DCA12_HUMAN
ID DCA12_HUMAN Reviewed; 453 AA.
AC Q5T6F0; A8KA70; D3DRL6; Q5T6E9; Q5T6F1; Q6P3V0; Q7L4F8; Q96PZ5; Q9NXA9;
AC Q9UFJ1;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=DDB1- and CUL4-associated factor 12 {ECO:0000305};
DE AltName: Full=Centrosome-related protein TCC52 {ECO:0000303|PubMed:18957058};
DE AltName: Full=Testis cancer centrosome-related protein {ECO:0000303|PubMed:18957058};
DE AltName: Full=WD repeat-containing protein 40A {ECO:0000312|HGNC:HGNC:19911};
GN Name=DCAF12 {ECO:0000303|PubMed:16949367, ECO:0000312|HGNC:HGNC:19911};
GN Synonyms=KIAA1892 {ECO:0000303|PubMed:11572484},
GN TCC52 {ECO:0000303|PubMed:18957058}, WDR40A {ECO:0000312|HGNC:HGNC:19911};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA He D., Li S., Hu X., Luo C., Ceng C.;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11572484; DOI=10.1093/dnares/8.4.179;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXI. The
RT complete sequences of 60 new cDNA clones from brain which code for large
RT proteins.";
RL DNA Res. 8:179-187(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hepatoma, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-131.
RC TISSUE=Lymph, and PNS;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 179-453.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP FUNCTION, INTERACTION WITH DDB1, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP MUTAGENESIS OF ARG-368.
RX PubMed=16949367; DOI=10.1016/j.molcel.2006.08.010;
RA Jin J., Arias E.E., Chen J., Harper J.W., Walter J.C.;
RT "A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is
RT required for S phase destruction of the replication factor Cdt1.";
RL Mol. Cell 23:709-721(2006).
RN [9]
RP FUNCTION.
RX PubMed=16964240; DOI=10.1038/nature05175;
RA Angers S., Li T., Yi X., MacCoss M.J., Moon R.T., Zheng N.;
RT "Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase
RT machinery.";
RL Nature 443:590-593(2006).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=18957058; DOI=10.1111/j.1349-7006.2008.00937.x;
RA Li S., Hu X., Cui S., He D.;
RT "Novel centrosome protein, TCC52, is a cancer-testis antigen.";
RL Cancer Sci. 99:2274-2279(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP FUNCTION, PATHWAY, AND IDENTIFICATION IN A DCX E3 UBIQUITIN-PROTEIN LIGASE
RP COMPLEX.
RX PubMed=29779948; DOI=10.1016/j.cell.2018.04.028;
RA Koren I., Timms R.T., Kula T., Xu Q., Li M.Z., Elledge S.J.;
RT "The eukaryotic proteome is shaped by E3 ubiquitin ligases targeting C-
RT terminal degrons.";
RL Cell 173:1622-1635(2018).
RN [13]
RP FUNCTION, PATHWAY, AND IDENTIFICATION IN A DCX E3 UBIQUITIN-PROTEIN LIGASE
RP COMPLEX.
RX PubMed=31267705; DOI=10.15252/embr.201847352;
RA Ravichandran R., Kodali K., Peng J., Potts P.R.;
RT "Regulation of MAGE-A3/6 by the CRL4-DCAF12 ubiquitin ligase and nutrient
RT availability.";
RL EMBO Rep. 20:e47352-e47352(2019).
RN [14] {ECO:0007744|PDB:3I7P}
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 45-57.
RX PubMed=19966799; DOI=10.1038/nsmb.1719;
RA Li T., Robert E.I., van Breugel P.C., Strubin M., Zheng N.;
RT "A promiscuous alpha-helical motif anchors viral hijackers and substrate
RT receptors to the CUL4-DDB1 ubiquitin ligase machinery.";
RL Nat. Struct. Mol. Biol. 17:105-111(2010).
CC -!- FUNCTION: Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3
CC ubiquitin-protein ligase complex of the DesCEND (destruction via C-end
CC degrons) pathway, which recognizes a C-degron located at the extreme C
CC terminus of target proteins, leading to their ubiquitination and
CC degradation (PubMed:16949367, PubMed:16964240, PubMed:29779948). The C-
CC degron recognized by the DesCEND pathway is usually a motif of less
CC than ten residues and can be present in full-length proteins, truncated
CC proteins or proteolytically cleaved forms (PubMed:29779948). The
CC DCX(DCAF12) complex specifically recognizes proteins with a diglutamate
CC (Glu-Glu) at the C-terminus, such as MAGEA3, MAGEA6 and CCT5, leading
CC to their ubiquitination and degradation (PubMed:29779948,
CC PubMed:31267705). Ubiquitination of MAGEA3, MAGEA6 by DCX(DCAF12)
CC complex is required for starvation-induced autophagy (PubMed:31267705).
CC {ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240,
CC ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:31267705}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:31267705}.
CC -!- SUBUNIT: Component of the DCX(DCAF12) E3 ubiquitin ligase complex, at
CC least composed of CUL4 (CUL4A or CUL4B), DDB1, DCAF12 and RBX1.
CC {ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240,
CC ECO:0000269|PubMed:31267705}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18957058}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:18957058}.
CC -!- TISSUE SPECIFICITY: Highly expressed in lung cancer tissues and some
CC cancer cell lines (PubMed:18957058). Restricted expression in normal
CC testis (PubMed:18957058). {ECO:0000269|PubMed:18957058}.
CC -!- SIMILARITY: Belongs to the WD repeat DCAF12 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91106.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB67785.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; DQ518909; ABG24246.1; -; mRNA.
DR EMBL; AB067479; BAB67785.1; ALT_INIT; mRNA.
DR EMBL; AK000354; BAA91106.1; ALT_FRAME; mRNA.
DR EMBL; AK292935; BAF85624.1; -; mRNA.
DR EMBL; AL354989; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58472.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58473.1; -; Genomic_DNA.
DR EMBL; BC008893; AAH08893.2; -; mRNA.
DR EMBL; BC063823; AAH63823.1; -; mRNA.
DR EMBL; AL117646; CAB56028.2; -; mRNA.
DR CCDS; CCDS6549.1; -.
DR PIR; T17338; T17338.
DR RefSeq; NP_056212.1; NM_015397.3.
DR RefSeq; XP_011516145.1; XM_011517843.1.
DR PDB; 3I7P; X-ray; 3.00 A; B=45-57.
DR PDBsum; 3I7P; -.
DR AlphaFoldDB; Q5T6F0; -.
DR SMR; Q5T6F0; -.
DR BioGRID; 117377; 32.
DR DIP; DIP-48760N; -.
DR IntAct; Q5T6F0; 18.
DR STRING; 9606.ENSP00000355114; -.
DR iPTMnet; Q5T6F0; -.
DR PhosphoSitePlus; Q5T6F0; -.
DR BioMuta; DCAF12; -.
DR DMDM; 74756352; -.
DR EPD; Q5T6F0; -.
DR jPOST; Q5T6F0; -.
DR MassIVE; Q5T6F0; -.
DR MaxQB; Q5T6F0; -.
DR PaxDb; Q5T6F0; -.
DR PeptideAtlas; Q5T6F0; -.
DR PRIDE; Q5T6F0; -.
DR ProteomicsDB; 64578; -.
DR Antibodypedia; 2916; 138 antibodies from 25 providers.
DR DNASU; 25853; -.
DR Ensembl; ENST00000361264.9; ENSP00000355114.3; ENSG00000198876.13.
DR GeneID; 25853; -.
DR KEGG; hsa:25853; -.
DR MANE-Select; ENST00000361264.9; ENSP00000355114.3; NM_015397.4; NP_056212.1.
DR UCSC; uc003ztt.3; human.
DR CTD; 25853; -.
DR DisGeNET; 25853; -.
DR GeneCards; DCAF12; -.
DR HGNC; HGNC:19911; DCAF12.
DR HPA; ENSG00000198876; Low tissue specificity.
DR neXtProt; NX_Q5T6F0; -.
DR OpenTargets; ENSG00000198876; -.
DR PharmGKB; PA165585735; -.
DR VEuPathDB; HostDB:ENSG00000198876; -.
DR eggNOG; ENOG502QR7U; Eukaryota.
DR GeneTree; ENSGT00940000158028; -.
DR HOGENOM; CLU_020124_1_0_1; -.
DR InParanoid; Q5T6F0; -.
DR OMA; FDMCWLD; -.
DR OrthoDB; 885170at2759; -.
DR PhylomeDB; Q5T6F0; -.
DR TreeFam; TF323731; -.
DR PathwayCommons; Q5T6F0; -.
DR SignaLink; Q5T6F0; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 25853; 19 hits in 1116 CRISPR screens.
DR ChiTaRS; DCAF12; human.
DR EvolutionaryTrace; Q5T6F0; -.
DR GenomeRNAi; 25853; -.
DR Pharos; Q5T6F0; Tbio.
DR PRO; PR:Q5T6F0; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q5T6F0; protein.
DR Bgee; ENSG00000198876; Expressed in trabecular bone tissue and 187 other tissues.
DR ExpressionAtlas; Q5T6F0; baseline and differential.
DR Genevisible; Q5T6F0; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0010506; P:regulation of autophagy; IDA:UniProtKB.
DR GO; GO:0140627; P:ubiquitin-dependent protein catabolic process via the C-end degron rule pathway; IDA:UniProtKB.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR SMART; SM00320; WD40; 4.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Cytoskeleton; Phosphoprotein; Reference proteome;
KW Repeat; Ubl conjugation pathway; WD repeat.
FT CHAIN 1..453
FT /note="DDB1- and CUL4-associated factor 12"
FT /id="PRO_0000306840"
FT REPEAT 81..122
FT /note="WD 1"
FT REPEAT 123..175
FT /note="WD 2"
FT REPEAT 176..242
FT /note="WD 3"
FT REPEAT 243..286
FT /note="WD 4"
FT REPEAT 287..331
FT /note="WD 5"
FT REPEAT 332..366
FT /note="WD 6"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 131
FT /note="R -> Q (in dbSNP:rs11557154)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_035322"
FT MUTAGEN 368
FT /note="R->A: Reduces association with DDB1."
FT /evidence="ECO:0000269|PubMed:16949367"
FT CONFLICT 149
FT /note="N -> H (in Ref. 3; BAA91106)"
FT /evidence="ECO:0000305"
FT HELIX 47..55
FT /evidence="ECO:0007829|PDB:3I7P"
SQ SEQUENCE 453 AA; 50517 MW; 07F3738BA6BB5355 CRC64;
MARKVVSRKR KAPASPGAGS DAQGPQFGWD HSLHKRKRLP PVKRSLVYYL KNREVRLQNE
TSYSRVLHGY AAQQLPSLLK EREFHLGTLN KVFASQWLNH RQVVCGTKCN TLFVVDVQTS
QITKIPILKD REPGGVTQQG CGIHAIELNP SRTLLATGGD NPNSLAIYRL PTLDPVCVGD
DGHKDWIFSI AWISDTMAVS GSRDGSMGLW EVTDDVLTKS DARHNVSRVP VYAHITHKAL
KDIPKEDTNP DNCKVRALAF NNKNKELGAV SLDGYFHLWK AENTLSKLLS TKLPYCRENV
CLAYGSEWSV YAVGSQAHVS FLDPRQPSYN VKSVCSRERG SGIRSVSFYE HIITVGTGQG
SLLFYDIRAQ RFLEERLSAC YGSKPRLAGE NLKLTTGKGW LNHDETWRNY FSDIDFFPNA
VYTHCYDSSG TKLFVAGGPL PSGLHGNYAG LWS
