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G3V8H4

- CBLC_RAT

UniProt

G3V8H4 - CBLC_RAT

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Protein

E3 ubiquitin-protein ligase CBL-C

Gene
Cblc, Cbl-3
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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 – 2641Phosphotyrosine By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi197 – 21014 By similarityAdd
BLAST
Zinc fingeri351 – 39040RING-typeAdd
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: Chromosome 1

Organism-specific databases

RGDi1307651. Cblc.

Subcellular locationi

GO - Cellular componenti

  1. 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 SRC By 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-PTBAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni7 – 1451394HAdd
BLAST
Regioni146 – 21873EF-hand-likeAdd
BLAST
Regioni219 – 321103SH2-likeAdd
BLAST
Regioni322 – 35029Linker By similarityAdd
BLAST
Regioni351 – 497147Interaction with RET By 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 By similarity.
The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme By similarity.

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri351 – 39040RING-typeAdd
BLAST

Keywords - Domaini

SH3-binding, Zinc-finger

Phylogenomic databases

eggNOGiNOG318595.
GeneTreeiENSGT00390000011617.
HOGENOMiHOG000294176.
HOVERGENiHBG005255.
InParanoidiQ3KRC9.
KOiK04707.
OMAiWQHSDSQ.
OrthoDBiEOG4P8FJ1.
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

MAAATAPQGW QWGEPRALGR AVKLLQRLEE QCRDLRLFVG PPSLRDLLPR    50
TAQLLREVAK ARSDKTRGDP EGPGGAGDFL VIYLTNLEAK GRQVAELLPH 100
RGKKDANQDV FPEGSRFRRQ LAKLALIFSH MHAELSALFP EGKYCGHLYQ 150
ITKGSANTFW RENCGVRCVL PWAEFQSLLC SCHPVEPGPI MQALRSTLDL 200
TCSGHVSVFE FDIFTRLFQP WPTLLKNWQL LAVNHPGYMA FLTYDEVQTR 250
LQAYRDKPGS YIFRPSCTRL GQWAIGYVSS NGSILQTIPL NKPLLQVLLK 300
GQKDGIFLYP DGKNHNPDLT ELCRAVLNQC IQVSQEQLQL YQAMNSTFEL 350
CKICTERDKD VRIEPCGHLL CSCCLAAWQH SDSQTCPFCR CEIKGREAVS 400
ICQAQERSME VRTTAGDSGD NCHQEAAEWK LESVTPSAPP LPPEVPCPQR 450
PQNKGWLTLA PFTLPRLRPP LPLPKMASVL WEVTSRPQVR EGATESS 497
Length:497
Mass (Da):55,775
Last modified:November 16, 2011 - v1
Checksum:iC6DFE4CADD9F908E
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti326 – 3261V → E in AAI05777. 1 Publication
Sequence conflicti453 – 4531N → D in AAI05777. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
AABR06003893 Genomic DNA. No translation available.
CH473979 Genomic DNA. Translation: EDM08131.1 .
BC105776 mRNA. Translation: AAI05777.1 .
RefSeqi NP_001030092.1. NM_001034920.2.
UniGenei Rn.20550.

3D structure databases

ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000025829.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000025829 ; ENSRNOP00000025829 ; ENSRNOG00000018953 .
GeneIDi 292699.
KEGGi rno:292699.

Organism-specific databases

CTDi 23624.
RGDi 1307651. Cblc.

Phylogenomic databases

eggNOGi NOG318595.
GeneTreei ENSGT00390000011617.
HOGENOMi HOG000294176.
HOVERGENi HBG005255.
InParanoidi Q3KRC9.
KOi K04707.
OMAi WQHSDSQ.
OrthoDBi EOG4P8FJ1.
TreeFami TF314210.

Miscellaneous databases

NextBioi 35584158.
PROi G3V8H4.

Family and domain databases

Gene3Di 1.10.238.10. 1 hit.
1.20.930.20. 1 hit.
3.30.40.10. 1 hit.
3.30.505.10. 1 hit.
InterProi IPR024162. 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 ]
PANTHERi PTHR23007. PTHR23007. 1 hit.
Pfami PF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
[Graphical view ]
SMARTi SM00184. RING. 1 hit.
[Graphical view ]
SUPFAMi SSF47668. SSF47668. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEi PS51506. CBL_PTB. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 20 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