dbPTM

GRB10_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	GRB10_MOUSE
UniProt AC	Q60760
Protein Name	Growth factor receptor-bound protein 10
Gene Name	Grb10
Organism	Mus musculus (Mouse).
Sequence Length	621
Subcellular Localization	Cytoplasm . When complexed with NEDD4 and IGF1R, follows IGF1R internalization, remaining associated with early endosomes. Uncouples from IGF1R before the sorting of the receptor to the lysosomal compartment.
Protein Description	Adapter protein which modulates coupling of a number of cell surface receptor kinases with specific signaling pathways. Binds to, and suppress signals from, activated receptors tyrosine kinases, including the insulin (INSR) and insulin-like growth factor (IGF1R) receptors. The inhibitory effect can be achieved by 2 mechanisms: interference with the signaling pathway and increased receptor degradation. Delays and reduces AKT1 phosphorylation in response to insulin stimulation. Blocks association between INSR and IRS1 and IRS2 and prevents insulin-stimulated IRS1 and IRS2 tyrosine phosphorylation. Recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased internalization and degradation by both the proteasomal and lysosomal pathways. A similar role in the mediation of ubiquitination has also been suggested with INSR. Negatively regulates Wnt signaling by interacting with LRP6 intracellular portion and interfering with the binding of AXIN1 to LRP6. Positive regulator of the KDR/VEGFR-2 signaling pathway. May inhibit NEDD4-mediated degradation of KDR/VEGFR-2..
Protein Sequence	MNNDINSSVESLNSACNMQSDTDTAPLLEDGQHASNQGAASSSRGQPQASPRQKMQRSQPVHILRRLQEEDQQLRTASLPAIPNPFPELTGAAPGSPPSVAPSSLPPPPSQPPAKHCGRCEKWIPGENTRGNGKRKIWRWQFPPGFQLSKLTRPGLWTKTTARFSKKQPKNQCPTDTVNPVARMPTSQMEKLRLRKDVKVFSEDGTSKVVEILTDMTARDLCQLLVYKSHCVDDNSWTLVEHHPQLGLERCLEDHEIVVQVESTMPSESKFLFRKNYAKYEFFKNPVNFFPDQMVNWCQQSNGGQAQLLQNFLNTSSCPEIQGFLQVKEVGRKSWKKLYVCLRRSGLYYSTKGTSKEPRHLQLLADLEESSIFYLIAGKKQYNAPNEHGMCIKPNKAKTEMKELRLLCAEDEQIRTCWMTAFRLLKYGMLLYQNYRIPQRKGLPPPFNAPMRSVSENSLVAMDFSGQIGRVIDNPAEAQSAALEEGHAWRKRSTRMNILSSQSPLHPSTLNAVIHRTQHWFHGRISREESHRIIKQQGLVDGLFLLRDSQSNPKAFVLTLCHHQKIKNFQILPCEDDGQTFFTLDDGNTKFSDLIQLVDFYQLNKGVLPCKLKHHCIRVAL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
8	Phosphorylation	MNNDINSSVESLNSA CCCHHHHHHHHHHHH	25.97	25338131
11	Phosphorylation	DINSSVESLNSACNM HHHHHHHHHHHHHCC	30.60	25338131
50	Phosphorylation	SRGQPQASPRQKMQR CCCCCCCCHHHHHHH	18.50	26824392
58	Phosphorylation	PRQKMQRSQPVHILR HHHHHHHHCHHHHHH	23.19	25338131
76	Phosphorylation	EEDQQLRTASLPAIP HHHHHHHHCCCCCCC	29.23	21659605
78	Phosphorylation	DQQLRTASLPAIPNP HHHHHHCCCCCCCCC	33.98	25777480
90	Phosphorylation	PNPFPELTGAAPGSP CCCCHHHCCCCCCCC	24.10	26824392
96	Phosphorylation	LTGAAPGSPPSVAPS HCCCCCCCCCCCCCC	32.36	26824392
99	Phosphorylation	AAPGSPPSVAPSSLP CCCCCCCCCCCCCCC	34.00	21659605
103	Phosphorylation	SPPSVAPSSLPPPPS CCCCCCCCCCCCCCC	34.47	26060331
104	Phosphorylation	PPSVAPSSLPPPPSQ CCCCCCCCCCCCCCC	43.78	21659605
104 (in isoform 3)	Phosphorylation	-	43.78	29514104
110	Phosphorylation	SSLPPPPSQPPAKHC CCCCCCCCCCCCCCC	62.18	25293948
126 (in isoform 3)	Phosphorylation	-	31.49	29514104
127 (in isoform 3)	Phosphorylation	-	50.50	29514104
160	Phosphorylation	RPGLWTKTTARFSKK CCCCCCHHCCCCCCC	20.50	20139300
165	Phosphorylation	TKTTARFSKKQPKNQ CHHCCCCCCCCCCCC	33.13	20139300
166	Ubiquitination	KTTARFSKKQPKNQC HHCCCCCCCCCCCCC	53.36	27667366
187	Phosphorylation	PVARMPTSQMEKLRL CCCCCCHHHHHHHHH	22.97	29514104
191	Ubiquitination	MPTSQMEKLRLRKDV CCHHHHHHHHHCCCC	33.30	22790023
202	Phosphorylation	RKDVKVFSEDGTSKV CCCCEEECCCCCHHH	37.45	26824392
206	Phosphorylation	KVFSEDGTSKVVEIL EEECCCCCHHHHHHH	37.38	26824392
207	Phosphorylation	VFSEDGTSKVVEILT EECCCCCHHHHHHHH	29.05	29514104
227	Phosphorylation	DLCQLLVYKSHCVDD HHHHHHHHHHHCCCC	13.52	29514104
272	Ubiquitination	MPSESKFLFRKNYAK CCCCCHHHEECCCCC	4.70	27667366
280	Phosphorylation	FRKNYAKYEFFKNPV EECCCCCCHHHCCCC	15.14	29514104
327	Ubiquitination	EIQGFLQVKEVGRKS HHHCCEEHHHHCCHH	6.58	27667366
339	Phosphorylation	RKSWKKLYVCLRRSG CHHHHHHHHHHHHCC	9.67	29514104
345	Phosphorylation	LYVCLRRSGLYYSTK HHHHHHHCCCEEECC	27.07	25338131
348	Phosphorylation	CLRRSGLYYSTKGTS HHHHCCCEEECCCCC	10.01	29514104
352	Ubiquitination	SGLYYSTKGTSKEPR CCCEEECCCCCCCCC	55.01	27667366
416	Phosphorylation	AEDEQIRTCWMTAFR CCCHHHHHHHHHHHH	16.49	21183079
430	Phosphorylation	RLLKYGMLLYQNYRI HHHHHHHHHHHCCCC	3.32	24719451
432	Phosphorylation	LKYGMLLYQNYRIPQ HHHHHHHHHCCCCCH	7.25	29514104
433	Phosphorylation	KYGMLLYQNYRIPQR HHHHHHHHCCCCCHH	40.21	24719451
435	Phosphorylation	GMLLYQNYRIPQRKG HHHHHHCCCCCHHCC	8.39	29514104
441	Ubiquitination	NYRIPQRKGLPPPFN CCCCCHHCCCCCCCC	60.60	22790023
453	Phosphorylation	PFNAPMRSVSENSLV CCCCCCCCCCCCCEE	24.60	27087446
455	Phosphorylation	NAPMRSVSENSLVAM CCCCCCCCCCCEEEE	32.10	27087446
458	Phosphorylation	MRSVSENSLVAMDFS CCCCCCCCEEEEECC	21.85	27087446
465	Phosphorylation	SLVAMDFSGQIGRVI CEEEEECCCCHHCEE	26.06	-
478	Phosphorylation	VIDNPAEAQSAALEE EECCHHHHHHHHHHH	15.67	24719451
480	Phosphorylation	DNPAEAQSAALEEGH CCHHHHHHHHHHHCC	23.66	29514104
494	Phosphorylation	HAWRKRSTRMNILSS CHHHHHHHHHHHHHC	37.66	29514104
500	Phosphorylation	STRMNILSSQSPLHP HHHHHHHHCCCCCCH	23.64	26824392
501	Phosphorylation	TRMNILSSQSPLHPS HHHHHHHCCCCCCHH	31.09	21659605
503	Phosphorylation	MNILSSQSPLHPSTL HHHHHCCCCCCHHHH	31.23	26824392
508	Phosphorylation	SQSPLHPSTLNAVIH CCCCCCHHHHHHHHH	34.48	25777480
509	Phosphorylation	QSPLHPSTLNAVIHR CCCCCHHHHHHHHHH	28.60	25777480
535	Ubiquitination	EESHRIIKQQGLVDG HHHHHHHHHCCCCCE	33.91	22790023

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
103	S	Phosphorylation	Kinase	MTOR	Q9JLN9	PSP
104	S	Phosphorylation	Kinase	MTOR	Q9JLN9	PSP
455	S	Phosphorylation	Kinase	AKT1	P31750	Uniprot
455	S	Phosphorylation	Kinase	MTOR	Q9JLN9	Uniprot
455	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
455	S	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM
501	S	Phosphorylation	Kinase	MTOR	P42345	PSP
503	S	Phosphorylation	Kinase	MTOR	P42345	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of GRB10_MOUSE !!

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of GRB10_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
NEDD4_MOUSE	Nedd4	physical	10446181
IRS2_MOUSE	Irs2	physical	12783867

Drug and Disease Associations

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

Regulatory Network of GRB10_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"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-458, AND MASSSPECTROMETRY.	17242355 [Abstract]