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Q8K4S7 (CBLB_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 87. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Cblb
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length938 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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.

Subcellular location

Cytoplasm. Note: In mast cells, translocates to lipid raft upon FCER1 engagement. Ref.3

Domain

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.

Post-translational modification

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.

Involvement in disease

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. Ref.1

Miscellaneous

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

Sequence similarities

Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain.

Contains 1 RING-type zinc finger.

Contains 1 UBA domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 938938E3 ubiquitin-protein ligase CBL-B
PRO_0000055862

Regions

Domain35 – 343309Cbl-PTB
Domain887 – 92640UBA
Calcium binding219 – 23214
Zinc finger373 – 41240RING-type
Region35 – 1671334H
Region168 – 24073EF-hand-like
Region241 – 343103SH2-like
Region344 – 37229Linker
Region543 – 56725Interaction with VAV1 By similarity
Region847 – 88337Interaction with SH3KBP1 By similarity
Compositional bias477 – 56690Pro-rich
Compositional bias672 – 6754Poly-Pro
Compositional bias774 – 881108Pro-rich

Sites

Binding site2861Phosphotyrosine By similarity

Amino acid modifications

Modified residue2821Phosphoserine; by PKC/PRKCQ By similarity
Modified residue5211Phosphoserine By similarity
Modified residue5251Phosphoserine By similarity
Modified residue5291Phosphoserine By similarity
Modified residue6331Phosphoserine Ref.4
Modified residue6641Phosphotyrosine By similarity
Modified residue7081Phosphotyrosine By similarity
Modified residue8451Phosphotyrosine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q8K4S7 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 8316D0E7F7252EC6

FASTA938104,652
        10         20         30         40         50         60 
MANSMNGRNP GGRGGNPRKG RILGIIDAIQ DAVGPPKQAA ADRRTVEKTW KLMDKVVRLC 

        70         80         90        100        110        120 
QNPKLQLKNS PPYILDILPD TYQHLRLILS KYDDNQKLAQ LSENEYFKIY IDSLMKKSKR 

       130        140        150        160        170        180 
AIRLFKEGKE RMYEEQSQDR RNLTKLSLIF SHMLAEIKAI FPNGQFQGDN FRITKADAAE 

       190        200        210        220        230        240 
FWRKFFGDKT IVPWKVFRQC LHEVHQISSG LEAMALKSTI DLTCNDYISV FEFDIFTRLF 

       250        260        270        280        290        300 
QPWGSILRNW NFLAVTHPGY MAFLTYDEVK ARLQKYSTKP GSYIFRLSCT RLGQWAIGYV 

       310        320        330        340        350        360 
TGDGNILQTI PHNKPLFQAL IDGSREGFYL YPDGRSYNPD LTGLCEPTPH DHIKVTQEQY 

       370        380        390        400        410        420 
ELYCEMGSTF QLCKICAEND KDVKIEPCGH LMCTSCLTAW QESDGQGCPF CRCEIKGTEP 

       430        440        450        460        470        480 
IIVDPFDPRD EGSRCCSIID PFSIPMLDLD DDDDREESLM MNRLASVRKC TDRQNSPVTS 

       490        500        510        520        530        540 
PGSSPLAQRR KPQPDPLQIP HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ 

       550        560        570        580        590        600 
DKPLPAPPPP LRDPPPPPER PPPIPPDSRL SRHFHHGESV PSRDQPMPLE AWCPRDAFGT 

       610        620        630        640        650        660 
NQVMGCRILG DGSPKPGVTA NSNLNGRHSR MGSDQVLMRK HRRHDLPSEG AKVFSNGHLA 

       670        680        690        700        710        720 
PEEYDVPPRL SPPPPVTALL PSIKCTGPIA NCLSEKTRDT VEEDDDEYKI PSSHPVSLNS 

       730        740        750        760        770        780 
QPSHCHNVKP PVRSCDNGHC ILNGTHGTPS EMKKSNIPDL GIYLKGEDAF DALPPSLPPP 

       790        800        810        820        830        840 
PPPARHSLIE HSKPPGSSSR PSSGQDLFLL PSDPFFDPAS GQVPLPPARR APGDGVKSNR 

       850        860        870        880        890        900 
ASQDYDQLPS SSDGSQAPAR PPKPRPRRTA PEIHHRKPHG PEAALENVDA KIAKLMGEGY 

       910        920        930 
AFEEVKRALE IAQNNLEVAR SILREFAFPP PVSPRLNL 

« Hide

References

« Hide 'large scale' references
[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].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB071283 mRNA. Translation: BAC05498.1.
AF199504 mRNA. Translation: AAF13271.1.
RefSeqNP_598285.1. NM_133601.1.
UniGeneRn.21799.

3D structure databases

ProteinModelPortalQ8K4S7.
SMRQ8K4S7. Positions 35-426, 885-928.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ8K4S7. 6 interactions.
MINTMINT-2880613.
STRING10116.ENSRNOP00000039085.

PTM databases

PhosphoSiteQ8K4S7.

Proteomic databases

PaxDbQ8K4S7.
PRIDEQ8K4S7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID171136.
KEGGrno:171136.
UCSCRGD:620535. rat.

Organism-specific databases

CTD868.
RGD620535. Cblb.

Phylogenomic databases

eggNOGNOG242251.
HOGENOMHOG000294176.
HOVERGENHBG005255.
InParanoidQ8K4S7.
KOK04707.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

GenevestigatorQ8K4S7.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
1.20.930.20. 1 hit.
3.30.40.10. 1 hit.
3.30.505.10. 1 hit.
InterProIPR024162. 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]
PANTHERPTHR23007. PTHR23007. 1 hit.
PfamPF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
SM00252. SH2. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMSSF47668. SSF47668. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEPS51506. CBL_PTB. 1 hit.
PS50030. UBA. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio621914.
PROQ8K4S7.

Entry information

Entry nameCBLB_RAT
AccessionPrimary (citable) accession number: Q8K4S7
Secondary accession number(s): Q9QZ69
Entry history
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: October 1, 2002
Last modified: April 16, 2014
This is version 87 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways