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G3V8H4

- CBLC_RAT

UniProt

G3V8H4 - CBLC_RAT

Protein

E3 ubiquitin-protein ligase CBL-C

Gene

Cblc

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 21 (01 Oct 2014)
      Sequence version 1 (16 Nov 2011)
      Previous versions | rss
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    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

    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

    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.
    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

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    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

    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:
    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

    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: October 1, 2014
    This is version 21 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