DCTD_HUMAN
ID DCTD_HUMAN Reviewed; 178 AA.
AC P32321; B2R836; D3DP49; D3DP50; Q5M7Z8; Q9BVD8;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2002, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Deoxycytidylate deaminase;
DE EC=3.5.4.12;
DE AltName: Full=dCMP deaminase;
GN Name=DCTD;
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] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=7685356; DOI=10.1016/s0021-9258(18)31483-2;
RA Weiner K.X., Weiner R.S., Maley F., Maley G.F.;
RT "Primary structure of human deoxycytidylate deaminase and overexpression of
RT its functional protein in Escherichia coli.";
RL J. Biol. Chem. 268:12983-12989(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Lung;
RX PubMed=7642519; DOI=10.1074/jbc.270.32.18727;
RA Weiner K.X., Ciesla J., Jaffe A.B., Ketring R., Maley F., Maley G.F.;
RT "Chromosomal location and structural organization of the human
RT deoxycytidylate deaminase gene.";
RL J. Biol. Chem. 270:18727-18729(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
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] (ISOFORMS 1 AND 2).
RC TISSUE=Cervix, and Testis;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-174, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 5-173 IN COMPLEX WITH ZINC.
RG Structural genomics consortium (SGC);
RT "The crystal structure of human dCMP deaminase.";
RL Submitted (NOV-2008) to the PDB data bank.
CC -!- FUNCTION: Supplies the nucleotide substrate for thymidylate synthetase.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dCMP + H(+) + H2O = dUMP + NH4(+); Xref=Rhea:RHEA:22924,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57566, ChEBI:CHEBI:246422; EC=3.5.4.12;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC -!- ACTIVITY REGULATION: Allosteric enzyme whose activity is greatly
CC influenced by the end products of its metabolic pathway, dCTP and dTTP.
CC -!- SUBUNIT: Homohexamer. {ECO:0000269|Ref.10}.
CC -!- INTERACTION:
CC P32321; O00154-4: ACOT7; NbExp=3; IntAct=EBI-739870, EBI-12007918;
CC P32321; P32321: DCTD; NbExp=5; IntAct=EBI-739870, EBI-739870;
CC P32321; P61328: FGF12; NbExp=3; IntAct=EBI-739870, EBI-6657662;
CC P32321; Q9H8Y8: GORASP2; NbExp=7; IntAct=EBI-739870, EBI-739467;
CC P32321; Q96EH3: MALSU1; NbExp=6; IntAct=EBI-739870, EBI-2339737;
CC P32321; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-739870, EBI-79165;
CC P32321; P25786: PSMA1; NbExp=3; IntAct=EBI-739870, EBI-359352;
CC P32321; O00560: SDCBP; NbExp=6; IntAct=EBI-739870, EBI-727004;
CC P32321; Q99757: TXN2; NbExp=3; IntAct=EBI-739870, EBI-2932492;
CC P32321; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-739870, EBI-10180829;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P32321-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P32321-2; Sequence=VSP_038094;
CC -!- SIMILARITY: Belongs to the cytidine and deoxycytidylate deaminase
CC family. {ECO:0000305}.
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DR EMBL; L12136; AAA35755.1; -; mRNA.
DR EMBL; L39874; AAC37579.1; -; Genomic_DNA.
DR EMBL; AK313221; BAG36033.1; -; mRNA.
DR EMBL; AC079766; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471056; EAX04697.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04698.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04700.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04701.1; -; Genomic_DNA.
DR EMBL; BC001286; AAH01286.1; -; mRNA.
DR EMBL; BC088357; AAH88357.2; -; mRNA.
DR CCDS; CCDS34108.1; -. [P32321-2]
DR CCDS; CCDS3831.1; -. [P32321-1]
DR PIR; A47288; A47288.
DR PIR; I55434; I55434.
DR RefSeq; NP_001012750.1; NM_001012732.1. [P32321-2]
DR RefSeq; NP_001912.2; NM_001921.2. [P32321-1]
DR RefSeq; XP_005262836.1; XM_005262779.3.
DR RefSeq; XP_005262837.1; XM_005262780.3.
DR RefSeq; XP_011529976.1; XM_011531674.2. [P32321-1]
DR RefSeq; XP_016863305.1; XM_017007816.1.
DR RefSeq; XP_016863306.1; XM_017007817.1.
DR RefSeq; XP_016863307.1; XM_017007818.1.
DR RefSeq; XP_016863308.1; XM_017007819.1.
DR RefSeq; XP_016863309.1; XM_017007820.1. [P32321-1]
DR RefSeq; XP_016863310.1; XM_017007821.1.
DR RefSeq; XP_016863311.1; XM_017007822.1. [P32321-1]
DR PDB; 2W4L; X-ray; 2.10 A; A/B/C/D/E/F=5-173.
DR PDBsum; 2W4L; -.
DR AlphaFoldDB; P32321; -.
DR SMR; P32321; -.
DR BioGRID; 108003; 21.
DR IntAct; P32321; 16.
DR MINT; P32321; -.
DR STRING; 9606.ENSP00000349576; -.
DR ChEMBL; CHEMBL5675; -.
DR DrugBank; DB00987; Cytarabine.
DR GlyGen; P32321; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P32321; -.
DR MetOSite; P32321; -.
DR PhosphoSitePlus; P32321; -.
DR BioMuta; DCTD; -.
DR DMDM; 23503055; -.
DR EPD; P32321; -.
DR jPOST; P32321; -.
DR MassIVE; P32321; -.
DR MaxQB; P32321; -.
DR PaxDb; P32321; -.
DR PeptideAtlas; P32321; -.
DR PRIDE; P32321; -.
DR ProteomicsDB; 54870; -. [P32321-1]
DR ProteomicsDB; 54871; -. [P32321-2]
DR Antibodypedia; 28704; 195 antibodies from 24 providers.
DR DNASU; 1635; -.
DR Ensembl; ENST00000357067.7; ENSP00000349576.3; ENSG00000129187.15. [P32321-2]
DR Ensembl; ENST00000438320.7; ENSP00000398194.2; ENSG00000129187.15. [P32321-1]
DR Ensembl; ENST00000510370.5; ENSP00000424017.1; ENSG00000129187.15. [P32321-1]
DR GeneID; 1635; -.
DR KEGG; hsa:1635; -.
DR MANE-Select; ENST00000438320.7; ENSP00000398194.2; NM_001921.3; NP_001912.2.
DR UCSC; uc003ivf.4; human. [P32321-1]
DR CTD; 1635; -.
DR DisGeNET; 1635; -.
DR GeneCards; DCTD; -.
DR HGNC; HGNC:2710; DCTD.
DR HPA; ENSG00000129187; Low tissue specificity.
DR MIM; 607638; gene.
DR neXtProt; NX_P32321; -.
DR OpenTargets; ENSG00000129187; -.
DR PharmGKB; PA138; -.
DR VEuPathDB; HostDB:ENSG00000129187; -.
DR eggNOG; KOG3127; Eukaryota.
DR GeneTree; ENSGT00940000153676; -.
DR InParanoid; P32321; -.
DR OrthoDB; 1569973at2759; -.
DR PhylomeDB; P32321; -.
DR TreeFam; TF105971; -.
DR BioCyc; MetaCyc:HS05252-MON; -.
DR PathwayCommons; P32321; -.
DR Reactome; R-HSA-499943; Interconversion of nucleotide di- and triphosphates.
DR SABIO-RK; P32321; -.
DR SignaLink; P32321; -.
DR BioGRID-ORCS; 1635; 15 hits in 1085 CRISPR screens.
DR ChiTaRS; DCTD; human.
DR EvolutionaryTrace; P32321; -.
DR GenomeRNAi; 1635; -.
DR Pharos; P32321; Tbio.
DR PRO; PR:P32321; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P32321; protein.
DR Bgee; ENSG00000129187; Expressed in stromal cell of endometrium and 196 other tissues.
DR ExpressionAtlas; P32321; baseline and differential.
DR Genevisible; P32321; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004132; F:dCMP deaminase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006231; P:dTMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0006226; P:dUMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0006220; P:pyrimidine nucleotide metabolic process; TAS:ProtInc.
DR CDD; cd01286; deoxycytidylate_deaminase; 1.
DR InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd.
DR InterPro; IPR002125; CMP_dCMP_dom.
DR InterPro; IPR016193; Cytidine_deaminase-like.
DR InterPro; IPR016473; dCMP_deaminase.
DR InterPro; IPR015517; dCMP_deaminase-rel.
DR InterPro; IPR035105; Deoxycytidylate_deaminase_dom.
DR PANTHER; PTHR11086; PTHR11086; 1.
DR Pfam; PF00383; dCMP_cyt_deam_1; 1.
DR PIRSF; PIRSF006019; dCMP_deaminase; 1.
DR SUPFAM; SSF53927; SSF53927; 1.
DR PROSITE; PS00903; CYT_DCMP_DEAMINASES_1; 1.
DR PROSITE; PS51747; CYT_DCMP_DEAMINASES_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Alternative splicing;
KW Direct protein sequencing; Hydrolase; Metal-binding;
KW Nucleotide biosynthesis; Phosphoprotein; Reference proteome; Zinc.
FT CHAIN 1..178
FT /note="Deoxycytidylate deaminase"
FT /id="PRO_0000171691"
FT DOMAIN 14..145
FT /note="CMP/dCMP-type deaminase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT ACT_SITE 86
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 84
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|Ref.10"
FT BINDING 110
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|Ref.10"
FT BINDING 113
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|Ref.10"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1
FT /note="M -> MVGGGQPCGPNM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038094"
FT CONFLICT 95
FT /note="S -> L (in Ref. 6; AAH01286)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="M -> T (in Ref. 1; AAA35755)"
FT /evidence="ECO:0000305"
FT HELIX 15..27
FT /evidence="ECO:0007829|PDB:2W4L"
FT STRAND 38..42
FT /evidence="ECO:0007829|PDB:2W4L"
FT STRAND 48..55
FT /evidence="ECO:0007829|PDB:2W4L"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:2W4L"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:2W4L"
FT TURN 79..81
FT /evidence="ECO:0007829|PDB:2W4L"
FT HELIX 85..91
FT /evidence="ECO:0007829|PDB:2W4L"
FT STRAND 102..107
FT /evidence="ECO:0007829|PDB:2W4L"
FT HELIX 111..119
FT /evidence="ECO:0007829|PDB:2W4L"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:2W4L"
FT TURN 131..134
FT /evidence="ECO:0007829|PDB:2W4L"
FT HELIX 136..148
FT /evidence="ECO:0007829|PDB:2W4L"
FT STRAND 151..154
FT /evidence="ECO:0007829|PDB:2W4L"
FT STRAND 160..165
FT /evidence="ECO:0007829|PDB:2W4L"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:2W4L"
SQ SEQUENCE 178 AA; 20016 MW; 2B8DA5EAC85F3666 CRC64;
MSEVSCKKRD DYLEWPEYFM AVAFLSAQRS KDPNSQVGAC IVNSENKIVG IGYNGMPNGC
SDDVLPWRRT AENKLDTKYP YVCHAELNAI MNKNSTDVKG CSMYVALFPC NECAKLIIQA
GIKEVIFMSD KYHDSDEATA ARLLFNMAGV TFRKFIPKCS KIVIDFDSIN SRPSQKLQ
