E3 ubiquitin-protein ligase CBL-B - Rattus norvegicus (Rat)

Contribute

Send feedback

Read comments (?) or add your own

Q8K4S7 (CBLB_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 79. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

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 names

Name:

Cblb

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	938 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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. May also be involved in EGFR ubiquitination and internalization. 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 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.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Disease	Diabetes mellitus
Domain	Repeat Zinc-finger
Ligand	Calcium Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell surface receptor signaling pathway Inferred from electronic annotation. Source: InterPro regulation of signaling Inferred from electronic annotation. Source: InterPro response to gravity Inferred from expression pattern PubMed 14715702. Source: RGD response to hormone stimulus Inferred from expression pattern PubMed 16984225. Source: RGD signal transduction Inferred from direct assay Ref.1. Source: RGD
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell membrane raft Inferred from direct assay Ref.3. Source: RGD nucleus Inferred from electronic annotation. Source: InterPro
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro signal transducer activity Inferred from electronic annotation. Source: InterPro ubiquitin-protein ligase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 938

938

E3 ubiquitin-protein ligase CBL-B

PRO_0000055862

Regions

Domain

35 – 343

309

Cbl-PTB

Domain

887 – 926

UBA

Calcium binding

219 – 232

Zinc finger

373 – 412

RING-type

Region

35 – 167

133

Region

168 – 240

EF-hand-like

Region

241 – 343

103

SH2-like

Region

344 – 372

Linker

Region

543 – 567

Interaction with VAV1 By similarity

Region

847 – 883

Interaction with SH3KBP1 By similarity

Compositional bias

477 – 566

Pro-rich

Compositional bias

672 – 675

Poly-Pro

Compositional bias

774 – 881

108

Pro-rich

Sites

Binding site

286

Phosphotyrosine By similarity

Amino acid modifications

Modified residue

282

Phosphoserine; by PKC/PRKCQ By similarity

Modified residue

521

Phosphoserine By similarity

Modified residue

525

Phosphoserine By similarity

Modified residue

529

Phosphoserine By similarity

Modified residue

664

Phosphotyrosine By similarity

Modified residue

708

Phosphotyrosine By similarity

Modified residue

845

Phosphotyrosine By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

Q8K4S7 [UniParc].

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

FASTA

938

104,652

        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

[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB071283 mRNA. Translation: BAC05498.1. AF199504 mRNA. Translation: AAF13271.1.
IPI	IPI00203552.
RefSeq	NP_598285.1. NM_133601.1.
UniGene	Rn.21799.
3D structure databases
ProteinModelPortal	Q8K4S7.
SMR	Q8K4S7. Positions 35-426, 885-928.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-2880613.
STRING	10116.ENSRNOP00000039085.
PTM databases
PhosphoSite	Q8K4S7.
Proteomic databases
PaxDb	Q8K4S7.
PRIDE	Q8K4S7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	171136.
KEGG	rno:171136.
UCSC	RGD:620535. rat.
Organism-specific databases
CTD	868.
RGD	620535. Cblb.
Phylogenomic databases
eggNOG	NOG242251.
HOGENOM	HOG000294176.
HOVERGEN	HBG005255.
InParanoid	Q8K4S7.
KO	K04707.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q8K4S7.
Genevestigator	Q8K4S7.
GermOnline	ENSRNOG00000001982. Rattus norvegicus.
Family and domain databases
Gene3D	1.10.238.10. 1 hit. 1.20.930.20. 1 hit. 3.30.40.10. 1 hit. 3.30.505.10. 1 hit.
InterPro	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-like_dom. IPR000980. SH2. IPR015940. UBA/transl_elong_EF1B_N_euk. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. IPR017907. Znf_RING_CS. [Graphical view]
PANTHER	PTHR23007. PTHR23007. 1 hit.
Pfam	PF02262. Cbl_N. 1 hit. PF02761. Cbl_N2. 1 hit. PF02762. Cbl_N3. 1 hit. [Graphical view]
SMART	SM00184. RING. 1 hit. SM00252. SH2. 1 hit. SM00165. UBA. 1 hit. [Graphical view]
SUPFAM	SSF47668. Adaptor_Cbl_N. 1 hit.
PROSITE	PS51506. CBL_PTB. 1 hit. PS50030. UBA. 1 hit. PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	621914.

Entry information

Entry name

CBLB_RAT

Accession

Primary (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 3, 2013
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents