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Q8K4S7

- CBLB_RAT

UniProt

Q8K4S7 - CBLB_RAT

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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

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 – 2861Phosphotyrosine By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi219 – 23214
Add
BLAST
Zinc fingeri373 – 41240RING-type
Add
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
Complete GO annotation...

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
Complete GO annotation...

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

GO - Cellular componenti

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

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-B
PRO_0000055862Add
BLAST

Amino acid modifications

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

Protein-protein interaction databases

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

Structurei

3D structure databases

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

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini35 – 343309Cbl-PTB
Add
BLAST
Domaini887 – 92640UBA
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni35 – 1671334H
Add
BLAST
Regioni168 – 24073EF-hand-like
Add
BLAST
Regioni241 – 343103SH2-like
Add
BLAST
Regioni344 – 37229Linker
Add
BLAST
Regioni543 – 56725Interaction with VAV1 By similarity
Add
BLAST
Regioni847 – 88337Interaction with SH3KBP1 By similarity
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi477 – 56690Pro-rich
Add
BLAST
Compositional biasi672 – 6754Poly-Pro
Compositional biasi774 – 881108Pro-rich
Add
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 UBA domain.

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...

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 88 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

Similar proteinsi