DegronMD - Q9NRF2(SH2B1)

FUNCTION: 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. Isoforms seem to be differentially involved in IGF-I and PDGF-induced mitogenesis (By similarity). {ECO:0000250, ECO:0000269|PubMed:11827956, ECO:0000269|PubMed:14565960, ECO:0000269|PubMed:15767667, ECO:0000269|PubMed:16569669, ECO:0000269|PubMed:17471236, ECO:0000269|PubMed:9694882, ECO:0000269|PubMed:9742218}. View more >>

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GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.D328E	TCGA-17-Z036	LUAD	TCGA	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation rewiring degron network	0.3056
p.D128Y	TCGA-43-6143	LUSC	TCGA	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation rewiring degron network	0.0833
p.D128Y	DO26428	LUSC	ICGC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation rewiring degron network	0.0833
p.A334D	TCGA-78-7150	LUAD	TCGA	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation rewiring degron network	0.3056
p.A334D	DO24411	LUAD	ICGC	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation rewiring degron network	0.3056
p.A334D	SIDM00190	Melanoma	GDSC	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation rewiring degron network	0.3056
p.A334D	CP66-MEL	skin	COSMIC	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation rewiring degron network	0.3056
p.R330W	TCGA-A8-A076	BRCA	TCGA	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation altering degron motif	0.7523
p.R330W	DO2617	BRCA	ICGC	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation altering degron motif	0.7523
p.R330W	DO222586	ESCA	ICGC	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation altering degron motif	0.7523
p.E341D	TCGA-AC-A23H	BRCA	TCGA	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation rewiring degron network	0.1111
p.E341D	TCGA-B0-5104	KIRC	TCGA	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation rewiring degron network	0.1111
p.A748V	TCGA-CK-4951	COAD	TCGA	RAINNQYS	CBL_APS	747:754	Mutation altering degron motif	0.6936
p.A748V	DO10582	COAD	ICGC	RAINNQYS	CBL_APS	747:754	Mutation altering degron motif	0.6936
p.T143A	TCGA-CM-4746	COAD	TCGA	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.1111
p.T143A	TCGA-CM-4746	COAD	TCGA	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation rewiring degron network	0.2778
p.T143A	DO7882	COAD	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.1111
p.T143A	DO7882	COAD	ICGC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation rewiring degron network	0.2778
p.R156H	TCGA-CM-6674	COAD	TCGA	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation altering degron motif	0.7133
p.R156H	TCGA-FP-A4BE	STAD	TCGA	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation altering degron motif	0.7133
p.R156H	DO10092	COAD	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation altering degron motif	0.7133
p.R156H	DO50660	ORCA	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation altering degron motif	0.7133
p.R156H	DO48016	STAD	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation altering degron motif	0.7133
p.S165L	TCGA-DD-A3A2	LIHC	TCGA	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation blocking phosphorylation signal	0.6111
p.S165L	DO44881	LIHC	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation blocking phosphorylation signal	0.6111
p.S324C	TCGA-EK-A3GK	CESC	TCGA	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation rewiring degron network	0.1944
p.S324C	DO49964	CESC	ICGC	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation rewiring degron network	0.1944
p.R152H	TCGA-EO-A22R	UCEC	TCGA	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation altering degron motif	0.8244
p.R152H	DO230320	COCA	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation altering degron motif	0.8244
p.R152H	DO42713	UCEC	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation altering degron motif	0.8244
p.D339H	TCGA-G2-A2EJ	BLCA	TCGA	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation rewiring degron network	0.1667
p.D339H	DO554	BLCA	ICGC	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation rewiring degron network	0.1667
p.R330G	TCGA-K4-A4AC	BLCA	TCGA	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation altering degron motif	0.6457
p.R330G	DO542	BLCA	ICGC	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation altering degron motif	0.6457
p.R163Q	TCGA-LB-A7SX	PAAD	TCGA	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.2222
p.R163Q	DO230347	COCA	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.2222
p.R163Q	DO49409	PAAD	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.2222
p.R156L	TCGA-MP-A4T4	LUAD	TCGA	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation altering degron motif	0.7316
p.R156L	DO45357	LUAD	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation altering degron motif	0.7316
p.R167C	DO222817	BTCA	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.1111
p.T148A	DO230334	COCA	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation substituting flanking lysine	0.3611
p.T148A	DO230334	COCA	ICGC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation substituting flanking lysine	0.25
p.T148A	DO228941	LICA	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation substituting flanking lysine	0.3611
p.T148A	DO228941	LICA	ICGC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation substituting flanking lysine	0.25
p.T148A	DO229047	LICA	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation substituting flanking lysine	0.3611
p.T148A	DO229047	LICA	ICGC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation substituting flanking lysine	0.25
p.T331I	DO224744	COCA	ICGC	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation altering degron motif	0.7078
p.R139H	DO222737	COCA	ICGC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation altering degron motif	0.8244
p.R139H	LS-1034	large intestine	COSMIC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation altering degron motif	0.8244
p.G169W	DO22237	LGG	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.0556
p.G169W	DO41235	UCEC	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.0556
p.T168R	DO24409	LUAD	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.0833
p.P138L	DO45517	LUSC	ICGC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation altering degron motif	0.7582
p.P153S	DO220872	MELA	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation altering degron motif	0.6752
p.H745Y	DO222837	MELA	ICGC	RAINNQYS	CBL_APS	747:754	Mutation rewiring degron network	0.2778
p.L149I	DO50682	ORCA	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.2778
p.L149I	DO50682	ORCA	ICGC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation rewiring degron network	0.1111
p.P141S	DO47263	SKCM	ICGC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation altering degron motif	0.6752
p.E165K	DO37418	SKCM	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation blocking phosphorylation signal	0.6111
p.P164L	DO229245	THCA	ICGC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.1944
p.P164L	KARPAS-45	haematopoietic and lymphoid tissue	COSMIC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.1944
p.S128L	DO41572	UCEC	ICGC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation rewiring degron network	0.0833
p.S128L	DO42793	UCEC	ICGC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation rewiring degron network	0.0833
p.V162I	SIDM00660	Colorectal Carcinoma	GDSC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.25
p.V162I	ACH-000985	Colon/Colorectal Cancer	CCLE	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.25
p.V162I	LS-411N	large intestine	COSMIC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.25
p.R320Q	ACH-000895	Colon/Colorectal Cancer	CCLE	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation blocking phosphorylation signal	0.5278
p.R320Q	CL-34	large intestine	COSMIC	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation blocking phosphorylation signal	0.5278
p.A145T	ACH-000911	Gastric Cancer	CCLE	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.1667
p.A145T	ACH-000911	Gastric Cancer	CCLE	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation rewiring degron network	0.2222
p.A145T	NUGC-3	stomach	COSMIC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.1667
p.A145T	NUGC-3	stomach	COSMIC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation rewiring degron network	0.2222
p.R165C	ACH-002189	Kidney Cancer	CCLE	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation blocking phosphorylation signal	0.6111
p.R165C	RCC-FG2	kidney	COSMIC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation blocking phosphorylation signal	0.6111
p.R139C	RCC-FG2	kidney	COSMIC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation altering degron motif	0.8301
p.P160L	MCC13	skin	COSMIC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.3056
p.P134T	TC-71	bone	COSMIC	VSSSS	DEG_SPOP_SBC_1	137:141	Mutation rewiring degron network	0.25
p.R165H	LS-1034	large intestine	COSMIC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation blocking phosphorylation signal	0.6111
p.A326V	LCLC-97TM1	lung	COSMIC	VRTTT	DEG_SPOP_SBC_1	329:333	Mutation rewiring degron network	0.25
p.P160T	TC-71	bone	COSMIC	KRFSLRSVG	DEG_APCC_DBOX_1	151:159	Mutation rewiring degron network	0.3056

DegronMD: protein-targeted degradation, mutation and drug response to degrons

SH2B1

UniProt ID: Q9NRF2

Entrez ID: 25970

Protein name: SH2B adapter protein 1 (Pro-rich, PH and SH2 domain-containing signaling mediator) (PSM) (SH2 domain-containing protein 1B)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for SH2B1 in