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Protein

E3 ubiquitin-protein ligase CBL-C

Gene

Cblc

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. Inhibits EGF stimulated MAPK1 activation. Promotes ubiquitination of SRC phosphorylated at 'Tyr-419', 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.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

Enzyme regulationi

Phosphorylation at Tyr-341 is necessary and sufficient for the activation of E3 activity.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei264PhosphotyrosineBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi197 – 210PROSITE-ProRule annotationAdd BLAST14
Zinc fingeri351 – 390RING-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
Gene namesi
Name:Cblc
Synonyms:Cbl-3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi1307651. Cblc.

Subcellular locationi

GO - Cellular componenti

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004248731 – 497E3 ubiquitin-protein ligase CBL-CAdd BLAST497

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei341Phosphotyrosine; by SRCBy similarity1

Post-translational modificationi

Phosphorylated on multiple tyrosine residues by SRC.By similarity
Autoubiquitinated, when phosphorylated at Tyr-341.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiG3V8H4.

Expressioni

Gene expression databases

BgeeiENSRNOG00000018953.
GenevisibleiG3V8H4. RN.

Interactioni

Subunit structurei

Interacts with Ubiquitin-conjugating enzyme E2 UBE2D2 and UBE2D3. 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'.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000025829.

Structurei

3D structure databases

SMRiG3V8H4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini7 – 321Cbl-PTBPROSITE-ProRule annotationAdd BLAST315

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni7 – 1454HAdd BLAST139
Regioni146 – 218EF-hand-likeAdd BLAST73
Regioni219 – 321SH2-likeAdd BLAST103
Regioni322 – 350LinkerBy similarityAdd BLAST29
Regioni351 – 497Interaction with RETBy similarityAdd BLAST147

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 fingeri351 – 390RING-typePROSITE-ProRule annotationAdd BLAST40

Keywords - Domaini

SH3-binding, Zinc-finger

Phylogenomic databases

eggNOGiKOG1785. Eukaryota.
ENOG410YDNH. LUCA.
GeneTreeiENSGT00390000011617.
HOGENOMiHOG000294176.
HOVERGENiHBG005255.
InParanoidiG3V8H4.
KOiK04707.
OMAiWQHSDSQ.
TreeFamiTF314210.

Family and domain databases

CDDicd00162. RING. 1 hit.
cd09920. 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.
IPR003153. Adaptor_Cbl_N_hlx.
IPR014742. Adaptor_Cbl_SH2-like.
IPR024159. Cbl_PTB.
IPR011992. EF-hand-dom_pair.
IPR000980. SH2.
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.

Sequencei

Sequence statusi: Complete.

G3V8H4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAATAPQGW QWGEPRALGR AVKLLQRLEE QCRDLRLFVG PPSLRDLLPR
60 70 80 90 100
TAQLLREVAK ARSDKTRGDP EGPGGAGDFL VIYLTNLEAK GRQVAELLPH
110 120 130 140 150
RGKKDANQDV FPEGSRFRRQ LAKLALIFSH MHAELSALFP EGKYCGHLYQ
160 170 180 190 200
ITKGSANTFW RENCGVRCVL PWAEFQSLLC SCHPVEPGPI MQALRSTLDL
210 220 230 240 250
TCSGHVSVFE FDIFTRLFQP WPTLLKNWQL LAVNHPGYMA FLTYDEVQTR
260 270 280 290 300
LQAYRDKPGS YIFRPSCTRL GQWAIGYVSS NGSILQTIPL NKPLLQVLLK
310 320 330 340 350
GQKDGIFLYP DGKNHNPDLT ELCRAVLNQC IQVSQEQLQL YQAMNSTFEL
360 370 380 390 400
CKICTERDKD VRIEPCGHLL CSCCLAAWQH SDSQTCPFCR CEIKGREAVS
410 420 430 440 450
ICQAQERSME VRTTAGDSGD NCHQEAAEWK LESVTPSAPP LPPEVPCPQR
460 470 480 490
PQNKGWLTLA PFTLPRLRPP LPLPKMASVL WEVTSRPQVR EGATESS
Length:497
Mass (Da):55,775
Last modified:November 16, 2011 - v1
Checksum:iC6DFE4CADD9F908E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti326V → E in AAI05777 (PubMed:15489334).Curated1
Sequence conflicti453N → D in AAI05777 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06003893 Genomic DNA. No translation available.
CH473979 Genomic DNA. Translation: EDM08131.1.
BC105776 mRNA. Translation: AAI05777.1.
RefSeqiNP_001030092.1. NM_001034920.2.
UniGeneiRn.20550.

Genome annotation databases

EnsembliENSRNOT00000025829; ENSRNOP00000025829; ENSRNOG00000018953.
ENSRNOT00000092048; ENSRNOP00000070090; ENSRNOG00000018953.
GeneIDi292699.
KEGGirno:292699.
UCSCiRGD:1307651. rat.

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.

Entry informationi

Entry nameiCBLC_RAT
AccessioniPrimary (citable) accession number: G3V8H4
Secondary accession number(s): Q3KRC9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 22, 2014
Last sequence update: November 16, 2011
Last modified: July 5, 2017
This is version 38 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