KCY_DICDI
ID KCY_DICDI Reviewed; 195 AA.
AC P20425; Q54KA2;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=UMP-CMP kinase {ECO:0000255|HAMAP-Rule:MF_03172};
DE EC=2.7.4.14 {ECO:0000255|HAMAP-Rule:MF_03172};
DE AltName: Full=Deoxycytidylate kinase {ECO:0000255|HAMAP-Rule:MF_03172};
DE Short=CK {ECO:0000255|HAMAP-Rule:MF_03172};
DE Short=dCMP kinase {ECO:0000255|HAMAP-Rule:MF_03172};
DE AltName: Full=Uridine monophosphate/cytidine monophosphate kinase {ECO:0000255|HAMAP-Rule:MF_03172};
DE Short=UMP/CMP kinase {ECO:0000255|HAMAP-Rule:MF_03172};
DE Short=UMP/CMPK {ECO:0000255|HAMAP-Rule:MF_03172};
GN Name=pyrK {ECO:0000255|HAMAP-Rule:MF_03172}; Synonyms=ctpS;
GN ORFNames=DDB_G0287495;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=2156849; DOI=10.1016/s0021-9258(19)39331-7;
RA Wiesmueller L., Noegel A.A., Barzu O., Gerisch G., Schleicher M.;
RT "cDNA-derived sequence of UMP-CMP kinase from Dictyostelium discoideum and
RT expression of the enzyme in Escherichia coli.";
RL J. Biol. Chem. 265:6339-6345(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2-195 IN COMPLEXES WITH SUBSTRATE
RP ANALOGS, AND COFACTOR.
RX PubMed=8703943; DOI=10.1021/bi960642s;
RA Scheffzek K., Kliche W., Wiesmuller L., Reinstein J.;
RT "Crystal structure of the complex of UMP/CMP kinase from Dictyostelium
RT discoideum and the bisubstrate inhibitor P1-(5'-adenosyl) P5-(5'-uridyl)
RT pentaphosphate (UP5A) and Mg2+ at 2.2-A: implications for water-mediated
RT specificity.";
RL Biochemistry 35:9716-9727(1996).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 2-195IN COMPLEX WITH ADP; CMP AND
RP UDP.
RX PubMed=9280438; DOI=10.1021/bi970974c;
RA Schlichting I., Reinstein J.;
RT "Structures of active conformations of UMP kinase from Dictyostelium
RT discoideum suggest phosphoryl transfer is associative.";
RL Biochemistry 36:9290-9296(1997).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 2-194 IN COMPLEX WITH ADP AND
RP CMP.
RX PubMed=10426946; DOI=10.1038/11485;
RA Schlichting I., Reinstein J.;
RT "pH influences fluoride coordination number of the AlFx phosphoryl transfer
RT transition state analog.";
RL Nat. Struct. Biol. 6:721-723(1999).
CC -!- FUNCTION: Catalyzes the phosphorylation of pyrimidine nucleoside
CC monophosphates at the expense of ATP. Plays an important role in de
CC novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP
CC as phosphate acceptors. {ECO:0000255|HAMAP-Rule:MF_03172,
CC ECO:0000269|PubMed:2156849}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CMP = ADP + CDP; Xref=Rhea:RHEA:11600,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58069, ChEBI:CHEBI:60377,
CC ChEBI:CHEBI:456216; EC=2.7.4.14; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03172, ECO:0000269|PubMed:2156849};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + dCMP = ADP + dCDP; Xref=Rhea:RHEA:25094,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57566, ChEBI:CHEBI:58593,
CC ChEBI:CHEBI:456216; EC=2.7.4.14; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03172, ECO:0000269|PubMed:2156849};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + UMP = ADP + UDP; Xref=Rhea:RHEA:24400,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57865, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:456216; EC=2.7.4.14; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03172, ECO:0000269|PubMed:2156849};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03172,
CC ECO:0000269|PubMed:8703943};
CC Note=Binds 1 Mg(2+) ion per monomer. The Mg(2+) ion binds to water and
CC substrates. {ECO:0000255|HAMAP-Rule:MF_03172,
CC ECO:0000269|PubMed:8703943};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=25 uM for ATP {ECO:0000269|PubMed:2156849};
CC KM=0.4 mM for UMP {ECO:0000269|PubMed:2156849};
CC KM=0.1 mM for CMP {ECO:0000269|PubMed:2156849};
CC -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_03172,
CC ECO:0000269|PubMed:10426946, ECO:0000269|PubMed:9280438}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03172}.
CC Nucleus {ECO:0000255|HAMAP-Rule:MF_03172}.
CC -!- DOMAIN: Consists of three domains, a large central CORE domain and two
CC small peripheral domains, NMPbind and LID, which undergo movements
CC during catalysis. The LID domain closes over the site of phosphoryl
CC transfer upon ATP binding. Assembling and dissambling the active center
CC during each catalytic cycle provides an effective means to prevent ATP
CC hydrolysis. {ECO:0000255|HAMAP-Rule:MF_03172,
CC ECO:0000305|PubMed:10426946, ECO:0000305|PubMed:8703943,
CC ECO:0000305|PubMed:9280438}.
CC -!- SIMILARITY: Belongs to the adenylate kinase family. UMP-CMP kinase
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_03172}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA33272.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M34568; AAA33272.1; ALT_INIT; mRNA.
DR EMBL; AAFI02000102; EAL63690.1; -; Genomic_DNA.
DR PIR; A35235; A35235.
DR RefSeq; XP_637196.1; XM_632104.1.
DR PDB; 1QF9; X-ray; 1.70 A; A=2-195.
DR PDB; 1UKE; X-ray; 2.20 A; A=2-195.
DR PDB; 2UKD; X-ray; 2.20 A; A=2-195.
DR PDB; 3UKD; X-ray; 1.90 A; A=2-195.
DR PDB; 4UKD; X-ray; 2.00 A; A=2-195.
DR PDB; 5UKD; X-ray; 1.90 A; A=2-195.
DR PDBsum; 1QF9; -.
DR PDBsum; 1UKE; -.
DR PDBsum; 2UKD; -.
DR PDBsum; 3UKD; -.
DR PDBsum; 4UKD; -.
DR PDBsum; 5UKD; -.
DR AlphaFoldDB; P20425; -.
DR SMR; P20425; -.
DR STRING; 44689.DDB0191367; -.
DR PaxDb; P20425; -.
DR PRIDE; P20425; -.
DR EnsemblProtists; EAL63690; EAL63690; DDB_G0287495.
DR GeneID; 8626154; -.
DR KEGG; ddi:DDB_G0287495; -.
DR dictyBase; DDB_G0287495; pyrK.
DR eggNOG; KOG3079; Eukaryota.
DR HOGENOM; CLU_032354_0_3_1; -.
DR InParanoid; P20425; -.
DR OMA; RFQFTHL; -.
DR PhylomeDB; P20425; -.
DR BRENDA; 2.7.4.14; 1939.
DR Reactome; R-DDI-499943; Interconversion of nucleotide di- and triphosphates.
DR SABIO-RK; P20425; -.
DR EvolutionaryTrace; P20425; -.
DR PRO; PR:P20425; -.
DR Proteomes; UP000002195; Chromosome 5.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IDA:dictyBase.
DR GO; GO:0036430; F:CMP kinase activity; IEA:RHEA.
DR GO; GO:0004127; F:cytidylate kinase activity; IDA:dictyBase.
DR GO; GO:0036431; F:dCMP kinase activity; IEA:RHEA.
DR GO; GO:0000287; F:magnesium ion binding; IDA:dictyBase.
DR GO; GO:0016776; F:phosphotransferase activity, phosphate group as acceptor; IDA:dictyBase.
DR GO; GO:0033862; F:UMP kinase activity; IDA:dictyBase.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IEA:InterPro.
DR GO; GO:0046705; P:CDP biosynthetic process; IDA:dictyBase.
DR GO; GO:0043173; P:nucleotide salvage; IDA:dictyBase.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0043100; P:pyrimidine nucleobase salvage; IDA:dictyBase.
DR GO; GO:0006225; P:UDP biosynthetic process; IDA:dictyBase.
DR CDD; cd01428; ADK; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_00235; Adenylate_kinase_Adk; 1.
DR HAMAP; MF_03172; Adenylate_kinase_UMP_CMP_kin; 1.
DR InterPro; IPR000850; Adenylat/UMP-CMP_kin.
DR InterPro; IPR033690; Adenylat_kinase_CS.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR006266; UMP_CMP_kinase.
DR PANTHER; PTHR23359; PTHR23359; 1.
DR PRINTS; PR00094; ADENYLTKNASE.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR01359; UMP_CMP_kin_fam; 1.
DR PROSITE; PS00113; ADENYLATE_KINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Nucleus;
KW Pyrimidine biosynthesis; Reference proteome; Transferase.
FT CHAIN 1..195
FT /note="UMP-CMP kinase"
FT /id="PRO_0000158948"
FT REGION 37..66
FT /note="NMP"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03172,
FT ECO:0000269|PubMed:10426946, ECO:0000269|PubMed:8703943,
FT ECO:0000269|PubMed:9280438"
FT REGION 131..141
FT /note="LID"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03172,
FT ECO:0000269|PubMed:10426946, ECO:0000269|PubMed:8703943,
FT ECO:0000269|PubMed:9280438"
FT BINDING 17..22
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03172,
FT ECO:0000269|PubMed:10426946, ECO:0000269|PubMed:8703943,
FT ECO:0000269|PubMed:9280438"
FT BINDING 43
FT /ligand="a ribonucleoside 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:58043"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03172,
FT ECO:0000269|PubMed:10426946, ECO:0000269|PubMed:8703943,
FT ECO:0000269|PubMed:9280438"
FT BINDING 64..66
FT /ligand="a ribonucleoside 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:58043"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03172,
FT ECO:0000269|PubMed:10426946, ECO:0000269|PubMed:8703943,
FT ECO:0000269|PubMed:9280438"
FT BINDING 91..94
FT /ligand="a ribonucleoside 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:58043"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03172,
FT ECO:0000269|PubMed:10426946, ECO:0000269|PubMed:8703943,
FT ECO:0000269|PubMed:9280438"
FT BINDING 98
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03172,
FT ECO:0000269|PubMed:10426946, ECO:0000269|PubMed:9280438"
FT BINDING 132
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03172,
FT ECO:0000269|PubMed:10426946, ECO:0000269|PubMed:8703943,
FT ECO:0000269|PubMed:9280438"
FT BINDING 138
FT /ligand="a ribonucleoside 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:58043"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03172,
FT ECO:0000269|PubMed:10426946, ECO:0000269|PubMed:9280438"
FT BINDING 149
FT /ligand="a ribonucleoside 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:58043"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03172,
FT ECO:0000269|PubMed:10426946, ECO:0000269|PubMed:8703943,
FT ECO:0000269|PubMed:9280438"
FT BINDING 177
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03172,
FT ECO:0000269|PubMed:10426946, ECO:0000269|PubMed:8703943,
FT ECO:0000269|PubMed:9280438"
FT STRAND 8..15
FT /evidence="ECO:0007829|PDB:1QF9"
FT HELIX 20..31
FT /evidence="ECO:0007829|PDB:1QF9"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:1QF9"
FT HELIX 38..47
FT /evidence="ECO:0007829|PDB:1QF9"
FT HELIX 53..61
FT /evidence="ECO:0007829|PDB:1QF9"
FT HELIX 68..80
FT /evidence="ECO:0007829|PDB:1QF9"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:1QF9"
FT HELIX 96..106
FT /evidence="ECO:0007829|PDB:1QF9"
FT TURN 107..109
FT /evidence="ECO:0007829|PDB:1QF9"
FT STRAND 111..119
FT /evidence="ECO:0007829|PDB:1QF9"
FT HELIX 122..133
FT /evidence="ECO:0007829|PDB:1QF9"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:1UKE"
FT HELIX 143..155
FT /evidence="ECO:0007829|PDB:1QF9"
FT HELIX 157..166
FT /evidence="ECO:0007829|PDB:1QF9"
FT STRAND 170..174
FT /evidence="ECO:0007829|PDB:1QF9"
FT HELIX 179..192
FT /evidence="ECO:0007829|PDB:1QF9"
SQ SEQUENCE 195 AA; 22074 MW; 076C6780DDC1C0F0 CRC64;
MMEKSKPNVV FVLGGPGSGK GTQCANIVRD FGWVHLSAGD LLRQEQQSGS KDGEMIATMI
KNGEIVPSIV TVKLLKNAID ANQGKNFLVD GFPRNEENNN SWEENMKDFV DTKFVLFFDC
PEEVMTQRLL KRGESSGRSD DNIESIKKRF NTFNVQTKLV IDHYNKFDKV KIIPANRDVN
EVYNDVENLF KSMGF
