dbPTM

CBL_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	CBL_MOUSE
UniProt AC	P22682
Protein Name	E3 ubiquitin-protein ligase CBL
Gene Name	Cbl
Organism	Mus musculus (Mouse).
Sequence Length	913
Subcellular Localization	Cytoplasm. Cell membrane. Colocalizes with FGFR2 in lipid rafts at the cell membrane..
Protein Description	Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The 'Tyr-737' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3..
Protein Sequence	MAGNVKKSSGAGGGGSGGSGAGGLIGLMKDAFQPHHHHHHLSPHPPCTVDKKMVEKCWKLMDKVVRLCQNPKLALKNSPPYILDLLPDTYQHLRTVLSRYEGKMETLGENEYFRVFMENLMKKTKQTISLFKEGKERMYEENSQPRRNLTKLSLIFSHMLAELKGIFPSGLFQGDTFRITKADAAEFWRKAFGEKTIVPWKSFRQALHEVHPISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWSSLLRNWNSLAVTHPGYMAFLTYDEVKARLQKFIHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFREGFYLFPDGRNQNPDLTGLCEPTPQDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPIVVDPFDPRGSGSLLRQGAEGAPSPNYDDDDDERADDSLFMMKELAGAKVERPSSPFSMAPQASLPPVPPRLDLLQQRAPVPASTSVLGTASKAASGSLHKDKPLPIPPTLRDLPPPPPPDRPYSVGAETRPQRRPLPCTPGDCPSRDKLPPVPSSRPGDSWLSRPIPKVPVATPNPGDPWNGRELTNRHSLPFSLPSQMEPRADVPRLGSTFSLDTSMTMNSSPVAGPESEHPKIKPSSSANAIYSLAARPLPMPKLPPGEQGESEEDTEYMTPTSRPVGVQKPEPKRPLEATQSSRACDCDQQIDSCTYEAMYNIQSQALSVAENSASGEGNLATAHTSTGPEESENEDDGYDVPKPPVPAVLARRTLSDISNASSSFGWLSLDGDPTNFNEGSQVPERPPKPFPRRINSERKASSYQQGGGATANPVATAPSPQLSSEIERLMSQGYSYQDIQKALVIAHNNIEMAKNILREFVSISSPAHVAT

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
8	Phosphorylation	MAGNVKKSSGAGGGG CCCCCCCCCCCCCCC	28.43	28833060
9	Phosphorylation	AGNVKKSSGAGGGGS CCCCCCCCCCCCCCC	41.35	28833060
16	Phosphorylation	SGAGGGGSGGSGAGG CCCCCCCCCCCCHHH	43.16	28833060
19	Phosphorylation	GGGGSGGSGAGGLIG CCCCCCCCCHHHHHH	29.06	28833060
201	Ubiquitination	EKTIVPWKSFRQALH CCCEECHHHHHHHHH	33.38	22790023
285	Succinylation	RLQKFIHKPGSYIFR HHHHHHCCCCCEEEE	46.38	23806337
285	Acetylation	RLQKFIHKPGSYIFR HHHHHHCCCCCEEEE	46.38	23806337
362	Phosphorylation	PQDHIKVTQEQYELY CCHHEEECHHHHHHH	22.76	25266776
369	Phosphorylation	TQEQYELYCEMGSTF CHHHHHHHHHCCCHH	3.71	26026062
437	Phosphorylation	DPFDPRGSGSLLRQG CCCCCCCCCHHHCCC	26.87	26026062
439	Phosphorylation	FDPRGSGSLLRQGAE CCCCCCCHHHCCCCC	26.40	22817900
450	Phosphorylation	QGAEGAPSPNYDDDD CCCCCCCCCCCCCCC	25.83	27087446
453	Phosphorylation	EGAPSPNYDDDDDER CCCCCCCCCCCCCHH	24.92	25521595
480	Phosphorylation	GAKVERPSSPFSMAP CCCCCCCCCCCCCCC	57.79	22942356
481	Phosphorylation	AKVERPSSPFSMAPQ CCCCCCCCCCCCCCC	32.42	27087446
484	Phosphorylation	ERPSSPFSMAPQASL CCCCCCCCCCCCCCC	19.88	22942356
490	Phosphorylation	FSMAPQASLPPVPPR CCCCCCCCCCCCCCC	35.84	28833060
512	Phosphorylation	APVPASTSVLGTASK CCCCCCCHHHHCCCC	16.92	29514104
522	Phosphorylation	GTASKAASGSLHKDK HCCCCCCCCCCCCCC	33.50	30635358
524	Phosphorylation	ASKAASGSLHKDKPL CCCCCCCCCCCCCCC	25.46	30635358
550	Phosphorylation	PPPPDRPYSVGAETR CCCCCCCCCCCCCCC	19.51	25367039
551	Phosphorylation	PPPDRPYSVGAETRP CCCCCCCCCCCCCCC	19.43	25367039
556	Phosphorylation	PYSVGAETRPQRRPL CCCCCCCCCCCCCCC	47.30	25367039
613	Phosphorylation	PWNGRELTNRHSLPF CCCCCCCCCCCCCCC	26.00	27180971
617	Phosphorylation	RELTNRHSLPFSLPS CCCCCCCCCCCCCCC	34.20	26824392
621	Phosphorylation	NRHSLPFSLPSQMEP CCCCCCCCCCCCCCC	37.11	25159016
624	Phosphorylation	SLPFSLPSQMEPRAD CCCCCCCCCCCCCCC	47.67	28285833
637	Phosphorylation	ADVPRLGSTFSLDTS CCCCCCCCEEEEECC	30.76	28833060
638	Phosphorylation	DVPRLGSTFSLDTSM CCCCCCCEEEEECCC	18.55	28833060
640	Phosphorylation	PRLGSTFSLDTSMTM CCCCCEEEEECCCCC	25.98	28833060
643	Phosphorylation	GSTFSLDTSMTMNSS CCEEEEECCCCCCCC	26.20	28833060
644	Phosphorylation	STFSLDTSMTMNSSP CEEEEECCCCCCCCC	16.36	28833060
646	Phosphorylation	FSLDTSMTMNSSPVA EEEECCCCCCCCCCC	16.99	28833060
649	Phosphorylation	DTSMTMNSSPVAGPE ECCCCCCCCCCCCCC	25.79	28833060
650	Phosphorylation	TSMTMNSSPVAGPES CCCCCCCCCCCCCCC	20.56	28833060
665	Phosphorylation	EHPKIKPSSSANAIY CCCCCCCCCCHHHHH	31.74	22499769
666	Phosphorylation	HPKIKPSSSANAIYS CCCCCCCCCHHHHHH	41.83	21082442
667	Phosphorylation	PKIKPSSSANAIYSL CCCCCCCCHHHHHHH	29.85	26824392
672	Phosphorylation	SSSANAIYSLAARPL CCCHHHHHHHHCCCC	8.67	26060331
673	Phosphorylation	SSANAIYSLAARPLP CCHHHHHHHHCCCCC	12.86	22499769
692	Phosphorylation	PPGEQGESEEDTEYM CCCCCCCCHHHCCCC	53.78	21082442
696	Phosphorylation	QGESEEDTEYMTPTS CCCCHHHCCCCCCCC	32.09	22499769
698	Phosphorylation	ESEEDTEYMTPTSRP CCHHHCCCCCCCCCC	14.37	12522270
700	Phosphorylation	EEDTEYMTPTSRPVG HHHCCCCCCCCCCCC	23.63	22499769
702	Phosphorylation	DTEYMTPTSRPVGVQ HCCCCCCCCCCCCCC	28.35	22499769
703	Phosphorylation	TEYMTPTSRPVGVQK CCCCCCCCCCCCCCC	35.47	22499769
720	Phosphorylation	PKRPLEATQSSRACD CCCCCCCCCCCCCCC	21.43	28833060
722	Phosphorylation	RPLEATQSSRACDCD CCCCCCCCCCCCCCC	19.89	27566939
723	Phosphorylation	PLEATQSSRACDCDQ CCCCCCCCCCCCCCH	17.68	28833060
737	Phosphorylation	QQIDSCTYEAMYNIQ HHHHHHHHHHHHCHH	13.15	22817900
773	Phosphorylation	TSTGPEESENEDDGY CCCCCCCCCCCCCCC	44.02	-
780	Phosphorylation	SENEDDGYDVPKPPV CCCCCCCCCCCCCCC	22.29	17139251
795	Phosphorylation	PAVLARRTLSDISNA CHHHHHCCHHHHCCC	25.67	26643407
797	Phosphorylation	VLARRTLSDISNASS HHHHCCHHHHCCCCC	32.08	26643407
800	Phosphorylation	RRTLSDISNASSSFG HCCHHHHCCCCCCCC	31.19	25293948
803	Phosphorylation	LSDISNASSSFGWLS HHHHCCCCCCCCCEE	30.66	21659605
804	Phosphorylation	SDISNASSSFGWLSL HHHCCCCCCCCCEEC	27.55	26643407
805	Phosphorylation	DISNASSSFGWLSLD HHCCCCCCCCCEECC	25.86	26643407
810	Phosphorylation	SSSFGWLSLDGDPTN CCCCCCEECCCCCCC	20.22	21659605
816	Phosphorylation	LSLDGDPTNFNEGSQ EECCCCCCCCCCCCC	58.12	26643407
838	Phosphorylation	PFPRRINSERKASSY CCCCCCCCHHCCCCC	36.09	22324799
843	Phosphorylation	INSERKASSYQQGGG CCCHHCCCCCCCCCC	32.39	28285833
844	Phosphorylation	NSERKASSYQQGGGA CCHHCCCCCCCCCCC	31.64	28285833
845	Phosphorylation	SERKASSYQQGGGAT CHHCCCCCCCCCCCC	11.45	29514104
873	Phosphorylation	SEIERLMSQGYSYQD HHHHHHHHCCCCHHH	25.66	25338131
877	Phosphorylation	RLMSQGYSYQDIQKA HHHHCCCCHHHHHHH	24.12	30635358
904	Phosphorylation	NILREFVSISSPAHV HHHHHHHHCCCCCCC	23.29	22942356
906	Phosphorylation	LREFVSISSPAHVAT HHHHHHCCCCCCCCC	23.82	28066266
907	Phosphorylation	REFVSISSPAHVAT- HHHHHCCCCCCCCC-	25.16	26643407
913	Phosphorylation	SSPAHVAT------- CCCCCCCC-------	37.75	28066266

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
698	Y	Phosphorylation	Kinase	ABL1	P00520	Uniprot
737	Y	Phosphorylation	Kinase	SYK	P48025	GPS
737	Y	Phosphorylation	Kinase	SRC	P05480	Uniprot

Functions of PTM Sites

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

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
LCK_MOUSE	Lck	physical	11741956
VGFR1_MOUSE	Flt1	physical	17962812
KIT_MOUSE	Kit	physical	19734451
FYN_MOUSE	Fyn	physical	19734451
KSYK_HUMAN	SYK	physical	19419964
EGFR_MOUSE	Egfr	physical	17139251
PGFRB_MOUSE	Pdgfrb	physical	17620338
VGFR1_MOUSE	Flt1	physical	15001553
EGFR_MOUSE	Egfr	physical	14691459
SH2B2_MOUSE	Sh2b2	physical	10854852
NCK1_MOUSE	Nck1	physical	7517397
TRAF6_MOUSE	Traf6	physical	11406619
TNR11_MOUSE	Tnfrsf11a	physical	11406619
P85A_MOUSE	Pik3r1	physical	11406619
ZAP70_MOUSE	Zap70	physical	8551236
FYN_MOUSE	Fyn	physical	8551236
LCK_MOUSE	Lck	physical	8551236
P85A_MOUSE	Pik3r1	physical	15581361
CRK_MOUSE	Crk	physical	15581361
CRK_MOUSE	Crk	physical	9013636
P85A_MOUSE	Pik3r1	physical	9013636
SRC_MOUSE	Src	physical	9013636
P85A_MOUSE	Pik3r1	physical	16798838
P85A_MOUSE	Pik3r1	physical	10799548
SRC_MOUSE	Src	physical	22138575
FGR_MOUSE	Fgr	physical	9687507
LYN_MOUSE	Lyn	physical	9687507
SH3K1_MOUSE	Sh3kbp1	physical	21725061
GRB2_MOUSE	Grb2	physical	21725061
SH2B2_MOUSE	Sh2b2	physical	11997497
FYN_MOUSE	Fyn	physical	9890970
P85A_MOUSE	Pik3r1	physical	9890970
PK3CG_MOUSE	Pik3cg	physical	9115297
P85A_MOUSE	Pik3r1	physical	9115297
ITK_MOUSE	Itk	physical	20670954
KSYK_MOUSE	Syk	physical	20670954
SYNEM_MOUSE	Synm	physical	15872089
HCK_MOUSE	Hck	physical	12032836
PAXI_MOUSE	Pxn	physical	8641358
ABL1_MOUSE	Abl1	physical	10391678
CRKL_MOUSE	Crkl	physical	10391678
P85A_MOUSE	Pik3r1	physical	10391678
P85A_MOUSE	Pik3r1	physical	15581362
CRK_MOUSE	Crk	physical	15581362
SLAP2_MOUSE	Sla2	physical	12024036
SH2B2_MOUSE	Sh2b2	physical	20298671
EGFR_MOUSE	Egfr	physical	20298671
ZAP70_MOUSE	Zap70	physical	20298671
GRB2_MOUSE	Grb2	physical	7657591
SHC1_MOUSE	Shc1	physical	7657591
EGFR_MOUSE	Egfr	physical	7657591
CSF1R_MOUSE	Csf1r	physical	17420256
P85A_MOUSE	Pik3r1	physical	17420256
GRB2_MOUSE	Grb2	physical	8635998
CRK_MOUSE	Crk	physical	10633073
P85A_MOUSE	Pik3r1	physical	10633073
EGFR_MOUSE	Egfr	physical	23027125
CRKL_MOUSE	Crkl	physical	11804588
P85A_MOUSE	Pik3r1	physical	8947469

Drug and Disease Associations

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

Regulatory Network of CBL_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Quantitative time-resolved phosphoproteomic analysis of mast cellsignaling."; Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,Kawakami T., Salomon A.R.; J. Immunol. 179:5864-5876(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-666; SER-667 ANDTYR-672, AND MASS SPECTROMETRY.	17947660 [Abstract]
"Profiling of tyrosine phosphorylation pathways in human cells usingmass spectrometry."; Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T.,Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.; Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-672; SER-692 ANDTYR-698, AND MASS SPECTROMETRY.	12522270 [Abstract]