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Protein

Denticleless protein homolog

Gene

Dtl

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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. KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration. 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.By similarity

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.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA replication, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-110314. Recognition of DNA damage by PCNA-containing replication complex.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Denticleless protein homolog
Alternative name(s):
Lethal(2) denticleless protein homolog
Meth A retinoic acid-regulated nuclear matrix-associated protein
Short name:
Meth A RAMP
Retinoic acid-regulated nuclear matrix-associated protein
Gene namesi
Name:Dtl
Synonyms:Cdt2, L2dtl, Ramp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1924093. Dtl.

Subcellular locationi

  • Nucleus By similarity
  • Nucleus membrane By similarity; Peripheral membrane protein By similarity; Nucleoplasmic side By similarity
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity
  • Chromosome By similarity

  • Note: Nuclear matrix-associated protein. Translocates from the interphase nucleus to the metaphase cytoplasm during mitosis (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Early embryonic lethality due to cell cycle progression failure, termination of cell division, and, eventually, embryonic death during the preimplantation stage.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 729729Denticleless protein homologPRO_0000274868Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei196 – 1961PhosphothreonineBy similarity
Modified residuei409 – 4091PhosphoserineBy similarity
Modified residuei425 – 4251PhosphoserineBy similarity
Modified residuei463 – 4631Phosphothreonine; by CDK1 and CDK2By similarity
Modified residuei484 – 4841PhosphoserineBy similarity
Modified residuei489 – 4891PhosphoserineBy similarity
Modified residuei494 – 4941PhosphoserineBy similarity
Modified residuei511 – 5111PhosphoserineCombined sources
Modified residuei515 – 5151PhosphothreonineCombined sources
Modified residuei556 – 5561PhosphoserineBy similarity
Modified residuei675 – 6751PhosphoserineBy similarity
Modified residuei678 – 6781PhosphoserineBy similarity
Modified residuei683 – 6831PhosphothreonineBy similarity
Modified residuei701 – 7011PhosphothreonineCombined sources

Post-translational modificationi

Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C). Autoubiquitinated through 'Lys-48'-polyubiquitin chains in a PCNA-independent reaction, allowing proteasomal turnover. Polyubiquitinated by SCF(FBXO11) when not phosphorylated, leading to its degradation. A tight regulation of the polyubiquitination by SCF(FBXO11) is involved in the control of different processes such as TGF-beta signaling, cell cycle progression and exit (By similarity).By similarity
Phosphorylated at Thr-463 by CDK1/Cyclin B and CDK2/Cycnlin A but not by CDK2/Cyclin E, MAPK1 or PLK1. Phosphorylation at Thr-463 inhibits the interaction with FBXO11 and decreases upon cell cycle exit induced by TGF-beta or serum starvation (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ3TLR7.
MaxQBiQ3TLR7.
PaxDbiQ3TLR7.
PeptideAtlasiQ3TLR7.
PRIDEiQ3TLR7.

PTM databases

iPTMnetiQ3TLR7.
PhosphoSiteiQ3TLR7.

Expressioni

Gene expression databases

BgeeiENSMUSG00000037474.
CleanExiMM_DTL.
ExpressionAtlasiQ3TLR7. baseline and differential.
GenevisibleiQ3TLR7. MM.

Interactioni

Subunit structurei

Component of the DCX(DTL) E3 ubiquitin ligase complex, at least composed of CUL4 (CUL4A or CUL4B), DDB1, DTL/CDT2 and RBX1. Interacts with CDKN1A and CDT1. Interacts with FBXO11; SCF(FBXWO11) controls DTL stability but DCX(DTL) does not control FBXO11 stability (By similarity).By similarity

Protein-protein interaction databases

BioGridi218345. 32 interactions.
IntActiQ3TLR7. 31 interactions.
STRINGi10090.ENSMUSP00000027933.

Structurei

3D structure databases

ProteinModelPortaliQ3TLR7.
SMRiQ3TLR7. Positions 60-415.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati47 – 8943WD 1Add
BLAST
Repeati96 – 13540WD 2Add
BLAST
Repeati138 – 17841WD 3Add
BLAST
Repeati214 – 25340WD 4Add
BLAST
Repeati269 – 30840WD 5Add
BLAST
Repeati313 – 35442WD 6Add
BLAST
Repeati358 – 39841WD 7Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi168 – 1714DDB1-binding motifBy similarity
Motifi197 – 2037Nuclear localization signalSequence analysis
Motifi243 – 2464DDB1-binding motifBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi424 – 546123Ser-richAdd
BLAST

Sequence similaritiesi

Belongs to the WD repeat cdt2 family.Curated
Contains 7 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0321. Eukaryota.
ENOG410XRWK. LUCA.
GeneTreeiENSGT00530000064210.
HOVERGENiHBG057737.
InParanoidiQ3TLR7.
KOiK11790.
OMAiICTYFHR.
OrthoDBiEOG091G04RK.
PhylomeDBiQ3TLR7.
TreeFamiTF324483.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF00400. WD40. 5 hits.
[Graphical view]
SMARTiSM00320. WD40. 5 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 2 hits.
PROSITEiPS00678. WD_REPEATS_1. 2 hits.
PS50082. WD_REPEATS_2. 5 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q3TLR7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLFNSVLRQP QLGVLRNGWS SHYPLQSLLS GYQCNCNDEH TSYGETGVPV
60 70 80 90 100
PPFGCTFCTA PSMEHILAVA NEEGFVRLYN TESQTSKKTC FKEWMAHWNA
110 120 130 140 150
VFDLAWVPGE LKLVTAAGDQ TAKFWDVRAG ELMGTCKGHQ CSLKSVAFPK
160 170 180 190 200
FQKAVFSTGG RDGNIMIWDT RCNKKDGFYR QVNQISGAHN TADKQTPSKP
210 220 230 240 250
KKKQNSKGLA PAVDSQQSVT VVLFQDENTL VSAGAVDGII KVWDLRKNYT
260 270 280 290 300
AYRQEPIASK SFLYPGTSTR KLGYSSLVLD STGSTLFANC TDDNIYMFNM
310 320 330 340 350
TGLKTSPVAV FNGHQNSTFY VKSSLSPDDQ FLISGSSDEA AYIWKVSMPW
360 370 380 390 400
HPPTVLLGHS QEVTSVCWCP SDFTKIATCS DDNTLKIWRL NRGLEEKPGD
410 420 430 440 450
KHSIVGWTSQ KKKEVKACPV TVPSSQSTPA KAPRAKSSPS ISSPSSAACT
460 470 480 490 500
PSCAGDLPLP SSTPTFSVKT TPATTRSSVS RRGSISSVSP KPLSSFKMSL
510 520 530 540 550
RNWVTRTPSS SPPVTPPASE TKISSPRKAL IPVSQKSSQA DACSESRNRV
560 570 580 590 600
KRRLDSSCLE SVKQKCVKSC NCVTELDGQA ESLRLDLCCL SGTQEVLSQD
610 620 630 640 650
SEGPTKSSKT EGAGTSISEP PSPVSPYASE GCGPLPLPLR PCGEGSEMVG
660 670 680 690 700
KENSSPENKN WLLAIAAKRK AENSSPRSPS SQTPSSRRQS GKTSPGPVTI
710 720
TPSSMRKICT YFRRKTQDDF CSPEHSTEL
Length:729
Mass (Da):79,131
Last modified:February 6, 2007 - v2
Checksum:iC828FAFBA9929360
GO
Isoform 2 (identifier: Q3TLR7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     699-729: TITPSSMRKICTYFRRKTQDDFCSPEHSTEL → SLNVGGHMSYLKGTRCSSQDCLGIQANNFALLLH

Note: No experimental confirmation available.
Show »
Length:732
Mass (Da):79,101
Checksum:iE64F9ACAE69103B4
GO
Isoform 3 (identifier: Q3TLR7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     214-216: DSQ → VR
     217-729: Missing.

Note: No experimental confirmation available.
Show »
Length:215
Mass (Da):23,883
Checksum:i4DBF06F1375457F8
GO
Isoform 4 (identifier: P85176-1) [UniParc]FASTAAdd to basket
Also known as: S35
The sequence of this isoform can be found in the external entry P85176.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by alternative splicing which extends exon 14 to produce a new open reading frame in the 3'region.
Length:26
Mass (Da):2,964
GO

Sequence cautioni

The sequence BAE36376 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BC060208 differs from that shown. Reason: Frameshift at position 163. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti110 – 1101E → G in BAE36376 (PubMed:16141072).Curated
Sequence conflicti149 – 1491P → S in BAE38725 (PubMed:16141072).Curated
Sequence conflicti200 – 2001P → L in BAB28549 (PubMed:16141072).Curated
Sequence conflicti300 – 3001M → T in BAC76405 (PubMed:12707369).Curated
Sequence conflicti300 – 3001M → T in BAC76404 (PubMed:12707369).Curated
Sequence conflicti369 – 3691C → Y in BAC76405 (PubMed:12707369).Curated
Sequence conflicti369 – 3691C → Y in BAC76404 (PubMed:12707369).Curated
Sequence conflicti593 – 5931T → A in BAE38725 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei214 – 2163DSQ → VR in isoform 3. 1 PublicationVSP_022884
Alternative sequencei217 – 729513Missing in isoform 3. 1 PublicationVSP_022885Add
BLAST
Alternative sequencei699 – 72931TITPS…HSTEL → SLNVGGHMSYLKGTRCSSQD CLGIQANNFALLLH in isoform 2. 1 PublicationVSP_022886Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB095735 mRNA. Translation: BAC76404.1.
AB095736 mRNA. Translation: BAC76405.1.
AK012919 mRNA. Translation: BAB28549.1.
AK054412 mRNA. Translation: BAC35769.1.
AK133177 mRNA. Translation: BAE21543.1.
AK161401 mRNA. Translation: BAE36376.1. Different initiation.
AK166351 mRNA. Translation: BAE38725.1.
BC060208 mRNA. No translation available.
CCDSiCCDS15621.1. [Q3TLR7-1]
RefSeqiNP_001292162.1. NM_001305233.1.
NP_084042.1. NM_029766.3. [Q3TLR7-1]
UniGeneiMm.189102.

Genome annotation databases

EnsembliENSMUST00000027933; ENSMUSP00000027933; ENSMUSG00000037474. [Q3TLR7-1]
GeneIDi76843.
KEGGimmu:76843.
UCSCiuc007eck.2. mouse. [Q3TLR7-1]
uc007ecn.2. mouse. [Q3TLR7-4]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB095735 mRNA. Translation: BAC76404.1.
AB095736 mRNA. Translation: BAC76405.1.
AK012919 mRNA. Translation: BAB28549.1.
AK054412 mRNA. Translation: BAC35769.1.
AK133177 mRNA. Translation: BAE21543.1.
AK161401 mRNA. Translation: BAE36376.1. Different initiation.
AK166351 mRNA. Translation: BAE38725.1.
BC060208 mRNA. No translation available.
CCDSiCCDS15621.1. [Q3TLR7-1]
RefSeqiNP_001292162.1. NM_001305233.1.
NP_084042.1. NM_029766.3. [Q3TLR7-1]
UniGeneiMm.189102.

3D structure databases

ProteinModelPortaliQ3TLR7.
SMRiQ3TLR7. Positions 60-415.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi218345. 32 interactions.
IntActiQ3TLR7. 31 interactions.
STRINGi10090.ENSMUSP00000027933.

PTM databases

iPTMnetiQ3TLR7.
PhosphoSiteiQ3TLR7.

Proteomic databases

EPDiQ3TLR7.
MaxQBiQ3TLR7.
PaxDbiQ3TLR7.
PeptideAtlasiQ3TLR7.
PRIDEiQ3TLR7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000027933; ENSMUSP00000027933; ENSMUSG00000037474. [Q3TLR7-1]
GeneIDi76843.
KEGGimmu:76843.
UCSCiuc007eck.2. mouse. [Q3TLR7-1]
uc007ecn.2. mouse. [Q3TLR7-4]

Organism-specific databases

CTDi51514.
MGIiMGI:1924093. Dtl.

Phylogenomic databases

eggNOGiKOG0321. Eukaryota.
ENOG410XRWK. LUCA.
GeneTreeiENSGT00530000064210.
HOVERGENiHBG057737.
InParanoidiQ3TLR7.
KOiK11790.
OMAiICTYFHR.
OrthoDBiEOG091G04RK.
PhylomeDBiQ3TLR7.
TreeFamiTF324483.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-110314. Recognition of DNA damage by PCNA-containing replication complex.

Miscellaneous databases

SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000037474.
CleanExiMM_DTL.
ExpressionAtlasiQ3TLR7. baseline and differential.
GenevisibleiQ3TLR7. MM.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF00400. WD40. 5 hits.
[Graphical view]
SMARTiSM00320. WD40. 5 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 2 hits.
PROSITEiPS00678. WD_REPEATS_1. 2 hits.
PS50082. WD_REPEATS_2. 5 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDTL_MOUSE
AccessioniPrimary (citable) accession number: Q3TLR7
Secondary accession number(s): Q3TTE9
, Q6PAN1, Q80WY1, Q80WY2, Q8BW38, Q9CZ76
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: September 7, 2016
This is version 101 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

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.