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Protein

E3 ubiquitin-protein ligase CBL-B

Gene

Cblb

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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 UB2D3.6 Publications

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 – 232PROSITE-ProRule annotationAdd BLAST14
Zinc fingeri373 – 412RING-typePROSITE-ProRule annotationAdd BLAST40

GO - Molecular functioni

GO - Biological processi

  • epidermal growth factor receptor signaling pathway Source: GO_Central
  • immune response Source: MGI
  • intracellular signal transduction Source: MGI
  • negative regulation of alpha-beta T cell proliferation Source: MGI
  • negative regulation of epidermal growth factor-activated receptor activity Source: GO_Central
  • negative regulation of T cell receptor signaling pathway Source: MGI
  • positive regulation of protein catabolic process Source: MGI
  • positive regulation of T cell anergy Source: MGI
  • proteolysis Source: GO_Central
  • T cell activation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi6.3.2.19. 3474.
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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:2146430. Cblb.

Subcellular locationi

  • Cytoplasm 1 Publication

  • Note: In adipocytes, translocates to the plasma membrane upon insulin stimulation.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Mice are fertile and grossly normal. However, they show a high sensitivity to autoimmune diseases and may develop a spontaneous generalized autoimmune disorder characterized by auto-antibody production, infiltration of activated T- and B-lymphocytes into various organs and parenchymal damage.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000558611 – 982E3 ubiquitin-protein ligase CBL-BAdd BLAST982

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei282Phosphoserine; by PKC/PRKCQBy similarity1
Modified residuei476PhosphoserineBy similarity1
Modified residuei480PhosphoserineCombined sources1
Modified residuei484PhosphoserineCombined sources1
Modified residuei521PhosphoserineCombined sources1
Modified residuei525PhosphoserineBy similarity1
Modified residuei529PhosphoserineBy similarity1
Modified residuei633PhosphoserineBy similarity1
Modified residuei664Phosphotyrosine1 Publication1
Modified residuei708Phosphotyrosine1 Publication1
Modified residuei889PhosphotyrosineCombined sources1

Post-translational modificationi

Phosphorylated on tyrosine and serine residues upon TCR or BCR activation. Phosphorylated on Tyr-664 and Tyr-708 in adipocytes following insulin stimulation.2 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

EPDiQ3TTA7.
MaxQBiQ3TTA7.
PaxDbiQ3TTA7.
PeptideAtlasiQ3TTA7.
PRIDEiQ3TTA7.

PTM databases

iPTMnetiQ3TTA7.
PhosphoSitePlusiQ3TTA7.

Expressioni

Gene expression databases

CleanExiMM_CBLB.

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).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Myd88P223662EBI-3649276,EBI-525108
Ticam1Q80UF72EBI-3649276,EBI-3649271

GO - Molecular functioni

Protein-protein interaction databases

BioGridi229001. 25 interactors.
IntActiQ3TTA7. 4 interactors.
MINTiMINT-5042139.
STRINGi10090.ENSMUSP00000110115.

Structurei

Secondary structure

1982
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi43 – 60Combined sources18
Helixi63 – 65Combined sources3
Beta strandi69 – 72Combined sources4
Helixi74 – 94Combined sources21
Helixi98 – 103Combined sources6
Helixi105 – 128Combined sources24
Helixi129 – 133Combined sources5
Helixi138 – 160Combined sources23
Helixi162 – 164Combined sources3
Helixi168 – 170Combined sources3
Helixi176 – 186Combined sources11
Beta strandi190 – 193Combined sources4
Helixi194 – 204Combined sources11
Helixi210 – 220Combined sources11
Beta strandi225 – 229Combined sources5
Helixi230 – 240Combined sources11
Helixi243 – 245Combined sources3
Helixi246 – 254Combined sources9
Beta strandi260 – 263Combined sources4
Helixi266 – 273Combined sources8
Helixi274 – 276Combined sources3
Beta strandi282 – 287Combined sources6
Beta strandi289 – 291Combined sources3
Beta strandi295 – 300Combined sources6
Beta strandi306 – 309Combined sources4
Beta strandi312 – 314Combined sources3
Helixi316 – 325Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5AXIX-ray2.50A/B/C38-343[»]
ProteinModelPortaliQ3TTA7.
SMRiQ3TTA7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 343Cbl-PTBPROSITE-ProRule annotationAdd BLAST309
Domaini931 – 970UBAPROSITE-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
Regioni891 – 927Interaction with SH3KBP1By similarityAdd BLAST37

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi477 – 566Pro-richAdd BLAST90
Compositional biasi672 – 675Poly-Pro4
Compositional biasi775 – 871Pro-richAdd BLAST97

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 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)DescriptionActionsGraphical viewLength
Zinc fingeri373 – 412RING-typePROSITE-ProRule annotationAdd BLAST40

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1785. Eukaryota.
ENOG410YDNH. LUCA.
HOGENOMiHOG000294176.
HOVERGENiHBG005255.
InParanoidiQ3TTA7.
KOiK04707.

Family and domain databases

CDDicd09920. SH2_Cbl-b_TKB. 1 hit.
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.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERiPTHR23007. PTHR23007. 2 hits.
PfamiPF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF47668. 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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q3TTA7-1) [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

        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 PPPIPPDNRL SRHFHHGESV PSRDQPMPLE AWCPRDAFGT
610 620 630 640 650
NQVMGCRILG DGSPKPGVTA NSSLNGRHSR MGSEQVLMRK HRRHDLPSEG
660 670 680 690 700
AKVFSNGHLA TEEYDVPPRL SPPPPVTTLL PSIKCTGPLA NCLSEKTRDT
710 720 730 740 750
VEDDDDEYKI PSSHPVSLNS QPSHCHNVKA PVRSCDNGHC ILNGTHGAPS
760 770 780 790 800
EMKKSNIPDL GIYLKGGGSD SASDPVPLPP ARPPPRDSPK HGSSVNRTPS
810 820 830 840 850
DYDLLIPPLG EDAFDALPPS LPPPPPPARH SLIEHSKPPG SSSRPSSGQD
860 870 880 890 900
LFLLPSDPFF DPTSGQVPLP PARRAAGDSG KANRASQDYD QLPSSSDGSQ
910 920 930 940 950
APARPPKPRP RRTAPEIHHR KPHGPEAALE NVDAKIAKLM GEGYAFEEVK
960 970 980
RALEIAQNNV EVARSILREF AFPPPVSPRL NL
Length:982
Mass (Da):109,092
Last modified:July 27, 2011 - v3
Checksum:i14B55C4106F84A86
GO
Isoform 2 (identifier: Q3TTA7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: Missing.

Show »
Length:830
Mass (Da):91,524
Checksum:iAD8C574827907824
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti176A → T in BAE36418 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0172221 – 152Missing in isoform 2. 1 PublicationAdd BLAST152

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK147367 mRNA. No translation available.
AK161486 mRNA. Translation: BAE36418.1.
AC117780 Genomic DNA. No translation available.
AC154251 Genomic DNA. No translation available.
AC154478 Genomic DNA. No translation available.
RefSeqiNP_001028410.1. NM_001033238.1.
XP_006522010.1. XM_006521947.1. [Q3TTA7-1]
XP_006522011.1. XM_006521948.1. [Q3TTA7-1]
XP_006522012.1. XM_006521949.1. [Q3TTA7-1]
XP_006522013.1. XM_006521950.2. [Q3TTA7-1]
XP_006522015.1. XM_006521952.3.
UniGeneiMm.328206.

Genome annotation databases

GeneIDi208650.
KEGGimmu:208650.
UCSCiuc007zlf.1. mouse. [Q3TTA7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK147367 mRNA. No translation available.
AK161486 mRNA. Translation: BAE36418.1.
AC117780 Genomic DNA. No translation available.
AC154251 Genomic DNA. No translation available.
AC154478 Genomic DNA. No translation available.
RefSeqiNP_001028410.1. NM_001033238.1.
XP_006522010.1. XM_006521947.1. [Q3TTA7-1]
XP_006522011.1. XM_006521948.1. [Q3TTA7-1]
XP_006522012.1. XM_006521949.1. [Q3TTA7-1]
XP_006522013.1. XM_006521950.2. [Q3TTA7-1]
XP_006522015.1. XM_006521952.3.
UniGeneiMm.328206.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5AXIX-ray2.50A/B/C38-343[»]
ProteinModelPortaliQ3TTA7.
SMRiQ3TTA7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi229001. 25 interactors.
IntActiQ3TTA7. 4 interactors.
MINTiMINT-5042139.
STRINGi10090.ENSMUSP00000110115.

PTM databases

iPTMnetiQ3TTA7.
PhosphoSitePlusiQ3TTA7.

Proteomic databases

EPDiQ3TTA7.
MaxQBiQ3TTA7.
PaxDbiQ3TTA7.
PeptideAtlasiQ3TTA7.
PRIDEiQ3TTA7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi208650.
KEGGimmu:208650.
UCSCiuc007zlf.1. mouse. [Q3TTA7-1]

Organism-specific databases

CTDi868.
MGIiMGI:2146430. Cblb.

Phylogenomic databases

eggNOGiKOG1785. Eukaryota.
ENOG410YDNH. LUCA.
HOGENOMiHOG000294176.
HOVERGENiHBG005255.
InParanoidiQ3TTA7.
KOiK04707.

Enzyme and pathway databases

UniPathwayiUPA00143.
BRENDAi6.3.2.19. 3474.

Miscellaneous databases

PROiQ3TTA7.
SOURCEiSearch...

Gene expression databases

CleanExiMM_CBLB.

Family and domain databases

CDDicd09920. SH2_Cbl-b_TKB. 1 hit.
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.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERiPTHR23007. PTHR23007. 2 hits.
PfamiPF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF47668. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiCBLB_MOUSE
AccessioniPrimary (citable) accession number: Q3TTA7
Secondary accession number(s): E9QMY2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 116 of the entry and version 3 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.