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UniProtKB - P22681 (CBL_HUMAN)

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Protein

E3 ubiquitin-protein ligase CBL

Gene

CBL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. 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. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The 'Tyr-731' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3.9 Publications

Miscellaneous

This protein has one functional calcium-binding site.

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.3 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei294PhosphotyrosineBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi227 – 240Add BLAST14
Zinc fingeri381 – 420RING-typePROSITE-ProRule annotationAdd BLAST40

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • calcium ion binding Source: InterPro
  • ephrin receptor binding Source: UniProtKB
  • epidermal growth factor receptor binding Source: Ensembl
  • phosphatidylinositol 3-kinase regulatory subunit binding Source: Ensembl
  • phosphotyrosine binding Source: InterPro
  • receptor tyrosine kinase binding Source: GO_Central
  • SH3 domain binding Source: BHF-UCL
  • signal transducer activity Source: InterPro
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc
  • ubiquitin protein ligase activity Source: GO_Central
  • ubiquitin-protein transferase activity Source: HGNC
Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi2.3.2.B10. 2681.
ReactomeiR-HSA-1236382. Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants.
R-HSA-1295596. Spry regulation of FGF signaling.
R-HSA-1433559. Regulation of KIT signaling.
R-HSA-182971. EGFR downregulation.
R-HSA-2173789. TGF-beta receptor signaling activates SMADs.
R-HSA-5637810. Constitutive Signaling by EGFRvIII.
R-HSA-5654726. Negative regulation of FGFR1 signaling.
R-HSA-5654727. Negative regulation of FGFR2 signaling.
R-HSA-5654732. Negative regulation of FGFR3 signaling.
R-HSA-5654733. Negative regulation of FGFR4 signaling.
R-HSA-6783589. Interleukin-6 family signaling.
R-HSA-6807004. Negative regulation of MET activity.
R-HSA-8849469. PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1.
R-HSA-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-HSA-8856828. Clathrin-mediated endocytosis.
R-HSA-8875360. InlB-mediated entry of Listeria monocytogenes into host cell.
R-HSA-912631. Regulation of signaling by CBL.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
SignaLinkiP22681.
SIGNORiP22681.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase CBL (EC:2.3.2.273 Publications)
Alternative name(s):
Casitas B-lineage lymphoma proto-oncogene
Proto-oncogene c-Cbl
RING finger protein 55
RING-type E3 ubiquitin transferase CBLCurated
Signal transduction protein CBL
Gene namesi
Name:CBL
Synonyms:CBL2, RNF55
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:1541. CBL.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects. Some have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia.
See also OMIM:613563
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064332367Q → P in NSLL. 1 PublicationCorresponds to variant dbSNP:rs267606704Ensembl.1
Natural variantiVAR_064333382K → E in NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling. 1 PublicationCorresponds to variant dbSNP:rs267606705Ensembl.1
Natural variantiVAR_064334390D → Y in NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling. 2 PublicationsCorresponds to variant dbSNP:rs267606707Ensembl.1
Natural variantiVAR_064335420R → Q in NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling. 2 PublicationsCorresponds to variant dbSNP:rs267606708Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi80S → D: Abolishes interaction with ZAP70. 1 Publication1
Mutagenesisi82P → A: Abolishes interaction with ZAP70. 1 Publication1
Mutagenesisi229D → Q: Abolishes interaction with ZAP70. 1 Publication1
Mutagenesisi240E → S: Abolishes interaction with ZAP70. 1 Publication1
Mutagenesisi294R → K: Abolishes interaction with ZAP70. 1 Publication1
Mutagenesisi306G → E: Abolishes interaction with ZAP70 and EPHB1, but does not affect interaction with SLA. 2 Publications1
Mutagenesisi371Y → F: Strongly reduces tyrosine phosphorylation by INSR; when associated with F-700 and F-774. 1 Publication1
Mutagenesisi381C → A: Loss of ubiquitin ligase activity. 1 Publication1
Mutagenesisi700Y → F: Strongly reduces tyrosine phosphorylation by INSR; when associated with F-371 and F-774. 1 Publication1
Mutagenesisi731Y → F: No effect on tyrosine phosphorylation by INSR. Loss of phosphorylation by SRC. Inhibition of bone resorption. Abolishes interaction with PIK3R1. 2 Publications1
Mutagenesisi774Y → F: Strongly reduces tyrosine phosphorylation by INSR; when associated with F-371 and F-700. 1 Publication1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi867.
MalaCardsiCBL.
MIMi613563. phenotype.
OpenTargetsiENSG00000110395.
Orphaneti86834. Juvenile myelomonocytic leukemia.
363972. Noonan syndrome-like disorder with juvenile myelomonocytic leukemia.
PharmGKBiPA26115.

Polymorphism and mutation databases

BioMutaiCBL.
DMDMi251757253.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000558581 – 906E3 ubiquitin-protein ligase CBLAdd BLAST906

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei371Phosphotyrosine; by INSR1 Publication1
Modified residuei439PhosphoserineCombined sources1
Modified residuei452PhosphoserineCombined sources1
Modified residuei483PhosphoserineCombined sources1
Modified residuei619PhosphoserineBy similarity1
Modified residuei642PhosphoserineBy similarity1
Modified residuei668PhosphoserineBy similarity1
Modified residuei669PhosphoserineCombined sources1
Modified residuei674Phosphotyrosine1 Publication1
Modified residuei700Phosphotyrosine; by ABL13 Publications1
Modified residuei731Phosphotyrosine; by SRC1 Publication1
Modified residuei774Phosphotyrosine2 Publications1
Modified residuei900PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on tyrosine residues by ALK, EGFR, SYK, FYN and ZAP70 (By similarity). Phosphorylated on tyrosine residues in response to FLT1 and KIT signaling. Phosphorylated on tyrosine residues by INSR and FGR. Phosphorylated on several tyrosine residues by constitutively activated FGFR3. Not phosphorylated at Tyr-731 by FGFR3. Phosphorylated on tyrosine residues by activated CSF1R, PDGFRA and PDGFRB. Phosphorylated on tyrosine residues by HCK.By similarity14 Publications
Ubiquitinated, leading to its degradation via the proteasome.2 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP22681.
MaxQBiP22681.
PaxDbiP22681.
PeptideAtlasiP22681.
PRIDEiP22681.

PTM databases

iPTMnetiP22681.
PhosphoSitePlusiP22681.

Miscellaneous databases

PMAP-CutDBiP22681.

Expressioni

Gene expression databases

BgeeiENSG00000110395.
CleanExiHS_CBL.
ExpressionAtlasiP22681. baseline and differential.
GenevisibleiP22681. HS.

Organism-specific databases

HPAiCAB004350.
HPA027956.

Interactioni

Subunit structurei

Interacts (phosphorylated at Tyr-731) with PIK3R1. Associates with NCK via its SH3 domain. The phosphorylated C-terminus interacts with CD2AP via its second SH3 domain. Binds to UBE2L3. Interacts with adapters SLA, SLA2 and with the phosphorylated C-terminus of SH2B2. Interacts with EGFR, SYK and ZAP70 via the highly conserved Cbl-N region. Also interacts with SORBS1 and INPPL1/SHIP2. Interacts with phosphorylated LAT2. May interact with CBLB (By similarity). Interacts with ALK, AXL, BLK, FGR and FGFR2. Interacts with CSF1R, EPHB1, FLT1, KDR, PDGFRA and PDGFRB; regulates receptor degradation through ubiquitination. Interacts with HCK and LYN. Interacts with TEK/TIE2 (tyrosine phosphorylated). Interacts with SH3KBP1 and this interaction is inhibited in the presence of SHKBP1 (By similarity).By similarity28 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • ephrin receptor binding Source: UniProtKB
  • epidermal growth factor receptor binding Source: Ensembl
  • phosphatidylinositol 3-kinase regulatory subunit binding Source: Ensembl
  • phosphotyrosine binding Source: InterPro
  • receptor tyrosine kinase binding Source: GO_Central
  • SH3 domain binding Source: BHF-UCL
Complete GO annotation...

Protein-protein interaction databases

BioGridi107315. 249 interactors.
DIPiDIP-189N.
IntActiP22681. 86 interactors.
MINTiMINT-109040.
STRINGi9606.ENSP00000264033.

Structurei

Secondary structure

1906
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi53 – 70Combined sources18
Helixi73 – 75Combined sources3
Beta strandi80 – 82Combined sources3
Helixi84 – 101Combined sources18
Turni102 – 104Combined sources3
Helixi106 – 111Combined sources6
Helixi113 – 136Combined sources24
Helixi137 – 141Combined sources5
Helixi146 – 168Combined sources23
Helixi170 – 172Combined sources3
Helixi176 – 178Combined sources3
Helixi184 – 194Combined sources11
Beta strandi198 – 201Combined sources4
Helixi202 – 212Combined sources11
Helixi218 – 228Combined sources11
Beta strandi233 – 237Combined sources5
Helixi238 – 247Combined sources10
Helixi251 – 253Combined sources3
Helixi254 – 261Combined sources8
Turni262 – 264Combined sources3
Beta strandi268 – 271Combined sources4
Helixi274 – 281Combined sources8
Helixi282 – 284Combined sources3
Beta strandi290 – 295Combined sources6
Beta strandi297 – 299Combined sources3
Beta strandi302 – 308Combined sources7
Turni310 – 312Combined sources3
Beta strandi314 – 317Combined sources4
Beta strandi320 – 322Combined sources3
Helixi324 – 333Combined sources10
Helixi350 – 352Combined sources3
Beta strandi354 – 356Combined sources3
Beta strandi360 – 362Combined sources3
Helixi365 – 378Combined sources14
Turni382 – 384Combined sources3
Beta strandi385 – 388Combined sources4
Beta strandi391 – 394Combined sources4
Beta strandi398 – 400Combined sources3
Helixi402 – 410Combined sources9
Turni417 – 419Combined sources3
Beta strandi425 – 428Combined sources4
Beta strandi430 – 432Combined sources3
Helixi856 – 866Combined sources11
Helixi871 – 880Combined sources10
Turni881 – 883Combined sources3
Helixi885 – 895Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B47X-ray2.20A/B/C47-350[»]
1FBVX-ray2.90A47-434[»]
1YVHX-ray2.05A25-351[»]
2CBLX-ray2.10A47-351[»]
2JUJNMR-A851-906[»]
2K4DNMR-A358-437[»]
2OO9X-ray2.10A/B/C856-895[»]
2Y1MX-ray2.67A/B/C/D/E/F47-435[»]
2Y1NX-ray2.00A/C47-435[»]
3BUMX-ray2.00B25-351[»]
3BUNX-ray2.00B25-351[»]
3BUOX-ray2.60B/D25-351[»]
3BUWX-ray1.45B/D25-351[»]
3BUXX-ray1.35B/D25-351[»]
3OB1X-ray2.20B25-351[»]
3OB2X-ray2.10B25-351[»]
3PLFX-ray1.92B/D25-351[»]
4A49X-ray2.21A354-435[»]
4A4BX-ray2.79A47-435[»]
4A4CX-ray2.70A47-435[»]
4GPLX-ray3.00B47-351[»]
5HKWX-ray2.25A/B/C47-351[»]
5HKXX-ray1.85A47-435[»]
5HKYX-ray1.80A47-351[»]
5HKZX-ray1.80A47-351[»]
5HL0X-ray2.20A47-351[»]
5J3XX-ray2.82A/B/C/D/E/F47-435[»]
ProteinModelPortaliP22681.
SMRiP22681.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22681.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini47 – 351Cbl-PTBPROSITE-ProRule annotationAdd BLAST305
Domaini856 – 895UBAPROSITE-ProRule annotationAdd BLAST40

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 357Sufficient for interaction with EPHB11 PublicationAdd BLAST357
Regioni47 – 1754HAdd BLAST129
Regioni176 – 248EF-hand-likeAdd BLAST73
Regioni249 – 351SH2-likeAdd BLAST103
Regioni352 – 380LinkerAdd BLAST29
Regioni648 – 906Interaction with CD2AP1 PublicationAdd BLAST259

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi357 – 476Asp/Glu-rich (acidic)Add BLAST120
Compositional biasi477 – 688Pro-richAdd BLAST212
Compositional biasi689 – 834Asp/Glu-rich (acidic)Add BLAST146

Domaini

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri381 – 420RING-typePROSITE-ProRule annotationAdd BLAST40

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1785. Eukaryota.
ENOG410YDNH. LUCA.
GeneTreeiENSGT00390000011617.
HOGENOMiHOG000294176.
HOVERGENiHBG005255.
InParanoidiP22681.
KOiK04707.
OMAiCEHPKIK.
OrthoDBiEOG091G0GPE.
PhylomeDBiP22681.
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.
IPR015940. UBA.
IPR009060. UBA-like.
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.
PF00627. UBA. 1 hit.
SMARTiView protein in SMART
SM00184. RING. 1 hit.
SM00165. UBA. 1 hit.
SUPFAMiSSF46934. SSF46934. 1 hit.
SSF47473. SSF47473. 1 hit.
SSF47668. SSF47668. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiView protein in PROSITE
PS51506. CBL_PTB. 1 hit.
PS50030. UBA. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.

Sequencei

Sequence statusi: Complete.

P22681-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGNVKKSSG AGGGSGSGGS GSGGLIGLMK DAFQPHHHHH HHLSPHPPGT 
        60         70         80         90        100
VDKKMVEKCW KLMDKVVRLC QNPKLALKNS PPYILDLLPD TYQHLRTILS 
       110        120        130        140        150
RYEGKMETLG ENEYFRVFME NLMKKTKQTI SLFKEGKERM YEENSQPRRN 
       160        170        180        190        200
LTKLSLIFSH MLAELKGIFP SGLFQGDTFR ITKADAAEFW RKAFGEKTIV 
       210        220        230        240        250
PWKSFRQALH EVHPISSGLE AMALKSTIDL TCNDYISVFE FDIFTRLFQP 
       260        270        280        290        300
WSSLLRNWNS LAVTHPGYMA FLTYDEVKAR LQKFIHKPGS YIFRLSCTRL 
       310        320        330        340        350
GQWAIGYVTA DGNILQTIPH NKPLFQALID GFREGFYLFP DGRNQNPDLT 
       360        370        380        390        400
GLCEPTPQDH IKVTQEQYEL YCEMGSTFQL CKICAENDKD VKIEPCGHLM 
       410        420        430        440        450
CTSCLTSWQE SEGQGCPFCR CEIKGTEPIV VDPFDPRGSG SLLRQGAEGA 
       460        470        480        490        500
PSPNYDDDDD ERADDTLFMM KELAGAKVER PPSPFSMAPQ ASLPPVPPRL 
       510        520        530        540        550
DLLPQRVCVP SSASALGTAS KAASGSLHKD KPLPVPPTLR DLPPPPPPDR 
       560        570        580        590        600
PYSVGAESRP QRRPLPCTPG DCPSRDKLPP VPSSRLGDSW LPRPIPKVPV 
       610        620        630        640        650
SAPSSSDPWT GRELTNRHSL PFSLPSQMEP RPDVPRLGST FSLDTSMSMN 
       660        670        680        690        700
SSPLVGPECD HPKIKPSSSA NAIYSLAARP LPVPKLPPGE QCEGEEDTEY 
       710        720        730        740        750
MTPSSRPLRP LDTSQSSRAC DCDQQIDSCT YEAMYNIQSQ APSITESSTF 
       760        770        780        790        800
GEGNLAAAHA NTGPEESENE DDGYDVPKPP VPAVLARRTL SDISNASSSF 
       810        820        830        840        850
GWLSLDGDPT TNVTEGSQVP ERPPKPFPRR INSERKAGSC QQGSGPAASA 
       860        870        880        890        900
ATASPQLSSE IENLMSQGYS YQDIQKALVI AQNNIEMAKN ILREFVSISS 

PAHVAT
Length:906
Mass (Da):99,633
Last modified:July 7, 2009 - v2
Checksum:i1AA6BF67377322CA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti15S → T in CAA40393 (PubMed:2030914).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071040287K → R Found in patients with acute myeloid leukemia; unknown pathological significance. 1 Publication1
Natural variantiVAR_071041365Q → QSK Found in patients with acute myeloid leukemia; unknown pathological significance; loss of the ability to negatively regulate signaling pathways; promotes cell cycle progression; decreases apoptosis. 1
Natural variantiVAR_064332367Q → P in NSLL. 1 PublicationCorresponds to variant dbSNP:rs267606704Ensembl.1
Natural variantiVAR_071042371Y → H Found in patients with acute myeloid leukemia; unknown pathological significance; loss of the ability to negatively regulate signaling pathways; promotes cell cycle progression; decreases apoptosis. 1 PublicationCorresponds to variant dbSNP:rs267606706Ensembl.1
Natural variantiVAR_064333382K → E in NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling. 1 PublicationCorresponds to variant dbSNP:rs267606705Ensembl.1
Natural variantiVAR_064334390D → Y in NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling. 2 PublicationsCorresponds to variant dbSNP:rs267606707Ensembl.1
Natural variantiVAR_064335420R → Q in NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling. 2 PublicationsCorresponds to variant dbSNP:rs267606708Ensembl.1
Natural variantiVAR_071043499R → L Found in patients with acute myeloid leukemia; unknown pathological significance. 1 Publication1
Natural variantiVAR_057211620L → F. Corresponds to variant dbSNP:rs2227988Ensembl.1
Natural variantiVAR_057212782P → L. Corresponds to variant dbSNP:rs2229073Ensembl.1
Natural variantiVAR_057213904V → I. Corresponds to variant dbSNP:rs17122769Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57110 mRNA. Translation: CAA40393.1.
AP002956 Genomic DNA. No translation available.
BC132733 mRNA. Translation: AAI32734.1.
BC136463 mRNA. Translation: AAI36464.1.
CCDSiCCDS8418.1.
PIRiA43817.
RefSeqiNP_005179.2. NM_005188.3.
UniGeneiHs.504096.

Genome annotation databases

EnsembliENST00000264033; ENSP00000264033; ENSG00000110395.
GeneIDi867.
KEGGihsa:867.
UCSCiuc001pwe.5. human.

Keywords - Coding sequence diversityi

Polymorphism

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 nameiCBL_HUMAN
AccessioniPrimary (citable) accession number: P22681
Secondary accession number(s): A3KMP8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: July 7, 2009
Last modified: July 5, 2017
This is version 210 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references