Q9ULV8 (CBLC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	474 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Zinc-finger
Ligand	Calcium Metal-binding Zinc
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell surface receptor linked signaling pathway Inferred from electronic annotation. Source: InterPro negative regulation of MAP kinase activity Inferred from direct assay Ref.2. Source: BHF-UCL negative regulation of epidermal growth factor-activated receptor activity Inferred from direct assay Ref.2. Source: BHF-UCL protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from direct assay. Source: BHF-UCL
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	SH3 domain binding Inferred from direct assay Ref.2. Source: BHF-UCL calcium ion binding Inferred from electronic annotation. Source: InterPro epidermal growth factor receptor binding Inferred from direct assay Ref.2. Source: BHF-UCL phosphotyrosine binding Inferred from direct assay. Source: BHF-UCL signal transducer activity Inferred from electronic annotation. Source: InterPro ubiquitin-protein ligase activity Inferred from direct assay. Source: BHF-UCL zinc ion binding Traceable author statement. Source: ProtInc
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 474

474

Signal transduction protein CBL-C

PRO_0000055866

Regions

Domain

7 – 321

315

Cbl-PTB

Calcium binding

197 – 210

14

By similarity

Zinc finger

351 – 390

40

RING-type

Region

7 – 145

139

4H

Region

146 – 218

73

EF-hand-like

Region

219 – 321

103

SH2-like

Region

322 – 350

29

Linker

Motif

89 – 92

4

Nuclear localization signal Potential

Sites

Binding site

264

1

Phosphotyrosine By similarity

Amino acid modifications

Modified residue

40

1

Phosphoserine Ref.4

Natural variations

Alternative sequence

261 – 306

46

Missing in isoform Short.

VSP_005732

Natural variant

405

1

H → Y. Ref.1 Ref.2
Corresponds to variant rs3208856 [ dbSNP | Ensembl ].

VAR_018298

Experimental info

Sequence conflict

234

1

N → T in BAA86298. Ref.1

Sequence conflict

413

1

S → P in AAH28915. Ref.3

Secondary structure

1

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474

Helix Strand Turn

Details...

Helix

13 – 17

5

Helix

21 – 31

11

Beta strand

40 – 42

3

Helix

44 – 63

20

Helix

79 – 97

19

Helix

108 – 111

4

Helix

116 – 138

23

Helix

154 – 163

10

Beta strand

168 – 170

3

Helix

172 – 178

7

Helix

190 – 198

9

Helix

208 – 217

10

Helix

221 – 223

3

Helix

224 – 231

8

Turn

232 – 234

3

Helix

244 – 250

7

Helix

251 – 256

6

Beta strand

273 – 275

3

Beta strand

284 – 287

4

Helix

294 – 299

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified February 6, 2007. Version 3. Checksum: 202634AEDE434544	FASTA	474	52,456
	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
	Isoform Short [UniParc]. Checksum: 7070EDF530032CA0	FASTA	428	47,418
	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 YLYPDGKTHN PDLTELGQAE PQQRIHVSEE QLQLYWAMDS 310 320 330 340 350 360 TFELCKICAE SNKDVKIEPC GHLLCSCCLA AWQHSDSQTC PFCRCEIKGW EAVSIYQFHG 370 380 390 400 410 420 QATAEDSGNS SDQEGRELEL GQVPLSAPPL PPRPDLPPRK PRNAQPKVRL LKGNSPPAAL GPQDPAPA

References

	« Hide 'large scale' referencesShow '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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00008459.
IPI00220418.

RefSeq

NP_001124324.1. NM_001130852.1.
NP_036248.3. NM_012116.3.

UniGene

Hs.466907.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3OP0	X-ray	2.52	A/B	9-323	[»]

ProteinModelPortal

Q9ULV8.

SMR

Q9ULV8. Positions 10-404.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9ULV8. 8 interactions.

MINT

MINT-247027.

STRING

Q9ULV8.

PTM databases

PhosphoSite

Q9ULV8.

Polymorphism databases

DMDM

125987803.

Proteomic databases

PRIDE

Q9ULV8.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000270279; ENSP00000270279; ENSG00000142273.

GeneID

23624.

KEGG

hsa:23624.

NMPDR

fig|9606.3.peg.16655.

UCSC

uc002ozs.1. human.
uc010ejt.1. human.

Organism-specific databases

CTD

23624.

GeneCards

GC19P045281.

H-InvDB

HIX0202847.

HGNC

HGNC:15961. CBLC.

HPA

CAB008087.

MIM

608453. gene.

neXtProt

NX_Q9ULV8.

PharmGKB

PA26117.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15459.

GeneTree

ENSGT00390000011617.

HOGENOM

HBG444458.

HOVERGEN

HBG005255.

InParanoid

Q9ULV8.

OMA

SYMHAEL.

OrthoDB

EOG4P8FJ1.

PhylomeDB

Q9ULV8.

Gene expression databases

ArrayExpress

Q9ULV8.

Bgee

Q9ULV8.

CleanEx

HS_CBLC.

Genevestigator

Q9ULV8.

GermOnline

ENSG00000142273. Homo sapiens.

Family and domain databases

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-like_dom.
IPR000980. SH2.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]

Gene3D

G3DSA: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.

KO

K04707.

PANTHER

PTHR23007. PTHR23007. 1 hit.

Pfam

PF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]

SMART

SM00184. RING. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]

SUPFAM

SSF47668. Adaptor_Cbl_N. 1 hit.

PROSITE

PS51506. CBL_PTB. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

46378.

SOURCE

Search...

Entry information

Entry name

CBLC_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.