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Basic Information Integrated Annotations
Tag Content
iUUCD ID IUUC-Hsa-046177
UUCD1 version UUC-HoS-00060
Ensembl Protein ID ENSP00000264033.3
UniProt Accession P22681; A3KMP8; CBL_HUMAN
Genbank Protein ID CAA40393.1; AAI32734.1; AAI36464.1
Protein Name E3 ubiquitin-protein ligase CBL; Casitas B-lineage lymphoma proto-oncogene; Proto-oncogene c-Cbl; RING finger protein 55; RING-type E3 ubiquitin transferase CBL; Signal transduction protein CBL
Genbank Nucleotide ID X57110; AP002956; BC136463
Gene Name CBL; CBL2; RNF55
Ensembl Information
Ensembl Gene ID Ensembl Transcript ID Ensembl Protein ID
ENSG00000110395.6 ENST00000264033.5 ENSP00000264033.3
ENSG00000110395.6 ENST00000634586.1 ENSP00000489218.1
ENSG00000110395.6 ENST00000634840.1 ENSP00000489324.1
ENSG00000110395.6 ENST00000637974.1 ENSP00000490763.1
ENSG00000110395.6 ENST00000634301.1 ENSP00000489556.1
Annotation
Cancer Mutation
TCGAICGCCOSMICCGAP
IntOGen
Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEOArrayExpressTCGAICGC
COSMICTHPAHPM
DNA & RNA Element
UTRdbAREsitecircBasecircRNADb
CircNetmiRTarBasemicroRNATRANSFAC
miRWalkTargetScanRepTarSomamiR
miRcodeRAID2
Protein-protein Interaction
IIDiRefIndexPINAHINT
MenthaInWeb_IM
Protein 3D Structure
PDBMMDB
Disease-associated Information
ClinVarGWASdbOMIM
Drug and target
TTD
Post-translational Modifications (PTMs)
CPLMdbPAFPhosSNPPhosphositePlus
dbPTMHPRDPhospho.ELMUniProt
PHOSIDABioGRID
DNA Methylation
MethyCancerTCGAICGCCOSMIC
Protein Expression/Proteomics
THPAHPMGPMDB
Status Reviewed
Details
Family Domain References (PMIDs)
E3 activity/RING/RING RING 10531381; 14989173; 18198176; 19578043; 19419964; 19265199; 19201892; 19081591; 14531861; 12145291; 18544533; 18519587; 17620338; 17446348; 17449471; 17395426; 16740632; 21041311; 11964285; 12881521; 12727845; 12649282; 15277517; 19880507; 19880496; 19401194; 16407834; 12593796; 12147253; 10854852; 17094949; 20643813; 17255943; 11904433; 12193575; 12218189; 21447956; 18034775; 16004964
UBD/Alpha-Helix/UBA UBA 17679095
Classification
Family E-value Score Start End
E3 activity/RING/RING 5.60e-07 31.6 381 420
UBD/Alpha-Helix/UBA 4.00e-05 25.2 857 892
Active Site
Position(s) Description Evidence
N/A N/A N/A
Domain Profile

   E3 activity/RING/RING
   S: 1    CaiCledfkdgplvlpCgHvfhadClqkwpglknssskefrCPlCr 46
           C iC e  kd +++ pCgH+++++Cl  w    + +s  + CP Cr
   Q: 381  CKICAENDKD-VKIEPCGHLMCTSCLTSW----Q-ESEGQGCPFCR 420
           99********.******************....5.555555****8 PP
   

   UBD/Alpha-Helix/UBA
   S: 3    dedkleqlveMGFdreealqaLraannnleaAveyL 38
           +++ +e+l+++G++ +++++aL  a nn+e+A + L
   Q: 857  LSSEIENLMSQGYSYQDIQKALVIAQNNIEMAKNIL 892
           6788****************************9988 PP
   
Organism Homo sapiens
Functional Description
(View)

Functional Description


     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.
 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.
Protein Sequence
(Fasta)
MAGNVKKSSG AGGGSGSGGS GSGGLIGLMK DAFQPHHHHH HHLSPHPPGT VDKKMVEKCW 60
KLMDKVVRLC QNPKLALKNS PPYILDLLPD TYQHLRTILS RYEGKMETLG ENEYFRVFME 120
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Protein Fasta Sequence


>IUUC-Hsa-046177|E3,RING;UBD,UBA|Homo sapiens
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Nucleotide Sequence
(Fasta)
TCCGCCCGGA TAGCCGGCGG CGGCGGCGGC GGCGGCGGCG GCGGCGGCCG GGAGAGGCCC 60
CTCCTTCACG CCCTGCTTCT CTCCCTCGCT CGCAGTCGAG CCGAGCCGGC GGACCCGCCT 120
It may take some time, please wait.

Nucleotide Fasta Sequence


>IUUC-Hsa-046177|E3,RING;UBD,UBA|Homo sapiens
Please wait for a moment...
Sequence Source Ensembl
Keyword

KW-0002--3D-structure
KW-0106--Calcium
KW-1003--Cell membrane
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0225--Disease mutation
KW-0472--Membrane
KW-0479--Metal-binding
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-0656--Proto-oncogene
KW-1185--Reference proteome
KW-0677--Repeat
KW-0808--Transferase
KW-0832--Ubl conjugation
KW-0833--Ubl conjugation pathway
KW-0862--Zinc
KW-0863--Zinc-finger
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
PROSITE

PS51506--CBL_PTB
PS50030--UBA
PS00518--ZF_RING_1
PS50089--ZF_RING_2
Pfam

PF02262--Cbl_N
PF02761--Cbl_N2
PF02762--Cbl_N3
PF00627--UBA
SMART

SM00184--RING
SM00165--UBA
Gene Ontology

GO:0030424--C:axon
GO:0005829--C:cytosol
GO:0016600--C:flotillin complex
GO:0005925--C:focal adhesion
GO:0030426--C:growth cone
GO:0042629--C:mast cell granule
GO:0045121--C:membrane raft
GO:0005634--C:nucleus
GO:0048471--C:perinuclear region of cytoplasm
GO:0005886--C:plasma membrane
GO:0045296--F:cadherin binding
GO:0005509--F:calcium ion binding
GO:0046875--F:ephrin receptor binding
GO:0030971--F:receptor tyrosine kinase binding
GO:0017124--F:SH3 domain binding
GO:0004871--F:signal transducer activity
GO:0003700--F:transcription factor activity, sequence-specific DNA binding
GO:0061630--F:ubiquitin protein ligase activity
GO:0004842--F:ubiquitin-protein transferase activity
GO:0008270--F:zinc ion binding
GO:0007166--P:cell surface receptor signaling pathway
GO:0006974--P:cellular response to DNA damage stimulus
GO:0071364--P:cellular response to epidermal growth factor stimulus
GO:1990090--P:cellular response to nerve growth factor stimulus
GO:0090650--P:cellular response to oxygen-glucose deprivation
GO:0036120--P:cellular response to platelet-derived growth factor stimulus
GO:0035635--P:entry of bacterium into host cell
GO:0007173--P:epidermal growth factor receptor signaling pathway
GO:0008543--P:fibroblast growth factor receptor signaling pathway
GO:0008584--P:male gonad development
GO:0043303--P:mast cell degranulation
GO:0061024--P:membrane organization
GO:0043066--P:negative regulation of apoptotic process
GO:0042059--P:negative regulation of epidermal growth factor receptor signaling pathway
GO:0007175--P:negative regulation of epidermal growth factor-activated receptor activity
GO:1901215--P:negative regulation of neuron death
GO:0070997--P:neuron death
GO:0045742--P:positive regulation of epidermal growth factor receptor signaling pathway
GO:0014068--P:positive regulation of phosphatidylinositol 3-kinase signaling
GO:0048260--P:positive regulation of receptor-mediated endocytosis
GO:0006513--P:protein monoubiquitination
GO:0000209--P:protein polyubiquitination
GO:0016567--P:protein ubiquitination
GO:0042787--P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0014823--P:response to activity
GO:0046677--P:response to antibiotic
GO:0045471--P:response to ethanol
GO:0010332--P:response to gamma radiation
GO:0042594--P:response to starvation
GO:0033574--P:response to testosterone
GO:0007179--P:transforming growth factor beta receptor signaling pathway
KEGG hsa:867
Orthology
iUUCD ID Species Identity E-value Score
IUUC-Aml-002357 Ailuropoda melanoleuca 91.42 0.00e+00 1482.00
IUUC-Apl-004041 Anas platyrhynchos 84.71 0.00e+00 1375.00
IUUC-Aca-004899 Anolis carolinensis 81.30 0.00e+00 1261.00
IUUC-Ame-010746 Astyanax mexicanus 60.11 0.00e+00 627.00
IUUC-Bta-012759 Bos taurus 92.36 0.00e+00 1534.00
IUUC-Cja-019207 Callithrix jacchus 97.47 0.00e+00 1631.00
IUUC-Cfa-020897 Canis familiaris 92.48 0.00e+00 1526.00
IUUC-Cpo-021453 Cavia porcellus 91.55 0.00e+00 1520.00
IUUC-Csa-023136 Chlorocebus sabaeus 98.46 0.00e+00 1630.00
IUUC-Cho-024282 Choloepus hoffmanni 85.78 0.00e+00 1265.00
IUUC-Cin-025574 Ciona intestinalis 71.54 2.00e-177 615.00
IUUC-Csv-025938 Ciona savignyi 69.87 8.00e-173 599.00
IUUC-Dre-027644 Danio rerio 68.88 0.00e+00 1038.00
IUUC-Dno-030025 Dasypus novemcinctus 92.97 0.00e+00 1488.00
IUUC-Dme-032213 Drosophila melanogaster 74.81 0.00e+00 644.00
IUUC-Ete-033118 Echinops telfairi 80.40 0.00e+00 819.00
IUUC-Eca-033900 Equus caballus 94.48 0.00e+00 1518.00
IUUC-Eeu-035142 Erinaceus europaeus 86.08 0.00e+00 960.00
IUUC-Fca-035455 Felis catus 92.48 0.00e+00 1521.00
IUUC-Fal-037182 Ficedula albicollis 95.02 0.00e+00 902.00
IUUC-Gmo-038698 Gadus morhua 87.30 0.00e+00 870.00
IUUC-Gga-040438 Gallus gallus 83.76 0.00e+00 1405.00
IUUC-Gac-042166 Gasterosteus aculeatus 76.24 0.00e+00 887.00
IUUC-Ggo-045618 Gorilla gorilla 99.89 0.00e+00 1653.00
IUUC-Itr-048795 Ictidomys tridecemlineatus 96.66 0.00e+00 1015.00
IUUC-Lch-050095 Latimeria chalumnae 74.70 0.00e+00 1171.00
IUUC-Loc-052570 Lepisosteus oculatus 71.77 0.00e+00 1125.00
IUUC-Laf-054008 Loxodonta africana 90.70 0.00e+00 1535.00
IUUC-Mcc-054676 Macaca mulatta 98.35 0.00e+00 1627.00
IUUC-Mga-059239 Meleagris gallopavo 83.39 0.00e+00 1407.00
IUUC-Mmr-060907 Microcebus murinus 92.43 0.00e+00 1533.00
IUUC-Mdo-062595 Monodelphis domestica 88.42 0.00e+00 1418.00
IUUC-Mmu-063725 Mus musculus 91.16 0.00e+00 1580.00
IUUC-Mpu-066771 Mustela putorius furo 92.46 0.00e+00 1536.00
IUUC-Mlu-067206 Myotis lucifugus 76.58 0.00e+00 1091.00
IUUC-Nle-069285 Nomascus leucogenys 96.37 0.00e+00 1533.00
IUUC-Opr-071026 Ochotona princeps 92.65 0.00e+00 1497.00
IUUC-Ont-071954 Oreochromis niloticus 70.56 0.00e+00 1040.00
IUUC-Ocu-074657 Oryctolagus cuniculus 92.59 0.00e+00 1463.00
IUUC-Ola-087165 Oryzias latipes 66.74 0.00e+00 1058.00
IUUC-Oga-088198 Otolemur garnettii 83.42 0.00e+00 1337.00
IUUC-Oar-090258 Ovis aries 91.79 0.00e+00 1466.00
IUUC-Ptr-090710 Pan troglodytes 100.00 0.00e+00 1642.00
IUUC-Pan-092785 Papio anubis 98.35 0.00e+00 1627.00
IUUC-Pfo-096990 Poecilia formosa 90.16 0.00e+00 818.00
IUUC-Pab-098526 Pongo abelii 99.01 0.00e+00 1634.00
IUUC-Pca-100984 Procavia capensis 79.19 3.00e-171 595.00
IUUC-Pva-102352 Pteropus vampyrus 97.07 0.00e+00 897.00
IUUC-Rno-105876 Rattus norvegicus 90.83 0.00e+00 1555.00
IUUC-Sha-107588 Sarcophilus harrisii 86.36 0.00e+00 1228.00
IUUC-Sar-112959 Sorex araneus 88.60 0.00e+00 1429.00
IUUC-Ssc-115261 Sus scrofa 92.47 0.00e+00 1540.00
IUUC-Tgu-116580 Taeniopygia guttata 81.79 0.00e+00 1315.00
IUUC-Tru-118731 Takifugu rubripes 68.23 0.00e+00 1033.00
IUUC-Tsy-118982 Tarsius syrichta 87.86 0.00e+00 1066.00
IUUC-Tni-120725 Tetraodon nigroviridis 68.71 0.00e+00 1031.00
IUUC-Tbe-128018 Tupaia belangeri 95.76 0.00e+00 1165.00
IUUC-Ttr-128927 Tursiops truncatus 94.46 0.00e+00 1592.00
IUUC-Vpa-130369 Vicugna pacos 93.95 0.00e+00 1452.00
IUUC-Xtr-132474 Xenopus tropicalis 73.64 0.00e+00 1145.00
Created Date 25-Jun-2017

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