 | |
Compositional biasi | 181 – 208 | Polar residuesSequence analysisAdd BLAST | 28 | |
Compositional biasi | 418 – 437 | Polar residuesSequence analysisAdd BLAST | 20 |
Sequence similaritiesi
Keywords - Domaini
SH2 domainPhylogenomic databases
eggNOGi | ENOG502QT43, Eukaryota |
GeneTreei | ENSGT00950000183191 |
HOGENOMi | CLU_014885_4_0_1 |
InParanoidi | Q91ZM2 |
OMAi | GILQWRS |
OrthoDBi | 556279at2759 |
PhylomeDBi | Q91ZM2 |
TreeFami | TF323184 |
Family and domain databases
CDDi | cd10346, SH2_SH2B_family, 1 hit |
Gene3Di | 2.30.29.30, 1 hit 3.30.505.10, 1 hit |
IDEALi | IID50098 |
InterProi | View 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 IPR030521, SH2B1 IPR035057, SH2B1_SH2 |
PANTHERi | PTHR10872, PTHR10872, 1 hit PTHR10872:SF3, PTHR10872:SF3, 1 hit |
Pfami | View protein in Pfam PF00169, PH, 1 hit PF08916, Phe_ZIP, 1 hit PF00017, SH2, 1 hit |
PRINTSi | PR00401, SH2DOMAIN |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00252, SH2, 1 hit |
SUPFAMi | SSF109805, SSF109805, 1 hit SSF55550, SSF55550, 1 hit |
PROSITEi | View protein in PROSITE PS50001, SH2, 1 hit |
s (6+)i Sequence
Sequence statusi: Complete.
This entry describes 6 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 6 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MNGAPSPEDG VFPSPPALPP PPPPSWQEFC ESHARAAALD LARRFRLYLA
60 70 80 90 100
SHPQYAEPGA EAAFSGRFAE LFLQHFEAEV ARASGSLSPP VLAPLSPGVE
110 120 130 140 150
IPPSHDLSLE SCRVGGPLAV LGPSRSSEDL AGPLPSSVPS STTSSKPKLK
160 170 180 190 200
KRFSLRSVGR SVRGSVRGIL QWRGAVDSPS QAGPLETTSG PPVLGGNSNS
210 220 230 240 250
NSSGGAGTVG RALANDGTSP GERWTHRFER LRLSRGGGTL KDGAGMIQRE
260 270 280 290 300
ELLSFMGAEE AAPDPAGVGR GGGAAGLTSG GGGQPQWQKC RLLLRSEGEG
310 320 330 340 350
GGGSRLEFFV PPKASRPRLS IPCSTITDVR TATALEMPDR ENTFVVKVEG
360 370 380 390 400
PSEYILETSD ALHVKAWVSD IQECLSPGPC PAISPRPMTL PLAPGTSFFT
410 420 430 440 450
KDNTDSLELP CLNHSESLPS QDLLLGPSES NDRLSQGAYG GLSDRPSASF
460 470 480 490 500
SPSSASIAAS HFDSMELLPP ELPPRIPIEE GPPAGTVHPL STPYPPLDTP
510 520 530 540 550
EAATGSFLFQ GESEGGEGDQ PLSGYPWFHG MLSRLKAAQL VLEGGTGSHG
560 570 580 590 600
VFLVRQSETR RGEYVLTFNF QGKAKHLRLS LNEEGQCRVQ HLWFQSIFDM
610 620 630 640 650
LEHFRVHPIP LESGGSSDVV LVSYVPSQRQ QERSTSRDPA QPSEPPPWTD
660 670 680 690 700
PPHPGAEEAS GAPEVAAATA AAAKERQEKE KAGSGGVQEE LVPVAELVPM
710 720 730 740 750
VELEEAIAPG TEAQGGAGSS GDLEVSLMVQ LQQLPLGGNG EEGGHPRAIN
NQYSFV
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A0U1RQ35 | A0A0U1RQ35_MOUSE | SH2B adapter protein 1 | Sh2b1 | 73 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 172 | W → C in AAD41655 (PubMed:10594240).Curated | 1 | |
Sequence conflicti | 399 | F → L in AAH11422 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 564 | Y → C in AAD41655 (PubMed:10594240).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_032029 | 437 – 443 | GAYGGLS → AVDSEKT in isoform 5. 1 Publication | 7 | |
Alternative sequenceiVSP_032030 | 441 – 460 | Missing in isoform 6. 1 PublicationAdd BLAST | 20 | |
Alternative sequenceiVSP_032031 | 444 – 756 | Missing in isoform 5. 1 PublicationAdd BLAST | 313 | |
Alternative sequenceiVSP_032032 | 632 – 756 | ERSTS…QYSFV → GREQAGSHAGVCEGDRCYPD ASSTLLPFGASDCVTEHLP in isoform 2. 3 PublicationsAdd BLAST | 125 | |
Alternative sequenceiVSP_032033 | 632 – 756 | ERSTS…QYSFV → GEQSRSAGEEVPVHPRSEAG SRLGAMQGCARATDATPMPP PPSCPSERVTV in isoform 3 and isoform 6. 3 PublicationsAdd BLAST | 125 | |
Alternative sequenceiVSP_032034 | 632 – 756 | ERSTS…QYSFV → GEQSRSAGEEVPVHPRSENG APPVTQPSPLNPLHGQIPHI LGQKRRRGRQKLRQPQPQQP KRGKRKRKRAVEGSRKSWSP WLSWSPWLNWKRP in isoform 4. 2 PublicationsAdd BLAST | 125 |
Sequence databases
Genome annotation databases
Ensembli | ENSMUST00000032978; ENSMUSP00000032978; ENSMUSG00000030733 [Q91ZM2-3] ENSMUST00000205340; ENSMUSP00000145953; ENSMUSG00000030733 [Q91ZM2-2] ENSMUST00000205440; ENSMUSP00000145554; ENSMUSG00000030733 [Q91ZM2-2] ENSMUST00000205497; ENSMUSP00000145842; ENSMUSG00000030733 [Q91ZM2-4] ENSMUST00000205733; ENSMUSP00000145754; ENSMUSG00000030733 [Q91ZM2-1] ENSMUST00000205889; ENSMUSP00000146282; ENSMUSG00000030733 [Q91ZM2-4] ENSMUST00000206664; ENSMUSP00000146121; ENSMUSG00000030733 [Q91ZM2-5] |
GeneIDi | 20399 |
KEGGi | mmu:20399 |
UCSCi | uc009jrh.2, mouse [Q91ZM2-2] uc009jrj.2, mouse [Q91ZM2-4] uc009jrk.2, mouse [Q91ZM2-3] uc009jrm.2, mouse [Q91ZM2-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2HDV | X-ray | 2.00 | A/B | 519-627 | [»] | |
2HDX | X-ray | 2.35 | A/B/C/D/E/F | 519-627 | [»] | |
AlphaFoldDBi | Q91ZM2 | |||||
SMRi | Q91ZM2 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 203201, 3 interactors |
IntActi | Q91ZM2, 4 interactors |
MINTi | Q91ZM2 |
STRINGi | 10090.ENSMUSP00000032978 |
PTM databases
iPTMneti | Q91ZM2 |
PhosphoSitePlusi | Q91ZM2 |
Proteomic databases
EPDi | Q91ZM2 |
jPOSTi | Q91ZM2 |
MaxQBi | Q91ZM2 |
PaxDbi | Q91ZM2 |
PeptideAtlasi | Q91ZM2 |
PRIDEi | Q91ZM2 |
ProteomicsDBi | 257132 [Q91ZM2-1] 257133 [Q91ZM2-2] 257134 [Q91ZM2-3] 257135 [Q91ZM2-4] 257136 [Q91ZM2-5] 257137 [Q91ZM2-6] |
Protocols and materials databases
Antibodypediai | 26583, 288 antibodies from 31 providers |
Genome annotation databases
Ensembli | ENSMUST00000032978; ENSMUSP00000032978; ENSMUSG00000030733 [Q91ZM2-3] ENSMUST00000205340; ENSMUSP00000145953; ENSMUSG00000030733 [Q91ZM2-2] ENSMUST00000205440; ENSMUSP00000145554; ENSMUSG00000030733 [Q91ZM2-2] ENSMUST00000205497; ENSMUSP00000145842; ENSMUSG00000030733 [Q91ZM2-4] ENSMUST00000205733; ENSMUSP00000145754; ENSMUSG00000030733 [Q91ZM2-1] ENSMUST00000205889; ENSMUSP00000146282; ENSMUSG00000030733 [Q91ZM2-4] ENSMUST00000206664; ENSMUSP00000146121; ENSMUSG00000030733 [Q91ZM2-5] |
GeneIDi | 20399 |
KEGGi | mmu:20399 |
UCSCi | uc009jrh.2, mouse [Q91ZM2-2] uc009jrj.2, mouse [Q91ZM2-4] uc009jrk.2, mouse [Q91ZM2-3] uc009jrm.2, mouse [Q91ZM2-1] |
Organism-specific databases
CTDi | 25970 |
MGIi | MGI:1201407, Sh2b1 |
VEuPathDBi | HostDB:ENSMUSG00000030733 |
Phylogenomic databases
eggNOGi | ENOG502QT43, Eukaryota |
GeneTreei | ENSGT00950000183191 |
HOGENOMi | CLU_014885_4_0_1 |
InParanoidi | Q91ZM2 |
OMAi | GILQWRS |
OrthoDBi | 556279at2759 |
PhylomeDBi | Q91ZM2 |
TreeFami | TF323184 |
Enzyme and pathway databases
Reactomei | R-MMU-1170546, Prolactin receptor signaling R-MMU-982772, Growth hormone receptor signaling R-MMU-983231, Factors involved in megakaryocyte development and platelet production |
Miscellaneous databases
BioGRID-ORCSi | 20399, 5 hits in 72 CRISPR screens |
ChiTaRSi | Sh2b1, mouse |
EvolutionaryTracei | Q91ZM2 |
PROi | PR:Q91ZM2 |
RNActi | Q91ZM2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000030733, Expressed in retinal neural layer and 307 other tissues |
Genevisiblei | Q91ZM2, MM |
Family and domain databases
CDDi | cd10346, SH2_SH2B_family, 1 hit |
Gene3Di | 2.30.29.30, 1 hit 3.30.505.10, 1 hit |
IDEALi | IID50098 |
InterProi | View 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 IPR030521, SH2B1 IPR035057, SH2B1_SH2 |
PANTHERi | PTHR10872, PTHR10872, 1 hit PTHR10872:SF3, PTHR10872:SF3, 1 hit |
Pfami | View protein in Pfam PF00169, PH, 1 hit PF08916, Phe_ZIP, 1 hit PF00017, SH2, 1 hit |
PRINTSi | PR00401, SH2DOMAIN |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00252, SH2, 1 hit |
SUPFAMi | SSF109805, SSF109805, 1 hit SSF55550, SSF55550, 1 hit |
PROSITEi | View protein in PROSITE PS50001, SH2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | SH2B1_MOUSE | |
Accessioni | Q91ZM2Primary (citable) accession number: Q91ZM2 Secondary accession number(s): O54867 Q9WVM5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 18, 2008 |
Last sequence update: | March 18, 2008 | |
Last modified: | May 25, 2022 | |
This is version 146 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families