CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-022441
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Denticleless protein homolog 
Protein Synonyms/Alias
 DDB1- and CUL4-associated factor 2; Lethal(2) denticleless protein homolog; Retinoic acid-regulated nuclear matrix-associated protein 
Gene Name
 DTL 
Gene Synonyms/Alias
 CDT2; CDW1; DCAF2; L2DTL; RAMP 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
123AAGDQTAKFWDVKAGubiquitination[1, 2, 3, 4]
128TAKFWDVKAGELIGTubiquitination[3, 4]
137GELIGTCKGHQCSLKubiquitination[4]
144KGHQCSLKSVAFSKFubiquitination[4]
150LKSVAFSKFEKAVFCubiquitination[3, 4]
153VAFSKFEKAVFCTGGubiquitination[4]
194GAHNTSDKQTPSKPKubiquitination[4]
201KQTPSKPKKKQNSKGubiquitination[4]
247IKVWDLRKNYTAYRQubiquitination[4]
260RQEPIASKSFLYPGSubiquitination[1, 2, 3, 4, 5]
386CSDDNTLKIWRLNRGubiquitination[3, 4]
397LNRGLEEKPGGDKLSubiquitination[1, 4]
402EEKPGGDKLSTVGWAubiquitination[4]
432SSQSTPAKAPRAKCNubiquitination[1, 5]
498PKPPSSFKMSIRNWVubiquitination[6]
564SSCLESVKQKCVKSCubiquitination[4]
708ITPSSMRKICTYFHRubiquitination[4]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [3] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [6] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965] 
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 and CDKN1A/p21(CIP1). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication. CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing. 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. 
Sequence Annotation
 REPEAT 47 89 WD 1.
 REPEAT 96 135 WD 2.
 REPEAT 138 178 WD 3.
 REPEAT 214 253 WD 4.
 REPEAT 267 308 WD 5.
 REPEAT 313 354 WD 6.
 REPEAT 358 398 WD 7.
 MOTIF 168 171 DDB1-binding motif.
 MOTIF 197 203 Nuclear localization signal (Potential).
 MOTIF 243 246 DDB1-binding motif.
 MOD_RES 410 410 Phosphoserine.
 MOD_RES 485 485 Phosphoserine.
 MOD_RES 490 490 Phosphoserine.
 MOD_RES 495 495 Phosphoserine.
 MOD_RES 512 512 Phosphoserine.
 MOD_RES 516 516 Phosphothreonine.
 MOD_RES 557 557 Phosphoserine.
 MOD_RES 599 599 Phosphoserine (By similarity).
 MOD_RES 676 676 Phosphoserine.
 MOD_RES 679 679 Phosphoserine.
 MOD_RES 684 684 Phosphothreonine.  
Keyword
 Alternative splicing; Complete proteome; Cytoplasm; Cytoskeleton; DNA damage; DNA replication; Membrane; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway; WD repeat. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 730 AA 
Protein Sequence
MLFNSVLRQP QLGVLRNGWS SQYPLQSLLT GYQCSGNDEH TSYGETGVPV PPFGCTFSSA 60
PNMEHVLAVA NEEGFVRLYN TESQSFRKKC FKEWMAHWNA VFDLAWVPGE LKLVTAAGDQ 120
TAKFWDVKAG ELIGTCKGHQ CSLKSVAFSK FEKAVFCTGG RDGNIMVWDT RCNKKDGFYR 180
QVNQISGAHN TSDKQTPSKP KKKQNSKGLA PSVDFQQSVT VVLFQDENTL VSAGAVDGII 240
KVWDLRKNYT AYRQEPIASK SFLYPGSSTR KLGYSSLILD STGSTLFANC TDDNIYMFNM 300
TGLKTSPVAI FNGHQNSTFY VKSSLSPDDQ FLVSGSSDEA AYIWKVSTPW QPPTVLLGHS 360
QEVTSVCWCP SDFTKIATCS DDNTLKIWRL NRGLEEKPGG DKLSTVGWAS QKKKESRPGL 420
VTVTSSQSTP AKAPRAKCNP SNSSPSSAAC APSCAGDLPL PSNTPTFSIK TSPAKARSPI 480
NRRGSVSSVS PKPPSSFKMS IRNWVTRTPS SSPPITPPAS ETKIMSPRKA LIPVSQKSSQ 540
AEACSESRNR VKRRLDSSCL ESVKQKCVKS CNCVTELDGQ VENLHLDLCC LAGNQEDLSK 600
DSLGPTKSSK IEGAGTSISE PPSPISPYAS ESCGTLPLPL RPCGEGSEMV GKENSSPENK 660
NWLLAMAAKR KAENPSPRSP SSQTPNSRRQ SGKKLPSPVT ITPSSMRKIC TYFHRKSQED 720
FCGPEHSTEL 730 
Gene Ontology
 GO:0005813; C:centrosome; IDA:UniProtKB.
 GO:0031464; C:Cul4A-RING ubiquitin ligase complex; IDA:UniProtKB.
 GO:0031465; C:Cul4B-RING ubiquitin ligase complex; IDA:UniProtKB.
 GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
 GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
 GO:0031572; P:G2 DNA damage checkpoint; IMP:UniProtKB.
 GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
 GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
 GO:0009411; P:response to UV; IDA:UniProtKB.
 GO:0019985; P:translesion synthesis; IDA:UniProtKB.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB. 
Interpro
 IPR015943; WD40/YVTN_repeat-like_dom.
 IPR001680; WD40_repeat.
 IPR019775; WD40_repeat_CS.
 IPR017986; WD40_repeat_dom. 
Pfam
 PF00400; WD40 
SMART
 SM00320; WD40 
PROSITE
 PS00678; WD_REPEATS_1
 PS50082; WD_REPEATS_2
 PS50294; WD_REPEATS_REGION 
PRINTS