dbPTM

CBLB_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	CBLB_HUMAN
UniProt AC	Q13191
Protein Name	E3 ubiquitin-protein ligase CBL-B
Gene Name	CBLB
Organism	Homo sapiens (Human).
Sequence Length	982
Subcellular Localization	Cytoplasm . Upon EGF stimulation, associates with endocytic vesicles.
Protein Description	E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3..
Protein Sequence	MANSMNGRNPGGRGGNPRKGRILGIIDAIQDAVGPPKQAAADRRTVEKTWKLMDKVVRLCQNPKLQLKNSPPYILDILPDTYQHLRLILSKYDDNQKLAQLSENEYFKIYIDSLMKKSKRAIRLFKEGKERMYEEQSQDRRNLTKLSLIFSHMLAEIKAIFPNGQFQGDNFRITKADAAEFWRKFFGDKTIVPWKVFRQCLHEVHQISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWGSILRNWNFLAVTHPGYMAFLTYDEVKARLQKYSTKPGSYIFRLSCTRLGQWAIGYVTGDGNILQTIPHNKPLFQALIDGSREGFYLYPDGRSYNPDLTGLCEPTPHDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTAWQESDGQGCPFCRCEIKGTEPIIVDPFDPRDEGSRCCSIIDPFGMPMLDLDDDDDREESLMMNRLANVRKCTDRQNSPVTSPGSSPLAQRRKPQPDPLQIPHLSLPPVPPRLDLIQKGIVRSPCGSPTGSPKSSPCMVRKQDKPLPAPPPPLRDPPPPPPERPPPIPPDNRLSRHIHHVESVPSRDPPMPLEAWCPRDVFGTNQLVGCRLLGEGSPKPGITASSNVNGRHSRVGSDPVLMRKHRRHDLPLEGAKVFSNGHLGSEEYDVPPRLSPPPPVTTLLPSIKCTGPLANSLSEKTRDPVEEDDDEYKIPSSHPVSLNSQPSHCHNVKPPVRSCDNGHCMLNGTHGPSSEKKSNIPDLSIYLKGDVFDSASDPVPLPPARPPTRDNPKHGSSLNRTPSDYDLLIPPLGEDAFDALPPSLPPPPPPARHSLIEHSKPPGSSSRPSSGQDLFLLPSDPFVDLASGQVPLPPARRLPGENVKTNRTSQDYDQLPSCSDGSQAPARPPKPRPRRTAPEIHHRKPHGPEAALENVDAKIAKLMGEGYAFEEVKRALEIAQNNVEVARSILREFAFPPPVSPRLNL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
8	Methylation	MANSMNGRNPGGRGG CCCCCCCCCCCCCCC	40.96	-
13	Methylation	NGRNPGGRGGNPRKG CCCCCCCCCCCCCCC	56.62	-
18	Methylation	GGRGGNPRKGRILGI CCCCCCCCCCCHHHH	59.05	-
48	Ubiquitination	ADRRTVEKTWKLMDK HHHHHHHHHHHHHHH	56.18	-
48	Acetylation	ADRRTVEKTWKLMDK HHHHHHHHHHHHHHH	56.18	25953088
48	Succinylation	ADRRTVEKTWKLMDK HHHHHHHHHHHHHHH	56.18	23954790
48	Malonylation	ADRRTVEKTWKLMDK HHHHHHHHHHHHHHH	56.18	26320211
64	Ubiquitination	VRLCQNPKLQLKNSP HHHHCCCCCCCCCCC	57.31	-
92	Phosphorylation	LRLILSKYDDNQKLA HHHHHHHCCCCHHHH	25.75	-
97	Ubiquitination	SKYDDNQKLAQLSEN HHCCCCHHHHHHCCC	52.63	-
106	Phosphorylation	AQLSENEYFKIYIDS HHHCCCHHHHHHHHH	23.04	-
133	Phosphorylation	KEGKERMYEEQSQDR HHHHHHHHHHHHHHH	23.64	-
175	Ubiquitination	GDNFRITKADAAEFW CCCEEEEHHHHHHHH	41.73	-
276	Phosphorylation	VKARLQKYSTKPGSY HHHHHHHHCCCCCCE	14.49	-
277	Phosphorylation	KARLQKYSTKPGSYI HHHHHHHCCCCCCEE	36.67	-
282	Phosphorylation	KYSTKPGSYIFRLSC HHCCCCCCEEEEEEC	24.47	19549985
336	Phosphorylation	YLYPDGRSYNPDLTG EECCCCCCCCCCCCC	34.49	28509920
337	Phosphorylation	LYPDGRSYNPDLTGL ECCCCCCCCCCCCCC	29.38	20090780
342	Phosphorylation	RSYNPDLTGLCEPTP CCCCCCCCCCCCCCC	35.17	28509920
348	Phosphorylation	LTGLCEPTPHDHIKV CCCCCCCCCCCCCEE	15.80	28509920
356	Phosphorylation	PHDHIKVTQEQYELY CCCCCEECHHHHHHH	22.76	28442448
360	Phosphorylation	IKVTQEQYELYCEMG CEECHHHHHHHHCCC	13.72	24927040
363	Phosphorylation	TQEQYELYCEMGSTF CHHHHHHHHCCCCHH	3.71	10635327
368	Phosphorylation	ELYCEMGSTFQLCKI HHHHCCCCHHHHHHH	25.41	28442448
369	Phosphorylation	LYCEMGSTFQLCKIC HHHCCCCHHHHHHHH	15.07	28442448
471	Phosphorylation	LANVRKCTDRQNSPV HHHHHHCCCCCCCCC	36.93	28450419
476	Phosphorylation	KCTDRQNSPVTSPGS HCCCCCCCCCCCCCC	16.65	22167270
479	Phosphorylation	DRQNSPVTSPGSSPL CCCCCCCCCCCCCCC	32.37	23401153
480	Phosphorylation	RQNSPVTSPGSSPLA CCCCCCCCCCCCCCH	27.74	29255136
483	Phosphorylation	SPVTSPGSSPLAQRR CCCCCCCCCCCHHCC	31.97	23401153
484	Phosphorylation	PVTSPGSSPLAQRRK CCCCCCCCCCHHCCC	29.82	29255136
491	Ubiquitination	SPLAQRRKPQPDPLQ CCCHHCCCCCCCCCC	50.63	-
516	Ubiquitination	PRLDLIQKGIVRSPC CCCCHHHCCCCCCCC	43.54	-
516	Acetylation	PRLDLIQKGIVRSPC CCCCHHHCCCCCCCC	43.54	25953088
521	Phosphorylation	IQKGIVRSPCGSPTG HHCCCCCCCCCCCCC	17.41	22167270
525	Phosphorylation	IVRSPCGSPTGSPKS CCCCCCCCCCCCCCC	26.46	22167270
527	Phosphorylation	RSPCGSPTGSPKSSP CCCCCCCCCCCCCCC	52.57	22167270
529	Phosphorylation	PCGSPTGSPKSSPCM CCCCCCCCCCCCCCE	31.47	22167270
531	Ubiquitination	GSPTGSPKSSPCMVR CCCCCCCCCCCCEEE	66.32	-
532	Phosphorylation	SPTGSPKSSPCMVRK CCCCCCCCCCCEEEC	42.78	25849741
533	Phosphorylation	PTGSPKSSPCMVRKQ CCCCCCCCCCEEECC	28.39	23090842
580	Phosphorylation	RHIHHVESVPSRDPP HCCCCCCCCCCCCCC	37.93	23312004
583	Phosphorylation	HHVESVPSRDPPMPL CCCCCCCCCCCCCCH	47.35	23312004
601	Phosphorylation	CPRDVFGTNQLVGCR CCCCCCCCCCEEECE	14.34	-
614	Phosphorylation	CRLLGEGSPKPGITA CEECCCCCCCCCCCC	26.00	22617229
616	Ubiquitination	LLGEGSPKPGITASS ECCCCCCCCCCCCCC	58.53	-
620	Phosphorylation	GSPKPGITASSNVNG CCCCCCCCCCCCCCC	26.80	-
634	Phosphorylation	GRHSRVGSDPVLMRK CCCCCCCCCCCCCCC	35.56	23401153
656	Phosphorylation	LEGAKVFSNGHLGSE CCCCEEECCCCCCCC	44.91	27080861
662	Phosphorylation	FSNGHLGSEEYDVPP ECCCCCCCCCCCCCC	33.35	26356563
665	Phosphorylation	GHLGSEEYDVPPRLS CCCCCCCCCCCCCCC	20.42	25159151
672	Phosphorylation	YDVPPRLSPPPPVTT CCCCCCCCCCCCCCC	36.32	29255136
678	Phosphorylation	LSPPPPVTTLLPSIK CCCCCCCCCCCCCCC	19.94	29255136
679	Phosphorylation	SPPPPVTTLLPSIKC CCCCCCCCCCCCCCC	26.91	29255136
683	Phosphorylation	PVTTLLPSIKCTGPL CCCCCCCCCCCCCHH	34.35	27080861
687	Phosphorylation	LLPSIKCTGPLANSL CCCCCCCCCHHHHCC	36.51	23403867
693	Phosphorylation	CTGPLANSLSEKTRD CCCHHHHCCCHHHCC	27.89	23403867
695	Phosphorylation	GPLANSLSEKTRDPV CHHHHCCCHHHCCCC	36.55	23403867
697	Ubiquitination	LANSLSEKTRDPVEE HHHCCCHHHCCCCCC	45.55	-
698	Phosphorylation	ANSLSEKTRDPVEED HHCCCHHHCCCCCCC	35.93	-
709	Phosphorylation	VEEDDDEYKIPSSHP CCCCCCCCCCCCCCC	22.63	25884760
735	Phosphorylation	NVKPPVRSCDNGHCM CCCCCCEECCCCEEE	26.51	-
761	Phosphorylation	KSNIPDLSIYLKGDV CCCCCCEEEEEECCC	19.30	28555341
763	Phosphorylation	NIPDLSIYLKGDVFD CCCCEEEEEECCCCC	10.05	30576142
790	Ubiquitination	PPTRDNPKHGSSLNR CCCCCCCCCCCCCCC	67.84	-
793	Phosphorylation	RDNPKHGSSLNRTPS CCCCCCCCCCCCCCC	31.22	24247654
798	Phosphorylation	HGSSLNRTPSDYDLL CCCCCCCCCCCCCCC	26.52	26657352
800	Phosphorylation	SSLNRTPSDYDLLIP CCCCCCCCCCCCCCC	48.46	29802988
802	Phosphorylation	LNRTPSDYDLLIPPL CCCCCCCCCCCCCCC	16.90	26657352
837	Ubiquitination	HSLIEHSKPPGSSSR CCCCCCCCCCCCCCC	58.08	-
841	Phosphorylation	EHSKPPGSSSRPSSG CCCCCCCCCCCCCCC	30.80	28348404
842	Phosphorylation	HSKPPGSSSRPSSGQ CCCCCCCCCCCCCCC	35.96	28348404
843	Phosphorylation	SKPPGSSSRPSSGQD CCCCCCCCCCCCCCC	50.32	28348404
846	Phosphorylation	PGSSSRPSSGQDLFL CCCCCCCCCCCCEEE	46.09	28348404
847	Phosphorylation	GSSSRPSSGQDLFLL CCCCCCCCCCCEEEE	43.06	28348404
856	Phosphorylation	QDLFLLPSDPFVDLA CCEEEECCCCCCCCC	58.86	22210691
864	Phosphorylation	DPFVDLASGQVPLPP CCCCCCCCCCCCCCH	36.74	22210691
881	Ubiquitination	RLPGENVKTNRTSQD CCCCCCCCCCCCCCC	52.22	-
882	Phosphorylation	LPGENVKTNRTSQDY CCCCCCCCCCCCCCH	26.17	27251275
885	Phosphorylation	ENVKTNRTSQDYDQL CCCCCCCCCCCHHHC	32.58	26657352
886	Phosphorylation	NVKTNRTSQDYDQLP CCCCCCCCCCHHHCC	20.16	28796482
889	Phosphorylation	TNRTSQDYDQLPSCS CCCCCCCHHHCCCCC	9.65	27273156
894	Phosphorylation	QDYDQLPSCSDGSQA CCHHHCCCCCCCCCC	34.54	30576142
896	Phosphorylation	YDQLPSCSDGSQAPA HHHCCCCCCCCCCCC	49.71	29978859
899	Phosphorylation	LPSCSDGSQAPARPP CCCCCCCCCCCCCCC	28.32	30576142
907	Ubiquitination	QAPARPPKPRPRRTA CCCCCCCCCCCCCCC	57.23	-
913	Phosphorylation	PKPRPRRTAPEIHHR CCCCCCCCCCCCCCC	48.09	28555341
977	Phosphorylation	FAFPPPVSPRLNL-- HCCCCCCCCCCCC--	15.29	29255136

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
282	S	Phosphorylation	Kinase	PKCT	Q04759	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	CBLB	Q13191	PMID:11375397

Functions of PTM Sites

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

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
GORS2_HUMAN	GORASP2	physical	16189514
CRY1_HUMAN	CRY1	physical	16189514
NCK2_HUMAN	NCK2	physical	16189514
VINEX_HUMAN	SORBS3	physical	16189514
NEDD4_HUMAN	NEDD4	physical	12907674
ZAP70_HUMAN	ZAP70	physical	10074432
GRB2_HUMAN	GRB2	physical	10086340
SHC1_HUMAN	SHC1	physical	9614102
GRB2_HUMAN	GRB2	physical	9614102
P85A_HUMAN	PIK3R1	physical	9614102
VAV_HUMAN	VAV1	physical	11857085
PLCG2_HUMAN	PLCG2	physical	12093870
SH3K1_HUMAN	SH3KBP1	physical	12177062
KIT_HUMAN	KIT	physical	12177062
KSYK_HUMAN	SYK	physical	10022120
GRB2_HUMAN	GRB2	physical	10022120
CRKL_HUMAN	CRKL	physical	10022120
P85A_HUMAN	PIK3R1	physical	10022120
EGFR_HUMAN	EGFR	physical	16702950
CAR11_HUMAN	CARD11	physical	19815501
CD2AP_HUMAN	CD2AP	physical	17020880
SH3K1_HUMAN	SH3KBP1	physical	12874286
FCERB_HUMAN	MS4A2	physical	16002993
MYD88_HUMAN	MYD88	physical	20639876
TCAM1_HUMAN	TICAM1	physical	20639876
PTN11_HUMAN	PTPN11	physical	17330819
ZAP70_HUMAN	ZAP70	physical	21453975
LCK_HUMAN	LCK	physical	21453975
P85A_HUMAN	PIK3R1	physical	19190244
P85B_HUMAN	PIK3R2	physical	19190244
UB2D2_HUMAN	UBE2D2	physical	22158902
CBLB_HUMAN	CBLB	physical	22158902
UBC_HUMAN	UBC	physical	16007098
VAV_HUMAN	VAV1	physical	9399639
EGFR_HUMAN	EGFR	physical	10635327
TGFI1_HUMAN	TGFB1I1	physical	23145173
UBC_HUMAN	UBC	physical	14661060
FAK2_HUMAN	PTK2B	physical	25099615
SIR2_HUMAN	SIRT2	physical	25285640
GRB2_HUMAN	GRB2	physical	25416956
NCK2_HUMAN	NCK2	physical	25416956
GLRX3_HUMAN	GLRX3	physical	25416956
GORS2_HUMAN	GORASP2	physical	25416956
UBS3B_HUMAN	UBASH3B	physical	25416956
CBLB_HUMAN	CBLB	physical	11375397
CD2AP_HUMAN	CD2AP	physical	23663663
SH3K1_HUMAN	SH3KBP1	physical	23663663
CRKL_HUMAN	CRKL	physical	25814554
CRK_HUMAN	CRK	physical	25814554
SP7_HUMAN	SP7	physical	25744063
KSYK_HUMAN	SYK	physical	27428901
TR10B_HUMAN	TNFRSF10B	physical	28972304
TRAF2_HUMAN	TRAF2	physical	28972304

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 CBLB_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"PKC-theta modulates the strength of T cell responses by targetingCbl-b for ubiquitination and degradation."; Gruber T., Hermann-Kleiter N., Hinterleitner R., Fresser F.,Schneider R., Gastl G., Penninger J.M., Baier G.; Sci. Signal. 2:RA30-RA30(2009). Cited for: PHOSPHORYLATION AT SER-282.	19549985 [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-521; SER-525 ANDSER-529, AND MASS SPECTROMETRY.	18669648 [Abstract]
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle."; Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.; Mol. Cell 31:438-448(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-614, AND MASSSPECTROMETRY.	18691976 [Abstract]
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-480 AND SER-484, ANDMASS SPECTROMETRY.	17081983 [Abstract]
"An extensive survey of tyrosine phosphorylation revealing new sitesin human mammary epithelial cells."; Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A.,Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D.,Wiley H.S., Qian W.-J.; J. Proteome Res. 8:3852-3861(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-363; TYR-665 ANDTYR-889, AND MASS SPECTROMETRY.	19534553 [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-889, AND MASSSPECTROMETRY.	18083107 [Abstract]
"Tyrosine phosphorylation and complex formation of Cbl-b upon T cellreceptor stimulation."; Elly C., Witte S., Zhang Z., Rosnet O., Lipkowitz S., Altman A.,Liu Y.-C.; Oncogene 18:1147-1156(1999). Cited for: TISSUE SPECIFICITY, MUTAGENESIS OF GLY-298; TYR-665 AND TYR-709,INTERACTION WITH GRB2 AND CRKL, PHOSPHORYLATION AT TYR-665 ANDTYR-709, AND FUNCTION.	10022120 [Abstract]