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Q9ULV8 (CBLC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Signal transduction protein CBL-C
Alternative name(s):
RING finger protein 57
SH3-binding protein CBL-3
SH3-binding protein CBL-C
Gene names
Name:CBLC
Synonyms:CBL3, RNF57
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length474 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Regulator of EGFR mediated signal transduction.

Subunit structure

Interacts with EGFR (tyrosine phosphorylated). Interacts with a restricted range of SH3 domain proteins.

Subcellular location

Nucleus Potential.

Tissue specificity

Ubiquitous.

Domain

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 By similarity.

Post-translational modification

Phosphorylated on tyrosines by EGFR. 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 Long (identifier: Q9ULV8-1)

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 Short (identifier: Q9ULV8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     261-306: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 474474Signal transduction protein CBL-C
PRO_0000055866

Regions

Domain7 – 321315Cbl-PTB
Calcium binding197 – 21014 By similarity
Zinc finger351 – 39040RING-type
Region7 – 1451394H
Region146 – 21873EF-hand-like
Region219 – 321103SH2-like
Region322 – 35029Linker
Motif89 – 924Nuclear localization signal Potential

Sites

Binding site2641Phosphotyrosine By similarity

Amino acid modifications

Modified residue401Phosphoserine Ref.4

Natural variations

Alternative sequence261 – 30646Missing in isoform Short.
VSP_005732
Natural variant4051H → Y. Ref.1 Ref.2
Corresponds to variant rs3208856 [ dbSNP | Ensembl ].
VAR_018298

Experimental info

Sequence conflict2341N → T in BAA86298. Ref.1
Sequence conflict4131S → P in AAH28915. Ref.3

Secondary structure

...................................... 474
Helix Strand Turn

Details...

Sequences

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

Last modified February 6, 2007. Version 3.
Checksum: 202634AEDE434544

FASTA47452,456
        10         20         30         40         50         60 
MALAVAPWGR QWEEARALGR AVRMLQRLEE QCVDPRLSVS PPSLRDLLPR TAQLLREVAH 

        70         80         90        100        110        120 
SRRAAGGGGP GGPGGSGDFL LIYLANLEAK SRQVAALLPP RGRRSANDEL FRAGSRLRRQ 

       130        140        150        160        170        180 
LAKLAIIFSH MHAELHALFP GGKYCGHMYQ LTKAPAHTFW RESCGARCVL PWAEFESLLG 

       190        200        210        220        230        240 
TCHPVEPGCT ALALRTTIDL TCSGHVSIFE FDVFTRLFQP WPTLLKNWQL LAVNHPGYMA 

       250        260        270        280        290        300 
FLTYDEVQER LQACRDKPGS YIFRPSCTRL GQWAIGYVSS DGSILQTIPA NKPLSQVLLE 

       310        320        330        340        350        360 
GQKDGFYLYP DGKTHNPDLT ELGQAEPQQR IHVSEEQLQL YWAMDSTFEL CKICAESNKD 

       370        380        390        400        410        420 
VKIEPCGHLL CSCCLAAWQH SDSQTCPFCR CEIKGWEAVS IYQFHGQATA EDSGNSSDQE 

       430        440        450        460        470 
GRELELGQVP LSAPPLPPRP DLPPRKPRNA QPKVRLLKGN SPPAALGPQD PAPA 

« Hide

Isoform Short [UniParc].

Checksum: 7070EDF530032CA0
Show »

FASTA42847,418

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of a novel cbl-family gene, cbl-c."
Kim M., Tezuka T., Suzuki Y., Sugano S., Hirai M., Yamamoto T.
Gene 239:145-154(1999) [PubMed: 10571044] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), VARIANT TYR-405.
[2]"cbl-3: a new mammalian cbl family protein."
Keane M.M., Ettenberg S.A., Nau M.M., Banerjee P., Cuello M., Penninger J., Lipkowitz S.
Oncogene 18:3365-3375(1999) [PubMed: 10362357] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), VARIANT TYR-405.
Tissue: Pancreatic adenocarcinoma.
[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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
Tissue: Skin.
[4]"Large-scale characterization of HeLa cell nuclear phosphoproteins."
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[5]"Crystal structure of Cbl-c (Cbl-3) TKB domain in complex with EGFR py1069 peptide."
Structural genomics consortium (SGC)
Submitted (OCT-2010) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 9-323 IN COMPLEX WITH EGFR PEPTIDE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB028645 mRNA. Translation: BAA86298.1.
AF117646 mRNA. Translation: AAD34341.1.
AF117647 mRNA. Translation: AAD34342.1.
BC028915 mRNA. Translation: AAH28915.1.
IPIIPI00008459.
IPI00220418.
RefSeqNP_001124324.1. NM_001130852.1.
NP_036248.3. NM_012116.3.
UniGeneHs.466907.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3OP0X-ray2.52A/B9-323[»]
ProteinModelPortalQ9ULV8.
SMRQ9ULV8. Positions 10-404.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9ULV8. 8 interactions.
MINTMINT-247027.
STRINGQ9ULV8.

PTM databases

PhosphoSiteQ9ULV8.

Polymorphism databases

DMDM125987803.

Proteomic databases

PRIDEQ9ULV8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000270279; ENSP00000270279; ENSG00000142273.
GeneID23624.
KEGGhsa:23624.
NMPDRfig|9606.3.peg.16655.
UCSCuc002ozs.1. human.
uc010ejt.1. human.

Organism-specific databases

CTD23624.
GeneCardsGC19P045281.
H-InvDBHIX0202847.
HGNCHGNC:15961. CBLC.
HPACAB008087.
MIM608453. gene.
neXtProtNX_Q9ULV8.
PharmGKBPA26117.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG15459.
GeneTreeENSGT00390000011617.
HOGENOMHBG444458.
HOVERGENHBG005255.
InParanoidQ9ULV8.
OMASYMHAEL.
OrthoDBEOG4P8FJ1.
PhylomeDBQ9ULV8.

Gene expression databases

ArrayExpressQ9ULV8.
BgeeQ9ULV8.
CleanExHS_CBLC.
GenevestigatorQ9ULV8.
GermOnlineENSG00000142273. Homo sapiens.

Family and domain databases

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-like_dom.
IPR000980. SH2.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
Gene3DG3DSA:1.20.930.20. Adaptor_Cbl_N. 1 hit.
G3DSA:1.10.238.10. EF-Hand_type. 1 hit.
G3DSA:3.30.505.10. SH2. 2 hits.
G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.
KOK04707.
PANTHERPTHR23007. PTHR23007. 1 hit.
PfamPF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF47668. Adaptor_Cbl_N. 1 hit.
PROSITEPS51506. CBL_PTB. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio46378.
SOURCESearch...

Entry information

Entry nameCBLC_HUMAN
AccessionPrimary (citable) accession number: Q9ULV8
Secondary accession number(s): Q8N1E5, Q9Y5Z2, Q9Y5Z3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: February 6, 2007
Last modified: January 25, 2012
This is version 115 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families