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G3V8H4 (CBLC_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 18. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase CBL-C

EC=6.3.2.-
Gene names
Name:Cblc
Synonyms:Cbl-3
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length497 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Functionally coupled with the E2 ubiquitin-protein ligases UB2D1, UB2D2 and UB2D3. Regulator of EGFR mediated signal transduction; upon EGF activation, ubiquitinates EGFR. Inhibits EGF stimulated MAPK1 activation. Promotes ubiquitination of SRC phosphorylated at 'Tyr-419', has the highest ubiquitin ligase activity among CBL family proteins. In collaboration with CD2AP may act as regulatory checkpoint for Ret signaling by modulating the rate of RET degradation after ligand activation; CD2AP converts it from an inhibitor to a promoter of RET degradation; the function limits the potency of GDNF on neuronal survival. Ref.4

Enzyme regulation

Phosphorylation at Tyr-341 is necessary and sufficient for the activation of E3 activity By similarity.

Subunit structure

Interacts with Ubiquitin-conjugating enzyme E2 UBE2D2 and UBE2D3. Interacts with EGFR (tyrosine phosphorylated). Interacts with the SH3 domain proteins LYN and CRK. Interacts (via RING-type zinc finger) with TGFB1I1 (via LIM zinc-binding domain 2); the interaction is direct and enhances the E3 activity. Interacts directly with RET (inactive) and CD2AP; dissociates from RET upon RET activation by GDNF which also increases the interaction with CD2AP suggesting dissociation as CBLC:CD2AP complex. Interacts with SRC; the interaction is enhanced when SRC is phosphorylated at 'Tyr-419'. Ref.4

Domain

EF-hand-like and Sh2-like domains are required for N-terminal inhibition of E3 activity By similarity.

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 By similarity.

The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme By similarity.

Post-translational modification

Phosphorylated on multiple tyrosine residues by SRC By similarity.

Autoubiquitinated, when phosphorylated at Tyr-341.

Miscellaneous

This protein has one functional calcium-binding site By similarity.

Sequence similarities

Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain.

Contains 1 RING-type zinc finger.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 497497E3 ubiquitin-protein ligase CBL-C
PRO_0000424873

Regions

Domain7 – 321315Cbl-PTB
Calcium binding197 – 21014 By similarity
Zinc finger351 – 39040RING-type
Region7 – 1451394H
Region146 – 21873EF-hand-like
Region219 – 321103SH2-like
Region322 – 35029Linker By similarity
Region351 – 497147Interaction with RET By similarity

Sites

Binding site2641Phosphotyrosine By similarity

Amino acid modifications

Modified residue3411Phosphotyrosine; by SRC By similarity

Experimental info

Sequence conflict3261V → E in AAI05777. Ref.3
Sequence conflict4531N → D in AAI05777. Ref.3

Sequences

Sequence LengthMass (Da)Tools
G3V8H4 [UniParc].

Last modified November 16, 2011. Version 1.
Checksum: C6DFE4CADD9F908E

FASTA49755,775
        10         20         30         40         50         60 
MAAATAPQGW QWGEPRALGR AVKLLQRLEE QCRDLRLFVG PPSLRDLLPR TAQLLREVAK 

        70         80         90        100        110        120 
ARSDKTRGDP EGPGGAGDFL VIYLTNLEAK GRQVAELLPH RGKKDANQDV FPEGSRFRRQ 

       130        140        150        160        170        180 
LAKLALIFSH MHAELSALFP EGKYCGHLYQ ITKGSANTFW RENCGVRCVL PWAEFQSLLC 

       190        200        210        220        230        240 
SCHPVEPGPI MQALRSTLDL TCSGHVSVFE FDIFTRLFQP WPTLLKNWQL LAVNHPGYMA 

       250        260        270        280        290        300 
FLTYDEVQTR LQAYRDKPGS YIFRPSCTRL GQWAIGYVSS NGSILQTIPL NKPLLQVLLK 

       310        320        330        340        350        360 
GQKDGIFLYP DGKNHNPDLT ELCRAVLNQC IQVSQEQLQL YQAMNSTFEL CKICTERDKD 

       370        380        390        400        410        420 
VRIEPCGHLL CSCCLAAWQH SDSQTCPFCR CEIKGREAVS ICQAQERSME VRTTAGDSGD 

       430        440        450        460        470        480 
NCHQEAAEWK LESVTPSAPP LPPEVPCPQR PQNKGWLTLA PFTLPRLRPP LPLPKMASVL 

       490 
WEVTSRPQVR EGATESS 

« Hide

References

« Hide 'large scale' references
[1]"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. expand/collapse author list , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway.
[2]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"CD2AP and Cbl-3/Cbl-c constitute a critical checkpoint in the regulation of ret signal transduction."
Tsui C.C., Pierchala B.A.
J. Neurosci. 28:8789-8800(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN RET STABILITY, INTERACTION WITH CD2AP AND RET.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AABR06003893 Genomic DNA. No translation available.
CH473979 Genomic DNA. Translation: EDM08131.1.
BC105776 mRNA. Translation: AAI05777.1.
RefSeqNP_001030092.1. NM_001034920.2.
UniGeneRn.20550.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000025829.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000025829; ENSRNOP00000025829; ENSRNOG00000018953.
GeneID292699.

Organism-specific databases

RGD1307651. Cblc.

Phylogenomic databases

eggNOGNOG318595.
GeneTreeENSGT00390000011617.
HOGENOMHOG000294176.
HOVERGENHBG005255.
InParanoidQ3KRC9.
KOK04707.
OMAIFSYMHA.
OrthoDBEOG4P8FJ1.
TreeFamTF314210.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
1.20.930.20. 1 hit.
3.30.40.10. 1 hit.
3.30.505.10. 1 hit.
InterProIPR024162. Adaptor_Cbl.
IPR014741. Adaptor_Cbl_EF_hand-like.
IPR003153. Adaptor_Cbl_N_hlx.
IPR014742. Adaptor_Cbl_SH2-like.
IPR024159. Cbl_PTB.
IPR011992. EF-hand-dom_pair.
IPR000980. SH2.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERPTHR23007. PTHR23007. 1 hit.
PfamPF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
[Graphical view]
SUPFAMSSF47668. SSF47668. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEPS51506. CBL_PTB. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio35584158.
PROG3V8H4.

Entry information

Entry nameCBLC_RAT
AccessionPrimary (citable) accession number: G3V8H4
Secondary accession number(s): Q3KRC9
Entry history
Integrated into UniProtKB/Swiss-Prot: January 22, 2014
Last sequence update: November 16, 2011
Last modified: April 16, 2014
This is version 18 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families