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P22682

- CBL_MOUSE

UniProt

P22682 - CBL_MOUSE

Protein

E3 ubiquitin-protein ligase CBL

Gene

Cbl

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 154 (01 Oct 2014)
      Sequence version 3 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. 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. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The 'Tyr-737' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3.5 Publications

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei292 – 2921PhosphotyrosineBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Calcium bindingi225 – 23814PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri379 – 41840RING-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. calcium ion binding Source: InterPro
    2. ephrin receptor binding Source: UniProtKB
    3. ligase activity Source: UniProtKB-KW
    4. protein binding Source: UniProtKB
    5. SH3 domain binding Source: BHF-UCL
    6. signal transducer activity Source: InterPro
    7. ubiquitin-protein transferase activity Source: InterPro
    8. zinc ion binding Source: InterPro

    GO - Biological processi

    1. bone resorption Source: UniProtKB
    2. cell surface receptor signaling pathway Source: InterPro
    3. negative regulation of apoptotic process Source: Ensembl
    4. positive regulation of phosphatidylinositol 3-kinase signaling Source: Ensembl
    5. protein phosphorylation Source: UniProtKB

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Ubl conjugation pathway

    Keywords - Ligandi

    Calcium, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_188194. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_198525. Negative regulation of FGFR signaling.
    REACT_198526. Spry regulation of FGF signaling.
    REACT_198634. Regulation of signaling by CBL.
    REACT_199118. Interleukin-6 signaling.
    REACT_199123. Signaling by constitutively active EGFR.
    REACT_203510. TGF-beta receptor signaling activates SMADs.
    REACT_203917. EGFR downregulation.
    REACT_227425. Regulation of KIT signaling.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    E3 ubiquitin-protein ligase CBL (EC:6.3.2.-)
    Alternative name(s):
    Casitas B-lineage lymphoma proto-oncogene
    Proto-oncogene c-Cbl
    Signal transduction protein CBL
    Gene namesi
    Name:Cbl
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 9

    Organism-specific databases

    MGIiMGI:88279. Cbl.

    Subcellular locationi

    Cytoplasm. Cell membrane By similarity
    Note: Colocalizes with FGFR2 in lipid rafts at the cell membrane.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: InterPro
    3. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Can be converted to an oncogenic protein by deletions or mutations that disturb its ability to down-regulate RTKs.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi304 – 3041G → E: Abolishes interaction with ZAP70, but does not affect interaction with SLA. 1 Publication

    Keywords - Diseasei

    Proto-oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 913913E3 ubiquitin-protein ligase CBLPRO_0000055859Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei139 – 1391PhosphotyrosineBy similarity
    Modified residuei369 – 3691PhosphotyrosineBy similarity
    Modified residuei450 – 4501PhosphoserineBy similarity
    Modified residuei453 – 4531PhosphotyrosineBy similarity
    Modified residuei550 – 5501PhosphotyrosineBy similarity
    Modified residuei665 – 6651PhosphoserineBy similarity
    Modified residuei666 – 6661Phosphoserine1 Publication
    Modified residuei667 – 6671Phosphoserine1 Publication
    Modified residuei672 – 6721Phosphotyrosine1 Publication
    Modified residuei673 – 6731PhosphoserineBy similarity
    Modified residuei698 – 6981Phosphotyrosine; by ABL1
    Modified residuei737 – 7371Phosphotyrosine; by SRCBy similarity
    Modified residuei780 – 7801PhosphotyrosineBy similarity
    Modified residuei907 – 9071PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylated on tyrosine residues by ALK, EGFR, FGR, INSR, SYK, FYN and ZAP70. Phosphorylated on several tyrosine residues by constitutively activated FGFR3. Phosphorylated on tyrosine residues by activated PDGFRA and PDGFRB By similarity. Phosphorylated on tyrosine residues in response to CSF1R, FLT1 and KIT signaling. Phosphorylated on tyrosine residues by HCK.By similarity9 Publications
    Ubiquitinated, leading to its degradation via the proteasome.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP22682.
    PaxDbiP22682.
    PRIDEiP22682.

    PTM databases

    PhosphoSiteiP22682.

    Expressioni

    Gene expression databases

    BgeeiP22682.
    CleanExiMM_CBL.
    GenevestigatoriP22682.

    Interactioni

    Subunit structurei

    Interacts (phosphorylated) with PIK3R1. Interacts with phosphorylated LAT2 By similarity. Associates with NCK via its SH3 domain. The phosphorylated C-terminus interacts with CD2AP via its second SH3 domain. Binds to UBE2L3. Interacts with adapters SLA, SLA2 and with the phosphorylated C-terminus of SH2B2. Interacts with EGFR, SYK and ZAP70 via the highly conserved Cbl-N region. Interacts with FGR. Also interacts with BLK, SORBS1 and INPPL1/SHIP2. May interact with CBLB. Interacts with TEK/TIE2 (tyrosine phosphorylated) By similarity. Interacts with ALK, AXL and FGFR2. Interacts with CSF1R, EPHB1, FLT1, KDR, PDGFRA and PDGFRB; regulates receptor degradation through ubiquitination. Interacts with HCK and LYN. Interacts with ATX2.By similarity12 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Ddx58Q6Q8993EBI-640919,EBI-6841237
    EGFRP005332EBI-640919,EBI-297353From a different organism.
    EgfrQ012792EBI-640919,EBI-6296235
    MetP160562EBI-640919,EBI-1798780

    Protein-protein interaction databases

    BioGridi198527. 54 interactions.
    IntActiP22682. 15 interactions.
    MINTiMINT-255892.

    Structurei

    Secondary structure

    1
    913
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi865 – 87410
    Helixi878 – 88710
    Turni888 – 8903
    Helixi892 – 90211

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2D9SNMR-A/B863-902[»]
    ProteinModelPortaliP22682.
    SMRiP22682. Positions 46-435, 857-913.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP22682.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini45 – 349305Cbl-PTBPROSITE-ProRule annotationAdd
    BLAST
    Domaini863 – 90240UBAPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 355355Sufficient for interaction with EPHB1Add
    BLAST
    Regioni45 – 1731294HAdd
    BLAST
    Regioni174 – 24673EF-hand-likeAdd
    BLAST
    Regioni247 – 349103SH2-likeAdd
    BLAST
    Regioni350 – 37829LinkerAdd
    BLAST
    Regioni646 – 913268Interaction with CD2APBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi372 – 474103Asp/Glu-rich (acidic)Add
    BLAST
    Compositional biasi475 – 686212Pro-richAdd
    BLAST
    Compositional biasi687 – 839153Asp/Glu-rich (acidic)Add
    BLAST

    Domaini

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

    Sequence similaritiesi

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

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri379 – 41840RING-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiNOG242251.
    GeneTreeiENSGT00390000011617.
    HOGENOMiHOG000294176.
    HOVERGENiHBG005255.
    InParanoidiQ3U527.
    KOiK04707.
    OMAiMEPRADV.
    OrthoDBiEOG7M0NQX.
    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.
    IPR009060. UBA-like.
    IPR015940. UBA/transl_elong_EF1B_N_euk.
    IPR000449. UBA/Ts_N.
    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.
    PF00627. UBA. 1 hit.
    [Graphical view]
    SMARTiSM00184. RING. 1 hit.
    SM00165. UBA. 1 hit.
    [Graphical view]
    SUPFAMiSSF46934. SSF46934. 1 hit.
    SSF47668. SSF47668. 1 hit.
    SSF55550. SSF55550. 1 hit.
    PROSITEiPS51506. CBL_PTB. 1 hit.
    PS50030. UBA. 1 hit.
    PS00518. ZF_RING_1. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P22682-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAGNVKKSSG AGGGGSGGSG AGGLIGLMKD AFQPHHHHHH LSPHPPCTVD    50
    KKMVEKCWKL MDKVVRLCQN PKLALKNSPP YILDLLPDTY QHLRTVLSRY 100
    EGKMETLGEN EYFRVFMENL MKKTKQTISL FKEGKERMYE ENSQPRRNLT 150
    KLSLIFSHML AELKGIFPSG LFQGDTFRIT KADAAEFWRK AFGEKTIVPW 200
    KSFRQALHEV HPISSGLEAM ALKSTIDLTC NDYISVFEFD IFTRLFQPWS 250
    SLLRNWNSLA VTHPGYMAFL TYDEVKARLQ KFIHKPGSYI FRLSCTRLGQ 300
    WAIGYVTADG NILQTIPHNK PLFQALIDGF REGFYLFPDG RNQNPDLTGL 350
    CEPTPQDHIK VTQEQYELYC EMGSTFQLCK ICAENDKDVK IEPCGHLMCT 400
    SCLTSWQESE GQGCPFCRCE IKGTEPIVVD PFDPRGSGSL LRQGAEGAPS 450
    PNYDDDDDER ADDSLFMMKE LAGAKVERPS SPFSMAPQAS LPPVPPRLDL 500
    LQQRAPVPAS TSVLGTASKA ASGSLHKDKP LPIPPTLRDL PPPPPPDRPY 550
    SVGAETRPQR RPLPCTPGDC PSRDKLPPVP SSRPGDSWLS RPIPKVPVAT 600
    PNPGDPWNGR ELTNRHSLPF SLPSQMEPRA DVPRLGSTFS LDTSMTMNSS 650
    PVAGPESEHP KIKPSSSANA IYSLAARPLP MPKLPPGEQG ESEEDTEYMT 700
    PTSRPVGVQK PEPKRPLEAT QSSRACDCDQ QIDSCTYEAM YNIQSQALSV 750
    AENSASGEGN LATAHTSTGP EESENEDDGY DVPKPPVPAV LARRTLSDIS 800
    NASSSFGWLS LDGDPTNFNE GSQVPERPPK PFPRRINSER KASSYQQGGG 850
    ATANPVATAP SPQLSSEIER LMSQGYSYQD IQKALVIAHN NIEMAKNILR 900
    EFVSISSPAH VAT 913
    Length:913
    Mass (Da):100,564
    Last modified:July 27, 2011 - v3
    Checksum:i22F8A5C29F0262B8
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti72 – 732KL → NV in CAA40394. (PubMed:2030914)Curated
    Sequence conflicti218 – 2181E → D in BAC26087. (PubMed:16141072)Curated
    Sequence conflicti592 – 5921P → T in CAA40394. (PubMed:2030914)Curated
    Sequence conflicti742 – 7421N → T in CAA40394. (PubMed:2030914)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti364 – 38017Missing in oncogenic variant 70Z/3.
    Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X57111 mRNA. Translation: CAA40394.1.
    AK028730 mRNA. Translation: BAC26087.1.
    AK153915 mRNA. Translation: BAE32253.1.
    BC125285 mRNA. Translation: AAI25286.1.
    CCDSiCCDS40598.1.
    PIRiB43817.
    RefSeqiNP_031645.2. NM_007619.2.
    UniGeneiMm.266871.

    Genome annotation databases

    EnsembliENSMUST00000037644; ENSMUSP00000041902; ENSMUSG00000034342.
    GeneIDi12402.
    KEGGimmu:12402.
    UCSCiuc009pce.1. mouse.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X57111 mRNA. Translation: CAA40394.1 .
    AK028730 mRNA. Translation: BAC26087.1 .
    AK153915 mRNA. Translation: BAE32253.1 .
    BC125285 mRNA. Translation: AAI25286.1 .
    CCDSi CCDS40598.1.
    PIRi B43817.
    RefSeqi NP_031645.2. NM_007619.2.
    UniGenei Mm.266871.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2D9S NMR - A/B 863-902 [» ]
    ProteinModelPortali P22682.
    SMRi P22682. Positions 46-435, 857-913.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198527. 54 interactions.
    IntActi P22682. 15 interactions.
    MINTi MINT-255892.

    PTM databases

    PhosphoSitei P22682.

    Proteomic databases

    MaxQBi P22682.
    PaxDbi P22682.
    PRIDEi P22682.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000037644 ; ENSMUSP00000041902 ; ENSMUSG00000034342 .
    GeneIDi 12402.
    KEGGi mmu:12402.
    UCSCi uc009pce.1. mouse.

    Organism-specific databases

    CTDi 867.
    MGIi MGI:88279. Cbl.

    Phylogenomic databases

    eggNOGi NOG242251.
    GeneTreei ENSGT00390000011617.
    HOGENOMi HOG000294176.
    HOVERGENi HBG005255.
    InParanoidi Q3U527.
    KOi K04707.
    OMAi MEPRADV.
    OrthoDBi EOG7M0NQX.
    TreeFami TF314210.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    Reactomei REACT_188194. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_198525. Negative regulation of FGFR signaling.
    REACT_198526. Spry regulation of FGF signaling.
    REACT_198634. Regulation of signaling by CBL.
    REACT_199118. Interleukin-6 signaling.
    REACT_199123. Signaling by constitutively active EGFR.
    REACT_203510. TGF-beta receptor signaling activates SMADs.
    REACT_203917. EGFR downregulation.
    REACT_227425. Regulation of KIT signaling.

    Miscellaneous databases

    EvolutionaryTracei P22682.
    NextBioi 281170.
    PROi P22682.
    SOURCEi Search...

    Gene expression databases

    Bgeei P22682.
    CleanExi MM_CBL.
    Genevestigatori P22682.

    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.
    IPR009060. UBA-like.
    IPR015940. UBA/transl_elong_EF1B_N_euk.
    IPR000449. UBA/Ts_N.
    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.
    PF00627. UBA. 1 hit.
    [Graphical view ]
    SMARTi SM00184. RING. 1 hit.
    SM00165. UBA. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46934. SSF46934. 1 hit.
    SSF47668. SSF47668. 1 hit.
    SSF55550. SSF55550. 1 hit.
    PROSITEi PS51506. CBL_PTB. 1 hit.
    PS50030. UBA. 1 hit.
    PS00518. ZF_RING_1. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif."
      Blake T.J., Shapiro M., Morse H.C. III, Langdon W.Y.
      Oncogene 6:653-657(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTANT 70Z/3.
    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].
      Strain: C57BL/6J and NOD.
      Tissue: Skin and Thymus.
    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].
      Tissue: Brain.
    4. "Tyrosine phosphorylation and translocation of the c-cbl protein after activation of tyrosine kinase signaling pathways."
      Tanaka S., Neff L., Baron R., Levy J.B.
      J. Biol. Chem. 270:14347-14351(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LYN, PHOSPHORYLATION.
    5. "Differential intrinsic enzymatic activity of Syk and Zap-70 protein-tyrosine kinases."
      Latour S., Chow L.M., Veillette A.
      J. Biol. Chem. 271:22782-22790(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY SYK.
    6. "Association of tyrosine protein kinase Zap-70 with the protooncogene product p120c-cbl in T lymphocytes."
      Fournel M., Davidson D., Weil R., Veillette A.
      J. Exp. Med. 183:301-306(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY ZAP70.
    7. "Identification of vascular endothelial growth factor receptor-1 tyrosine phosphorylation sites and binding of SH2 domain-containing molecules."
      Ito N., Wernstedt C., Engstrom U., Claesson-Welsh L.
      J. Biol. Chem. 273:23410-23418(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FLT1.
    8. "A novel, multifunctional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes."
      Ribon V., Printen J.A., Hoffman N.G., Kay B.K., Saltiel A.R.
      Mol. Cell. Biol. 18:872-879(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SORBS1.
    9. "The tyrosine kinase regulator Cbl enhances the ubiquitination and degradation of the platelet-derived growth factor receptor alpha."
      Miyake S., Lupher M.L. Jr., Druker B., Band H.
      Proc. Natl. Acad. Sci. U.S.A. 95:7927-7932(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "The proto-oncogene p120(Cbl) is a downstream substrate of the Hck protein-tyrosine kinase."
      Howlett C.J., Bisson S.A., Resek M.E., Tigley A.W., Robbins S.M.
      Biochem. Biophys. Res. Commun. 257:129-138(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY HCK, INTERACTION WITH HCK.
    11. "The Cbl protooncoprotein stimulates CSF-1 receptor multiubiquitination and endocytosis, and attenuates macrophage proliferation."
      Lee P.S., Wang Y., Dominguez M.G., Yeung Y.G., Murphy M.A., Bowtell D.D., Stanley E.R.
      EMBO J. 18:3616-3628(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Functional cooperation between c-Cbl and Src-like adaptor protein 2 in the negative regulation of T-cell receptor signaling."
      Loreto M.P., Berry D.M., McGlade C.J.
      Mol. Cell. Biol. 22:4241-4255(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SLA2 AND ZAP70, MUTAGENESIS OF GLY-304.
    13. "Vascular endothelial growth factor-dependent down-regulation of Flk-1/KDR involves Cbl-mediated ubiquitination. Consequences on nitric oxide production from endothelial cells."
      Duval M., Bedard-Goulet S., Delisle C., Gratton J.P.
      J. Biol. Chem. 278:20091-20097(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH KDR, FUNCTION.
    14. "The roles of Cbl-b and c-Cbl in insulin-stimulated glucose transport."
      Liu J., DeYoung S.M., Hwang J.B., O'Leary E.E., Saltiel A.R.
      J. Biol. Chem. 278:36754-36762(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CBLB.
    15. "The c-Cbl/CD2AP complex regulates VEGF-induced endocytosis and degradation of Flt-1 (VEGFR-1)."
      Kobayashi S., Sawano A., Nojima Y., Shibuya M., Maru Y.
      FASEB J. 18:929-931(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FLT1 AND CD2AP, PHOSPHORYLATION IN RESPONSE TO VEGFA.
    16. "The Src-like adaptor protein 2 regulates colony-stimulating factor-1 receptor signaling and down-regulation."
      Pakuts B., Debonneville C., Liontos L.M., Loreto M.P., McGlade C.J.
      J. Biol. Chem. 282:17953-17963(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, INTERACTION WITH SLA2 AND CSF1R.
    17. "Binding of Cbl to a phospholipase Cgamma1-docking site on platelet-derived growth factor receptor beta provides a dual mechanism of negative regulation."
      Reddi A.L., Ying G., Duan L., Chen G., Dimri M., Douillard P., Druker B.J., Naramura M., Band V., Band H.
      J. Biol. Chem. 282:29336-29347(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PDGFRB.
    18. "Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
      Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
      J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-666; SER-667 AND TYR-672, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Mast cell.
    19. "Ataxin-2 associates with the endocytosis complex and affects EGF receptor trafficking."
      Nonis D., Schmidt M.H., van de Loo S., Eich F., Dikic I., Nowock J., Auburger G.
      Cell. Signal. 20:1725-1739(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ATX2.
    20. "Ligand binding induces Cbl-dependent EphB1 receptor degradation through the lysosomal pathway."
      Fasen K., Cerretti D.P., Huynh-Do U.
      Traffic 9:251-266(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EPHB1, PHOSPHORYLATION.
    21. "The D816V mutation of c-Kit circumvents a requirement for Src family kinases in c-Kit signal transduction."
      Sun J., Pedersen M., Ronnstrand L.
      J. Biol. Chem. 284:11039-11047(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN UBIQUITINATION OF KIT, PHOSPHORYLATION.
    22. "The SAM domains of Anks family proteins are critically involved in modulating the degradation of EphA receptors."
      Kim J., Lee H., Kim Y., Yoo S., Park E., Park S.
      Mol. Cell. Biol. 30:1582-1592(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN UBIQUITINATION OF EPHA8.

    Entry informationi

    Entry nameiCBL_MOUSE
    AccessioniPrimary (citable) accession number: P22682
    Secondary accession number(s): Q3U527, Q8CEA1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1991
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 154 of the entry and version 3 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3