SH2B1_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: SH2B1_RAT
• UniProt AC: Q62985
• Protein Name: SH2B adapter protein 1
• Gene Name: Sh2b1
• Organism: Rattus norvegicus (Rat).
• 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. Isoforms seem to be differentially involved in IGF-I and PDGF-induced mitogenesis (By similarity)..
• Protein Sequence: MNGAPSPEDGVFPSPPALPPPPPPSWQEFCESHARAAALDLARRFRLYLASHPQYAEPGAEAAFSGRFAELFLQHFEAEVARASGSLSPPVLAPLSPGVEIPPSHDLSLESCRVGGPLAVLGPSRSSEDLAGPLPSSVSSSTTSSKPKLKKRFSLRSVGRSVRGSVRGILQWRGAVESPSQAGPLETTSGPPVLGGNSNSNSSGGAGTVGRALANDGTSPGERWTHRFERLRLSRGGGTLRDGAGVIQREELLSFMGAEEAAPDPAGVGRGGGAAGLTSGGGGQPQWQKCRLLLRSEGEGGGGSRLEFFVPPKASRPRLSIPCSTITDVRTATALEMPDRENTFVVKVEGPSEYILETTDALHVKAWVSDIQECLSPGPCPAISPRPMTLPLAPGTSFLTKDNTESLELPCLNHSESLPSQDLLLGPSESNDRLSQGAYGGLSDRPSASFSPSSASIAASHFDSMELLPPELPPRIPIEEGPPAGTVHPLSTPYPPLDTPEAATGSFLFQGEAEGGEGDQPLSGYPWFHGMLSRLKAAQLVLEGGTSSHGVFLVRQSETRRGEYVLTFNFQGKAKHLRLSLNEEGQCRVQHLWFQSIFDMLEHFRVHPIPLESGGSSDVVLVSYVPSQRQQERSTSRDPTQPSEPPPWTDPPHPGAEEASGAPEVAAATAAAAKERQEKEKAGGGGVQEELVPMAELVPMAELEEAIAPGTEAQGGAGSSGDLEVSLMVQLQQLPLGGNGEEGGHPRAINNQYSFV

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
48	Phosphorylation	LARRFRLYLASHPQY HHHHHHHHHHHCCCC	8.93	16641100
51	Phosphorylation	RFRLYLASHPQYAEP HHHHHHHHCCCCCCC	32.86	16641100
65	Phosphorylation	PGAEAAFSGRFAELF CCHHHHHHHHHHHHH	25.08	16641100
84	Phosphorylation	EAEVARASGSLSPPV HHHHHHHCCCCCCCE	24.30	27097102
86	Phosphorylation	EVARASGSLSPPVLA HHHHHCCCCCCCEEE	24.15	27097102
88	Phosphorylation	ARASGSLSPPVLAPL HHHCCCCCCCEEECC	28.93	27097102
96	Phosphorylation	PPVLAPLSPGVEIPP CCEEECCCCCCCCCC	20.67	27097102
104	Phosphorylation	PGVEIPPSHDLSLES CCCCCCCCCCCCCCC	25.03	27097102
108	Phosphorylation	IPPSHDLSLESCRVG CCCCCCCCCCCCCCC	35.83	27097102
111	Phosphorylation	SHDLSLESCRVGGPL CCCCCCCCCCCCCCE	16.71	27097102
124	Phosphorylation	PLAVLGPSRSSEDLA CEEEECCCCCCCCCC	42.89	23984901
126	Phosphorylation	AVLGPSRSSEDLAGP EEECCCCCCCCCCCC	42.28	29779826
127	Phosphorylation	VLGPSRSSEDLAGPL EECCCCCCCCCCCCC	33.74	27097102
139	Phosphorylation	GPLPSSVSSSTTSSK CCCCCCCCCCCCCCC	22.10	28689409
140	Phosphorylation	PLPSSVSSSTTSSKP CCCCCCCCCCCCCCC	29.55	28689409
154	Phosphorylation	PKLKKRFSLRSVGRS CCHHHCEEEHHHCHH	27.23	25532521
161	Phosphorylation	SLRSVGRSVRGSVRG EEHHHCHHHHHHHHH	15.38	-
165	Phosphorylation	VGRSVRGSVRGILQW HCHHHHHHHHHHEEE	9.70	-
178	Phosphorylation	QWRGAVESPSQAGPL EECCCCCCHHHCCCC	24.21	25575281
180	Phosphorylation	RGAVESPSQAGPLET CCCCCCHHHCCCCCC	41.77	25575281
187	Phosphorylation	SQAGPLETTSGPPVL HHCCCCCCCCCCCCC	33.66	25575281
188	Phosphorylation	QAGPLETTSGPPVLG HCCCCCCCCCCCCCC	23.47	25575281
189	Phosphorylation	AGPLETTSGPPVLGG CCCCCCCCCCCCCCC	57.64	25575281
218	Phosphorylation	RALANDGTSPGERWT HHHCCCCCCCCCHHH	34.31	27097102
219	Phosphorylation	ALANDGTSPGERWTH HHCCCCCCCCCHHHH	36.12	27097102
270	Methylation	PDPAGVGRGGGAAGL CCCCCCCCCCCCCCC	37.87	-
320	Phosphorylation	KASRPRLSIPCSTIT CCCCCCEECCCCCCC	26.26	25575281
376	Phosphorylation	SDIQECLSPGPCPAI HHHHHHCCCCCCCCC	39.20	27097102
384	Phosphorylation	PGPCPAISPRPMTLP CCCCCCCCCCCCCCC	19.57	27097102
404	Phosphorylation	SFLTKDNTESLELPC CEECCCCCCCCCCCC	36.76	27097102
406	Phosphorylation	LTKDNTESLELPCLN ECCCCCCCCCCCCCC	25.71	27097102
415	Phosphorylation	ELPCLNHSESLPSQD CCCCCCCCCCCCCCC	28.01	28689409
417	Phosphorylation	PCLNHSESLPSQDLL CCCCCCCCCCCCCEE	48.90	27097102
420	Phosphorylation	NHSESLPSQDLLLGP CCCCCCCCCCEECCC	41.44	27097102
428	Phosphorylation	QDLLLGPSESNDRLS CCEECCCCCCCCCCC	52.43	27097102
430	Phosphorylation	LLLGPSESNDRLSQG EECCCCCCCCCCCCC	48.66	27097102
435	Phosphorylation	SESNDRLSQGAYGGL CCCCCCCCCCCCCCC	27.71	30181290
439	Phosphorylation	DRLSQGAYGGLSDRP CCCCCCCCCCCCCCC	20.67	12551917
494	Phosphorylation	VHPLSTPYPPLDTPE CCCCCCCCCCCCCCC	19.99	10757801

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
96	S	Phosphorylation	Kinase	MAPK1	P63086	Uniprot
96	S	Phosphorylation	Kinase	MAPK3	P21708	Uniprot
96	S	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
439	Y	Phosphorylation	Kinase	JAK1	G3V9W2	GPS
439	Y	Phosphorylation	Kinase	JAK2	Q62689	Uniprot
439	Y	Phosphorylation	Kinase	PDGFRB	Q05030	GPS
439	Y	Phosphorylation	Kinase	PDGFR-FAMILY	-	GPS
439	Y	Phosphorylation	Kinase	PDGFR	-	Uniprot
439	Y	Phosphorylation	Kinase	JAK1	-	Uniprot
494	Y	Phosphorylation	Kinase	JAK1	G3V9W2	GPS
494	Y	Phosphorylation	Kinase	JAK2	Q62689	Uniprot
494	Y	Phosphorylation	Kinase	JAK1	-	Uniprot

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of SH2B1_RAT !!

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_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
JAK2_RAT	Jak2	physical	17565041
JAK2_MOUSE	Jak2	physical	12551917
PGFRB_HUMAN	PDGFRB	physical	12551917
JAK2_MOUSE	Jak2	physical	10757801
NTRK1_RAT	Ntrk1	physical	22028877

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"YXXL motifs in SH2-Bbeta are phosphorylated by JAK2, JAK1, andplatelet-derived growth factor receptor and are required for membraneruffling.";
O'Brien K.B., Argetsinger L.S., Diakonova M., Carter-Su C.;
J. Biol. Chem. 278:11970-11978(2003).
Cited for: PHOSPHORYLATION AT TYR-439 AND TYR-494, AND MUTAGENESIS OF TYR-439 ANDTYR-494.
PubMed: 12551917