DB code: S00680

RLCP classification 3.103.70035.360 : Transfer
CATH domain 3.40.50.300 : Rossmann fold Catalytic domain
E.C. 2.7.1.48
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.300 : Rossmann fold S00527 S00547 S00548 S00550 S00554 S00555 S00671 S00672 S00676 S00682 S00913 S00914 S00301 S00302 S00303 S00304 S00307 S00308 S00305 S00306 S00309 S00310 S00311 M00114 M00199 D00129 D00130 D00540 M00186

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q9BZX2 Uridine-cytidine kinase 2
UCK 2
EC 2.7.1.48
Uridine monophosphokinase 2
Cytidine monophosphokinase 2
NP_036606.2 (Protein)
NM_012474.4 (DNA/RNA sequence)
PF00485 (PRK)
[Graphical View]
Q9HA47 Uridine-cytidine kinase 1
UCK 1
EC 2.7.1.48
Uridine monophosphokinase 1
Cytidine monophosphokinase 1
NP_001129426.1 (Protein)
NM_001135954.1 (DNA/RNA sequence)
NP_001248379.1 (Protein)
NM_001261450.1 (DNA/RNA sequence)
NP_001248380.1 (Protein)
NM_001261451.1 (DNA/RNA sequence)
NP_113620.1 (Protein)
NM_031432.2 (DNA/RNA sequence)
PF00485 (PRK)
[Graphical View]

KEGG enzyme name
Uridine kinase
Pyrimidine ribonucleoside kinase
Uridine-cytidine kinase
Uridine kinase (phosphorylating)
Uridine phosphokinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q9BZX2 UCK2_HUMAN ATP + uridine = ADP + UMP. ATP + cytidine = ADP + CMP. Homotetramer.
Q9HA47 UCK1_HUMAN ATP + uridine = ADP + UMP. ATP + cytidine = ADP + CMP.

KEGG Pathways
Map code Pathways E.C.
MAP00240 Pyrimidine metabolism
MAP00983 Drug metabolism - other enzymes

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00299 C00475 C00008 C00105 C00055
E.C.
Compound Magnesium ATP Uridine Cytidine ADP UMP CMP
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide amide group,nucleoside amine group,nucleoside amine group,nucleotide amide group,nucleotide amine group,nucleotide
ChEBI 18420
 18420
 		15422
 15422
 		16704
 16704
 		17562
 17562
 		16761
 16761
 		16695
 16695
 		17361
 17361
PubChem 888
 888
 		5957
 5957
 		6029
 6029
 		6175
 6175
 		6022
 6022
 		6030
 6030
 		6131
 6131
1udwA00 Unbound Unbound Unbound Unbound Unbound Unbound Analogue:CTP
1udwB00 Unbound Unbound Unbound Unbound Unbound Unbound Analogue:CTP
1ueiA00 Unbound Unbound Unbound Unbound Unbound Analogue:UTP Unbound
1ueiB00 Unbound Unbound Unbound Unbound Unbound Analogue:UTP Unbound
1uejA00 Unbound Unbound Unbound Bound:CTN Unbound Unbound Unbound
1uejB00 Unbound Unbound Unbound Bound:CTN Unbound Unbound Unbound
1ufqA00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ufqB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ufqC00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ufqD00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1uj2A00 Bound:_MG Unbound Unbound Unbound Bound:ADP Unbound Bound:C5P
1uj2B00 Bound:_MG Unbound Unbound Unbound Bound:ADP Unbound Bound:C5P
1xrjA00 Bound:_MG Unbound Unbound Unbound Bound:ADP Unbound Bound:C5P
1xrjB00 Bound:_MG Unbound Unbound Unbound Bound:ADP Unbound Bound:C5P
2jeoA00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2uvqA00 Unbound Unbound Unbound Unbound Bound:ADP Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [3] & [5]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1udwA00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33 invisible 45-52
1udwB00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33 invisible 47-50
1ueiA00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33 invisible 45-52
1ueiB00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33 invisible 47-50
1uejA00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33 invisible 47-52
1uejB00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33 invisible 47-52
1ufqA00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33
1ufqB00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33
1ufqC00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33
1ufqD00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33
1uj2A00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33
1uj2B00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33
1xrjA00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33
1xrjB00 LYS 33;ASP 62;ARG 169;ARG 174 SER 34(Magnesium binding) ALA 30;SER 31;GLY 32;LYS 33
2jeoA00 LYS 36;ASP 65;ARG 172; SER 37(Magnesium binding) ALA 33;SER 34;GLY 35;LYS 36 invisible 176-178
2uvqA00 LYS 36;ASP 65;ARG 172; SER 37(Magnesium binding) ALA 33;SER 34;GLY 35;LYS 36 invisible 176-178

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
p.762
[5]
Fig.1, p. 2716, Fig.7, p.2720

References
[1]
Resource
Comments
Medline ID
PubMed ID 7914091
Journal Biochemistry
Year 1994
Volume 33
Pages 9343-50
Authors Charlier HA Jr, Runquist JA, Miziorko HM
Title Evidence supporting catalytic roles for aspartate residues in phosphoribulokinase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 11306702
Journal Mol Pharmacol
Year 2001
Volume 59
Pages 1181-6
Authors Van Rompay AR, Norda A, Linden K, Johansson M, Karlsson A
Title Phosphorylation of uridine and cytidine nucleoside analogs by two human uridine-cytidine kinases.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 15130468
Journal Structure
Year 2004
Volume 12
Pages 751-64
Authors Suzuki NN, Koizumi K, Fukushima M, Matsuda A, Inagaki F
Title Structural basis for the specificity, catalysis, and regulation of human uridine-cytidine kinase.
Related PDB 1udw 1uei 1uej 1ufq iuj2
Related UniProtKB Q9BZX2
[4]
Resource
Comments
Medline ID
PubMed ID 15735337
Journal Acta Crystallogr D Biol Crystallogr
Year 2005
Volume 61
Pages 278-84
Authors Appleby TC, Larson G, Cheney IW, Walker H, Wu JZ, Zhong W, Hong Z, Yao N
Title Structure of human uridine-cytidine kinase 2 determined by SIRAS using a rotating-anode X-ray generator and a single samarium derivative.
Related PDB 1xrj
Related UniProtKB Q9BZX2
[5]
Resource
Comments
Medline ID
PubMed ID 19532987
Journal Org Biomol Chem
Year 2009
Volume 7
Pages 2716-24
Authors Smith AJ, Li Y, Houk KN
Title Quantum mechanics/molecular mechanics investigation of the mechanism of phosphate transfer in human uridine-cytidine kinase 2.
Related PDB
Related UniProtKB

Comments
This enzyme is homologous to shikimate kinase (S00304 in EzCatDB) and adenylate kinase (S00305 in EzCatDB).
According to the literature [3], the reaction proceeds as follows:
(0) Magnesium ion, which is bound to Ser34, is bridging beta- and gamma-phosphate groups of ATP. Arg169 and Arg174 interact with the transferred gamma-phosphate, whereas Lys33 interacts with both beta- and gamma-phosphate groups. Meanwhile, mainchain amide groups of Ala30-Ser31-Gly32-Lys33 interact mainly with beta-phosphate group of ATP.
(1) Asp62 acts as a general base to deprotonate the acceptor group, 5'-hydroxyl group of uridine or cytidine.
(2) The activated 5'-hydroxyl oxygen makes a nucleophilic attack on the gamma-phosphate group, leading to transition-state. The transferred gamma-phsophate group in the transition state can be stabilized by Lys33, Arg169 and Arg174, along with the magnesium ion, whereas the leaving alpha- and beta-phosphate groups can be stabilized by the mainchain amide groups and the magnesium ion.
(3) The reaction completes via SN2-like mechanism.

Created Updated
2009-08-11 2011-12-15