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Q80XL1 (CBLC_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase CBL-C

EC=6.3.2.-
Alternative name(s):
SH3-binding protein CBL-3
SH3-binding protein CBL-C
Signal transduction protein CBL-C
Gene names
Name:Cblc
Synonyms:Cbl3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length496 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Enzyme regulation

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

Subunit structure

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.

Tissue specificity

Widely expressed in tissues, where the expression is restricted to epithelial cells (at protein level). Ref.1 Ref.4

Developmental stage

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

Domain

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 By similarity.

The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme By similarity.

Post-translational modification

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.

Disruption phenotype

No visible phenotype. Ref.4

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.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q80XL1-1)

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.
Isoform 2 (identifier: Q80XL1-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 496496E3 ubiquitin-protein ligase CBL-C
PRO_0000055867

Regions

Domain7 – 320314Cbl-PTB
Calcium binding196 – 20914 By similarity
Zinc finger350 – 38940RING-type
Region7 – 1441384H
Region145 – 21773EF-hand-like
Region218 – 320103SH2-like
Region321 – 34929Linker By similarity
Region350 – 494145Interaction with RET By similarity

Sites

Binding site2631Phosphotyrosine By similarity

Amino acid modifications

Modified residue3401Phosphotyrosine; by SRC By similarity

Natural variations

Alternative sequence2591S → R in isoform 2.
VSP_014946
Alternative sequence260 – 496237Missing in isoform 2.
VSP_014947

Experimental info

Sequence conflict81R → Q in AAK01405. Ref.1
Sequence conflict3711S → G in AAK01405. Ref.1
Sequence conflict3751A → S in BAB26782. Ref.2
Sequence conflict4161G → D in AAH46337. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 16, 2005. Version 2.
Checksum: 4DBE4A14C3D1BF57

FASTA49655,715
        10         20         30         40         50         60 
MAAAAAPRGW QRGEPRALSR AVKLLQRLEE QCRDPRMVTG PPSLRDLLPR TAQLLGEVAK 

        70         80         90        100        110        120 
ARREAREDPE GPGGADDFLA IYLANLEVKG RQVAELLPPR GKKDVNQDVF REGSRFRRQL 

       130        140        150        160        170        180 
AKLALIFSHM HAELSALFPA GKYCGHLYQL TKGSAHIFWR QNCGVRCVLP WAEFQSLLCA 

       190        200        210        220        230        240 
CHPVEPGPTM QALRSTLDLT CNGHVSVFEF DVFTRLFQPW PTLLRNWQLL AVNHPGYMAF 

       250        260        270        280        290        300 
LTYDEVQTRL QAYRDKPGSY IFRPSCTRLG QWAIGYVSSD GSILQTIPLN KPLLQVLLKG 

       310        320        330        340        350        360 
QKDGIFLFPD GKKHNPDLTE LCRVEPYQRI QVSEEQLLLY QAMNSTFQLC KICAERDKDV 

       370        380        390        400        410        420 
RIEPCGHLLC SCCLAAWQDS DSQTCPFCRC EIKGREAVSI CQAQERPTEV RTAADGSRDN 

       430        440        450        460        470        480 
CHQEAAEQKL GPVIPSAPSL LPEDQFPQGP QDKGWLTLAP LALPRLRPPL PLPKMASVLW 

       490 
EVTSRPRARE EATESS 

« Hide

Isoform 2 [UniParc].

Checksum: 5EA7613675F647DF
Show »

FASTA25929,316

References

« Hide 'large scale' references
[1]"Characterization of the mouse Cblc/Cbl3 gene."
Fiore F., Ollendorff V., Birnbaum D.
Biochem. Biophys. Res. Commun. 280:182-187(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Strain: C57BL/6.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Strain: C57BL/6J.
Tissue: Tongue.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: FVB/N.
Tissue: Colon.
[4]"Cbl-3-deficient mice exhibit normal epithelial development."
Griffiths E.K., Sanchez O., Mill P., Krawczyk C., Hojilla C.V., Rubin E., Nau M.M., Khokha R., Lipkowitz S., Hui C.C., Penninger J.M.
Mol. Cell. Biol. 23:7708-7718(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF319956 mRNA. Translation: AAK01405.1.
AK009399 mRNA. Translation: BAB26265.1.
AK010228 mRNA. Translation: BAB26782.1.
BC046337 mRNA. Translation: AAH46337.1.
RefSeqNP_075713.3. NM_023224.5.
UniGeneMm.81698.

3D structure databases

ProteinModelPortalQ80XL1.
SMRQ80XL1. Positions 8-400.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid219812. 2 interactions.

PTM databases

PhosphoSiteQ80XL1.

Proteomic databases

PaxDbQ80XL1.
PRIDEQ80XL1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000043822; ENSMUSP00000039955; ENSMUSG00000040525. [Q80XL1-1]
GeneID80794.
KEGGmmu:80794.
UCSCuc009fnh.2. mouse. [Q80XL1-1]
uc009fni.2. mouse. [Q80XL1-2]

Organism-specific databases

CTD23624.
MGIMGI:1931457. Cblc.

Phylogenomic databases

eggNOGNOG318595.
GeneTreeENSGT00390000011617.
HOGENOMHOG000294176.
HOVERGENHBG005255.
InParanoidQ80XL1.
KOK04707.
OMAIFSYMHA.
PhylomeDBQ80XL1.
TreeFamTF314210.

Gene expression databases

ArrayExpressQ80XL1.
BgeeQ80XL1.
CleanExMM_CBLC.
GenevestigatorQ80XL1.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
1.20.930.20. 1 hit.
3.30.40.10. 1 hit.
3.30.505.10. 1 hit.
InterProIPR024162. 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.
[Graphical view]
PANTHERPTHR23007. PTHR23007. 1 hit.
PfamPF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF47668. SSF47668. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEPS51506. CBL_PTB. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio350129.
PROQ80XL1.
SOURCESearch...

Entry information

Entry nameCBLC_MOUSE
AccessionPrimary (citable) accession number: Q80XL1
Secondary accession number(s): Q99PB6, Q9D6L2, Q9D7A9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: August 16, 2005
Last modified: April 16, 2014
This is version 96 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot