CDD_HUMAN
ID CDD_HUMAN Reviewed; 146 AA.
AC P32320;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Cytidine deaminase {ECO:0000305};
DE EC=3.5.4.5 {ECO:0000269|PubMed:7923172, ECO:0000269|PubMed:9596658};
DE AltName: Full=Cytidine aminohydrolase;
GN Name=CDA {ECO:0000312|HGNC:HGNC:1712}; Synonyms=CDD;
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], CATALYTIC ACTIVITY, AND FUNCTION.
RC TISSUE=Liver;
RX PubMed=7923172;
RA Laliberte J., Momparler R.L.;
RT "Human cytidine deaminase: purification of enzyme, cloning, and expression
RT of its complementary DNA.";
RL Cancer Res. 54:5401-5407(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9878810; DOI=10.1016/s0167-4781(98)00235-8;
RA Demontis S., Terao M., Brivio M., Zanotta S., Bruschi M., Garattini E.;
RT "Isolation and characterization of the gene coding for human cytidine
RT deaminase.";
RL Biochim. Biophys. Acta 1443:323-333(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Blood;
RX PubMed=9596658;
RA Gran C., Boyum A., Johansen R.F., Lovhaug D., Seeberg E.C.;
RT "Growth inhibition of granulocyte-macrophage colony forming cells by human
RT cytidine deaminase requires the catalytic function of the protein.";
RL Blood 91:4127-4135(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-27.
RC TISSUE=Liver;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-146, AND VARIANT GLN-27.
RX PubMed=8422236; DOI=10.1006/bbrc.1993.1001;
RA Kuhn K., Bertling W.M., Emmrich F.;
RT "Cloning of a functional cDNA for human cytidine deaminase (CDD) and its
RT use as a marker of monocyte/macrophage differentiation.";
RL Biochem. Biophys. Res. Commun. 190:1-7(1993).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 7-146 IN COMPLEX WITH SUBSTRATE
RP ANALOG AND ZINC IONS, AND SUBUNIT.
RX PubMed=15689149; DOI=10.1021/jm0496279;
RA Chung S.J., Fromme J.C., Verdine G.L.;
RT "Structure of human cytidine deaminase bound to a potent inhibitor.";
RL J. Med. Chem. 48:658-660(2005).
CC -!- FUNCTION: This enzyme scavenges exogenous and endogenous cytidine and
CC 2'-deoxycytidine for UMP synthesis. {ECO:0000269|PubMed:7923172,
CC ECO:0000269|PubMed:9596658}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cytidine + H(+) + H2O = NH4(+) + uridine;
CC Xref=Rhea:RHEA:16069, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16704, ChEBI:CHEBI:17562, ChEBI:CHEBI:28938; EC=3.5.4.5;
CC Evidence={ECO:0000269|PubMed:7923172};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2'-deoxycytidine + H(+) + H2O = 2'-deoxyuridine + NH4(+);
CC Xref=Rhea:RHEA:13433, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15698, ChEBI:CHEBI:16450, ChEBI:CHEBI:28938; EC=3.5.4.5;
CC Evidence={ECO:0000269|PubMed:9596658};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13434;
CC Evidence={ECO:0000305|PubMed:9596658};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:15689149}.
CC -!- INTERACTION:
CC P32320; Q96EY9: ADAT3; NbExp=3; IntAct=EBI-9250559, EBI-3922811;
CC P32320; Q96B67: ARRDC3; NbExp=5; IntAct=EBI-9250559, EBI-2875665;
CC P32320; P32320: CDA; NbExp=4; IntAct=EBI-9250559, EBI-9250559;
CC P32320; Q96D03: DDIT4L; NbExp=5; IntAct=EBI-9250559, EBI-742054;
CC P32320; Q9BVV2: FNDC11; NbExp=6; IntAct=EBI-9250559, EBI-744935;
CC P32320; O15353: FOXN1; NbExp=3; IntAct=EBI-9250559, EBI-11319000;
CC P32320; Q9H8Y8: GORASP2; NbExp=3; IntAct=EBI-9250559, EBI-739467;
CC P32320; Q0VD86: INCA1; NbExp=3; IntAct=EBI-9250559, EBI-6509505;
CC P32320; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-9250559, EBI-12111050;
CC P32320; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-9250559, EBI-10261141;
CC P32320; Q8TBB1: LNX1; NbExp=9; IntAct=EBI-9250559, EBI-739832;
CC P32320; Q96HA8: NTAQ1; NbExp=9; IntAct=EBI-9250559, EBI-741158;
CC P32320; Q96CS7: PLEKHB2; NbExp=6; IntAct=EBI-9250559, EBI-373552;
CC P32320; P25786: PSMA1; NbExp=3; IntAct=EBI-9250559, EBI-359352;
CC P32320; P43115-12: PTGER3; NbExp=3; IntAct=EBI-9250559, EBI-10234038;
CC P32320; O00560: SDCBP; NbExp=6; IntAct=EBI-9250559, EBI-727004;
CC P32320; O43167: ZBTB24; NbExp=6; IntAct=EBI-9250559, EBI-744471;
CC -!- TISSUE SPECIFICITY: Highly expressed in granulocytes while expression
CC is very low in fibroblasts, chondrocytes, monocytes, and T- as well as
CC B-cell lines.
CC -!- SIMILARITY: Belongs to the cytidine and deoxycytidylate deaminase
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CDAID998ch1p36.html";
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DR EMBL; L27943; AAA57254.1; -; mRNA.
DR EMBL; AF061658; AAD15828.1; -; Genomic_DNA.
DR EMBL; AF061655; AAD15828.1; JOINED; Genomic_DNA.
DR EMBL; AF061656; AAD15828.1; JOINED; Genomic_DNA.
DR EMBL; AF061657; AAD15828.1; JOINED; Genomic_DNA.
DR EMBL; AJ000474; CAA04113.1; -; mRNA.
DR EMBL; AL391357; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC054036; AAH54036.1; -; mRNA.
DR EMBL; S52873; AAB24946.1; -; mRNA.
DR CCDS; CCDS210.1; -.
DR PIR; I52710; I52710.
DR RefSeq; NP_001776.1; NM_001785.2.
DR PDB; 1MQ0; X-ray; 2.40 A; A/B=11-146.
DR PDBsum; 1MQ0; -.
DR AlphaFoldDB; P32320; -.
DR SMR; P32320; -.
DR BioGRID; 107416; 51.
DR IntAct; P32320; 27.
DR STRING; 9606.ENSP00000364212; -.
DR BindingDB; P32320; -.
DR ChEMBL; CHEMBL4502; -.
DR DrugBank; DB03185; 1-Beta-Ribofuranosyl-1,3-Diazepinone.
DR DrugBank; DB00928; Azacitidine.
DR DrugBank; DB01101; Capecitabine.
DR DrugBank; DB15694; Cedazuridine.
DR DrugBank; DB00987; Cytarabine.
DR DrugBank; DB01262; Decitabine.
DR DrugBank; DB00441; Gemcitabine.
DR GuidetoPHARMACOLOGY; 3133; -.
DR iPTMnet; P32320; -.
DR PhosphoSitePlus; P32320; -.
DR BioMuta; CDA; -.
DR DMDM; 1705718; -.
DR EPD; P32320; -.
DR jPOST; P32320; -.
DR MassIVE; P32320; -.
DR MaxQB; P32320; -.
DR PaxDb; P32320; -.
DR PeptideAtlas; P32320; -.
DR PRIDE; P32320; -.
DR ProteomicsDB; 54869; -.
DR TopDownProteomics; P32320; -.
DR Antibodypedia; 29806; 322 antibodies from 30 providers.
DR DNASU; 978; -.
DR Ensembl; ENST00000375071.4; ENSP00000364212.3; ENSG00000158825.6.
DR GeneID; 978; -.
DR KEGG; hsa:978; -.
DR MANE-Select; ENST00000375071.4; ENSP00000364212.3; NM_001785.3; NP_001776.1.
DR UCSC; uc001bdk.4; human.
DR CTD; 978; -.
DR DisGeNET; 978; -.
DR GeneCards; CDA; -.
DR HGNC; HGNC:1712; CDA.
DR HPA; ENSG00000158825; Tissue enhanced (bone marrow, esophagus, liver).
DR MIM; 123920; gene.
DR neXtProt; NX_P32320; -.
DR OpenTargets; ENSG00000158825; -.
DR PharmGKB; PA98; -.
DR VEuPathDB; HostDB:ENSG00000158825; -.
DR eggNOG; KOG0833; Eukaryota.
DR GeneTree; ENSGT00390000000911; -.
DR HOGENOM; CLU_097262_1_2_1; -.
DR InParanoid; P32320; -.
DR OMA; LTHFTCV; -.
DR OrthoDB; 1400471at2759; -.
DR PhylomeDB; P32320; -.
DR TreeFam; TF314486; -.
DR BioCyc; MetaCyc:HS08334-MON; -.
DR BRENDA; 3.5.4.5; 2681.
DR PathwayCommons; P32320; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-73614; Pyrimidine salvage.
DR SABIO-RK; P32320; -.
DR SignaLink; P32320; -.
DR BioGRID-ORCS; 978; 16 hits in 1072 CRISPR screens.
DR ChiTaRS; CDA; human.
DR EvolutionaryTrace; P32320; -.
DR GeneWiki; Cytidine_deaminase; -.
DR GenomeRNAi; 978; -.
DR Pharos; P32320; Tclin.
DR PRO; PR:P32320; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P32320; protein.
DR Bgee; ENSG00000158825; Expressed in lower esophagus mucosa and 113 other tissues.
DR Genevisible; P32320; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR GO; GO:0004126; F:cytidine deaminase activity; IDA:UniProtKB.
DR GO; GO:0047844; F:deoxycytidine deaminase activity; IEA:RHEA.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0001882; F:nucleoside binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0071217; P:cellular response to external biotic stimulus; IEA:Ensembl.
DR GO; GO:0009972; P:cytidine deamination; IDA:UniProtKB.
DR GO; GO:0019858; P:cytosine metabolic process; TAS:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0045980; P:negative regulation of nucleotide metabolic process; IDA:UniProtKB.
DR GO; GO:0008655; P:pyrimidine-containing compound salvage; NAS:UniProtKB.
DR GO; GO:0046898; P:response to cycloheximide; IEA:Ensembl.
DR GO; GO:0044206; P:UMP salvage; IEA:Ensembl.
DR InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd.
DR InterPro; IPR002125; CMP_dCMP_dom.
DR InterPro; IPR006262; Cyt_deam_tetra.
DR InterPro; IPR016193; Cytidine_deaminase-like.
DR Pfam; PF00383; dCMP_cyt_deam_1; 1.
DR SUPFAM; SSF53927; SSF53927; 1.
DR TIGRFAMs; TIGR01354; cyt_deam_tetra; 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; Hydrolase; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..146
FT /note="Cytidine deaminase"
FT /id="PRO_0000171682"
FT DOMAIN 13..140
FT /note="CMP/dCMP-type deaminase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT ACT_SITE 67
FT /note="Proton donor"
FT BINDING 54..60
FT /ligand="substrate"
FT BINDING 65
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 102
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT VARIANT 27
FT /note="K -> Q (in dbSNP:rs2072671)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8422236"
FT /id="VAR_021559"
FT HELIX 15..25
FT /evidence="ECO:0007829|PDB:1MQ0"
FT HELIX 26..28
FT /evidence="ECO:0007829|PDB:1MQ0"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:1MQ0"
FT STRAND 38..43
FT /evidence="ECO:0007829|PDB:1MQ0"
FT STRAND 49..53
FT /evidence="ECO:0007829|PDB:1MQ0"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:1MQ0"
FT HELIX 66..76
FT /evidence="ECO:0007829|PDB:1MQ0"
FT STRAND 83..90
FT /evidence="ECO:0007829|PDB:1MQ0"
FT HELIX 100..107
FT /evidence="ECO:0007829|PDB:1MQ0"
FT STRAND 111..118
FT /evidence="ECO:0007829|PDB:1MQ0"
FT STRAND 124..128
FT /evidence="ECO:0007829|PDB:1MQ0"
FT HELIX 129..132
FT /evidence="ECO:0007829|PDB:1MQ0"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:1MQ0"
SQ SEQUENCE 146 AA; 16185 MW; AF33D09EE4E176B3 CRC64;
MAQKRPACTL KPECVQQLLV CSQEAKKSAY CPYSHFPVGA ALLTQEGRIF KGCNIENACY
PLGICAERTA IQKAVSEGYK DFRAIAIASD MQDDFISPCG ACRQVMREFG TNWPVYMTKP
DGTYIVMTVQ ELLPSSFGPE DLQKTQ
