Reviewed, UniProtKB/Swiss-Prot P22681 (CBL_HUMAN)

Names and origin

Protein names

Recommended name:
    E3 ubiquitin-protein ligase CBL
    EC=6.3.2.-
Alternative name(s):
    Signal transduction protein CBL
    Proto-oncogene c-CBL
    Casitas B-lineage lymphoma proto-oncogene
    RING finger protein 55

Gene names

Name:	CBL
Synonyms:	CBL2, RNF55

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	906 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Participates in signal transduction in hematopoietic cells. Adapter protein that functions as a negative regulator of many signaling pathways that start from receptors at the cell surface. 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 PDGFA, EGF and CSF1, and terminates signaling. Ref.3
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Associates with NCK via its SH3 domain. The phosphorylated C-terminus interacts with CD2AP via its second SH3 domain. Binds to UBE2L3. Interacts with adapters SLA, SLA2 and with the phosphorylated C-terminus of SH2B2. Interacts with EGFR, SYK and ZAP70 via the highly conserved Cbl-N region. Also interacts with SORBS1 and INPPL1/SHIP2. Interacts with phosphorylated LAT2. May interact with CBLB By similarity. Ref.5 Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15
Subcellular location	Cytoplasm.
Domain	The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme. The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain.
Post-translational modification	Phosphorylated on tyrosine residues by EGFR, SYK, FYN and ZAP70 By similarity. Phosphorylated on tyrosine residues by INSR. Ref.14 Ref.4 Ref.6 Ref.8 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.22
Miscellaneous	This protein has one functional calcium-binding site.
Sequence similarities	Contains 1 CBL N-terminal domain. Contains 2 EF-hand-like domains. Contains 1 RING-type zinc finger. Contains 1 SH2 domain. Contains 1 UBA domain.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Proto-oncogene
Domain	Repeat SH2 domain Zinc-finger
Ligand	Calcium Metal-binding Zinc
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	epidermal growth factor receptor signaling pathway Traceable author statement. Source: HGNC modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of receptor-mediated endocytosis Traceable author statement. Source: HGNC protein ubiquitination Traceable author statement. Source: HGNC
Cellular component	cytosol Inferred from Experiment. Source: Reactome nucleus Inferred from electronic annotation. Source: InterPro
Molecular function	SH3 domain binding Inferred from physical interaction. Source: UniProtKB calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW signal transducer activity Inferred from electronic annotation. Source: InterPro transcription factor activity Ref.1 Traceable author statement. Source: ProtInc ubiquitin-protein ligase activity Traceable author statement. Source: HGNC zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
drk	Q08012	1	EBI-518228,EBI-161391	From a different organism.
EGFR	P00533	1	EBI-518228,EBI-297353
KHDRBS1	Q07666	1	EBI-518228,EBI-1364
PTPRB	P23467	1	EBI-518228,EBI-1265766
PTPRC	P08575	1	EBI-518228,EBI-1341
PTPRG	P23470	1	EBI-518228,EBI-2258115
PTPRJ	Q12913	1	EBI-518228,EBI-2264500
PTPRK	Q15262	1	EBI-518228,EBI-474052
PTPRO	Q16827	1	EBI-518228,EBI-723739

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 906

906

E3 ubiquitin-protein ligase CBL

PRO_0000055858

Regions

Domain

46 – 357

312

CBL N-terminal

Domain

212 – 220

9

EF-hand-like 1

Domain

229 – 240

12

EF-hand-like 2

Domain

267 – 341

75

SH2; atypical

Domain

856 – 895

40

UBA

Zinc finger

381 – 420

40

RING-type

Region

46 – 177

132

4H

Region

342 – 380

39

Linker

Region

648 – 906

259

Interaction with CD2AP

Compositional bias

357 – 476

120

Asp/Glu-rich (acidic)

Compositional bias

477 – 688

212

Pro-rich

Compositional bias

689 – 834

146

Asp/Glu-rich (acidic)

Sites

Binding site

294

1

Phosphotyrosine By similarity

Amino acid modifications

Modified residue

141

1

Phosphotyrosine Ref.21

Modified residue

197

1

N6-acetyllysine Ref.23

Modified residue

371

1

Phosphotyrosine; by INSR Ref.14 Ref.16

Modified residue

452

1

Phosphoserine Ref.22

Modified residue

552

1

Phosphotyrosine Ref.16

Modified residue

667

1

Phosphoserine Ref.18

Modified residue

668

1

Phosphoserine By similarity

Modified residue

669

1

Phosphoserine Ref.8

Modified residue

674

1

Phosphotyrosine Ref.8 Ref.17 Ref.21

Modified residue

675

1

Phosphoserine Ref.18

Modified residue

700

1

Phosphotyrosine Ref.14

Modified residue

774

1

Phosphotyrosine Ref.14 Ref.21

Modified residue

900

1

Phosphoserine Ref.19

Natural variations

Natural variant

620

1

L → F: dbSNP rs2227988.

VAR_057211

Natural variant

782

1

P → L: dbSNP rs2229073.

VAR_057212

Natural variant

904

1

V → I: dbSNP rs17122769.

VAR_057213

Experimental info

Mutagenesis

80

1

S → D: Abolishes interaction with ZAP70. Ref.24

Mutagenesis

82

1

P → A: Abolishes interaction with ZAP70. Ref.24

Mutagenesis

229

1

D → Q: Abolishes interaction with ZAP70. Ref.24

Mutagenesis

240

1

E → S: Abolishes interaction with ZAP70. Ref.24

Mutagenesis

294

1

R → K: Abolishes interaction with ZAP70. Ref.24

Mutagenesis

306

1

G → E: Abolishes interaction with ZAP70, but does not affect interaction with SLA. Ref.11 Ref.24

Mutagenesis

371

1

Y → F: Strongly reduces tyrosine phosphorylation by INSR; when associated with F-700 and F-774. Ref.14

Mutagenesis

700

1

Y → F: Strongly reduces tyrosine phosphorylation by INSR; when associated with F-371 and F-774. Ref.14

Mutagenesis

731

1

Y → F: No effect on tyrosine phosphorylation by INSR. Ref.14

Mutagenesis

774

1

Y → F: Strongly reduces tyrosine phosphorylation by INSR; when associated with F-371 and F-700. Ref.14

Sequence conflict

15

1

S → T in CAA40393. Ref.1

Secondary structure

1

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906

Helix Strand Turn

Details...

Helix

53 – 70

18

Helix

73 – 75

3

Helix

84 – 101

18

Helix

106 – 111

6

Helix

113 – 136

24

Helix

137 – 141

5

Helix

146 – 168

23

Helix

170 – 172

3

Helix

176 – 178

3

Helix

184 – 194

11

Beta strand

198 – 201

4

Helix

202 – 210

9

Helix

218 – 228

11

Beta strand

233 – 237

5

Helix

238 – 247

10

Helix

251 – 253

3

Helix

254 – 261

8

Helix

274 – 281

8

Helix

282 – 284

3

Beta strand

290 – 295

6

Beta strand

297 – 299

3

Beta strand

302 – 308

7

Beta strand

314 – 317

4

Beta strand

320 – 322

3

Helix

324 – 333

10

Beta strand

354 – 356

3

Helix

365 – 372

8

Turn

382 – 384

3

Beta strand

385 – 388

4

Beta strand

394 – 396

3

Helix

402 – 410

9

Turn

417 – 419

3

Helix

856 – 866

11

Helix

871 – 880

10

Turn

881 – 883

3

Helix

885 – 895

11

Sequences

	Sequence		Length	Mass (Da)
	P22681-1 [UniParc]. Last modified July 7, 2009. Version 2. Checksum: 1AA6BF67377322CA	FASTA	906	99,633
	10 20 30 40 50 60 MAGNVKKSSG AGGGSGSGGS GSGGLIGLMK DAFQPHHHHH HHLSPHPPGT VDKKMVEKCW 70 80 90 100 110 120 KLMDKVVRLC QNPKLALKNS PPYILDLLPD TYQHLRTILS RYEGKMETLG ENEYFRVFME 130 140 150 160 170 180 NLMKKTKQTI SLFKEGKERM YEENSQPRRN LTKLSLIFSH MLAELKGIFP SGLFQGDTFR 190 200 210 220 230 240 ITKADAAEFW RKAFGEKTIV PWKSFRQALH EVHPISSGLE AMALKSTIDL TCNDYISVFE 250 260 270 280 290 300 FDIFTRLFQP WSSLLRNWNS LAVTHPGYMA FLTYDEVKAR LQKFIHKPGS YIFRLSCTRL 310 320 330 340 350 360 GQWAIGYVTA DGNILQTIPH NKPLFQALID GFREGFYLFP DGRNQNPDLT GLCEPTPQDH 370 380 390 400 410 420 IKVTQEQYEL YCEMGSTFQL CKICAENDKD VKIEPCGHLM CTSCLTSWQE SEGQGCPFCR 430 440 450 460 470 480 CEIKGTEPIV VDPFDPRGSG SLLRQGAEGA PSPNYDDDDD ERADDTLFMM KELAGAKVER 490 500 510 520 530 540 PPSPFSMAPQ ASLPPVPPRL DLLPQRVCVP SSASALGTAS KAASGSLHKD KPLPVPPTLR 550 560 570 580 590 600 DLPPPPPPDR PYSVGAESRP QRRPLPCTPG DCPSRDKLPP VPSSRLGDSW LPRPIPKVPV 610 620 630 640 650 660 SAPSSSDPWT GRELTNRHSL PFSLPSQMEP RPDVPRLGST FSLDTSMSMN SSPLVGPECD 670 680 690 700 710 720 HPKIKPSSSA NAIYSLAARP LPVPKLPPGE QCEGEEDTEY MTPSSRPLRP LDTSQSSRAC 730 740 750 760 770 780 DCDQQIDSCT YEAMYNIQSQ APSITESSTF GEGNLAAAHA NTGPEESENE DDGYDVPKPP 790 800 810 820 830 840 VPAVLARRTL SDISNASSSF GWLSLDGDPT TNVTEGSQVP ERPPKPFPRR INSERKAGSC 850 860 870 880 890 900 QQGSGPAASA ATASPQLSSE IENLMSQGYS YQDIQKALVI AQNNIEMAKN ILREFVSISS PAHVAT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif." Blake T.J., Shapiro M., Morse H.C. III, Langdon W.Y. Oncogene 6:653-657(1991) [PubMed: 2030914] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase." Joazeiro C.A., Wing S.S., Huang H.-K., Leverson J.D., Hunter T., Liu Y.-C. Science 286:309-312(1999) [PubMed: 10514377] [Abstract] Cited for: FUNCTION.
[4]	"Tyrosine phosphorylation of the c-cbl proto-oncogene protein product and association with epidermal growth factor (EGF) receptor upon EGF stimulation." Galisteo M.L., Dikic I., Batzer A.G., Langdon W.Y., Schlessinger J. J. Biol. Chem. 270:20242-20245(1995) [PubMed: 7657591] [Abstract] Cited for: PHOSPHORYLATION BY EGFR.
[5]	"The Cbl phosphotyrosine-binding domain selects a D(N/D)XpY motif and binds to the Tyr292 negative regulatory phosphorylation site of ZAP-70." Lupher M.L. Jr., Songyang Z., Shoelson S.E., Cantley L.C., Band H. J. Biol. Chem. 272:33140-33144(1997) [PubMed: 9407100] [Abstract] Cited for: INTERACTION WITH ZAP70.
[6]	"Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk tyrosine kinases." Deckert M., Elly C., Altman A., Liu Y.C. J. Biol. Chem. 273:8867-8874(1998) [PubMed: 9535867] [Abstract] Cited for: PHOSPHORYLATION BY SYK AND FYN.
[7]	"Non-T cell activation linker (NTAL): a transmembrane adaptor protein involved in immunoreceptor signaling." Brdicka T., Imrich M., Angelisova P., Brdickova N., Horvath O., Spicka J., Hilgert I., Luskova P., Draber P., Novak P., Engels N., Wienands J., Simeoni L., Oesterreicher J., Aguado E., Malissen M., Schraven B., Horejsi V. J. Exp. Med. 196:1617-1626(2002) [PubMed: 12486104] [Abstract] Cited for: INTERACTION WITH LAT2.
[8]	"Profiling of tyrosine phosphorylation pathways in human cells using mass 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) [PubMed: 12522270] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-669 AND TYR-674, MASS SPECTROMETRY.
[9]	"APS, an adaptor protein containing pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl." Wakioka T., Sasaki A., Mitsui K., Yokouchi M., Inoue A., Komiya S., Yoshimura A. Leukemia 13:760-767(1999) [PubMed: 10374881] [Abstract] Cited for: INTERACTION WITH SH2B2.
[10]	"APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis." Yokouchi M., Wakioka T., Sakamoto H., Yasukawa H., Ohtsuka S., Sasaki A., Ohtsubo M., Valius M., Inoue A., Komiya S., Yoshimura A. Oncogene 18:759-767(1999) [PubMed: 9989826] [Abstract] Cited for: INTERACTION WITH SH2B2.
[11]	"SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling." Tang J., Sawasdikosol S., Chang J.-H., Burakoff S.J. Proc. Natl. Acad. Sci. U.S.A. 96:9775-9780(1999) [PubMed: 10449770] [Abstract] Cited for: INTERACTION WITH SLA AND ZAP70, MUTAGENESIS OF GLY-306.
[12]	"Functional cloning of Src-like adapter protein-2 (SLAP-2), a novel inhibitor of antigen receptor signaling." Holland S.J., Liao X.C., Mendenhall M.K., Zhou X., Pardo J., Chu P., Spencer C., Fu A.C., Sheng N., Yu P., Pali E., Nagin A., Shen M., Yu S., Chan E., Wu X., Li C., Woisetschlager M. , Aversa G., Kolbinger F., Bennett M.K., Molineaux S., Luo Y., Payan D.G., Mancebo H.S.Y., Wu J. J. Exp. Med. 194:1263-1276(2001) [PubMed: 11696592] [Abstract] Cited for: INTERACTION WITH SLA2.
[13]	"The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl through a tyrosine phosphorylation-regulated Src homology 3 domain interaction." Kirsch K.H., Georgescu M.M., Shishido T., Langdon W.Y., Birge R.B., Hanafusa H. J. Biol. Chem. 276:4957-4963(2001) [PubMed: 11067845] [Abstract] Cited for: INTERACTION WITH CD2AP.
[14]	"APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes." Liu J., Kimura A., Baumann C.A., Saltiel A.R. Mol. Cell. Biol. 22:3599-3609(2002) [PubMed: 11997497] [Abstract] Cited for: INTERACTION WITH SH2B2, MUTAGENESIS OF TYR-371; TYR-700; TYR-731 AND TYR-774, PHOSPHORYLATION AT TYR-371; TYR-700 AND TYR-774.
[15]	"The c-Cbl-associated protein and c-Cbl are two new partners of the SH2-containing inositol polyphosphate 5-phosphatase SHIP2." Vandenbroere I., Paternotte N., Dumont J.E., Erneux C., Pirson I. Biochem. Biophys. Res. Commun. 300:494-500(2003) [PubMed: 12504111] [Abstract] Cited for: INTERACTION WITH INPPL1.
[16]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-371 AND TYR-552, MASS SPECTROMETRY. Tissue: Epithelium.
[17]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-674, MASS SPECTROMETRY.
[18]	"Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry." Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J., Bodenmiller B., Watts J.D., Hood L., Aebersold R. Nat. Methods 2:591-598(2005) [PubMed: 16094384] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-667 AND SER-675, MASS SPECTROMETRY. Tissue: T-cell.
[19]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-900, MASS SPECTROMETRY. Tissue: Epithelium.
[20]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[21]	"An extensive survey of tyrosine phosphorylation revealing new sites in 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) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-141; TYR-674 AND TYR-774, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[22]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-452, MASS SPECTROMETRY. Tissue: T-cell.
[23]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-197, MASS SPECTROMETRY.
[24]	"Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase." Meng W., Sawasdikosol S., Burakoff S.J., Eck M.J. Nature 398:84-90(1999) [PubMed: 10078535] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 47-350, CALCIUM-BINDING SITE, MUTAGENESIS OF SER-80; PRO-82; ASP-229; GLU-240; ARG-294 AND GLY-306.
[25]	"Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases." Zheng N., Wang P., Jeffrey P.D., Pavletich N.P. Cell 102:533-539(2000) [PubMed: 10966114] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 47-434 IN COMPLEX WITH ZAP70 AND UBE2L3.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X57110 mRNA. Translation: CAA40393.1.
BC132733 mRNA. Translation: AAI32734.1.
BC136463 mRNA. Translation: AAI36464.1.

IPI

IPI00027269.

PIR

A43817.

RefSeq

NP_005179.2.

UniGene

Hs.504096

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B47	X-ray	2.20	A/B/C	47-350	[»]
1FBV	X-ray	2.90	A	47-434	[»]
1YVH	X-ray	2.05	A	23-351	[»]
2CBL	X-ray	2.10	A	47-351	[»]
2JUJ	NMR	-	A	851-906	[»]
2K4D	NMR	-	A	358-437	[»]
2OO9	X-ray	2.10	A/B/C	856-895	[»]
3BUM	X-ray	2.00	B	25-351	[»]
3BUN	X-ray	2.00	B	25-351	[»]
3BUO	X-ray	2.60	B/D	25-351	[»]
3BUW	X-ray	1.45	B/D	25-351	[»]
3BUX	X-ray	1.35	B/D	25-351	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-189N.

IntAct

P22681. 9 interactions.

STRING

P22681.

PTM databases

PhosphoSite

P22681.

Proteomic databases

PRIDE

P22681.

Genome annotation databases

Ensembl

ENST00000264033; ENSP00000264033; ENSG00000110395; Homo sapiens. [Genome view]

GeneID

867.

KEGG

hsa:867.

Organism-specific databases

CTD

867.

GeneCards

GC11P118582.

H-InvDB

HIX0010191.

HGNC

HGNC:1541. CBL.

HPA

CAB004350.

MIM

165360. gene.

PharmGKB

PA26115.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG714021.

HOVERGEN

P22681.

InParanoid

P22681.

OMA

ASANAIY.

OrthoDB

EOG973SB5.

Enzyme and pathway databases

Pathway_Interaction_DB

epha_fwdpathway. EPHA forward signaling.
epha2_fwdpathway. EPHA2 forward signaling.
epopathway. EPO signaling pathway.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
fgf_pathway. FGF signaling pathway.
ifngpathway. IFN-gamma pathway.
il4_2pathway. IL4-mediated signaling events.
insulin_pathway. Insulin Pathway.
avb3_integrin_pathway. Integrins in angiogenesis.
a4b1_paxdep_pathway. Paxillin-dependent events mediated by a4b1.
a4b1_paxindep_pathway. Paxillin-independent events mediated by a4b1 and a4b7.
pdgfrbpathway. PDGFR-beta signaling pathway.
reelinpathway. Reelin signaling pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
vegfr1_pathway. VEGFR1 specific signals.

Reactome

REACT_9417. Signaling by EGFR.

Gene expression databases

ArrayExpress

P22681.

Bgee

P22681.

CleanEx

HS_CBL.

Genevestigator

P22681.

GermOnline

ENSG00000110395. Homo sapiens.

Family and domain databases

InterPro

IPR014741. Adaptor_Cbl_EF_Hand-like.
IPR003153. Adaptor_Cbl_N.
IPR014742. Adaptor_Cbl_SH2-like.
IPR011992. EF-hand-like_dom.
IPR000980. SH2.
IPR000449. UBA/transl_elong_EF1B_N.
IPR015940. UBA/transl_elong_EF1B_N_euk.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR017907. Znf_RING_CS.
[Graphical view]

Gene3D

G3DSA:1.20.930.20. Adaptor_Cbl_N. 1 hit.
G3DSA:1.10.238.10. EF-Hand_type. 1 hit.
G3DSA:3.30.505.10. SH2. 1 hit.

Pfam

PF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
PF00627. UBA. 1 hit.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]

SMART

SM00184. RING. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]

PROSITE

PS50001. SH2. False negative.
PS50030. UBA. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

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Other Resources

NextBio

3618.

PMAP-CutDB

P22681.

SOURCE

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Entry information

Entry name

CBL_HUMAN

Accession

Primary (citable) accession number: P22681
Secondary accession number(s): A3KMP8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	July 7, 2009
Last modified:	January 19, 2010
This is version 128 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.