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Q13191

- CBLB_HUMAN

UniProt

Q13191 - CBLB_HUMAN

Protein

E3 ubiquitin-protein ligase CBL-B

Gene

CBLB

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 160 (01 Oct 2014)
      Sequence version 2 (07 Feb 2006)
      Previous versions | rss
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    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 UB2D3.6 Publications

    Pathwayi

    Sites

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

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Calcium bindingi219 – 23214PROSITE-ProRule annotationAdd
    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 binding Source: IntAct
    4. signal transducer activity Source: InterPro
    5. ubiquitin-protein transferase activity Source: InterPro
    6. zinc ion binding Source: ProtInc

    GO - Biological processi

    1. cell surface receptor signaling pathway Source: InterPro
    2. immune response Source: Ensembl
    3. intracellular signal transduction Source: Ensembl
    4. negative regulation of alpha-beta T cell proliferation Source: Ensembl
    5. negative regulation of T cell receptor signaling pathway Source: Ensembl
    6. NLS-bearing protein import into nucleus Source: ProtInc
    7. positive regulation of protein catabolic process Source: Ensembl
    8. positive regulation of T cell anergy Source: Ensembl
    9. signal transduction Source: ProtInc
    10. T cell activation Source: Ensembl

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Ubl conjugation pathway

    Keywords - Ligandi

    Calcium, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
    SignaLinkiQ13191.
    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
    RING finger protein 56
    SH3-binding protein CBL-B
    Signal transduction protein CBL-B
    Gene namesi
    Name:CBLB
    Synonyms:RNF56
    ORF Names:Nbla00127
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:1542. CBLB.

    Subcellular locationi

    Cytoplasm 1 Publication
    Note: Upon EGF stimulation, associates with endocytic vesicles.

    GO - Cellular componenti

    1. cytoplasm Source: HPA
    2. cytosol Source: Reactome
    3. nucleus Source: HPA
    4. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi298 – 2981G → E: Inhibits interaction with SYK. No effect on E3 activity. 2 Publications
    Mutagenesisi363 – 3631Y → E: Decreases affinity for E2 ubiquitin-conjugating enzymes. 1 Publication
    Mutagenesisi373 – 3731C → A: Abolishes E3 activity but does not affect binding to substrates. 2 Publications
    Mutagenesisi665 – 6651Y → F: Slightly inhibits interaction with CRKL. Abolishes interaction with CRKL; when associated with F-709. 1 Publication
    Mutagenesisi709 – 7091Y → F: Inhibits interaction with CRKL. Abolishes interaction with CRKL; when associated with F-665. 1 Publication
    Mutagenesisi904 – 9041R → A: No effect on interaction with CD2AP. Reduced interaction with SH3KBP1. Strongly reduced interaction with SH3KBP1; when associated with A-911. 2 Publications
    Mutagenesisi907 – 9071K → A: No effect on interaction with SH3KBP1. Reduced interaction with CD2AP. Strongly reduced interaction with CD2AP; when associated with A-911. 1 Publication
    Mutagenesisi911 – 9111R → A: Reduced interaction with CD2AP and with SH3KBP1. Strongly reduced interaction with CD2AP; when associated with A-907. Strongly reduced interaction with SH3KBP1; when associated with A-904. 2 Publications
    Mutagenesisi937 – 9371A → E: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation. 1 Publication
    Mutagenesisi940 – 9401M → A: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation. 1 Publication
    Mutagenesisi943 – 9442GY → AQ: Abolishes interaction with ubiquitinated proteins.
    Mutagenesisi946 – 9461F → A: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation. 1 Publication
    Mutagenesisi966 – 9661I → E: Interferes with dimerization. Reduced E3 ubiquitin-protein ligase activity. Reduced levels of tyrosine phosphorylation. 1 Publication
    Mutagenesisi967 – 9671L → A: No effect on interaction with ubiquitinated proteins. 1 Publication

    Organism-specific databases

    PharmGKBiPA26116.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 982982E3 ubiquitin-protein ligase CBL-BPRO_0000055860Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei282 – 2821Phosphoserine; by PKC/PRKCQ2 Publications
    Modified residuei363 – 3631Phosphotyrosine2 Publications
    Modified residuei521 – 5211Phosphoserine2 Publications
    Modified residuei525 – 5251Phosphoserine2 Publications
    Modified residuei529 – 5291Phosphoserine2 Publications
    Modified residuei634 – 6341PhosphoserineBy similarity
    Modified residuei665 – 6651Phosphotyrosine2 Publications
    Modified residuei709 – 7091Phosphotyrosine2 Publications
    Modified residuei889 – 8891PhosphotyrosineBy similarity

    Post-translational modificationi

    Phosphorylated on tyrosine and serine residues upon TCR or BCR activation, and upon various types of cell stimulation.5 Publications
    Auto-ubiquitinated upon EGF-mediated cell activation or upon T-cell costimulation by CD28; which promotes proteasomal degradation.1 Publication

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ13191.
    PaxDbiQ13191.
    PRIDEiQ13191.

    PTM databases

    PhosphoSiteiQ13191.

    Expressioni

    Tissue specificityi

    Expressed in placenta, heart, lung, kidney, spleen, ovary and testis, as well as fetal brain and liver and hematopoietic cell lines, but not in adult brain, liver, pancreas, salivary gland, or skeletal muscle. Present in lymphocytes (at protein level).2 Publications

    Gene expression databases

    ArrayExpressiQ13191.
    BgeeiQ13191.
    CleanExiHS_CBLB.
    GenevestigatoriQ13191.

    Organism-specific databases

    HPAiHPA018327.
    HPA019880.

    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).10 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ASAP1Q9ULH12EBI-744027,EBI-346622
    CD2APQ9Y5K611EBI-744027,EBI-298152
    GRB2P629935EBI-744027,EBI-401755
    SH3KBP1Q96B9719EBI-744027,EBI-346595

    Protein-protein interaction databases

    BioGridi107316. 47 interactions.
    DIPiDIP-33091N.
    IntActiQ13191. 20 interactions.
    MINTiMINT-256380.
    STRINGi9606.ENSP00000264122.

    Structurei

    Secondary structure

    1
    982
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi43 – 6018
    Helixi63 – 653
    Beta strandi69 – 724
    Helixi74 – 9118
    Helixi95 – 1028
    Helixi105 – 12824
    Helixi129 – 1335
    Helixi138 – 16023
    Helixi162 – 1643
    Helixi168 – 1703
    Helixi176 – 18611
    Beta strandi190 – 1934
    Helixi194 – 20411
    Helixi210 – 22011
    Beta strandi225 – 2295
    Helixi230 – 23910
    Helixi243 – 2453
    Helixi246 – 2538
    Beta strandi260 – 2634
    Helixi266 – 2738
    Helixi274 – 2763
    Beta strandi282 – 2876
    Beta strandi289 – 2913
    Beta strandi295 – 3006
    Beta strandi306 – 3094
    Beta strandi312 – 3143
    Helixi316 – 32510
    Helixi332 – 3343
    Helixi342 – 3443
    Beta strandi352 – 3543
    Helixi357 – 3648
    Turni365 – 3673
    Beta strandi370 – 3723
    Turni374 – 3763
    Beta strandi377 – 3804
    Beta strandi383 – 3864
    Helixi394 – 4029
    Turni409 – 4113
    Beta strandi417 – 4204
    Beta strandi422 – 4243
    Helixi933 – 9419
    Helixi946 – 95510
    Turni956 – 9583
    Helixi960 – 97011

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2AK5X-ray1.85D904-911[»]
    2BZ8X-ray2.00C902-912[»]
    2DO6NMR-A/B931-970[»]
    2J6FX-ray1.70C902-912[»]
    2JNHNMR-A926-971[»]
    2LDRNMR-A351-426[»]
    2OOAX-ray1.56A/B924-973[»]
    2OOBX-ray1.90A924-973[»]
    3PFVX-ray2.27A/B38-344[»]
    3VGOX-ray3.10A/B/C39-426[»]
    3ZNIX-ray2.21A/E/I/M36-427[»]
    ProteinModelPortaliQ13191.
    SMRiQ13191. Positions 38-427, 929-972.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ13191.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini35 – 343309Cbl-PTBPROSITE-ProRule annotationAdd
    BLAST
    Domaini931 – 97040UBAPROSITE-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 – 56826Interaction with VAV1Add
    BLAST
    Regioni891 – 92737Interaction with SH3KBP1Add
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi477 – 925449Pro-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.

    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.
    HOVERGENiHBG005255.
    InParanoidiQ13191.
    KOiK04707.
    OMAiSSPCMVR.
    OrthoDBiEOG7M0NQX.
    PhylomeDBiQ13191.
    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.
    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.
    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]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform Long (identifier: Q13191-1) [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

    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 PFGMPMLDLD 450
    DDDDREESLM MNRLANVRKC TDRQNSPVTS PGSSPLAQRR KPQPDPLQIP 500
    HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ DKPLPAPPPP 550
    LRDPPPPPPE RPPPIPPDNR LSRHIHHVES VPSRDPPMPL EAWCPRDVFG 600
    TNQLVGCRLL GEGSPKPGIT ASSNVNGRHS RVGSDPVLMR KHRRHDLPLE 650
    GAKVFSNGHL GSEEYDVPPR LSPPPPVTTL LPSIKCTGPL ANSLSEKTRD 700
    PVEEDDDEYK IPSSHPVSLN SQPSHCHNVK PPVRSCDNGH CMLNGTHGPS 750
    SEKKSNIPDL SIYLKGDVFD SASDPVPLPP ARPPTRDNPK HGSSLNRTPS 800
    DYDLLIPPLG EDAFDALPPS LPPPPPPARH SLIEHSKPPG SSSRPSSGQD 850
    LFLLPSDPFV DLASGQVPLP PARRLPGENV KTNRTSQDYD QLPSCSDGSQ 900
    APARPPKPRP RRTAPEIHHR KPHGPEAALE NVDAKIAKLM GEGYAFEEVK 950
    RALEIAQNNV EVARSILREF AFPPPVSPRL NL 982
    Length:982
    Mass (Da):109,450
    Last modified:February 7, 2006 - v2
    Checksum:iB4E307D31B9F0779
    GO
    Isoform Truncated 1 (identifier: Q13191-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         812-982: Missing.

    Show »
    Length:811
    Mass (Da):90,883
    Checksum:iA63D22F7C9C677DB
    GO
    Isoform Truncated 2 (identifier: Q13191-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         767-770: DVFD → TYRI
         771-982: Missing.

    Show »
    Length:770
    Mass (Da):86,582
    Checksum:iDEE458DFFEE1AF2F
    GO

    Sequence cautioni

    The sequence CAH56175.1 differs from that shown. Reason: Probable cloning artifact.
    The sequence BAE45748.1 differs from that shown. Reason: Erroneous termination at position 904. Translated as Arg.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti210 – 2101G → S in AAB09291. (PubMed:7784085)Curated
    Sequence conflicti210 – 2101G → S in AAB09292. (PubMed:7784085)Curated
    Sequence conflicti210 – 2101G → S in AAB09293. (PubMed:7784085)Curated
    Sequence conflicti911 – 9111R → C in CAH56175. (PubMed:17974005)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti584 – 5841R → K.1 Publication
    Corresponds to variant rs17853100 [ dbSNP | Ensembl ].
    VAR_025303
    Natural varianti883 – 8831N → D.
    Corresponds to variant rs35835913 [ dbSNP | Ensembl ].
    VAR_039241

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei767 – 7704DVFD → TYRI in isoform Truncated 2. 1 PublicationVSP_005730
    Alternative sequencei771 – 982212Missing in isoform Truncated 2. 1 PublicationVSP_005731Add
    BLAST
    Alternative sequencei812 – 982171Missing in isoform Truncated 1. 1 PublicationVSP_005729Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U26710 mRNA. Translation: AAB09291.1.
    U26711 mRNA. Translation: AAB09292.1.
    U26712 mRNA. Translation: AAB09293.1.
    DQ349203 mRNA. Translation: ABC86700.1.
    AK292792 mRNA. Translation: BAF85481.1.
    AC016138 Genomic DNA. No translation available.
    CH471052 Genomic DNA. Translation: EAW79752.1.
    CH471052 Genomic DNA. Translation: EAW79753.1.
    CH471052 Genomic DNA. Translation: EAW79754.1.
    BC032851 mRNA. Translation: AAH32851.1.
    AB075490 mRNA. Translation: BAE45748.1. Sequence problems.
    BX537484 mRNA. Translation: CAH56175.1. Sequence problems.
    CCDSiCCDS2948.1. [Q13191-1]
    RefSeqiNP_733762.2. NM_170662.3. [Q13191-1]
    XP_005247910.1. XM_005247853.1. [Q13191-1]
    UniGeneiHs.430589.

    Genome annotation databases

    EnsembliENST00000264122; ENSP00000264122; ENSG00000114423. [Q13191-1]
    ENST00000403724; ENSP00000384816; ENSG00000114423. [Q13191-3]
    GeneIDi868.
    KEGGihsa:868.
    UCSCiuc003dwc.3. human. [Q13191-1]
    uc003dwe.2. human. [Q13191-3]

    Polymorphism databases

    DMDMi88911265.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U26710 mRNA. Translation: AAB09291.1 .
    U26711 mRNA. Translation: AAB09292.1 .
    U26712 mRNA. Translation: AAB09293.1 .
    DQ349203 mRNA. Translation: ABC86700.1 .
    AK292792 mRNA. Translation: BAF85481.1 .
    AC016138 Genomic DNA. No translation available.
    CH471052 Genomic DNA. Translation: EAW79752.1 .
    CH471052 Genomic DNA. Translation: EAW79753.1 .
    CH471052 Genomic DNA. Translation: EAW79754.1 .
    BC032851 mRNA. Translation: AAH32851.1 .
    AB075490 mRNA. Translation: BAE45748.1 . Sequence problems.
    BX537484 mRNA. Translation: CAH56175.1 . Sequence problems.
    CCDSi CCDS2948.1. [Q13191-1 ]
    RefSeqi NP_733762.2. NM_170662.3. [Q13191-1 ]
    XP_005247910.1. XM_005247853.1. [Q13191-1 ]
    UniGenei Hs.430589.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2AK5 X-ray 1.85 D 904-911 [» ]
    2BZ8 X-ray 2.00 C 902-912 [» ]
    2DO6 NMR - A/B 931-970 [» ]
    2J6F X-ray 1.70 C 902-912 [» ]
    2JNH NMR - A 926-971 [» ]
    2LDR NMR - A 351-426 [» ]
    2OOA X-ray 1.56 A/B 924-973 [» ]
    2OOB X-ray 1.90 A 924-973 [» ]
    3PFV X-ray 2.27 A/B 38-344 [» ]
    3VGO X-ray 3.10 A/B/C 39-426 [» ]
    3ZNI X-ray 2.21 A/E/I/M 36-427 [» ]
    ProteinModelPortali Q13191.
    SMRi Q13191. Positions 38-427, 929-972.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107316. 47 interactions.
    DIPi DIP-33091N.
    IntActi Q13191. 20 interactions.
    MINTi MINT-256380.
    STRINGi 9606.ENSP00000264122.

    PTM databases

    PhosphoSitei Q13191.

    Polymorphism databases

    DMDMi 88911265.

    Proteomic databases

    MaxQBi Q13191.
    PaxDbi Q13191.
    PRIDEi Q13191.

    Protocols and materials databases

    DNASUi 868.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000264122 ; ENSP00000264122 ; ENSG00000114423 . [Q13191-1 ]
    ENST00000403724 ; ENSP00000384816 ; ENSG00000114423 . [Q13191-3 ]
    GeneIDi 868.
    KEGGi hsa:868.
    UCSCi uc003dwc.3. human. [Q13191-1 ]
    uc003dwe.2. human. [Q13191-3 ]

    Organism-specific databases

    CTDi 868.
    GeneCardsi GC03M105374.
    H-InvDB HIX0003518.
    HGNCi HGNC:1542. CBLB.
    HPAi HPA018327.
    HPA019880.
    MIMi 604491. gene.
    neXtProti NX_Q13191.
    PharmGKBi PA26116.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG242251.
    HOVERGENi HBG005255.
    InParanoidi Q13191.
    KOi K04707.
    OMAi SSPCMVR.
    OrthoDBi EOG7M0NQX.
    PhylomeDBi Q13191.
    TreeFami TF314210.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    Reactomei REACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
    SignaLinki Q13191.

    Miscellaneous databases

    ChiTaRSi CBLB. human.
    EvolutionaryTracei Q13191.
    GeneWikii CBLB_(gene).
    GenomeRNAii 868.
    NextBioi 3622.
    PROi Q13191.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q13191.
    Bgeei Q13191.
    CleanExi HS_CBLB.
    Genevestigatori Q13191.

    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.
    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.
    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. "Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene."
      Keane M.M., Rivero-Lezcano O.M., Mitchell J.A., Robbins K.C., Lipkowitz S.
      Oncogene 10:2367-2377(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG; TRUNCATED 1 AND TRUNCATED 2).
    2. "Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation."
      Bustelo X.R., Crespo P., Lopez-Barahona M., Gutkind J.S., Barbacid M.
      Oncogene 15:2511-2520(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), TISSUE SPECIFICITY, INTERACTION WITH VAV1.
    3. "Cbl-b in Taiwan population."
      Shen C.-R., Chen Y.-J., Pai L.-M., Liu C.-L.
      Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
    4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
      Tissue: Trachea.
    5. "The DNA sequence, annotation and analysis of human chromosome 3."
      Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J.
      , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
      Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "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 LONG), VARIANT LYS-584.
      Tissue: Testis.
    8. "Neuroblastoma oligo-capping cDNA project: toward the understanding of the genesis and biology of neuroblastoma."
      Ohira M., Morohashi A., Nakamura Y., Isogai E., Furuya K., Hamano S., Machida T., Aoyama M., Fukumura M., Miyazaki K., Suzuki Y., Sugano S., Hirato J., Nakagawara A.
      Cancer Lett. 197:63-68(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 543-982 (ISOFORM LONG).
      Tissue: Neuroblastoma.
    9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 857-982 (ISOFORM LONG).
      Tissue: Small intestine.
    10. "Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation."
      Elly C., Witte S., Zhang Z., Rosnet O., Lipkowitz S., Altman A., Liu Y.-C.
      Oncogene 18:1147-1156(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, MUTAGENESIS OF GLY-298; TYR-665 AND TYR-709, INTERACTION WITH GRB2 AND CRKL, PHOSPHORYLATION AT TYR-665 AND TYR-709, FUNCTION.
    11. Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH GRB2 AND PIK3R1.
    12. "Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells."
      Fang D., Wang H.-Y., Fang N., Altman Y., Elly C., Liu Y.-C.
      J. Biol. Chem. 276:4872-4878(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH PIK3R1, MUTAGENESIS OF GLY-298 AND CYS-373.
    13. "Cbl-b-dependent coordinated degradation of the epidermal growth factor receptor signaling complex."
      Ettenberg S.A., Magnifico A., Cuello M., Nau M.M., Rubinstein Y.R., Yarden Y., Weissman A.M., Lipkowitz S.
      J. Biol. Chem. 276:27677-27684(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION, MUTAGENESIS OF CYS-373.
    14. "Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells."
      Fang D., Liu Y.-C.
      Nat. Immunol. 2:870-875(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    15. "CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases."
      Szymkiewicz I., Kowanetz K., Soubeyran P., Dinarina A., Lipkowitz S., Dikic I.
      J. Biol. Chem. 277:39666-39672(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SH3KBP1, SUBCELLULAR LOCATION.
    16. "Cbl-c suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation."
      Kim M., Tezuka T., Tanaka K., Yamamoto T.
      Oncogene 23:1645-1655(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    17. "Cbl-b interacts with ubiquitinated proteins; differential functions of the UBA domains of c-Cbl and Cbl-b."
      Davies G.C., Ettenberg S.A., Coats A.O., Mussante M., Ravichandran S., Collins J., Nau M.M., Lipkowitz S.
      Oncogene 23:7104-7115(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH UBIQUITINATED PROTEINS, MUTAGENESIS OF 943-GLY-TYR-944 AND LEU-967.
    18. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    19. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521; SER-525 AND SER-529, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    20. "PKC-theta modulates the strength of T cell responses by targeting Cbl-b for ubiquitination and degradation."
      Gruber T., Hermann-Kleiter N., Hinterleitner R., Fresser F., Schneider R., Gastl G., Penninger J.M., Baier G.
      Sci. Signal. 2:RA30-RA30(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-282.
    21. "The N terminus of Cbl-c regulates ubiquitin ligase activity by modulating affinity for the ubiquitin-conjugating enzyme."
      Ryan P.E., Sivadasan-Nair N., Nau M.M., Nicholas S., Lipkowitz S.
      J. Biol. Chem. 285:23687-23698(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS E3 UBIQUITIN-PROTEIN LIGASE, PHOSPHORYLATION AT TYR-363, MUTAGENESIS OF TYR-363.
    22. Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 899-914 IN COMPLEXES WITH SH3KBP1 AND ARHGEF7, MUTAGENESIS OF ARG-904 AND ARG-911, SUBUNIT.
    23. "Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain."
      Moncalian G., Cardenes N., Deribe Y.L., Spinola-Amilibia M., Dikic I., Bravo J.
      J. Biol. Chem. 281:38845-38853(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 902-912 IN COMPLEX WITH CD2AP, MUTAGENESIS OF ARG-904; LYS-907 AND ARG-911, SUBUNIT.
    24. "Structural basis for ubiquitin-mediated dimerization and activation of the ubiquitin protein ligase Cbl-b."
      Peschard P., Kozlov G., Lin T., Mirza I.A., Berghuis A.M., Lipkowitz S., Park M., Gehring K.
      Mol. Cell 27:474-485(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 924-973 IN COMPLEX WITH UBIQUITIN, STRUCTURE BY NMR OF 924-973, TYROSINE PHOSPHORYLATION, MUTAGENESIS OF ALA-937; MET-940; PHE-946 AND ILE-966.
    25. "Solution structure of RSGI RUH-065, a UBA domain from human cDNA."
      RIKEN structural genomics initiative (RSGI)
      Submitted (MAY-2007) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 931-970.
    26. "Crystal structure of Cbl-b TKB domain in complex with EGFR pY1069 peptide."
      Structural genomics consortium (SGC)
      Submitted (OCT-2010) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 38-344 IN COMPLEX WITH PHOSPHO-EGFR PEPTIDE, INTERACTION WITH EGFR, HETERODIMER.

    Entry informationi

    Entry nameiCBLB_HUMAN
    AccessioniPrimary (citable) accession number: Q13191
    Secondary accession number(s): A8K9S7
    , B7WNM4, Q13192, Q13193, Q3LIC0, Q63Z43, Q8IVC5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: February 7, 2006
    Last modified: October 1, 2014
    This is version 160 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    This protein has one functional calcium-binding site.By similarity

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 3
      Human chromosome 3: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3