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Protein

E3 ubiquitin-protein ligase CBL

Gene

CBL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. In association with CBLB, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity).By similarity9 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

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BRENDAi2.3.2.B10 2681
ReactomeiR-HSA-1059683 Interleukin-6 signaling
R-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-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
UniPathwayi
UPA00143

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000110395.5
HGNCiHGNC:1541 CBL
MIMi165360 gene
neXtProtiNX_P22681

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Golgi apparatus, 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:rs267606704EnsemblClinVar.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:rs267606705EnsemblClinVar.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:rs267606707EnsemblClinVar.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:rs267606708EnsemblClinVar.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 (PubMed:11896602, PubMed:20094046). Ubiquitination is negatively regulated by IFT20 (PubMed:29237719).3 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP22681
MaxQBiP22681
PaxDbiP22681
PeptideAtlasiP22681
PRIDEiP22681
ProteomicsDBi54017

PTM databases

iPTMnetiP22681
PhosphoSitePlusiP22681

Miscellaneous databases

PMAP-CutDBiP22681

Expressioni

Gene expression databases

BgeeiENSG00000110395 Expressed in 210 organ(s), highest expression level in blood
CleanExiHS_CBL
ExpressionAtlasiP22681 baseline and differential
GenevisibleiP22681 HS

Organism-specific databases

HPAiCAB004350
HPA027956

Interactioni

Subunit structurei

Forms homodimers; IFT20 promotes the formation of stable homodimers (PubMed:29237719). 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 (By similarity). Interacts with CBLB (PubMed:29237719). 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). Interacts with SIGLEC10 (By similarity). Interacts with IFT20 (PubMed:29237719).By similarity29 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107315, 252 interactors
CORUMiP22681
DIPiDIP-189N
IntActiP22681, 93 interactors
MINTiP22681
STRINGi9606.ENSP00000264033

Structurei

Secondary structure

1906
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiKTVEKCW
OrthoDBiEOG091G0GPE
PhylomeDBiP22681
TreeFamiTF314210

Family and domain databases

CDDicd16709 RING-HC_Cbl-b, 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
IPR036537 Adaptor_Cbl_N_dom_sf
IPR003153 Adaptor_Cbl_N_hlx
IPR014742 Adaptor_Cbl_SH2-like
IPR039520 CBL-B_RING-HC
IPR024159 Cbl_PTB
IPR011992 EF-hand-dom_pair
IPR036860 SH2_dom_sf
IPR015940 UBA
IPR009060 UBA-like_sf
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0U1RR39A0A0U1RR39_HUMAN
E3 ubiquitin-protein ligase CBL
CBL
862Annotation score:
A0A1B0GW38A0A1B0GW38_HUMAN
E3 ubiquitin-protein ligase CBL
CBL
869Annotation score:
A0A0U1RQX8A0A0U1RQX8_HUMAN
E3 ubiquitin-protein ligase CBL
CBL
882Annotation score:
A0A0U1RRJ5A0A0U1RRJ5_HUMAN
E3 ubiquitin-protein ligase CBL
CBL
89Annotation score:

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:rs267606704EnsemblClinVar.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:rs267606706EnsemblClinVar.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:rs267606705EnsemblClinVar.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:rs267606707EnsemblClinVar.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:rs267606708EnsemblClinVar.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:rs2227988EnsemblClinVar.1
Natural variantiVAR_057212782P → L. Corresponds to variant dbSNP:rs2229073EnsemblClinVar.1
Natural variantiVAR_057213904V → I. Corresponds to variant dbSNP:rs17122769EnsemblClinVar.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

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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

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[»]
5O76X-ray2.47A/C47-435[»]
ProteinModelPortaliP22681
SMRiP22681
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107315, 252 interactors
CORUMiP22681
DIPiDIP-189N
IntActiP22681, 93 interactors
MINTiP22681
STRINGi9606.ENSP00000264033

PTM databases

iPTMnetiP22681
PhosphoSitePlusiP22681

Polymorphism and mutation databases

BioMutaiCBL
DMDMi251757253

Proteomic databases

EPDiP22681
MaxQBiP22681
PaxDbiP22681
PeptideAtlasiP22681
PRIDEiP22681
ProteomicsDBi54017

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi867
DisGeNETi867
EuPathDBiHostDB:ENSG00000110395.5
GeneCardsiCBL
HGNCiHGNC:1541 CBL
HPAiCAB004350
HPA027956
MalaCardsiCBL
MIMi165360 gene
613563 phenotype
neXtProtiNX_P22681
OpenTargetsiENSG00000110395
Orphaneti86834 Juvenile myelomonocytic leukemia
363972 Noonan syndrome-like disorder with juvenile myelomonocytic leukemia
PharmGKBiPA26115
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1785 Eukaryota
ENOG410YDNH LUCA
GeneTreeiENSGT00390000011617
HOGENOMiHOG000294176
HOVERGENiHBG005255
InParanoidiP22681
KOiK04707
OMAiKTVEKCW
OrthoDBiEOG091G0GPE
PhylomeDBiP22681
TreeFamiTF314210

Enzyme and pathway databases

UniPathwayi
UPA00143

BRENDAi2.3.2.B10 2681
ReactomeiR-HSA-1059683 Interleukin-6 signaling
R-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-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

Miscellaneous databases

ChiTaRSiCBL human
EvolutionaryTraceiP22681
GeneWikiiCBL_(gene)
GenomeRNAii867
PMAP-CutDBiP22681
PROiPR:P22681
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000110395 Expressed in 210 organ(s), highest expression level in blood
CleanExiHS_CBL
ExpressionAtlasiP22681 baseline and differential
GenevisibleiP22681 HS

Family and domain databases

CDDicd16709 RING-HC_Cbl-b, 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
IPR036537 Adaptor_Cbl_N_dom_sf
IPR003153 Adaptor_Cbl_N_hlx
IPR014742 Adaptor_Cbl_SH2-like
IPR039520 CBL-B_RING-HC
IPR024159 Cbl_PTB
IPR011992 EF-hand-dom_pair
IPR036860 SH2_dom_sf
IPR015940 UBA
IPR009060 UBA-like_sf
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
ProtoNetiSearch...

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: November 7, 2018
This is version 224 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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