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Q9NZJ0 (DTL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Denticleless protein homolog
Alternative name(s):
DDB1- and CUL4-associated factor 2
Lethal(2) denticleless protein homolog
Retinoic acid-regulated nuclear matrix-associated protein
Gene names
Name:DTL
Synonyms:CDT2, CDW1, DCAF2, L2DTL, RAMP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length730 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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) and SETD8. 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. SETD8 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. Ref.2 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.18 Ref.20 Ref.27 Ref.28

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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. Ref.2 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.27 Ref.28

Subcellular location

Nucleus. Nucleus membrane; Peripheral membrane protein; Nucleoplasmic side. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Chromosome. Note: Nuclear matrix-associated protein. Translocates from the interphase nucleus to the metaphase cytoplasm during mitosis. Ref.8 Ref.26

Tissue specificity

Expressed in placenta and testis, very low expression seen in skeletal muscle. Detected in all hematopoietic tissues examined, with highest expression in thymus and bone marrow. A low level detected in the spleen and lymph node, and barely detectable level in the peripheral leukocytes. RA treatment down-regulated the expression in NT2 cell. Ref.1 Ref.8

Developmental stage

Expressed in all fetal tissues examined, included brain, lung, liver, and kidney. Protein levels peak at G1 and decrease through S-phase. Ref.1 Ref.26

Induction

Induced by TGF-beta, the up-regulation is immediate and transient. Ref.27

Post-translational modification

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. Ref.28

Phosphorylated at Thr-464 by CDK1/Cyclin-B and CDK2/Cyclin-A but not by CDK2/Cyclin-E, MAPK1 or PLK1. Phosphorylation at Thr-464 inhibits the interaction with FBXO11 and decreases upon cell cycle exit induced by TGF-beta or serum starvation. Ref.28

Sequence similarities

Belongs to the WD repeat cdt2 family.

Contains 7 WD repeats.

Sequence caution

The sequence BAA91552.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAA91586.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processDNA damage
DNA replication
Ubl conjugation pathway
   Cellular componentChromosome
Cytoplasm
Cytoskeleton
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
WD repeat
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA replication

Inferred from electronic annotation. Source: UniProtKB-KW

G2 DNA damage checkpoint

Inferred from mutant phenotype Ref.9. Source: UniProtKB

cellular response to DNA damage stimulus

Inferred from direct assay Ref.20. Source: UniProtKB

protein monoubiquitination

Inferred from direct assay Ref.20. Source: UniProtKB

protein polyubiquitination

Inferred from direct assay Ref.13. Source: UniProtKB

regulation of cell cycle

Inferred from mutant phenotype Ref.9. Source: UniProtKB

response to UV

Inferred from direct assay Ref.13. Source: UniProtKB

translesion synthesis

Inferred from direct assay Ref.20. Source: UniProtKB

ubiquitin-dependent protein catabolic process

Inferred from direct assay Ref.13. Source: UniProtKB

   Cellular_componentCul4A-RING ubiquitin ligase complex

Inferred from direct assay Ref.9Ref.13Ref.20. Source: UniProtKB

Cul4B-RING ubiquitin ligase complex

Inferred from direct assay Ref.13. Source: UniProtKB

centrosome

Inferred from direct assay Ref.8. Source: UniProtKB

chromosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay. Source: HPA

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

nuclear membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleolus

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay Ref.8. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DDB1Q165313EBI-1176075,EBI-350322

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NZJ0-1)

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.
Isoform 2 (identifier: Q9NZJ0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     18-59: Missing.
     240-253: IKVWDLRKNYTAYR → FKSDFGFHWLYFIC
     254-730: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 730730Denticleless protein homolog
PRO_0000274867

Regions

Repeat47 – 8943WD 1
Repeat96 – 13540WD 2
Repeat138 – 17841WD 3
Repeat214 – 25340WD 4
Repeat267 – 30842WD 5
Repeat313 – 35442WD 6
Repeat358 – 39841WD 7
Motif168 – 1714DDB1-binding motif
Motif197 – 2037Nuclear localization signal Potential
Motif243 – 2464DDB1-binding motif

Amino acid modifications

Modified residue11N-acetylmethionine Ref.24
Modified residue4101Phosphoserine Ref.21
Modified residue4641Phosphothreonine; by CDK1 and CDK2 Ref.28
Modified residue4851Phosphoserine Ref.16
Modified residue4901Phosphoserine Ref.16 Ref.21
Modified residue4951Phosphoserine Ref.16
Modified residue5121Phosphoserine Ref.16 Ref.19 Ref.21 Ref.23
Modified residue5161Phosphothreonine Ref.16 Ref.19 Ref.21 Ref.23
Modified residue5571Phosphoserine Ref.16
Modified residue6761Phosphoserine Ref.16
Modified residue6791Phosphoserine Ref.16
Modified residue6841Phosphothreonine Ref.16

Natural variations

Alternative sequence18 – 5942Missing in isoform 2.
VSP_022879
Alternative sequence240 – 25314IKVWD…YTAYR → FKSDFGFHWLYFIC in isoform 2.
VSP_022880
Alternative sequence254 – 730477Missing in isoform 2.
VSP_022881
Natural variant4251S → N.
Corresponds to variant rs35137676 [ dbSNP | Ensembl ].
VAR_062095
Natural variant4361A → V. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.7
Corresponds to variant rs3135474 [ dbSNP | Ensembl ].
VAR_030353
Natural variant6941K → T. Ref.1 Ref.2 Ref.3 Ref.4 Ref.7
Corresponds to variant rs6540718 [ dbSNP | Ensembl ].
VAR_030354

Experimental info

Mutagenesis2461R → A: Blocks association with DDB1 and ubiquitination by DCX(DTL). No effect on ubiquitination by SCF(FBXO11). Ref.10 Ref.27
Mutagenesis4571D → A: Increases protein stability, but no effect on interaction with FBXO11 and polyubiquitination. Delays cell migration. Ref.27
Mutagenesis4621S → A: Blocks interaction with FBXO11 and ubiquitination, increasing protein stability. Delays cell migration. Ref.27
Mutagenesis4631N → A: No effect on interaction with FBXO11. Increases protein stability. Ref.28
Mutagenesis4641T → A: Blocks interaction with FBXO11 and increases protein stability. Not phosphorylated by CDK1 or CDK2. Ref.28
Mutagenesis4641T → D: Blocks interaction with FBXO11. Ref.28
Mutagenesis4651P → A: Inhibits phosphorylation on T-464. No effect on interaction with FBXO11. Ref.28
Mutagenesis4661T → A: No effect on interaction with FBXO11. Ref.28
Mutagenesis4661T → D: No effect on interaction with FBXO11. Ref.28
Mutagenesis4671F → A: No effect on interaction with FBXO11. Ref.28
Mutagenesis4681S → A: No effect on interaction with FBXO11. Ref.28
Mutagenesis4681S → D: No effect on interaction with FBXO11. Ref.28
Mutagenesis4711T → A: No effect on interaction with FBXO11. Ref.28
Mutagenesis4711T → D: No effect on interaction with FBXO11. Ref.28
Mutagenesis4721S → A: No effect on interaction with FBXO11. Ref.28
Mutagenesis4721S → D: No effect on interaction with FBXO11. Ref.28
Sequence conflict831S → P in BAA91355. Ref.4
Sequence conflict3561L → F in BAF85032. Ref.4
Sequence conflict5321I → T in BAA91552. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 10, 2010. Version 3.
Checksum: CE8D54234D44F002

FASTA73079,468
        10         20         30         40         50         60 
MLFNSVLRQP QLGVLRNGWS SQYPLQSLLT GYQCSGNDEH TSYGETGVPV PPFGCTFSSA 

        70         80         90        100        110        120 
PNMEHVLAVA NEEGFVRLYN TESQSFRKKC FKEWMAHWNA VFDLAWVPGE LKLVTAAGDQ 

       130        140        150        160        170        180 
TAKFWDVKAG ELIGTCKGHQ CSLKSVAFSK FEKAVFCTGG RDGNIMVWDT RCNKKDGFYR 

       190        200        210        220        230        240 
QVNQISGAHN TSDKQTPSKP KKKQNSKGLA PSVDFQQSVT VVLFQDENTL VSAGAVDGII 

       250        260        270        280        290        300 
KVWDLRKNYT AYRQEPIASK SFLYPGSSTR KLGYSSLILD STGSTLFANC TDDNIYMFNM 

       310        320        330        340        350        360 
TGLKTSPVAI FNGHQNSTFY VKSSLSPDDQ FLVSGSSDEA AYIWKVSTPW QPPTVLLGHS 

       370        380        390        400        410        420 
QEVTSVCWCP SDFTKIATCS DDNTLKIWRL NRGLEEKPGG DKLSTVGWAS QKKKESRPGL 

       430        440        450        460        470        480 
VTVTSSQSTP AKAPRAKCNP SNSSPSSAAC APSCAGDLPL PSNTPTFSIK TSPAKARSPI 

       490        500        510        520        530        540 
NRRGSVSSVS PKPPSSFKMS IRNWVTRTPS SSPPITPPAS ETKIMSPRKA LIPVSQKSSQ 

       550        560        570        580        590        600 
AEACSESRNR VKRRLDSSCL ESVKQKCVKS CNCVTELDGQ VENLHLDLCC LAGNQEDLSK 

       610        620        630        640        650        660 
DSLGPTKSSK IEGAGTSISE PPSPISPYAS ESCGTLPLPL RPCGEGSEMV GKENSSPENK 

       670        680        690        700        710        720 
NWLLAMAAKR KAENPSPRSP SSQTPNSRRQ SGKKLPSPVT ITPSSMRKIC TYFHRKSQED 

       730 
FCGPEHSTEL 

« Hide

Isoform 2 [UniParc].

Checksum: 23E4B52CFC514F80
Show »

FASTA21123,682

References

« Hide 'large scale' references
[1]"Cloning and expression of a novel nuclear matrix-associated protein that is regulated during the retinoic acid-induced neuronal differentiation."
Cheung W.M., Chu A.H., Chu P.W., Ip N.Y.
J. Biol. Chem. 276:17083-17091(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, VARIANTS VAL-436 AND THR-694.
[2]"L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage."
Higa L.A., Banks D., Wu M., Kobayashi R., Sun H., Zhang H.
Cell Cycle 5:1675-1680(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, IDENTIFICATION IN A DCX (DDB1-CUL4-X-BOX) E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY, VARIANTS VAL-436 AND THR-694.
[3]"Identification of L2DTL, a human WD-40 repeat gene homolog of the Drosophila lethal (2) denticleless heat shock gene [l(2)dtl]."
Mueller R., Ziegler B.L.
Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS VAL-436 AND THR-694.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS VAL-436 AND THR-694.
Tissue: Hepatoma, Teratocarcinoma and Testis.
[5]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT VAL-436.
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS VAL-436 AND THR-694.
Tissue: Lymph and Testis.
[8]"Role of L2DTL, cell cycle-regulated nuclear and centrosome protein, in aggressive hepatocellular carcinoma."
Pan H.W., Chou H.Y., Liu S.H., Peng S.Y., Liu C.L., Hsu H.C.
Cell Cycle 5:2676-2687(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, UBIQUITINATION.
[9]"DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint."
Sansam C.L., Shepard J.L., Lai K., Ianari A., Danielian P.S., Amsterdam A., Hopkins N., Lees J.A.
Genes Dev. 20:3117-3129(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A DCX (DDB1-CUL4-X-BOX) E3 UBIQUITIN-PROTEIN LIGASE COMPLEX.
[10]"A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1."
Jin J., Arias E.E., Chen J., Harper J.W., Walter J.C.
Mol. Cell 23:709-721(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DDB1, IDENTIFICATION IN A DCX (DDB1-CUL4-X-BOX) E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, MUTAGENESIS OF ARG-246.
[11]"CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation."
Higa L.A., Wu M., Ye T., Kobayashi R., Sun H., Zhang H.
Nat. Cell Biol. 8:1277-1283(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A DCX (DDB1-CUL4-X-BOX) E3 UBIQUITIN-PROTEIN LIGASE COMPLEX.
[12]"Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery."
Angers S., Li T., Yi X., MacCoss M.J., Moon R.T., Zheng N.
Nature 443:590-593(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex."
Abbas T., Sivaprasad U., Terai K., Amador V., Pagano M., Dutta A.
Genes Dev. 22:2496-2506(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A DCX (DDB1-CUL4-X-BOX) E3 UBIQUITIN-PROTEIN LIGASE COMPLEX.
[14]"The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to control replication licensing."
Kim Y., Starostina N.G., Kipreos E.T.
Genes Dev. 22:2507-2519(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A DCX (DDB1-CUL4-X-BOX) E3 UBIQUITIN-PROTEIN LIGASE COMPLEX.
[15]"CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation."
Nishitani H., Shiomi Y., Iida H., Michishita M., Takami T., Tsurimoto T.
J. Biol. Chem. 283:29045-29052(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-485; SER-490; SER-495; SER-512; THR-516; SER-557; SER-676; SER-679 AND THR-684, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[17]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Ionizing radiation induces ATM-independent degradation of p21Cip1 in transformed cells."
Stuart S.A., Wang J.Y.
J. Biol. Chem. 284:15061-15070(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-512 AND THR-516, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[20]"CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis."
Terai K., Abbas T., Jazaeri A.A., Dutta A.
Mol. Cell 37:143-149(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[21]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-410; SER-490; SER-512 AND THR-516, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-512 AND THR-516, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]"Regulation of TGF-beta signaling, exit from the cell cycle, and cellular migration through cullin cross-regulation: SCF-FBXO11 turns off CRL4-Cdt2."
Abbas T., Keaton M., Dutta A.
Cell Cycle 12:2175-2182(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[27]"CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-Set7/Set8-mediated cellular migration."
Abbas T., Mueller A.C., Shibata E., Keaton M., Rossi M., Dutta A.
Mol. Cell 49:1147-1158(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DDB1 AND FBXO11, INDUCTION, UBIQUITINATION, MUTAGENESIS OF ARG-246; ASP-457 AND SER-462.
[28]"Regulation of the CRL4(Cdt2) ubiquitin ligase and cell-cycle exit by the SCF(Fbxo11) ubiquitin ligase."
Rossi M., Duan S., Jeong Y.T., Horn M., Saraf A., Florens L., Washburn M.P., Antebi A., Pagano M.
Mol. Cell 49:1159-1166(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH FBXO11, IDENTIFICATION IN THE DCX(DTL) COMPLEX, UBIQUITINATION, PHOSPHORYLATION AT THR-464 BY CDK1 AND CDK2, MUTAGENESIS OF ASN-463; THR-464; PRO-465; THR-466; PHE-467; SER-468; THR-471 AND SER-472.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF345896 mRNA. Translation: AAK54706.1.
DQ641253 mRNA. Translation: ABG23317.1.
AF195765 mRNA. Translation: AAF35182.1.
AK000742 mRNA. Translation: BAA91355.1.
AK001206 mRNA. Translation: BAA91552.1. Different initiation.
AK001261 mRNA. Translation: BAA91586.1. Different initiation.
AK027651 mRNA. Translation: BAB55267.1.
AK292343 mRNA. Translation: BAF85032.1.
AL606468, AC092814, AL592297 Genomic DNA. Translation: CAH70697.1.
AL592297, AC092814, AL606468 Genomic DNA. Translation: CAH73803.1.
CH471100 Genomic DNA. Translation: EAW93395.1.
CH471100 Genomic DNA. Translation: EAW93397.1.
BC033540 mRNA. Translation: AAH33540.1.
BC033297 mRNA. Translation: AAH33297.1.
RefSeqNP_001273158.1. NM_001286229.1.
NP_057532.3. NM_016448.3.
UniGeneHs.656473.

3D structure databases

ProteinModelPortalQ9NZJ0.
SMRQ9NZJ0. Positions 9-393.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119582. 32 interactions.
IntActQ9NZJ0. 8 interactions.
STRING9606.ENSP00000355958.

PTM databases

PhosphoSiteQ9NZJ0.

Polymorphism databases

DMDM302393825.

Proteomic databases

PaxDbQ9NZJ0.
PRIDEQ9NZJ0.

Protocols and materials databases

DNASU51514.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000366991; ENSP00000355958; ENSG00000143476. [Q9NZJ0-1]
GeneID51514.
KEGGhsa:51514.
UCSCuc001hiz.4. human. [Q9NZJ0-1]

Organism-specific databases

CTD51514.
GeneCardsGC01P212208.
H-InvDBHIX0020157.
HGNCHGNC:30288. DTL.
HPAHPA028016.
HPA032023.
HPA032031.
HPA032032.
MIM610617. gene.
neXtProtNX_Q9NZJ0.
PharmGKBPA142671941.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2319.
HOVERGENHBG057737.
InParanoidQ9NZJ0.
KOK11790.
OMAICTYFHR.
OrthoDBEOG7W153G.
PhylomeDBQ9NZJ0.
TreeFamTF324483.

Enzyme and pathway databases

SignaLinkQ9NZJ0.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9NZJ0.
BgeeQ9NZJ0.
CleanExHS_DTL.
GenevestigatorQ9NZJ0.

Family and domain databases

Gene3D2.130.10.10. 1 hit.
InterProIPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamPF00400. WD40. 4 hits.
[Graphical view]
SMARTSM00320. WD40. 6 hits.
[Graphical view]
SUPFAMSSF50978. SSF50978. 2 hits.
PROSITEPS00678. WD_REPEATS_1. 2 hits.
PS50082. WD_REPEATS_2. 5 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiDTL_(gene).
GenomeRNAi51514.
NextBio55210.
PROQ9NZJ0.
SOURCESearch...

Entry information

Entry nameDTL_HUMAN
AccessionPrimary (citable) accession number: Q9NZJ0
Secondary accession number(s): A8K8H8 expand/collapse secondary AC list , D3DT98, Q5VT77, Q96SN0, Q9NW03, Q9NW34, Q9NWM5
Entry history
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: August 10, 2010
Last modified: April 16, 2014
This is version 112 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM