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Q80XL1

- CBLC_MOUSE

UniProt

Q80XL1 - CBLC_MOUSE

Protein

E3 ubiquitin-protein ligase CBL-C

Gene

Cblc

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 100 (01 Oct 2014)
      Sequence version 2 (16 Aug 2005)
      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. Isoform 1, but not isoform 2, inhibits EGF stimulated MAPK1 activation. Promotes ubiquitination of SRC phosphorylated at 'Tyr-424', 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 By similarity.By similarity

    Enzyme regulationi

    Phosphorylation at Tyr-340 is necessary and sufficient for the activation of E3 activity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei263 – 2631PhosphotyrosineBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Calcium bindingi196 – 20914PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri350 – 38940RING-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: MGI
    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
    5. ubiquitin-dependent protein catabolic process Source: MGI

    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.-)
    Alternative name(s):
    SH3-binding protein CBL-3
    SH3-binding protein CBL-C
    Signal transduction protein CBL-C
    Gene namesi
    Name:Cblc
    Synonyms:Cbl3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 7

    Organism-specific databases

    MGIiMGI:1931457. Cblc.

    Subcellular locationi

    GO - Cellular componenti

    1. nucleus Source: InterPro
    2. ubiquitin ligase complex Source: MGI

    Pathology & Biotechi

    Disruption phenotypei

    No visible phenotype.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 496496E3 ubiquitin-protein ligase CBL-CPRO_0000055867Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei340 – 3401Phosphotyrosine; by SRCBy similarity

    Post-translational modificationi

    Phosphorylated on tyrosines by EGFR.By similarity
    Phosphorylated on multiple tyrosine residues by SRC. Isoform 1, but not isoform 2, is phosphorylated on tyrosines by EGFR By similarity.By similarity
    Autoubiquitinated, when phosphorylated at Tyr-340.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ80XL1.
    PRIDEiQ80XL1.

    PTM databases

    PhosphoSiteiQ80XL1.

    Expressioni

    Tissue specificityi

    Widely expressed in tissues, where the expression is restricted to epithelial cells (at protein level).2 Publications

    Developmental stagei

    Expressed at E14.5 in liver, lung and brain.1 Publication

    Gene expression databases

    ArrayExpressiQ80XL1.
    BgeeiQ80XL1.
    CleanExiMM_CBLC.
    GenevestigatoriQ80XL1.

    Interactioni

    Subunit structurei

    Interacts with Ubiquitin-conjugating enzyme E2 UBE2D2 and UBE2D3. Isoform 1 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' By similarity.By similarity

    Protein-protein interaction databases

    BioGridi219812. 2 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliQ80XL1.
    SMRiQ80XL1. Positions 8-400.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini7 – 320314Cbl-PTBPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni7 – 1441384HAdd
    BLAST
    Regioni145 – 21773EF-hand-likeAdd
    BLAST
    Regioni218 – 320103SH2-likeAdd
    BLAST
    Regioni321 – 34929LinkerBy similarityAdd
    BLAST
    Regioni350 – 494145Interaction 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 fingeri350 – 38940RING-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, SH3-binding, Zinc-finger

    Phylogenomic databases

    eggNOGiNOG318595.
    GeneTreeiENSGT00390000011617.
    HOGENOMiHOG000294176.
    HOVERGENiHBG005255.
    InParanoidiQ80XL1.
    KOiK04707.
    OMAiWQHSDSQ.
    PhylomeDBiQ80XL1.
    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.
    SM00252. SH2. 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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q80XL1-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAAAAAPRGW QRGEPRALSR AVKLLQRLEE QCRDPRMVTG PPSLRDLLPR    50
    TAQLLGEVAK ARREAREDPE GPGGADDFLA IYLANLEVKG RQVAELLPPR 100
    GKKDVNQDVF REGSRFRRQL AKLALIFSHM HAELSALFPA GKYCGHLYQL 150
    TKGSAHIFWR QNCGVRCVLP WAEFQSLLCA CHPVEPGPTM QALRSTLDLT 200
    CNGHVSVFEF DVFTRLFQPW PTLLRNWQLL AVNHPGYMAF LTYDEVQTRL 250
    QAYRDKPGSY IFRPSCTRLG QWAIGYVSSD GSILQTIPLN KPLLQVLLKG 300
    QKDGIFLFPD GKKHNPDLTE LCRVEPYQRI QVSEEQLLLY QAMNSTFQLC 350
    KICAERDKDV RIEPCGHLLC SCCLAAWQDS DSQTCPFCRC EIKGREAVSI 400
    CQAQERPTEV RTAADGSRDN CHQEAAEQKL GPVIPSAPSL LPEDQFPQGP 450
    QDKGWLTLAP LALPRLRPPL PLPKMASVLW EVTSRPRARE EATESS 496
    Length:496
    Mass (Da):55,715
    Last modified:August 16, 2005 - v2
    Checksum:i4DBE4A14C3D1BF57
    GO
    Isoform 2 (identifier: Q80XL1-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         259-259: S → R
         260-496: Missing.

    Show »
    Length:259
    Mass (Da):29,316
    Checksum:i5EA7613675F647DF
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti8 – 81R → Q in AAK01405. (PubMed:11162497)Curated
    Sequence conflicti371 – 3711S → G in AAK01405. (PubMed:11162497)Curated
    Sequence conflicti375 – 3751A → S in BAB26782. (PubMed:16141072)Curated
    Sequence conflicti416 – 4161G → D in AAH46337. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei259 – 2591S → R in isoform 2. 1 PublicationVSP_014946
    Alternative sequencei260 – 496237Missing in isoform 2. 1 PublicationVSP_014947Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF319956 mRNA. Translation: AAK01405.1.
    AK009399 mRNA. Translation: BAB26265.1.
    AK010228 mRNA. Translation: BAB26782.1.
    BC046337 mRNA. Translation: AAH46337.1.
    CCDSiCCDS39804.1. [Q80XL1-1]
    RefSeqiNP_075713.3. NM_023224.5. [Q80XL1-1]
    UniGeneiMm.81698.

    Genome annotation databases

    EnsembliENSMUST00000043822; ENSMUSP00000039955; ENSMUSG00000040525. [Q80XL1-1]
    GeneIDi80794.
    KEGGimmu:80794.
    UCSCiuc009fnh.2. mouse. [Q80XL1-1]
    uc009fni.2. mouse. [Q80XL1-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF319956 mRNA. Translation: AAK01405.1 .
    AK009399 mRNA. Translation: BAB26265.1 .
    AK010228 mRNA. Translation: BAB26782.1 .
    BC046337 mRNA. Translation: AAH46337.1 .
    CCDSi CCDS39804.1. [Q80XL1-1 ]
    RefSeqi NP_075713.3. NM_023224.5. [Q80XL1-1 ]
    UniGenei Mm.81698.

    3D structure databases

    ProteinModelPortali Q80XL1.
    SMRi Q80XL1. Positions 8-400.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 219812. 2 interactions.

    PTM databases

    PhosphoSitei Q80XL1.

    Proteomic databases

    PaxDbi Q80XL1.
    PRIDEi Q80XL1.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000043822 ; ENSMUSP00000039955 ; ENSMUSG00000040525 . [Q80XL1-1 ]
    GeneIDi 80794.
    KEGGi mmu:80794.
    UCSCi uc009fnh.2. mouse. [Q80XL1-1 ]
    uc009fni.2. mouse. [Q80XL1-2 ]

    Organism-specific databases

    CTDi 23624.
    MGIi MGI:1931457. Cblc.

    Phylogenomic databases

    eggNOGi NOG318595.
    GeneTreei ENSGT00390000011617.
    HOGENOMi HOG000294176.
    HOVERGENi HBG005255.
    InParanoidi Q80XL1.
    KOi K04707.
    OMAi WQHSDSQ.
    PhylomeDBi Q80XL1.
    TreeFami TF314210.

    Miscellaneous databases

    NextBioi 350129.
    PROi Q80XL1.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q80XL1.
    Bgeei Q80XL1.
    CleanExi MM_CBLC.
    Genevestigatori Q80XL1.

    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.
    SM00252. SH2. 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. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
      Strain: C57BL/6.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
      Strain: C57BL/6J.
      Tissue: Tongue.
    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] (ISOFORM 1).
      Strain: FVB/N.
      Tissue: Colon.
    4. Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiCBLC_MOUSE
    AccessioniPrimary (citable) accession number: Q80XL1
    Secondary accession number(s): Q99PB6, Q9D6L2, Q9D7A9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 16, 2005
    Last sequence update: August 16, 2005
    Last modified: October 1, 2014
    This is version 100 of the entry and version 2 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3