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Protein

E3 ubiquitin-protein ligase CBL-C

Gene

Cblc

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Functionally coupled with the E2 ubiquitin-protein ligases UB2D1, UB2D2 and UB2D3. Regulator of EGFR mediated signal transduction; upon EGF activation, ubiquitinates EGFR. Isoform 1, but not isoform 2, inhibits EGF stimulated MAPK1 activation. Promotes ubiquitination of SRC phosphorylated at 'Tyr-424', has the highest ubiquitin ligase activity among CBL family proteins. In collaboration with CD2AP may act as regulatory checkpoint for Ret signaling by modulating the rate of RET degradation after ligand activation; CD2AP converts it from an inhibitor to a promoter of RET degradation; the function limits the potency of GDNF on neuronal survival.By similarity

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

Activity regulationi

Phosphorylation at Tyr-340 is necessary and sufficient for the activation of E3 activity.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei263PhosphotyrosineBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi196 – 209PROSITE-ProRule annotationAdd BLAST14
Zinc fingeri350 – 389RING-typePROSITE-ProRule annotationAdd BLAST40

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase CBL-C (EC:2.3.2.27By similarity)
Alternative name(s):
RING-type E3 ubiquitin transferase CBL-CCurated
SH3-binding protein CBL-3
SH3-binding protein CBL-C
Signal transduction protein CBL-C
Gene namesi
Name:Cblc
Synonyms:Cbl3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1931457 Cblc

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

Pathology & Biotechi

Disruption phenotypei

No visible phenotype.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000558671 – 496E3 ubiquitin-protein ligase CBL-CAdd BLAST496

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei340Phosphotyrosine; by SRCBy similarity1

Post-translational modificationi

Phosphorylated on tyrosines by EGFR.By similarity
Phosphorylated on multiple tyrosine residues by SRC. Isoform 1, but not isoform 2, is phosphorylated on tyrosines by EGFR.By similarity
Autoubiquitinated, when phosphorylated at Tyr-340.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ80XL1
PRIDEiQ80XL1

PTM databases

PhosphoSitePlusiQ80XL1

Expressioni

Tissue specificityi

Widely expressed in tissues, where the expression is restricted to epithelial cells (at protein level).2 Publications

Developmental stagei

Expressed at E14.5 in liver, lung and brain.1 Publication

Gene expression databases

BgeeiENSMUSG00000040525 Expressed in 128 organ(s), highest expression level in colon
CleanExiMM_CBLC
ExpressionAtlasiQ80XL1 baseline and differential
GenevisibleiQ80XL1 MM

Interactioni

Subunit structurei

Interacts with Ubiquitin-conjugating enzyme E2 UBE2D2 and UBE2D3. Isoform 1 interacts with EGFR (tyrosine phosphorylated). Interacts with the SH3 domain proteins LYN and CRK. Interacts (via RING-type zinc finger) with TGFB1I1 (via LIM zinc-binding domain 2); the interaction is direct and enhances the E3 activity. Interacts directly with RET (inactive) and CD2AP; dissociates from RET upon RET activation by GDNF which also increases the interaction with CD2AP suggesting dissociation as CBLC:CD2AP complex. Interacts with SRC; the interaction is enhanced when SRC is phosphorylated at 'Tyr-419'.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi219812, 2 interactors
STRINGi10090.ENSMUSP00000039955

Structurei

3D structure databases

ProteinModelPortaliQ80XL1
SMRiQ80XL1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini7 – 320Cbl-PTBPROSITE-ProRule annotationAdd BLAST314

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni7 – 1444HAdd BLAST138
Regioni145 – 217EF-hand-likeAdd BLAST73
Regioni218 – 320SH2-likeAdd BLAST103
Regioni321 – 349LinkerBy similarityAdd BLAST29
Regioni350 – 494Interaction with RETBy similarityAdd BLAST145

Domaini

EF-hand-like and Sh2-like domains are required for N-terminal inhibition of E3 activity.By similarity
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.PROSITE-ProRule annotation
The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri350 – 389RING-typePROSITE-ProRule annotationAdd BLAST40

Keywords - Domaini

Repeat, SH3-binding, Zinc-finger

Phylogenomic databases

eggNOGiKOG1785 Eukaryota
ENOG410YDNH LUCA
GeneTreeiENSGT00390000011617
HOGENOMiHOG000294176
HOVERGENiHBG005255
InParanoidiQ80XL1
KOiK22518
OMAiQWAVGYV
OrthoDBiEOG091G06R9
PhylomeDBiQ80XL1
TreeFamiTF314210

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
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR23007 PTHR23007, 1 hit
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
SUPFAMiSSF47473 SSF47473, 1 hit
SSF47668 SSF47668, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS51506 CBL_PTB, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q80XL1-1) [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
MAAAAAPRGW QRGEPRALSR AVKLLQRLEE QCRDPRMVTG PPSLRDLLPR
60 70 80 90 100
TAQLLGEVAK ARREAREDPE GPGGADDFLA IYLANLEVKG RQVAELLPPR
110 120 130 140 150
GKKDVNQDVF REGSRFRRQL AKLALIFSHM HAELSALFPA GKYCGHLYQL
160 170 180 190 200
TKGSAHIFWR QNCGVRCVLP WAEFQSLLCA CHPVEPGPTM QALRSTLDLT
210 220 230 240 250
CNGHVSVFEF DVFTRLFQPW PTLLRNWQLL AVNHPGYMAF LTYDEVQTRL
260 270 280 290 300
QAYRDKPGSY IFRPSCTRLG QWAIGYVSSD GSILQTIPLN KPLLQVLLKG
310 320 330 340 350
QKDGIFLFPD GKKHNPDLTE LCRVEPYQRI QVSEEQLLLY QAMNSTFQLC
360 370 380 390 400
KICAERDKDV RIEPCGHLLC SCCLAAWQDS DSQTCPFCRC EIKGREAVSI
410 420 430 440 450
CQAQERPTEV RTAADGSRDN CHQEAAEQKL GPVIPSAPSL LPEDQFPQGP
460 470 480 490
QDKGWLTLAP LALPRLRPPL PLPKMASVLW EVTSRPRARE EATESS
Length:496
Mass (Da):55,715
Last modified:August 16, 2005 - v2
Checksum:i4DBE4A14C3D1BF57
GO
Isoform 2 (identifier: Q80XL1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     259-259: S → R
     260-496: Missing.

Show »
Length:259
Mass (Da):29,316
Checksum:i5EA7613675F647DF
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3X9U0G3X9U0_MOUSE
Casitas B-lineage lymphoma c, isofo...
Cblc mCG_4886
452Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8R → Q in AAK01405 (PubMed:11162497).Curated1
Sequence conflicti371S → G in AAK01405 (PubMed:11162497).Curated1
Sequence conflicti375A → S in BAB26782 (PubMed:16141072).Curated1
Sequence conflicti416G → D in AAH46337 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_014946259S → R in isoform 2. 1 Publication1
Alternative sequenceiVSP_014947260 – 496Missing in isoform 2. 1 PublicationAdd BLAST237

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF319956 mRNA Translation: AAK01405.1
AK009399 mRNA Translation: BAB26265.1
AK010228 mRNA Translation: BAB26782.1
BC046337 mRNA Translation: AAH46337.1
CCDSiCCDS39804.1 [Q80XL1-1]
RefSeqiNP_075713.3, NM_023224.5 [Q80XL1-1]
UniGeneiMm.81698

Genome annotation databases

EnsembliENSMUST00000043822; ENSMUSP00000039955; ENSMUSG00000040525 [Q80XL1-1]
GeneIDi80794
KEGGimmu:80794
UCSCiuc009fnh.2 mouse [Q80XL1-1]
uc009fni.2 mouse [Q80XL1-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF319956 mRNA Translation: AAK01405.1
AK009399 mRNA Translation: BAB26265.1
AK010228 mRNA Translation: BAB26782.1
BC046337 mRNA Translation: AAH46337.1
CCDSiCCDS39804.1 [Q80XL1-1]
RefSeqiNP_075713.3, NM_023224.5 [Q80XL1-1]
UniGeneiMm.81698

3D structure databases

ProteinModelPortaliQ80XL1
SMRiQ80XL1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi219812, 2 interactors
STRINGi10090.ENSMUSP00000039955

PTM databases

PhosphoSitePlusiQ80XL1

Proteomic databases

PaxDbiQ80XL1
PRIDEiQ80XL1

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000043822; ENSMUSP00000039955; ENSMUSG00000040525 [Q80XL1-1]
GeneIDi80794
KEGGimmu:80794
UCSCiuc009fnh.2 mouse [Q80XL1-1]
uc009fni.2 mouse [Q80XL1-2]

Organism-specific databases

CTDi23624
MGIiMGI:1931457 Cblc

Phylogenomic databases

eggNOGiKOG1785 Eukaryota
ENOG410YDNH LUCA
GeneTreeiENSGT00390000011617
HOGENOMiHOG000294176
HOVERGENiHBG005255
InParanoidiQ80XL1
KOiK22518
OMAiQWAVGYV
OrthoDBiEOG091G06R9
PhylomeDBiQ80XL1
TreeFamiTF314210

Miscellaneous databases

PROiPR:Q80XL1
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000040525 Expressed in 128 organ(s), highest expression level in colon
CleanExiMM_CBLC
ExpressionAtlasiQ80XL1 baseline and differential
GenevisibleiQ80XL1 MM

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
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR23007 PTHR23007, 1 hit
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
SUPFAMiSSF47473 SSF47473, 1 hit
SSF47668 SSF47668, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS51506 CBL_PTB, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCBLC_MOUSE
AccessioniPrimary (citable) accession number: Q80XL1
Secondary accession number(s): Q99PB6, Q9D6L2, Q9D7A9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: August 16, 2005
Last modified: November 7, 2018
This is version 128 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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