Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q8K4S7

- CBLB_RAT

UniProt

Q8K4S7 - CBLB_RAT

Protein

E3 ubiquitin-protein ligase CBL-B

Gene

Cblb

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 89 (01 Oct 2014)
      Sequence version 1 (01 Oct 2002)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3.1 Publication

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei286 – 2861PhosphotyrosineBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Calcium bindingi219 – 23214Add
    BLAST
    Zinc fingeri373 – 41240RING-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

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

    GO - Biological processi

    1. cell surface receptor signaling pathway Source: InterPro
    2. regulation of signaling Source: InterPro
    3. response to gravity Source: RGD
    4. response to hormone Source: RGD
    5. signal transduction Source: RGD

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Ubl conjugation pathway

    Keywords - Ligandi

    Calcium, Metal-binding, Zinc

    Enzyme and pathway databases

    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    E3 ubiquitin-protein ligase CBL-B (EC:6.3.2.-)
    Alternative name(s):
    Casitas B-lineage lymphoma proto-oncogene b
    SH3-binding protein CBL-B
    Signal transduction protein CBL-B
    Gene namesi
    Name:Cblb
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi620535. Cblb.

    Subcellular locationi

    Cytoplasm 1 Publication
    Note: In mast cells, translocates to lipid raft upon FCER1 engagement.

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Lack of Cblb expression is the cause of the Komeda diabetes-prone (KDP) phenotype, characterized by autoimmune destruction of pancreatic beta cells and rapid onset of overt diabetes with no sex difference and no significant T-cell lymphopenia. The KPD rat is a spontaneous animal model for human type 1 diabetes mellitus.1 Publication

    Keywords - Diseasei

    Diabetes mellitus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 938938E3 ubiquitin-protein ligase CBL-BPRO_0000055862Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei282 – 2821Phosphoserine; by PKC/PRKCQBy similarity
    Modified residuei521 – 5211PhosphoserineBy similarity
    Modified residuei525 – 5251PhosphoserineBy similarity
    Modified residuei529 – 5291PhosphoserineBy similarity
    Modified residuei633 – 6331Phosphoserine1 Publication
    Modified residuei664 – 6641PhosphotyrosineBy similarity
    Modified residuei708 – 7081PhosphotyrosineBy similarity
    Modified residuei845 – 8451PhosphotyrosineBy similarity

    Post-translational modificationi

    Phosphorylated on tyrosine and serine residues upon TCR or BCR activation, and upon various types of cell stimulation.By similarity
    Auto-ubiquitinated upon EGF-mediated cell activation or upon T-cell costimulation by CD28; which promotes proteasomal degradation.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ8K4S7.
    PRIDEiQ8K4S7.

    PTM databases

    PhosphoSiteiQ8K4S7.

    Expressioni

    Gene expression databases

    GenevestigatoriQ8K4S7.

    Interactioni

    Subunit structurei

    Interacts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. May interact with CBL. Interacts with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two copies of the other protein. Interacts with poly-ubiquitinated proteins. Dimerization is required for the binding of poly-ubiquitin, but not for the binding of mono-ubiquitin. Interacts with EGFR (phosphorylated) By similarity.By similarity

    Protein-protein interaction databases

    IntActiQ8K4S7. 6 interactions.
    MINTiMINT-2880613.
    STRINGi10116.ENSRNOP00000039085.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8K4S7.
    SMRiQ8K4S7. Positions 35-426, 885-928.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini35 – 343309Cbl-PTBPROSITE-ProRule annotationAdd
    BLAST
    Domaini887 – 92640UBAPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni35 – 1671334HAdd
    BLAST
    Regioni168 – 24073EF-hand-likeAdd
    BLAST
    Regioni241 – 343103SH2-likeAdd
    BLAST
    Regioni344 – 37229LinkerAdd
    BLAST
    Regioni543 – 56725Interaction with VAV1By similarityAdd
    BLAST
    Regioni847 – 88337Interaction with SH3KBP1By similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi477 – 56690Pro-richAdd
    BLAST
    Compositional biasi672 – 6754Poly-Pro
    Compositional biasi774 – 881108Pro-richAdd
    BLAST

    Domaini

    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.
    The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.
    The UBA domain interacts with poly-ubiquitinated proteins.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
    Contains 1 UBA domain.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri373 – 41240RING-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiNOG242251.
    HOGENOMiHOG000294176.
    HOVERGENiHBG005255.
    InParanoidiQ8K4S7.
    KOiK04707.

    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.
    IPR015940. UBA/transl_elong_EF1B_N_euk.
    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.
    SM00165. UBA. 1 hit.
    [Graphical view]
    SUPFAMiSSF47668. 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.

    Q8K4S7-1 [UniParc]FASTAAdd to Basket

    « Hide

    MANSMNGRNP GGRGGNPRKG RILGIIDAIQ DAVGPPKQAA ADRRTVEKTW    50
    KLMDKVVRLC QNPKLQLKNS PPYILDILPD TYQHLRLILS KYDDNQKLAQ 100
    LSENEYFKIY IDSLMKKSKR AIRLFKEGKE RMYEEQSQDR RNLTKLSLIF 150
    SHMLAEIKAI FPNGQFQGDN FRITKADAAE FWRKFFGDKT IVPWKVFRQC 200
    LHEVHQISSG LEAMALKSTI DLTCNDYISV FEFDIFTRLF QPWGSILRNW 250
    NFLAVTHPGY MAFLTYDEVK ARLQKYSTKP GSYIFRLSCT RLGQWAIGYV 300
    TGDGNILQTI PHNKPLFQAL IDGSREGFYL YPDGRSYNPD LTGLCEPTPH 350
    DHIKVTQEQY ELYCEMGSTF QLCKICAEND KDVKIEPCGH LMCTSCLTAW 400
    QESDGQGCPF CRCEIKGTEP IIVDPFDPRD EGSRCCSIID PFSIPMLDLD 450
    DDDDREESLM MNRLASVRKC TDRQNSPVTS PGSSPLAQRR KPQPDPLQIP 500
    HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ DKPLPAPPPP 550
    LRDPPPPPER PPPIPPDSRL SRHFHHGESV PSRDQPMPLE AWCPRDAFGT 600
    NQVMGCRILG DGSPKPGVTA NSNLNGRHSR MGSDQVLMRK HRRHDLPSEG 650
    AKVFSNGHLA PEEYDVPPRL SPPPPVTALL PSIKCTGPIA NCLSEKTRDT 700
    VEEDDDEYKI PSSHPVSLNS QPSHCHNVKP PVRSCDNGHC ILNGTHGTPS 750
    EMKKSNIPDL GIYLKGEDAF DALPPSLPPP PPPARHSLIE HSKPPGSSSR 800
    PSSGQDLFLL PSDPFFDPAS GQVPLPPARR APGDGVKSNR ASQDYDQLPS 850
    SSDGSQAPAR PPKPRPRRTA PEIHHRKPHG PEAALENVDA KIAKLMGEGY 900
    AFEEVKRALE IAQNNLEVAR SILREFAFPP PVSPRLNL 938
    Length:938
    Mass (Da):104,652
    Last modified:October 1, 2002 - v1
    Checksum:i8316D0E7F7252EC6
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB071283 mRNA. Translation: BAC05498.1.
    AF199504 mRNA. Translation: AAF13271.1.
    RefSeqiNP_598285.1. NM_133601.1.
    UniGeneiRn.21799.

    Genome annotation databases

    GeneIDi171136.
    KEGGirno:171136.
    UCSCiRGD:620535. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB071283 mRNA. Translation: BAC05498.1 .
    AF199504 mRNA. Translation: AAF13271.1 .
    RefSeqi NP_598285.1. NM_133601.1.
    UniGenei Rn.21799.

    3D structure databases

    ProteinModelPortali Q8K4S7.
    SMRi Q8K4S7. Positions 35-426, 885-928.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q8K4S7. 6 interactions.
    MINTi MINT-2880613.
    STRINGi 10116.ENSRNOP00000039085.

    PTM databases

    PhosphoSitei Q8K4S7.

    Proteomic databases

    PaxDbi Q8K4S7.
    PRIDEi Q8K4S7.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 171136.
    KEGGi rno:171136.
    UCSCi RGD:620535. rat.

    Organism-specific databases

    CTDi 868.
    RGDi 620535. Cblb.

    Phylogenomic databases

    eggNOGi NOG242251.
    HOGENOMi HOG000294176.
    HOVERGENi HBG005255.
    InParanoidi Q8K4S7.
    KOi K04707.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .

    Miscellaneous databases

    NextBioi 621914.
    PROi Q8K4S7.

    Gene expression databases

    Genevestigatori Q8K4S7.

    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.
    IPR015940. UBA/transl_elong_EF1B_N_euk.
    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.
    SM00165. UBA. 1 hit.
    [Graphical view ]
    SUPFAMi 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. "Cblb is a major susceptibility gene for rat type 1 diabetes mellitus."
      Yokoi N., Komeda K., Wang H.-Y., Yano H., Kitada K., Saitoh Y., Seino Y., Yasuda K., Serikawa T., Seino S.
      Nat. Genet. 31:391-394(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], DISEASE.
      Tissue: Spleen.
    2. "Identification of cbl-b as a putative binding partner of SH3 domains of erythroid and non-erythroid alpha-spectrin (alpha-fodrin)."
      Nicolas G., Galand C., Lecomte M.-C.
      Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 738-938.
      Strain: Sprague-Dawley.
      Tissue: Kidney.
    3. "Negative regulation of FcepsilonRI-mediated mast cell activation by a ubiquitin-protein ligase Cbl-b."
      Qu X., Sada K., Kyo S., Maeno K., Miah S.M., Yamamura H.
      Blood 103:1779-1786(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    4. "Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
      Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
      Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-633, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiCBLB_RAT
    AccessioniPrimary (citable) accession number: Q8K4S7
    Secondary accession number(s): Q9QZ69
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 7, 2006
    Last sequence update: October 1, 2002
    Last modified: October 1, 2014
    This is version 89 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. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3