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Q80XL1

- CBLC_MOUSE

UniProt

Q80XL1 - CBLC_MOUSE

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Protein

E3 ubiquitin-protein ligase CBL-C

Gene
Cblc, Cbl3
Organism
Mus musculus (Mouse)
Status
Reviewed - 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. 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 regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei263 – 2631Phosphotyrosine By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi196 – 20914 By similarityAdd
BLAST
Zinc fingeri350 – 38940RING-typeAdd
BLAST

GO - Molecular functioni

  1. calcium ion binding Source: InterPro
  2. ligase activity Source: UniProtKB-KW
  3. signal transducer activity Source: InterPro
  4. ubiquitin-protein transferase activity Source: MGI
  5. zinc ion binding Source: InterPro

GO - Biological processi

  1. cell surface receptor signaling pathway Source: InterPro
  2. negative regulation of epidermal growth factor-activated receptor activity Source: Ensembl
  3. negative regulation of MAP kinase activity Source: Ensembl
  4. protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: Ensembl
  5. ubiquitin-dependent protein catabolic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Cblc
Synonyms:Cbl3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:1931457. Cblc.

Subcellular locationi

GO - Cellular componenti

  1. nucleus Source: InterPro
  2. ubiquitin ligase complex Source: MGI
Complete GO annotation...

Pathology & Biotechi

Disruption phenotypei

No visible phenotype.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 496496E3 ubiquitin-protein ligase CBL-CPRO_0000055867Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei340 – 3401Phosphotyrosine; by SRC By similarity

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

PhosphoSiteiQ80XL1.

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

ArrayExpressiQ80XL1.
BgeeiQ80XL1.
CleanExiMM_CBLC.
GenevestigatoriQ80XL1.

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.

Protein-protein interaction databases

BioGridi219812. 2 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ80XL1.
SMRiQ80XL1. Positions 8-400.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini7 – 320314Cbl-PTBAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni7 – 1441384HAdd
BLAST
Regioni145 – 21773EF-hand-likeAdd
BLAST
Regioni218 – 320103SH2-likeAdd
BLAST
Regioni321 – 34929Linker By similarityAdd
BLAST
Regioni350 – 494145Interaction with RET By similarityAdd
BLAST

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

Sequence similaritiesi

Keywords - Domaini

Repeat, SH3-binding, Zinc-finger

Phylogenomic databases

eggNOGiNOG318595.
GeneTreeiENSGT00390000011617.
HOGENOMiHOG000294176.
HOVERGENiHBG005255.
InParanoidiQ80XL1.
KOiK04707.
OMAiWQHSDSQ.
PhylomeDBiQ80XL1.
TreeFamiTF314210.

Family and domain databases

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.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERiPTHR23007. PTHR23007. 1 hit.
PfamiPF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF47668. SSF47668. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS51506. CBL_PTB. 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. Align

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

MAAAAAPRGW QRGEPRALSR AVKLLQRLEE QCRDPRMVTG PPSLRDLLPR    50
TAQLLGEVAK ARREAREDPE GPGGADDFLA IYLANLEVKG RQVAELLPPR 100
GKKDVNQDVF REGSRFRRQL AKLALIFSHM HAELSALFPA GKYCGHLYQL 150
TKGSAHIFWR QNCGVRCVLP WAEFQSLLCA CHPVEPGPTM QALRSTLDLT 200
CNGHVSVFEF DVFTRLFQPW PTLLRNWQLL AVNHPGYMAF LTYDEVQTRL 250
QAYRDKPGSY IFRPSCTRLG QWAIGYVSSD GSILQTIPLN KPLLQVLLKG 300
QKDGIFLFPD GKKHNPDLTE LCRVEPYQRI QVSEEQLLLY QAMNSTFQLC 350
KICAERDKDV RIEPCGHLLC SCCLAAWQDS DSQTCPFCRC EIKGREAVSI 400
CQAQERPTEV RTAADGSRDN CHQEAAEQKL GPVIPSAPSL LPEDQFPQGP 450
QDKGWLTLAP LALPRLRPPL PLPKMASVLW EVTSRPRARE EATESS 496
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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei259 – 2591S → R in isoform 2. VSP_014946
Alternative sequencei260 – 496237Missing in isoform 2. VSP_014947Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti8 – 81R → Q in AAK01405. 1 Publication
Sequence conflicti371 – 3711S → G in AAK01405. 1 Publication
Sequence conflicti375 – 3751A → S in BAB26782. 1 Publication
Sequence conflicti416 – 4161G → D in AAH46337. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF319956 mRNA. Translation: AAK01405.1 .
AK009399 mRNA. Translation: BAB26265.1 .
AK010228 mRNA. Translation: BAB26782.1 .
BC046337 mRNA. Translation: AAH46337.1 .
CCDSi CCDS39804.1. [Q80XL1-1 ]
RefSeqi NP_075713.3. NM_023224.5. [Q80XL1-1 ]
UniGenei Mm.81698.

3D structure databases

ProteinModelPortali Q80XL1.
SMRi Q80XL1. Positions 8-400.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 219812. 2 interactions.

PTM databases

PhosphoSitei Q80XL1.

Proteomic databases

PaxDbi Q80XL1.
PRIDEi Q80XL1.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000043822 ; ENSMUSP00000039955 ; ENSMUSG00000040525 . [Q80XL1-1 ]
GeneIDi 80794.
KEGGi mmu:80794.
UCSCi uc009fnh.2. mouse. [Q80XL1-1 ]
uc009fni.2. mouse. [Q80XL1-2 ]

Organism-specific databases

CTDi 23624.
MGIi MGI:1931457. Cblc.

Phylogenomic databases

eggNOGi NOG318595.
GeneTreei ENSGT00390000011617.
HOGENOMi HOG000294176.
HOVERGENi HBG005255.
InParanoidi Q80XL1.
KOi K04707.
OMAi WQHSDSQ.
PhylomeDBi Q80XL1.
TreeFami TF314210.

Miscellaneous databases

NextBioi 350129.
PROi Q80XL1.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q80XL1.
Bgeei Q80XL1.
CleanExi MM_CBLC.
Genevestigatori Q80XL1.

Family and domain databases

Gene3Di 1.10.238.10. 1 hit.
1.20.930.20. 1 hit.
3.30.40.10. 1 hit.
3.30.505.10. 1 hit.
InterProi 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.
[Graphical view ]
PANTHERi PTHR23007. PTHR23007. 1 hit.
Pfami PF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
[Graphical view ]
SMARTi SM00184. RING. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view ]
SUPFAMi SSF47668. SSF47668. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEi PS51506. CBL_PTB. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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.
    , 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. Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.

Entry informationi

Entry nameiCBLC_MOUSE
AccessioniPrimary (citable) accession number: Q80XL1
Secondary accession number(s): Q99PB6, Q9D6L2, Q9D7A9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: August 16, 2005
Last modified: September 3, 2014
This is version 99 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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