Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

E3 ubiquitin-protein ligase CBL-C

Gene

Cblc

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei264 – 2641PhosphotyrosineBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi197 – 21014PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri351 – 39040RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. calcium ion binding Source: InterPro
  2. ligase activity Source: UniProtKB-KW
  3. signal transducer activity Source: InterPro
  4. ubiquitin-protein transferase activity Source: Ensembl
  5. zinc ion binding Source: InterPro

GO - Biological processi

  1. cell surface receptor signaling pathway Source: InterPro
  2. negative regulation of epidermal growth factor-activated receptor activity Source: Ensembl
  3. negative regulation of MAP kinase activity Source: Ensembl
  4. protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase CBL-C (EC:6.3.2.-)
Gene namesi
Name:Cblc
Synonyms:Cbl-3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi1307651. Cblc.

Subcellular locationi

GO - Cellular componenti

  1. extracellular vesicular exosome Source: Ensembl
  2. nucleus Source: InterPro
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 497497E3 ubiquitin-protein ligase CBL-CPRO_0000424873Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei341 – 3411Phosphotyrosine; by SRCBy similarity

Post-translational modificationi

Phosphorylated on multiple tyrosine residues by SRC.By similarity
Autoubiquitinated, when phosphorylated at Tyr-341.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

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'.1 Publication

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000025829.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini7 – 321315Cbl-PTBPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni7 – 1451394HAdd
BLAST
Regioni146 – 21873EF-hand-likeAdd
BLAST
Regioni219 – 321103SH2-likeAdd
BLAST
Regioni322 – 35029LinkerBy similarityAdd
BLAST
Regioni351 – 497147Interaction with RETBy similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri351 – 39040RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

SH3-binding, Zinc-finger

Phylogenomic databases

eggNOGiNOG318595.
GeneTreeiENSGT00390000011617.
HOGENOMiHOG000294176.
HOVERGENiHBG005255.
InParanoidiG3V8H4.
KOiK04707.
OMAiGQKDGFY.
OrthoDBiEOG73BVCF.
TreeFamiTF314210.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
1.20.930.20. 1 hit.
3.30.40.10. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR024162. 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]
PANTHERiPTHR23007. PTHR23007. 1 hit.
PfamiPF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF47668. SSF47668. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS51506. CBL_PTB. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

G3V8H4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAATAPQGW QWGEPRALGR AVKLLQRLEE QCRDLRLFVG PPSLRDLLPR
60 70 80 90 100
TAQLLREVAK ARSDKTRGDP EGPGGAGDFL VIYLTNLEAK GRQVAELLPH
110 120 130 140 150
RGKKDANQDV FPEGSRFRRQ LAKLALIFSH MHAELSALFP EGKYCGHLYQ
160 170 180 190 200
ITKGSANTFW RENCGVRCVL PWAEFQSLLC SCHPVEPGPI MQALRSTLDL
210 220 230 240 250
TCSGHVSVFE FDIFTRLFQP WPTLLKNWQL LAVNHPGYMA FLTYDEVQTR
260 270 280 290 300
LQAYRDKPGS YIFRPSCTRL GQWAIGYVSS NGSILQTIPL NKPLLQVLLK
310 320 330 340 350
GQKDGIFLYP DGKNHNPDLT ELCRAVLNQC IQVSQEQLQL YQAMNSTFEL
360 370 380 390 400
CKICTERDKD VRIEPCGHLL CSCCLAAWQH SDSQTCPFCR CEIKGREAVS
410 420 430 440 450
ICQAQERSME VRTTAGDSGD NCHQEAAEWK LESVTPSAPP LPPEVPCPQR
460 470 480 490
PQNKGWLTLA PFTLPRLRPP LPLPKMASVL WEVTSRPQVR EGATESS
Length:497
Mass (Da):55,775
Last modified:November 16, 2011 - v1
Checksum:iC6DFE4CADD9F908E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti326 – 3261V → E in AAI05777 (PubMed:15489334).Curated
Sequence conflicti453 – 4531N → D in AAI05777 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06003893 Genomic DNA. No translation available.
CH473979 Genomic DNA. Translation: EDM08131.1.
BC105776 mRNA. Translation: AAI05777.1.
RefSeqiNP_001030092.1. NM_001034920.2.
UniGeneiRn.20550.

Genome annotation databases

EnsembliENSRNOT00000025829; ENSRNOP00000025829; ENSRNOG00000018953.
GeneIDi292699.
KEGGirno:292699.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06003893 Genomic DNA. No translation available.
CH473979 Genomic DNA. Translation: EDM08131.1.
BC105776 mRNA. Translation: AAI05777.1.
RefSeqiNP_001030092.1. NM_001034920.2.
UniGeneiRn.20550.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000025829.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000025829; ENSRNOP00000025829; ENSRNOG00000018953.
GeneIDi292699.
KEGGirno:292699.

Organism-specific databases

CTDi23624.
RGDi1307651. Cblc.

Phylogenomic databases

eggNOGiNOG318595.
GeneTreeiENSGT00390000011617.
HOGENOMiHOG000294176.
HOVERGENiHBG005255.
InParanoidiG3V8H4.
KOiK04707.
OMAiGQKDGFY.
OrthoDBiEOG73BVCF.
TreeFamiTF314210.

Miscellaneous databases

NextBioi35584158.
PROiG3V8H4.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
1.20.930.20. 1 hit.
3.30.40.10. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR024162. 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]
PANTHERiPTHR23007. PTHR23007. 1 hit.
PfamiPF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF47668. SSF47668. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS51506. CBL_PTB. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiCBLC_RAT
AccessioniPrimary (citable) accession number: G3V8H4
Secondary accession number(s): Q3KRC9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 22, 2014
Last sequence update: November 16, 2011
Last modified: April 1, 2015
This is version 24 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.