dbPTM

GRB10_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	GRB10_HUMAN
UniProt AC	Q13322
Protein Name	Growth factor receptor-bound protein 10
Gene Name	GRB10
Organism	Homo sapiens (Human).
Sequence Length	594
Subcellular Localization	Cytoplasm. When complexed with NEDD4 and IGF1R, follows IGF1R internalization, remaining associated with early endosomes. Uncouples from IGF1R-containing endosomes before the sorting of the receptor to the lysosomal compartment (By similarity)..
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. May play a role in mediating insulin-stimulated ubiquitination of INSR, leading to proteasomal degradation. 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	MALAGCPDSFLHHPYYQDKVEQTPRSQQDPAGPGLPAQSDRLANHQEDDVDLEALVNDMNASLESLYSACSMQSDTVPLLQNGQHARSQPRASGPPRSIQPQVSPRQRVQRSQPVHILAVRRLQEEDQQFRTSSLPAIPNPFPELCGPGSPPVLTPGSLPPSQAAAKQDVKVFSEDGTSKVVEILADMTARDLCQLLVYKSHCVDDNSWTLVEHHPHLGLERCLEDHELVVQVESTMASESKFLFRKNYAKYEFFKNPMNFFPEQMVTWCQQSNGSQTQLLQNFLNSSSCPEIQGFLHVKELGKKSWKKLYVCLRRSGLYCSTKGTSKEPRHLQLLADLEDSNIFSLIAGRKQYNAPTDHGLCIKPNKVRNETKELRLLCAEDEQTRTCWMTAFRLLKYGMLLYQNYRIPQQRKALLSPFSTPVRSVSENSLVAMDFSGQTGRVIENPAEAQSAALEEGHAWRKRSTRMNILGSQSPLHPSTLSTVIHRTQHWFHGRISREESHRIIKQQGLVDGLFLLRDSQSNPKAFVLTLCHHQKIKNFQILPCEDDGQTFFSLDDGNTKFSDLIQLVDFYQLNKGVLPCKLKHHCIRVAL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
15	Phosphorylation	DSFLHHPYYQDKVEQ CHHCCCCHHHHCCCC	14.92	25627689
16	Phosphorylation	SFLHHPYYQDKVEQT HHCCCCHHHHCCCCC	18.06	25627689
23	Phosphorylation	YQDKVEQTPRSQQDP HHHCCCCCCHHHCCC	13.73	22210691
62	Phosphorylation	LVNDMNASLESLYSA HHHHHHHHHHHHHHH	27.89	28348404
65	Phosphorylation	DMNASLESLYSACSM HHHHHHHHHHHHHHC	37.59	28348404
67	Phosphorylation	NASLESLYSACSMQS HHHHHHHHHHHHCCC	11.96	22817900
68	Phosphorylation	ASLESLYSACSMQSD HHHHHHHHHHHCCCC	28.26	28348404
71	Phosphorylation	ESLYSACSMQSDTVP HHHHHHHHCCCCCCC	21.41	28348404
74	Phosphorylation	YSACSMQSDTVPLLQ HHHHHCCCCCCCCCC	26.97	28348404
98	Phosphorylation	RASGPPRSIQPQVSP CCCCCCCCCCCCCCH	31.20	23403867
104	Phosphorylation	RSIQPQVSPRQRVQR CCCCCCCCHHHCHHH	14.76	19664994
112	Phosphorylation	PRQRVQRSQPVHILA HHHCHHHCCCEEEEE	23.03	29214152
132	Phosphorylation	EEDQQFRTSSLPAIP HHHHHHHHCCCCCCC	24.77	28270605
133	Phosphorylation	EDQQFRTSSLPAIPN HHHHHHHCCCCCCCC	26.14	28270605
134	Phosphorylation	DQQFRTSSLPAIPNP HHHHHHCCCCCCCCC	37.45	29496963
150	Phosphorylation	PELCGPGSPPVLTPG HHHCCCCCCCCCCCC	29.21	29978859
155	Phosphorylation	PGSPPVLTPGSLPPS CCCCCCCCCCCCCHH	26.32	29978859
158	Phosphorylation	PPVLTPGSLPPSQAA CCCCCCCCCCHHHHH	38.62	29978859
162	Phosphorylation	TPGSLPPSQAAAKQD CCCCCCHHHHHHHCC	30.43	28270605
171	Sumoylation	AAAKQDVKVFSEDGT HHHHCCCEEECCCCC	45.94	-
171	Ubiquitination	AAAKQDVKVFSEDGT HHHHCCCEEECCCCC	45.94	-
171	Sumoylation	AAAKQDVKVFSEDGT HHHHCCCEEECCCCC	45.94	-
174	Phosphorylation	KQDVKVFSEDGTSKV HCCCEEECCCCCHHH	37.45	20068231
178	Phosphorylation	KVFSEDGTSKVVEIL EEECCCCCHHHHHHH	37.38	20068231
179	Phosphorylation	VFSEDGTSKVVEILA EECCCCCHHHHHHHH	29.05	20068231
189	Phosphorylation	VEILADMTARDLCQL HHHHHHCCHHHHHHH	21.06	28851738
294	Ubiquitination	SSSCPEIQGFLHVKE CCCCCHHHCEEEHHH	34.62	29967540
300	Acetylation	IQGFLHVKELGKKSW HHCEEEHHHHCCCCH	36.15	22361499
304	Acetylation	LHVKELGKKSWKKLY EEHHHHCCCCHHHHH	57.15	22360989
304	Ubiquitination	LHVKELGKKSWKKLY EEHHHHCCCCHHHHH	57.15	-
306	Ubiquitination	VKELGKKSWKKLYVC HHHHCCCCHHHHHHH	47.84	29967540
311	Phosphorylation	KKSWKKLYVCLRRSG CCCHHHHHHHHHHCC	9.67	29496907
316	Methylation	KLYVCLRRSGLYCST HHHHHHHHCCCEECC	23.33	-
320	Phosphorylation	CLRRSGLYCSTKGTS HHHHCCCEECCCCCC	6.46	29496907
322	O-linked_Glycosylation	RRSGLYCSTKGTSKE HHCCCEECCCCCCCC	21.43	30620550
352	Ubiquitination	FSLIAGRKQYNAPTD HHHHCCCCCCCCCCC	57.10	-
399	Phosphorylation	TAFRLLKYGMLLYQN HHHHHHHHHHHHHCC	14.03	26434776
404	Phosphorylation	LKYGMLLYQNYRIPQ HHHHHHHHCCCCCHH	7.25	21082442
407	Phosphorylation	GMLLYQNYRIPQQRK HHHHHCCCCCHHHHH	8.39	23403867
418	Phosphorylation	QQRKALLSPFSTPVR HHHHHHHCCCCCCCC	25.42	22167270
421	Phosphorylation	KALLSPFSTPVRSVS HHHHCCCCCCCCCCC	34.87	22167270
422	Phosphorylation	ALLSPFSTPVRSVSE HHHCCCCCCCCCCCC	26.61	22167270
426	Phosphorylation	PFSTPVRSVSENSLV CCCCCCCCCCCCCEE	30.17	23401153
428	Phosphorylation	STPVRSVSENSLVAM CCCCCCCCCCCEEEE	32.10	23401153
430	Phosphorylation	PVRSVSENSLVAMDF CCCCCCCCCEEEEEC	32.89	32645325
431	Phosphorylation	VRSVSENSLVAMDFS CCCCCCCCEEEEECC	21.85	28555341
438	Phosphorylation	SLVAMDFSGQTGRVI CEEEEECCCCCCCEE	26.23	23403867
441	Phosphorylation	AMDFSGQTGRVIENP EEECCCCCCCEECCH	30.40	23403867
474	Phosphorylation	TRMNILGSQSPLHPS HHCEECCCCCCCCHH	24.84	29255136
476	Phosphorylation	MNILGSQSPLHPSTL CEECCCCCCCCHHHH	31.00	9006901
481	Phosphorylation	SQSPLHPSTLSTVIH CCCCCCHHHHHHHHH	31.09	29255136
482	Phosphorylation	QSPLHPSTLSTVIHR CCCCCHHHHHHHHHH	29.22	29255136
484	Phosphorylation	PLHPSTLSTVIHRTQ CCCHHHHHHHHHHCC	22.25	29255136
485	Phosphorylation	LHPSTLSTVIHRTQH CCHHHHHHHHHHCCC	26.96	28450419
508	Ubiquitination	EESHRIIKQQGLVDG HHHHHHHHHCCCCCE	33.91	-
514	Phosphorylation	IKQQGLVDGLFLLRD HHHCCCCCEEEEEEC	53.79	32645325
525	Phosphorylation	LLRDSQSNPKAFVLT EEECCCCCCCEEEEE	34.16	32645325

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
67	Y	Phosphorylation	Kinase	FYN	P06241	PSP
67	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
67	Y	Phosphorylation	Kinase	TEC	P42680	Uniprot
67	Y	Phosphorylation	Kinase	SRC	P12931	PSP
150	S	Phosphorylation	Kinase	MK03	P27361	PhosphoELM
150	S	Phosphorylation	Kinase	MTOR	P42345	Uniprot
150	S	Phosphorylation	Kinase	ERK1	Q7M0H9	PSP
150	S	Phosphorylation	Kinase	MK01	P28482	PhosphoELM
150	S	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
155	T	Phosphorylation	Kinase	MTOR	P42345	PSP
418	S	Phosphorylation	Kinase	MAPK3	P27361	Uniprot
418	S	Phosphorylation	Kinase	MAPK1	P28482	Uniprot
418	S	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
428	S	Phosphorylation	Kinase	MTOR	P42345	Uniprot
428	S	Phosphorylation	Kinase	AKT1	P31749	Uniprot
476	S	Phosphorylation	Kinase	MK01	P28482	PhosphoELM
476	S	Phosphorylation	Kinase	MK03	P27361	PhosphoELM
476	S	Phosphorylation	Kinase	MTOR	P42345	Uniprot
476	S	Phosphorylation	Kinase	ERK1	Q7M0H9	PSP
476	S	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of GRB10_HUMAN !!

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_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
GGYF2_HUMAN	GIGYF2	physical	12771153
GGYF1_HUMAN	GIGYF1	physical	12771153
IGF1R_HUMAN	IGF1R	physical	12697834
INSR_HUMAN	INSR	physical	10871840
INSR_HUMAN	INSR	physical	8621530
IRS1_HUMAN	IRS1	physical	8621530
RAF1_HUMAN	RAF1	physical	10585452
INSR_HUMAN	INSR	physical	7479769
VGFR2_HUMAN	KDR	physical	11494124
INSR_HUMAN	INSR	physical	9506989
IGF1R_HUMAN	IGF1R	physical	9506989
EGFR_HUMAN	EGFR	physical	9506989
KIT_HUMAN	KIT	physical	11809791
RAF1_HUMAN	RAF1	physical	9553107
MP2K1_HUMAN	MAP2K1	physical	9553107
RET_HUMAN	RET	physical	7665556
GHR_HUMAN	GHR	physical	9632636
JAK2_HUMAN	JAK2	physical	9632636
INSR_HUMAN	INSR	physical	9006901
NEDD4_HUMAN	NEDD4	physical	15060076
NOA1_HUMAN	NOA1	physical	21900206
IRS1_HUMAN	IRS1	physical	12783867
IRS2_HUMAN	IRS2	physical	12783867
INSR_HUMAN	INSR	physical	15664450
A4_HUMAN	APP	physical	21832049
AKT1_HUMAN	AKT1	physical	15722337
1433E_HUMAN	YWHAE	physical	15722337
CHFR_HUMAN	CHFR	physical	25578860
SYNC_HUMAN	NARS	physical	26344197
BAIP2_HUMAN	BAIAP2	physical	25814554
RCAN3_HUMAN	RCAN3	physical	25814554
NED4L_HUMAN	NEDD4L	physical	27146988
NED4L_HUMAN	NEDD4L	physical	27742835

Drug and Disease Associations

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

Regulatory Network of GRB10_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling."; Hsu P.P., Kang S.A., Rameseder J., Zhang Y., Ottina K.A., Lim D.,Peterson T.R., Choi Y., Gray N.S., Yaffe M.B., Marto J.A.,Sabatini D.M.; Science 332:1317-1322(2011). Cited for: PHOSPHORYLATION AT SER-150; SER-428 AND SER-476 BY MTOR, AND ENZYMEREGULATION.	21659604 [Abstract]
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-104, AND MASSSPECTROMETRY.	19413330 [Abstract]
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-104; SER-418 ANDTHR-422, AND MASS SPECTROMETRY.	18669648 [Abstract]
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT forefficient phosphoproteomic analysis."; Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,Yates J.R. III; J. Proteome Res. 7:1346-1351(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-418, AND MASSSPECTROMETRY.	18220336 [Abstract]
"A probability-based approach for high-throughput proteinphosphorylation analysis and site localization."; Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; Nat. Biotechnol. 24:1285-1292(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-104, AND MASSSPECTROMETRY.	16964243 [Abstract]
"Phosphorylation of Grb10 by mitogen-activated protein kinase:identification of Ser150 and Ser476 of human Grb10zeta as majorphosphorylation sites."; Langlais P., Wang C., Dong L.Q., Carroll C.A., Weintraub S.T., Liu F.; Biochemistry 44:8890-8897(2005). Cited for: PROTEIN SEQUENCE OF 415-425, PHOSPHORYLATION AT SER-150; SER-418 ANDSER-476, AND MUTAGENESIS OF SER-104; SER-150; SER-418 AND SER-476.	15952796 [Abstract]
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer."; Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; Cell 131:1190-1203(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-404, AND MASSSPECTROMETRY.	18083107 [Abstract]
"Grb10/GrbIR as an in vivo substrate of Tec tyrosine kinase."; Mano H., Ohya K., Miyazato A., Yamashita Y., Ogawa W., Inazawa J.,Ikeda U., Shimada K., Hatake K., Kasuga M., Ozawa K., Kajigaya S.; Genes Cells 3:431-441(1998). Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PHOSPHORYLATION AT TYR-67.	9753425 [Abstract]