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Protein

E3 ubiquitin-protein ligase CBL-B

Gene

Cblb

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

Miscellaneous

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

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei286PhosphotyrosineBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi219 – 232Add BLAST14
Zinc fingeri373 – 412RING-typePROSITE-ProRule annotationAdd BLAST40

GO - Molecular functioni

GO - Biological processi

  • epidermal growth factor receptor signaling pathway Source: GO_Central
  • negative regulation of epidermal growth factor-activated receptor activity Source: GO_Central
  • proteolysis Source: GO_Central
  • response to gravity Source: RGD
  • response to hormone Source: RGD
  • signal transduction Source: RGD

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase CBL-B (EC:2.3.2.27By similarity)
Alternative name(s):
Casitas B-lineage lymphoma proto-oncogene b
RING-type E3 ubiquitin transferase CBL-BCurated
SH3-binding protein CBL-B
Signal transduction protein CBL-B
Gene namesi
Name:Cblb
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620535 Cblb

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
ChainiPRO_00000558621 – 938E3 ubiquitin-protein ligase CBL-BAdd BLAST938

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei282Phosphoserine; by PKC/PRKCQBy similarity1
Modified residuei363PhosphotyrosineBy similarity1
Modified residuei476PhosphoserineCombined sources1
Modified residuei480PhosphoserineBy similarity1
Modified residuei484PhosphoserineBy similarity1
Modified residuei521PhosphoserineBy similarity1
Modified residuei525PhosphoserineBy similarity1
Modified residuei529PhosphoserineBy similarity1
Modified residuei633PhosphoserineCombined sources1
Modified residuei664PhosphotyrosineBy similarity1
Modified residuei708PhosphotyrosineBy similarity1
Modified residuei845PhosphotyrosineBy similarity1

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

iPTMnetiQ8K4S7
PhosphoSitePlusiQ8K4S7

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

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ8K4S7, 6 interactors
MINTiQ8K4S7
STRINGi10116.ENSRNOP00000002719

Structurei

3D structure databases

ProteinModelPortaliQ8K4S7
SMRiQ8K4S7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 343Cbl-PTBPROSITE-ProRule annotationAdd BLAST309
Domaini887 – 926UBAPROSITE-ProRule annotationAdd BLAST40

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni35 – 1674HAdd BLAST133
Regioni168 – 240EF-hand-likeAdd BLAST73
Regioni241 – 343SH2-likeAdd BLAST103
Regioni344 – 372LinkerAdd BLAST29
Regioni543 – 567Interaction with VAV1By similarityAdd BLAST25
Regioni847 – 883Interaction with SH3KBP1By similarityAdd BLAST37

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi477 – 566Pro-richAdd BLAST90
Compositional biasi672 – 675Poly-Pro4
Compositional biasi774 – 881Pro-richAdd BLAST108

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri373 – 412RING-typePROSITE-ProRule annotationAdd BLAST40

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1785 Eukaryota
ENOG410YDNH LUCA
HOGENOMiHOG000294176
HOVERGENiHBG005255
InParanoidiQ8K4S7
KOiK22517

Family and domain databases

CDDicd09920 SH2_Cbl-b_TKB, 1 hit
Gene3Di1.20.930.20, 1 hit
3.30.40.10, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR024162 Adaptor_Cbl
IPR014741 Adaptor_Cbl_EF_hand-like
IPR036537 Adaptor_Cbl_N_dom_sf
IPR003153 Adaptor_Cbl_N_hlx
IPR014742 Adaptor_Cbl_SH2-like
IPR024159 Cbl_PTB
IPR011992 EF-hand-dom_pair
IPR036860 SH2_dom_sf
IPR015940 UBA
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR23007 PTHR23007, 2 hits
PfamiView protein in Pfam
PF02262 Cbl_N, 1 hit
PF02761 Cbl_N2, 1 hit
PF02762 Cbl_N3, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
SM00165 UBA, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
SSF47668 SSF47668, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS51506 CBL_PTB, 1 hit
PS50030 UBA, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q8K4S7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MANSMNGRNP GGRGGNPRKG RILGIIDAIQ DAVGPPKQAA ADRRTVEKTW
60 70 80 90 100
KLMDKVVRLC QNPKLQLKNS PPYILDILPD TYQHLRLILS KYDDNQKLAQ
110 120 130 140 150
LSENEYFKIY IDSLMKKSKR AIRLFKEGKE RMYEEQSQDR RNLTKLSLIF
160 170 180 190 200
SHMLAEIKAI FPNGQFQGDN FRITKADAAE FWRKFFGDKT IVPWKVFRQC
210 220 230 240 250
LHEVHQISSG LEAMALKSTI DLTCNDYISV FEFDIFTRLF QPWGSILRNW
260 270 280 290 300
NFLAVTHPGY MAFLTYDEVK ARLQKYSTKP GSYIFRLSCT RLGQWAIGYV
310 320 330 340 350
TGDGNILQTI PHNKPLFQAL IDGSREGFYL YPDGRSYNPD LTGLCEPTPH
360 370 380 390 400
DHIKVTQEQY ELYCEMGSTF QLCKICAEND KDVKIEPCGH LMCTSCLTAW
410 420 430 440 450
QESDGQGCPF CRCEIKGTEP IIVDPFDPRD EGSRCCSIID PFSIPMLDLD
460 470 480 490 500
DDDDREESLM MNRLASVRKC TDRQNSPVTS PGSSPLAQRR KPQPDPLQIP
510 520 530 540 550
HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ DKPLPAPPPP
560 570 580 590 600
LRDPPPPPER PPPIPPDSRL SRHFHHGESV PSRDQPMPLE AWCPRDAFGT
610 620 630 640 650
NQVMGCRILG DGSPKPGVTA NSNLNGRHSR MGSDQVLMRK HRRHDLPSEG
660 670 680 690 700
AKVFSNGHLA PEEYDVPPRL SPPPPVTALL PSIKCTGPIA NCLSEKTRDT
710 720 730 740 750
VEEDDDEYKI PSSHPVSLNS QPSHCHNVKP PVRSCDNGHC ILNGTHGTPS
760 770 780 790 800
EMKKSNIPDL GIYLKGEDAF DALPPSLPPP PPPARHSLIE HSKPPGSSSR
810 820 830 840 850
PSSGQDLFLL PSDPFFDPAS GQVPLPPARR APGDGVKSNR ASQDYDQLPS
860 870 880 890 900
SSDGSQAPAR PPKPRPRRTA PEIHHRKPHG PEAALENVDA KIAKLMGEGY
910 920 930
AFEEVKRALE IAQNNLEVAR SILREFAFPP PVSPRLNL
Length:938
Mass (Da):104,652
Last modified:October 1, 2002 - v1
Checksum:i8316D0E7F7252EC6
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

Similar proteinsi

Entry informationi

Entry nameiCBLB_RAT
AccessioniPrimary (citable) accession number: Q8K4S7
Secondary accession number(s): Q9QZ69
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: October 1, 2002
Last modified: May 23, 2018
This is version 112 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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