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Basic Information Integrated Annotations
Tag Content
iUUCD ID IUUC-Hsa-045862
UUCD1 version UUC-HoS-00405
Ensembl Protein ID ENSP00000355958.4
UniProt Accession Q9NZJ0; A8K8H8; D3DT98; Q5VT77; Q96SN0; Q9NW03; Q9NW34; Q9NWM5; DTL_HUMAN
Genbank Protein ID AAK54706.1; ABG23317.1; AAF35182.1; BAA91355.1; BAA91552.1; BAA91586.1; BAB55267.1; BAF85032.1; CAH70697.1; CAH70697.1; CAH70697.1; CAH73803.1; CAH73803.1; CAH73803.1; EAW93395.1; EAW93397.1; AAH33540.1; AAH33297.1
Protein Name Denticleless protein homolog; DDB1- and CUL4-associated factor 2; Lethal(2) denticleless protein homolog; Retinoic acid-regulated nuclear matrix-associated protein
Genbank Nucleotide ID AF345896; DQ641253; AF195765; AK000742; AK001206; AK001261; AK027651; AK292343; AL606468; AC092814; AL592297; AL592297; AC092814; AL606468; CH471100; CH471100; BC033540; BC033297
Gene Name DTL; CDT2; CDW1; DCAF2; L2DTL; RAMP
Ensembl Information
Ensembl Gene ID Ensembl Transcript ID Ensembl Protein ID
ENSG00000143476.17 ENST00000366991.4 ENSP00000355958.4
ENSG00000143476.17 ENST00000542077.5 ENSP00000443870.1
Annotation
Cancer Mutation
TCGAICGCCOSMICCGAP
IntOGen
Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEOArrayExpressTCGAICGC
COSMICTHPAHPM
DNA & RNA Element
UTRdbAREsitecircBasecircRNADb
CircNetmiRTarBasemicroRNATRANSFAC
TargetScanmiRecordsRepTarSomamiR
miRcodeRAID2
Protein-protein Interaction
IIDiRefIndexPINAHINT
MenthaInWeb_IM
Disease-associated Information
GWASdbGWAS CentralOMIM
Post-translational Modifications (PTMs)
CPLMdbPAFPhosphositePlusdbPTM
HPRDPhospho.ELMUniProtPHOSIDA
BioGRIDmUbiSiDa
DNA Methylation
TCGAICGC
Protein Expression/Proteomics
THPAHPMGPMDB
Status Reviewed
Details
Family Domain References (PMIDs)
E3 adaptor/Cullin RING/DCX/DWD WD_repeat 19595719; 20932471; 21035370; 18703516; 20086099; 19081066
Classification
Family E-value Score Start End
E3 adaptor/Cullin RING/DCX/DWD 2.90e-33 114.1 358 395
Active Site
Position(s) Description Evidence
N/A N/A N/A
Domain Profile

   E3 adaptor/Cullin RING/DCX/DWD
   S: 1    gHtdsvtclaf..sd.tllvsGsdDgtikvWDlrtgvl 35
           gH+ +vt++++  sd t ++++sdD+t+k+W+l +g  
   Q: 358  GHSQEVTSVCWcpSDfTKIATCSDDNTLKIWRLNRGLE 395
           8***********999*****************988866 PP
   
Organism Homo sapiens
Functional Description
(View)

Functional Description


     Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBXO18/FBH1 and KMT5A (PubMed:16861906, PubMed:16949367, PubMed:16964240, PubMed:17085480, PubMed:18703516, PubMed:18794347, PubMed:18794348, PubMed:19332548, PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication (PubMed:16861906, PubMed:16949367, PubMed:17085480). CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing (PubMed:18794348, PubMed:19332548). KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration (PubMed:23478445). Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis (PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613).
 Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBXO18/FBH1 and KMT5A (PubMed:16861906, PubMed:16949367, PubMed:16964240, PubMed:17085480, PubMed:18703516, PubMed:18794347, PubMed:18794348, PubMed:19332548, PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication (PubMed:16861906, PubMed:16949367, PubMed:17085480). CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing (PubMed:18794348, PubMed:19332548). KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration (PubMed:23478445). Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis (PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613).
Protein Sequence
(Fasta)
MLFNSVLRQP QLGVLRNGWS SQYPLQSLLT GYQCSGNDEH TSYGETGVPV PPFGCTFSSA 60
PNMEHVLAVA NEEGFVRLYN TESQSFRKKC FKEWMAHWNA VFDLAWVPGE LKLVTAAGDQ 120
It may take some time, please wait.

Protein Fasta Sequence


>IUUC-Hsa-045862|E3,WD_repeat|Homo sapiens
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Nucleotide Sequence
(Fasta)
GTTACGCATG CGCCCTGGTC ACCCCGCGGT TTGTCCGCGC CTCTGCTACC CCCTGCGCAG 60
GCGCTCAAGG AGCTCTTGGA CTCCAGGTTC CCGCGGCTGG GAGAAAAGGA GGCGGGGATC 120
It may take some time, please wait.

Nucleotide Fasta Sequence


>IUUC-Hsa-045862|E3,WD_repeat|Homo sapiens
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Sequence Source Ensembl
Keyword

KW-0007--Acetylation
KW-0025--Alternative splicing
KW-0158--Chromosome
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0206--Cytoskeleton
KW-0227--DNA damage
KW-0235--DNA replication
KW-0472--Membrane
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-1185--Reference proteome
KW-0677--Repeat
KW-0832--Ubl conjugation
KW-0833--Ubl conjugation pathway
KW-0853--WD repeat
Interpro

IPR011042--6-blade_b-propeller_TolB-like
IPR015943--WD40/YVTN_repeat-like_dom
IPR001680--WD40_repeat
IPR019775--WD40_repeat_CS
IPR017986--WD40_repeat_dom
PROSITE

PS00678--WD_REPEATS_1
PS50082--WD_REPEATS_2
PS50294--WD_REPEATS_REGION
Pfam

PF00400--WD40
SMART

SM00320--WD40
Gene Ontology

GO:0005813--C:centrosome
GO:0005694--C:chromosome
GO:0031464--C:Cul4A-RING E3 ubiquitin ligase complex
GO:0031465--C:Cul4B-RING E3 ubiquitin ligase complex
GO:0005829--C:cytosol
GO:0031965--C:nuclear membrane
GO:0005730--C:nucleolus
GO:0005654--C:nucleoplasm
GO:0005634--C:nucleus
GO:0006974--P:cellular response to DNA damage stimulus
GO:0042769--P:DNA damage response, detection of DNA damage
GO:0006260--P:DNA replication
GO:0031572--P:G2 DNA damage checkpoint
GO:0006513--P:protein monoubiquitination
GO:0000209--P:protein polyubiquitination
GO:0051726--P:regulation of cell cycle
GO:0009411--P:response to UV
GO:0019985--P:translesion synthesis
GO:0006511--P:ubiquitin-dependent protein catabolic process
KEGG hsa:51514
Orthology
iUUCD ID Species Identity E-value Score
IUUC-Aml-002111 Ailuropoda melanoleuca 93.29 0.00e+00 1266.00
IUUC-Atr-003097 Amborella trichopoda 35.36 4.00e-63 236.00
IUUC-Apl-004088 Anas platyrhynchos 62.89 0.00e+00 806.00
IUUC-Aca-004732 Anolis carolinensis 56.94 0.00e+00 684.00
IUUC-Aly-005686 Arabidopsis lyrata 33.15 1.00e-57 217.00
IUUC-Ath-006970 Arabidopsis thaliana 33.24 7.00e-57 214.00
IUUC-Acl-008219 Aspergillus clavatus 24.72 2.00e-22 101.00
IUUC-Afu-008784 Aspergillus fumigatus 24.84 4.00e-23 103.00
IUUC-Ani-009304 Aspergillus nidulans 26.75 2.00e-18 87.80
IUUC-Ang-009842 Aspergillus niger 24.52 1.00e-24 108.00
IUUC-Aor-009883 Aspergillus oryzae 25.28 1.00e-22 102.00
IUUC-Ate-010454 Aspergillus terreus 26.71 8.00e-23 101.00
IUUC-Ame-010949 Astyanax mexicanus 47.77 3.00e-166 578.00
IUUC-Bta-012333 Bos taurus 90.55 0.00e+00 1221.00
IUUC-Bci-013733 Botrytis cinerea 26.86 1.00e-21 98.60
IUUC-Bdi-014494 Brachypodium distachyon 33.89 3.00e-55 209.00
IUUC-Bol-015301 Brassica oleracea 35.44 2.00e-57 216.00
IUUC-Bra-017384 Brassica rapa 33.33 1.00e-57 217.00
IUUC-Cel-018498 Caenorhabditis elegans 27.60 4.00e-32 133.00
IUUC-Cja-019534 Callithrix jacchus 97.54 0.00e+00 1367.00
IUUC-Cfa-020847 Canis familiaris 93.01 0.00e+00 1233.00
IUUC-Cpo-021695 Cavia porcellus 89.65 0.00e+00 1201.00
IUUC-Cre-022762 Chlamydomonas reinhardtii 29.10 5.00e-41 164.00
IUUC-Csa-023748 Chlorocebus sabaeus 98.36 0.00e+00 1358.00
IUUC-Cho-024445 Choloepus hoffmanni 73.56 0.00e+00 952.00
IUUC-Cgl-026664 Colletotrichum gloeosporioides 24.50 3.00e-17 84.00
IUUC-Cne-027008 Cryptococcus neoformans 23.91 1.00e-12 70.10
IUUC-Dre-027536 Danio rerio 46.10 1.00e-162 566.00
IUUC-Dno-030035 Dasypus novemcinctus 82.35 0.00e+00 1140.00
IUUC-Dor-030814 Dipodomys ordii 82.34 5.00e-141 495.00
IUUC-Dse-031354 Dothistroma septosporum 23.85 6.00e-26 112.00
IUUC-Dme-031691 Drosophila melanogaster 42.33 1.00e-81 298.00
IUUC-Ete-032814 Echinops telfairi 81.01 0.00e+00 815.00
IUUC-Eca-033332 Equus caballus 93.15 0.00e+00 1240.00
IUUC-Fca-035571 Felis catus 93.15 0.00e+00 1232.00
IUUC-Fal-037421 Ficedula albicollis 61.01 0.00e+00 779.00
IUUC-Fox-038069 Fusarium oxysporum 23.19 8.00e-16 79.00
IUUC-Fso-038192 Fusarium solani 22.72 3.00e-16 80.50
IUUC-Gmo-039365 Gadus morhua 66.10 1.00e-158 553.00
IUUC-Ggr-039904 Gaeumannomyces graminis 24.56 4.00e-16 80.10
IUUC-Gga-041153 Gallus gallus 61.90 0.00e+00 797.00
IUUC-Gac-041984 Gasterosteus aculeatus 61.38 4.00e-160 558.00
IUUC-Gma-043734 Glycine max 35.08 3.00e-56 213.00
IUUC-Ggo-044419 Gorilla gorilla 99.32 0.00e+00 1349.00
IUUC-Hvu-047728 Hordeum vulgare 33.06 3.00e-58 219.00
IUUC-Itr-048786 Ictidomys tridecemlineatus 93.70 0.00e+00 1302.00
IUUC-Lch-050616 Latimeria chalumnae 54.91 0.00e+00 669.00
IUUC-Lpe-051222 Leersia perrieri 33.81 3.00e-55 209.00
IUUC-Loc-052564 Lepisosteus oculatus 52.19 2.00e-175 608.00
IUUC-Lma-053098 Leptosphaeria maculans 25.22 4.00e-25 109.00
IUUC-Laf-053892 Loxodonta africana 88.93 0.00e+00 1169.00
IUUC-Mcc-055854 Macaca mulatta 98.08 0.00e+00 1350.00
IUUC-Mor-057144 Magnaporthe oryzae 26.55 1.00e-16 81.60
IUUC-Mtr-058510 Medicago truncatula 33.43 4.00e-54 206.00
IUUC-Mla-058823 Melampsora laricipopulina 25.64 6.00e-21 95.90
IUUC-Mga-060128 Meleagris gallopavo 61.55 0.00e+00 805.00
IUUC-Mvi-060475 Microbotryum violaceum 31.50 1.00e-42 167.00
IUUC-Mmr-061331 Microcebus murinus 94.11 0.00e+00 1259.00
IUUC-Mdo-063020 Monodelphis domestica 73.61 0.00e+00 1013.00
IUUC-Mmu-063713 Mus musculus 89.45 0.00e+00 1152.00
IUUC-Mac-064653 Musa acuminata 33.51 5.00e-56 212.00
IUUC-Mpu-066490 Mustela putorius furo 93.01 0.00e+00 1231.00
IUUC-Mlu-067900 Myotis lucifugus 90.27 0.00e+00 1184.00
IUUC-Nfi-068433 Neosartorya fischeri 25.05 2.00e-24 107.00
IUUC-Ncr-068776 Neurospora crassa 27.90 4.00e-26 113.00
IUUC-Nle-069675 Nomascus leucogenys 93.43 0.00e+00 1235.00
IUUC-Opr-070769 Ochotona princeps 68.63 0.00e+00 803.00
IUUC-Ont-071441 Oreochromis niloticus 62.53 2.00e-155 543.00
IUUC-Oan-072757 Ornithorhynchus anatinus 68.73 0.00e+00 906.00
IUUC-Ocu-074670 Oryctolagus cuniculus 94.93 0.00e+00 1292.00
IUUC-Oba-075844 Oryza barthii 32.68 5.00e-54 205.00
IUUC-Obr-076625 Oryza brachyantha 35.75 1.00e-58 220.00
IUUC-Ogl-077771 Oryza glaberrima 32.68 5.00e-54 205.00
IUUC-Ogu-078475 Oryza glumaepatula 31.56 2.00e-46 180.00
IUUC-Oin-079958 Oryza indica 32.68 4.00e-54 205.00
IUUC-Olo-080311 Oryza longistaminata 32.01 4.00e-45 175.00
IUUC-Ome-081985 Oryza meridionalis 31.84 9.00e-53 201.00
IUUC-Oni-082921 Oryza nivara 32.68 4.00e-54 205.00
IUUC-Opu-083174 Oryza punctata 31.44 1.00e-54 207.00
IUUC-Oru-084338 Oryza rufipogon 31.33 4.00e-54 205.00
IUUC-Osa-085609 Oryza sativa 41.11 5.00e-19 87.80
IUUC-Olu-087907 Ostreococcus lucimarinus 26.39 8.00e-29 121.00
IUUC-Oga-088358 Otolemur garnettii 94.52 0.00e+00 1328.00
IUUC-Oar-089994 Ovis aries 90.41 0.00e+00 1217.00
IUUC-Ptr-091338 Pan troglodytes 99.59 0.00e+00 1393.00
IUUC-Pan-091759 Papio anubis 98.22 0.00e+00 1353.00
IUUC-Psi-093211 Pelodiscus sinensis 59.65 0.00e+00 702.00
IUUC-Pma-094588 Petromyzon marinus 59.15 4.00e-99 354.00
IUUC-Pno-094964 Phaeosphaeria nodorum 25.69 4.00e-26 113.00
IUUC-Ppa-095159 Physcomitrella patens 37.88 7.00e-63 234.00
IUUC-Pfo-096592 Poecilia formosa 43.32 4.00e-146 511.00
IUUC-Pab-098597 Pongo abelii 82.35 0.00e+00 1048.00
IUUC-Pop-099255 Populus trichocarpa 36.44 5.00e-61 228.00
IUUC-Pca-100593 Procavia capensis 72.92 0.00e+00 890.00
IUUC-Ppe-101333 Prunus persica 34.96 8.00e-56 211.00
IUUC-Pva-102283 Pteropus vampyrus 88.63 0.00e+00 1162.00
IUUC-Pgr-103383 Puccinia graminis 27.56 1.00e-21 98.20
IUUC-Ptt-103974 Puccinia triticina 29.33 4.00e-20 92.80
IUUC-Pte-104329 Pyrenophora teres 24.73 2.00e-24 107.00
IUUC-Pyt-104424 Pyrenophora triticirepentis 24.89 6.00e-24 105.00
IUUC-Rno-105720 Rattus norvegicus 87.53 0.00e+00 1121.00
IUUC-Sha-106891 Sarcophilus harrisii 69.14 0.00e+00 895.00
IUUC-Sja-107723 Schizosaccharomyces japonicus 27.52 1.00e-26 114.00
IUUC-Spo-108060 Schizosaccharomyces pombe 25.69 4.00e-20 92.80
IUUC-Ssl-108481 Sclerotinia sclerotiorum 27.61 1.00e-18 88.60
IUUC-Sit-109862 Setaria italica 33.05 5.00e-55 208.00
IUUC-Sly-111468 Solanum lycopersicum 34.35 1.00e-58 221.00
IUUC-Stu-112346 Solanum tuberosum 33.90 4.00e-56 212.00
IUUC-Sar-113734 Sorex araneus 80.45 1.00e-102 367.00
IUUC-Sbi-114076 Sorghum bicolor 33.43 1.00e-56 214.00
IUUC-Sre-114918 Sporisorium reilianum 22.94 4.00e-14 73.60
IUUC-Ssc-115561 Sus scrofa 90.01 0.00e+00 1203.00
IUUC-Tgu-117011 Taeniopygia guttata 62.99 0.00e+00 778.00
IUUC-Tru-118411 Takifugu rubripes 60.45 8.00e-152 530.00
IUUC-Tsy-119367 Tarsius syrichta 83.97 0.00e+00 1089.00
IUUC-Tni-120301 Tetraodon nigroviridis 59.68 8.00e-152 530.00
IUUC-Tca-121265 Theobroma cacao 34.71 6.00e-58 218.00
IUUC-Tre-121997 Trichoderma reesei 25.89 4.00e-18 86.70
IUUC-Tvi-122292 Trichoderma virens 25.91 5.00e-19 89.70
IUUC-Tae-123660 Triticum aestivum 31.94 1.00e-56 214.00
IUUC-Tur-126794 Triticum urartu 30.93 4.00e-42 166.00
IUUC-Tme-127090 Tuber melanosporum 25.24 5.00e-17 82.00
IUUC-Tbe-127646 Tupaia belangeri 89.74 0.00e+00 790.00
IUUC-Ttr-128171 Tursiops truncatus 91.23 0.00e+00 1239.00
IUUC-Uma-129525 Ustilago maydis 25.64 4.00e-20 93.60
IUUC-Vda-129871 Verticillium dahliae 28.57 3.00e-19 90.50
IUUC-Vpa-130554 Vicugna pacos 80.33 4.00e-147 515.00
IUUC-Vvi-131698 Vitis vinifera 34.48 2.00e-59 223.00
IUUC-Xtr-131962 Xenopus tropicalis 56.99 0.00e+00 753.00
IUUC-Xma-133803 Xiphophorus maculatus 44.52 1.00e-155 543.00
IUUC-Zma-135693 Zea mays 31.56 7.00e-54 205.00
Created Date 25-Jun-2017

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