SH2B1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: SH2B1_MOUSE
• UniProt AC: Q91ZM2
• Protein Name: SH2B adapter protein 1
• Gene Name: Sh2b1
• Organism: Mus musculus (Mouse).
• Sequence Length: 756
• Subcellular Localization: Cytoplasm. Membrane . Nucleus. Shuttles between the nucleus and the cytoplasm..
• Protein Description: 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..
• Protein Sequence: MNGAPSPEDGVFPSPPALPPPPPPSWQEFCESHARAAALDLARRFRLYLASHPQYAEPGAEAAFSGRFAELFLQHFEAEVARASGSLSPPVLAPLSPGVEIPPSHDLSLESCRVGGPLAVLGPSRSSEDLAGPLPSSVPSSTTSSKPKLKKRFSLRSVGRSVRGSVRGILQWRGAVDSPSQAGPLETTSGPPVLGGNSNSNSSGGAGTVGRALANDGTSPGERWTHRFERLRLSRGGGTLKDGAGMIQREELLSFMGAEEAAPDPAGVGRGGGAAGLTSGGGGQPQWQKCRLLLRSEGEGGGGSRLEFFVPPKASRPRLSIPCSTITDVRTATALEMPDRENTFVVKVEGPSEYILETSDALHVKAWVSDIQECLSPGPCPAISPRPMTLPLAPGTSFFTKDNTDSLELPCLNHSESLPSQDLLLGPSESNDRLSQGAYGGLSDRPSASFSPSSASIAASHFDSMELLPPELPPRIPIEEGPPAGTVHPLSTPYPPLDTPEAATGSFLFQGESEGGEGDQPLSGYPWFHGMLSRLKAAQLVLEGGTGSHGVFLVRQSETRRGEYVLTFNFQGKAKHLRLSLNEEGQCRVQHLWFQSIFDMLEHFRVHPIPLESGGSSDVVLVSYVPSQRQQERSTSRDPAQPSEPPPWTDPPHPGAEEASGAPEVAAATAAAAKERQEKEKAGSGGVQEELVPVAELVPMVELEEAIAPGTEAQGGAGSSGDLEVSLMVQLQQLPLGGNGEEGGHPRAINNQYSFV

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
51	Phosphorylation	RFRLYLASHPQYAEP HHHHHHHHCCCCCCC	32.86	28066266
55	Phosphorylation	YLASHPQYAEPGAEA HHHHCCCCCCCCHHH	19.86	28066266
84	Phosphorylation	EAEVARASGSLSPPV HHHHHHHCCCCCCCE	24.30	25293948
86	Phosphorylation	EVARASGSLSPPVLA HHHHHCCCCCCCEEE	24.15	26745281
88	Phosphorylation	ARASGSLSPPVLAPL HHHCCCCCCCEEECC	28.93	25266776
96	Phosphorylation	PPVLAPLSPGVEIPP CCEEECCCCCCCCCC	20.67	25266776
104	Phosphorylation	PGVEIPPSHDLSLES CCCCCCCCCCCCCCC	25.03	26745281
124	Phosphorylation	PLAVLGPSRSSEDLA CEEEECCCCCCCCCC	42.89	26239621
126	Phosphorylation	AVLGPSRSSEDLAGP EEECCCCCCCCCCCC	42.28	27742792
127	Phosphorylation	VLGPSRSSEDLAGPL EECCCCCCCCCCCCC	33.74	27742792
136	Phosphorylation	DLAGPLPSSVPSSTT CCCCCCCCCCCCCCC	52.21	25619855
137	Phosphorylation	LAGPLPSSVPSSTTS CCCCCCCCCCCCCCC	35.79	25619855
140	Phosphorylation	PLPSSVPSSTTSSKP CCCCCCCCCCCCCCC	37.85	25619855
141	Phosphorylation	LPSSVPSSTTSSKPK CCCCCCCCCCCCCCC	29.63	25619855
142	Phosphorylation	PSSVPSSTTSSKPKL CCCCCCCCCCCCCCH	34.73	25619855
143	Phosphorylation	SSVPSSTTSSKPKLK CCCCCCCCCCCCCHH	32.71	25619855
144	Phosphorylation	SVPSSTTSSKPKLKK CCCCCCCCCCCCHHH	36.13	25619855
145	Phosphorylation	VPSSTTSSKPKLKKR CCCCCCCCCCCHHHC	51.38	25619855
154	Phosphorylation	PKLKKRFSLRSVGRS CCHHHCEEEHHCCHH	27.23	30372032
157	Phosphorylation	KKRFSLRSVGRSVRG HHCEEEHHCCHHHHH	33.93	29514104
161	Phosphorylation	SLRSVGRSVRGSVRG EEHHCCHHHHHHHHH	15.38	29514104
165	Phosphorylation	VGRSVRGSVRGILQW CCHHHHHHHHHHEEE	9.70	29514104
200	Phosphorylation	VLGGNSNSNSSGGAG CCCCCCCCCCCCCCC	37.60	29514104
202	Phosphorylation	GGNSNSNSSGGAGTV CCCCCCCCCCCCCHH	30.13	29514104
218	Phosphorylation	RALANDGTSPGERWT HHHCCCCCCCCCHHH	34.31	25521595
219	Phosphorylation	ALANDGTSPGERWTH HHCCCCCCCCCHHHH	36.12	25521595
225	Phosphorylation	TSPGERWTHRFERLR CCCCCHHHHHHHEEE	14.92	25338131
235	Methylation	FERLRLSRGGGTLKD HHEEEECCCCCCCCC	52.98	58859439
239	Phosphorylation	RLSRGGGTLKDGAGM EECCCCCCCCCCCCE	33.63	30387612
270	Methylation	PDPAGVGRGGGAAGL CCCCCCCCCCCCCCC	37.87	24129315
320	Phosphorylation	KASRPRLSIPCSTIT CCCCCCEECCCCCCC	26.26	22807455
369	Phosphorylation	LHVKAWVSDIQECLS EEHHHHHHHHHHHCC	20.49	26745281
376	Phosphorylation	SDIQECLSPGPCPAI HHHHHHCCCCCCCCC	39.20	22006019
384	Phosphorylation	PGPCPAISPRPMTLP CCCCCCCCCCCCCCC	19.57	30482847
389	Phosphorylation	AISPRPMTLPLAPGT CCCCCCCCCCCCCCC	28.10	26745281
396	Phosphorylation	TLPLAPGTSFFTKDN CCCCCCCCCCCCCCC	22.69	26745281
397	Phosphorylation	LPLAPGTSFFTKDNT CCCCCCCCCCCCCCC	25.03	26745281
415	Phosphorylation	ELPCLNHSESLPSQD CCCCCCCCCCCCCCC	28.01	21743459
417	Phosphorylation	PCLNHSESLPSQDLL CCCCCCCCCCCCCEE	48.90	21743459
420	Phosphorylation	NHSESLPSQDLLLGP CCCCCCCCCCEECCC	41.44	21743459
439	Phosphorylation	DRLSQGAYGGLSDRP CCCCCCCCCCCCCCC	20.67	28066266
443	Phosphorylation	QGAYGGLSDRPSASF CCCCCCCCCCCCCCC	34.54	28066266
494	Phosphorylation	VHPLSTPYPPLDTPE CCCCCCCCCCCCCCC	19.99	-
604 (in isoform 6)	Phosphorylation	-	6.78	29514104
613	Phosphorylation	VHPIPLESGGSSDVV ECCEECCCCCCCCEE	57.02	25338131
616	Phosphorylation	IPLESGGSSDVVLVS EECCCCCCCCEEEEE	27.22	29514104
617 (in isoform 6)	Phosphorylation	-	37.39	25338131
624	Phosphorylation	SDVVLVSYVPSQRQQ CCEEEEEECCCHHHH	14.65	29514104
624 (in isoform 3)	Phosphorylation	-	14.65	29514104
624 (in isoform 4)	Phosphorylation	-	14.65	29514104
637 (in isoform 3)	Phosphorylation	-	54.76	25338131
637 (in isoform 4)	Phosphorylation	-	54.76	25338131
753	Phosphorylation	PRAINNQYSFV---- CCCCCCCCCCC----	13.24	29514104

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
439	Y	Phosphorylation	Kinase	JAK1	P52332	Uniprot
439	Y	Phosphorylation	Kinase	JAK2	Q62120	Uniprot
439	Y	Phosphorylation	Kinase	PDGFR	-	Uniprot
494	Y	Phosphorylation	Kinase	JAK1	P52332	Uniprot
494	Y	Phosphorylation	Kinase	JAK2	Q62120	Uniprot

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of SH2B1_MOUSE !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of SH2B1_MOUSE !!

Protein-Protein Interaction

Oops, there are no PPI records of SH2B1_MOUSE !!

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"Large-scale phosphorylation analysis of mouse liver.";
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126 AND SER-127, ANDMASS SPECTROMETRY.
PubMed: 17242355