Full text data of CMPK1
CMPK1
(CMK, CMPK, UCK, UMK, UMPK)
[Confidence: low (only semi-automatic identification from reviews)]
UMP-CMP kinase; 2.7.4.14 (Deoxycytidylate kinase; CK; dCMP kinase; Nucleoside-diphosphate kinase; 2.7.4.6; Uridine monophosphate/cytidine monophosphate kinase; UMP/CMP kinase; UMP/CMPK)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UMP-CMP kinase; 2.7.4.14 (Deoxycytidylate kinase; CK; dCMP kinase; Nucleoside-diphosphate kinase; 2.7.4.6; Uridine monophosphate/cytidine monophosphate kinase; UMP/CMP kinase; UMP/CMPK)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P30085
ID KCY_HUMAN Reviewed; 196 AA.
AC P30085; B4DPU7; E9PGI8; Q53GB7; Q5SVZ0; Q96C07; Q9UBQ8; Q9UIA2;
read moreDT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 3.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=UMP-CMP kinase;
DE EC=2.7.4.14;
DE AltName: Full=Deoxycytidylate kinase;
DE Short=CK;
DE Short=dCMP kinase;
DE AltName: Full=Nucleoside-diphosphate kinase;
DE EC=2.7.4.6;
DE AltName: Full=Uridine monophosphate/cytidine monophosphate kinase;
DE Short=UMP/CMP kinase;
DE Short=UMP/CMPK;
GN Name=CMPK1; Synonyms=CMK, CMPK, UCK, UMK, UMPK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=10462544;
RA Van Rompay A.R., Johansson M., Karlsson A.;
RT "Phosphorylation of deoxycytidine analog monophosphates by UMP-CMP
RT kinase: molecular characterization of the human enzyme.";
RL Mol. Pharmacol. 56:562-569(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY,
RP CHROMOSOMAL LOCATION, AND IDENTIFICATION OF START CODON.
RC TISSUE=Macrophage;
RX PubMed=11681623; DOI=10.1016/S0024-3205(01)01322-4;
RA Pearman A.T., Castro-Faria-Neto H.C., McIntyre T.M., Prescott S.M.,
RA Stafforini D.M.;
RT "Characterization of human UMP-CMP kinase enzymatic activity and 5'
RT untranslated region.";
RL Life Sci. 69:2361-2370(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11912132;
RA Liou J.-Y., Dutschman G.E., Lam W., Jiang Z., Cheng Y.-C.;
RT "Characterization of human UMP/CMP kinase and its phosphorylation of
RT D- and L-form deoxycytidine analogue monophosphates.";
RL Cancer Res. 62:1624-1631(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Pituitary;
RA Song H., Peng Y., Dai M., Huang Q., Mao Y., Zhang Q., Mao M., Fu G.,
RA Luo M., Chen J., Hu R.;
RT "Human UMP-CMP kinase gene.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Fan Y.X., Yu L., Dai F.Y., Zhou Y., Huang J., Zhao S.Y.;
RT "Cloning and characterization of a new human cDNA homologous to pig
RT UMP-CMP kinase mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hypothalamus;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Small intestine;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
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.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA 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.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA 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.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA 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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PROTEIN SEQUENCE OF 1-29.
RC TISSUE=Liver;
RX PubMed=8313870; DOI=10.1002/elps.11501401181;
RA Hughes G.J., Frutiger S., Paquet N., Pasquali C., Sanchez J.-C.,
RA Tissot J.-D., Bairoch A., Appel R.D., Hochstrasser D.F.;
RT "Human liver protein map: update 1993.";
RL Electrophoresis 14:1216-1222(1993).
RN [12]
RP PROTEIN SEQUENCE OF 1-10.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [13]
RP PROTEIN SEQUENCE OF 1-16; 62-73; 89-106; 152-171 AND 180-196, LACK OF
RP N-TERMINAL ACETYLATION, AND MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Bilsland A.E., Keith W.N.;
RL Submitted (JAN-2010) to UniProtKB.
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-55, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23416111; DOI=10.1016/j.biocel.2013.02.004;
RA Amiri M., Conserva F., Panayiotou C., Karlsson A., Solaroli N.;
RT "The human adenylate kinase 9 is a nucleoside mono- and diphosphate
RT kinase.";
RL Int. J. Biochem. Cell Biol. 45:925-931(2013).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=15163660; DOI=10.1074/jbc.M401989200;
RA Segura-Pena D., Sekulic N., Ort S., Konrad M., Lavie A.;
RT "Substrate-induced conformational changes in human UMP/CMP kinase.";
RL J. Biol. Chem. 279:33882-33889(2004).
CC -!- FUNCTION: Catalyzes the phosphorylation of pyrimidine nucleoside
CC monophosphates at the expense of ATP. Plays an important role in
CC de novo pyrimidine nucleotide biosynthesis. Has preference for UMP
CC and CMP as phosphate acceptors. Also displays broad nucleoside
CC diphosphate kinase activity.
CC -!- CATALYTIC ACTIVITY: ATP + (d)CMP = ADP + (d)CDP.
CC -!- CATALYTIC ACTIVITY: ATP + UMP = ADP + UDP.
CC -!- CATALYTIC ACTIVITY: ATP + nucleoside diphosphate = ADP +
CC nucleoside triphosphate.
CC -!- COFACTOR: Binds 1 magnesium ion per monomer.
CC -!- SUBUNIT: Monomer (By similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Predominantly
CC nuclear.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P30085-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P30085-2; Sequence=VSP_046683;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- DOMAIN: Consists of three domains, a large central CORE domain and
CC two small peripheral domains, NMPbind and LID, which undergo
CC movements during catalysis. The LID domain closes over the site of
CC phosphoryl transfer upon ATP binding. Assembling and dissambling
CC the active center during each catalytic cycle provides an
CC effective means to prevent ATP hydrolysis.
CC -!- SIMILARITY: Belongs to the adenylate kinase family. UMP-CMP kinase
CC subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF17709.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAH14961.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAD96734.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAG60709.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=CAI13471.1; Type=Erroneous gene model prediction;
CC Sequence=CAI14972.1; Type=Erroneous gene model prediction;
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DR EMBL; AF070416; AAF17709.1; ALT_INIT; mRNA.
DR EMBL; AF259961; AAG22609.1; -; mRNA.
DR EMBL; AF110643; AAD48583.1; -; mRNA.
DR EMBL; AF087865; AAP97174.1; -; mRNA.
DR EMBL; AF112216; AAF17204.1; -; mRNA.
DR EMBL; AK223014; BAD96734.1; ALT_INIT; mRNA.
DR EMBL; AK298502; BAG60709.1; ALT_INIT; mRNA.
DR EMBL; AL513322; CAI13471.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL607122; CAI13471.1; JOINED; Genomic_DNA.
DR EMBL; AL607122; CAI14972.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL513322; CAI14972.1; JOINED; Genomic_DNA.
DR EMBL; BC014961; AAH14961.1; ALT_INIT; mRNA.
DR PIR; B45482; B45482.
DR RefSeq; NP_001129612.1; NM_001136140.1.
DR RefSeq; NP_057392.1; NM_016308.2.
DR UniGene; Hs.731647; -.
DR PDB; 1TEV; X-ray; 2.10 A; A=1-196.
DR PDBsum; 1TEV; -.
DR ProteinModelPortal; P30085; -.
DR SMR; P30085; 3-196.
DR IntAct; P30085; 1.
DR MINT; MINT-5000978; -.
DR STRING; 9606.ENSP00000360939; -.
DR ChEMBL; CHEMBL5681; -.
DR DrugBank; DB00441; Gemcitabine.
DR PhosphoSite; P30085; -.
DR DMDM; 12644008; -.
DR OGP; P30085; -.
DR SWISS-2DPAGE; P30085; -.
DR PaxDb; P30085; -.
DR PRIDE; P30085; -.
DR DNASU; 51727; -.
DR Ensembl; ENST00000371873; ENSP00000360939; ENSG00000162368.
DR Ensembl; ENST00000450808; ENSP00000398192; ENSG00000162368.
DR GeneID; 51727; -.
DR KEGG; hsa:51727; -.
DR UCSC; uc010omp.2; human.
DR CTD; 51727; -.
DR GeneCards; GC01P047799; -.
DR HGNC; HGNC:18170; CMPK1.
DR MIM; 191710; gene.
DR neXtProt; NX_P30085; -.
DR PharmGKB; PA162382539; -.
DR eggNOG; COG0563; -.
DR HOVERGEN; HBG108060; -.
DR InParanoid; P30085; -.
DR KO; K13800; -.
DR OrthoDB; EOG7X0VJ0; -.
DR BioCyc; MetaCyc:HS08663-MONOMER; -.
DR BRENDA; 2.7.4.14; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P30085; -.
DR EvolutionaryTrace; P30085; -.
DR GeneWiki; CMPK; -.
DR GenomeRNAi; 51727; -.
DR NextBio; 35473968; -.
DR PRO; PR:P30085; -.
DR ArrayExpress; P30085; -.
DR Bgee; P30085; -.
DR CleanEx; HS_CMPK1; -.
DR Genevestigator; P30085; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004127; F:cytidylate kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB.
DR GO; GO:0033862; F:UMP kinase activity; IEA:Ensembl.
DR GO; GO:0004849; F:uridine kinase activity; TAS:ProtInc.
DR GO; GO:0046705; P:CDP biosynthetic process; IEA:Ensembl.
DR GO; GO:0006240; P:dCDP biosynthetic process; IEA:Ensembl.
DR GO; GO:0006227; P:dUDP biosynthetic process; IEA:Ensembl.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
DR GO; GO:0009142; P:nucleoside triphosphate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0022602; P:ovulation cycle process; IEA:Ensembl.
DR GO; GO:0018963; P:phthalate metabolic process; IEA:Ensembl.
DR GO; GO:0006225; P:UDP biosynthetic process; IEA:Ensembl.
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; 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; Acetylation; Alternative splicing; ATP-binding;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Kinase;
KW Nucleotide-binding; Nucleus; Pyrimidine biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1 196 UMP-CMP kinase.
FT /FTId=PRO_0000158949.
FT NP_BIND 13 18 ATP (By similarity).
FT NP_BIND 61 63 NMP (By similarity).
FT NP_BIND 93 96 NMP (By similarity).
FT REGION 33 63 NMPbind.
FT REGION 133 143 LID.
FT BINDING 39 39 NMP (By similarity).
FT BINDING 100 100 CMP (By similarity).
FT BINDING 134 134 ATP (By similarity).
FT BINDING 140 140 NMP (By similarity).
FT BINDING 151 151 NMP (By similarity).
FT BINDING 179 179 ATP; via carbonyl oxygen (By similarity).
FT SITE 1 1 Not acetylated.
FT MOD_RES 55 55 N6-acetyllysine.
FT VAR_SEQ 26 74 Missing (in isoform 2).
FT /FTId=VSP_046683.
FT CONFLICT 27 27 Y -> I (in Ref. 11; AA sequence).
FT STRAND 4 9
FT HELIX 16 27
FT STRAND 30 33
FT HELIX 34 43
FT HELIX 50 58
FT HELIX 65 82
FT STRAND 88 93
FT HELIX 98 108
FT TURN 109 111
FT STRAND 113 121
FT HELIX 124 136
FT HELIX 145 168
FT STRAND 172 176
FT HELIX 181 194
SQ SEQUENCE 196 AA; 22222 MW; 6837B1E6D7543768 CRC64;
MKPLVVFVLG GPGAGKGTQC ARIVEKYGYT HLSAGELLRD ERKNPDSQYG ELIEKYIKEG
KIVPVEITIS LLKREMDQTM AANAQKNKFL IDGFPRNQDN LQGWNKTMDG KADVSFVLFF
DCNNEICIER CLERGKSSGR SDDNRESLEK RIQTYLQSTK PIIDLYEEMG KVKKIDASKS
VDEVFDEVVQ IFDKEG
//
ID KCY_HUMAN Reviewed; 196 AA.
AC P30085; B4DPU7; E9PGI8; Q53GB7; Q5SVZ0; Q96C07; Q9UBQ8; Q9UIA2;
read moreDT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 3.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=UMP-CMP kinase;
DE EC=2.7.4.14;
DE AltName: Full=Deoxycytidylate kinase;
DE Short=CK;
DE Short=dCMP kinase;
DE AltName: Full=Nucleoside-diphosphate kinase;
DE EC=2.7.4.6;
DE AltName: Full=Uridine monophosphate/cytidine monophosphate kinase;
DE Short=UMP/CMP kinase;
DE Short=UMP/CMPK;
GN Name=CMPK1; Synonyms=CMK, CMPK, UCK, UMK, UMPK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=10462544;
RA Van Rompay A.R., Johansson M., Karlsson A.;
RT "Phosphorylation of deoxycytidine analog monophosphates by UMP-CMP
RT kinase: molecular characterization of the human enzyme.";
RL Mol. Pharmacol. 56:562-569(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY,
RP CHROMOSOMAL LOCATION, AND IDENTIFICATION OF START CODON.
RC TISSUE=Macrophage;
RX PubMed=11681623; DOI=10.1016/S0024-3205(01)01322-4;
RA Pearman A.T., Castro-Faria-Neto H.C., McIntyre T.M., Prescott S.M.,
RA Stafforini D.M.;
RT "Characterization of human UMP-CMP kinase enzymatic activity and 5'
RT untranslated region.";
RL Life Sci. 69:2361-2370(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11912132;
RA Liou J.-Y., Dutschman G.E., Lam W., Jiang Z., Cheng Y.-C.;
RT "Characterization of human UMP/CMP kinase and its phosphorylation of
RT D- and L-form deoxycytidine analogue monophosphates.";
RL Cancer Res. 62:1624-1631(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Pituitary;
RA Song H., Peng Y., Dai M., Huang Q., Mao Y., Zhang Q., Mao M., Fu G.,
RA Luo M., Chen J., Hu R.;
RT "Human UMP-CMP kinase gene.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Fan Y.X., Yu L., Dai F.Y., Zhou Y., Huang J., Zhao S.Y.;
RT "Cloning and characterization of a new human cDNA homologous to pig
RT UMP-CMP kinase mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hypothalamus;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Small intestine;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
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.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA 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.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA 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.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA 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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PROTEIN SEQUENCE OF 1-29.
RC TISSUE=Liver;
RX PubMed=8313870; DOI=10.1002/elps.11501401181;
RA Hughes G.J., Frutiger S., Paquet N., Pasquali C., Sanchez J.-C.,
RA Tissot J.-D., Bairoch A., Appel R.D., Hochstrasser D.F.;
RT "Human liver protein map: update 1993.";
RL Electrophoresis 14:1216-1222(1993).
RN [12]
RP PROTEIN SEQUENCE OF 1-10.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [13]
RP PROTEIN SEQUENCE OF 1-16; 62-73; 89-106; 152-171 AND 180-196, LACK OF
RP N-TERMINAL ACETYLATION, AND MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Bilsland A.E., Keith W.N.;
RL Submitted (JAN-2010) to UniProtKB.
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-55, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23416111; DOI=10.1016/j.biocel.2013.02.004;
RA Amiri M., Conserva F., Panayiotou C., Karlsson A., Solaroli N.;
RT "The human adenylate kinase 9 is a nucleoside mono- and diphosphate
RT kinase.";
RL Int. J. Biochem. Cell Biol. 45:925-931(2013).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=15163660; DOI=10.1074/jbc.M401989200;
RA Segura-Pena D., Sekulic N., Ort S., Konrad M., Lavie A.;
RT "Substrate-induced conformational changes in human UMP/CMP kinase.";
RL J. Biol. Chem. 279:33882-33889(2004).
CC -!- FUNCTION: Catalyzes the phosphorylation of pyrimidine nucleoside
CC monophosphates at the expense of ATP. Plays an important role in
CC de novo pyrimidine nucleotide biosynthesis. Has preference for UMP
CC and CMP as phosphate acceptors. Also displays broad nucleoside
CC diphosphate kinase activity.
CC -!- CATALYTIC ACTIVITY: ATP + (d)CMP = ADP + (d)CDP.
CC -!- CATALYTIC ACTIVITY: ATP + UMP = ADP + UDP.
CC -!- CATALYTIC ACTIVITY: ATP + nucleoside diphosphate = ADP +
CC nucleoside triphosphate.
CC -!- COFACTOR: Binds 1 magnesium ion per monomer.
CC -!- SUBUNIT: Monomer (By similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Predominantly
CC nuclear.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P30085-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P30085-2; Sequence=VSP_046683;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- DOMAIN: Consists of three domains, a large central CORE domain and
CC two small peripheral domains, NMPbind and LID, which undergo
CC movements during catalysis. The LID domain closes over the site of
CC phosphoryl transfer upon ATP binding. Assembling and dissambling
CC the active center during each catalytic cycle provides an
CC effective means to prevent ATP hydrolysis.
CC -!- SIMILARITY: Belongs to the adenylate kinase family. UMP-CMP kinase
CC subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF17709.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAH14961.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAD96734.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAG60709.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=CAI13471.1; Type=Erroneous gene model prediction;
CC Sequence=CAI14972.1; Type=Erroneous gene model prediction;
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DR EMBL; AF070416; AAF17709.1; ALT_INIT; mRNA.
DR EMBL; AF259961; AAG22609.1; -; mRNA.
DR EMBL; AF110643; AAD48583.1; -; mRNA.
DR EMBL; AF087865; AAP97174.1; -; mRNA.
DR EMBL; AF112216; AAF17204.1; -; mRNA.
DR EMBL; AK223014; BAD96734.1; ALT_INIT; mRNA.
DR EMBL; AK298502; BAG60709.1; ALT_INIT; mRNA.
DR EMBL; AL513322; CAI13471.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL607122; CAI13471.1; JOINED; Genomic_DNA.
DR EMBL; AL607122; CAI14972.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL513322; CAI14972.1; JOINED; Genomic_DNA.
DR EMBL; BC014961; AAH14961.1; ALT_INIT; mRNA.
DR PIR; B45482; B45482.
DR RefSeq; NP_001129612.1; NM_001136140.1.
DR RefSeq; NP_057392.1; NM_016308.2.
DR UniGene; Hs.731647; -.
DR PDB; 1TEV; X-ray; 2.10 A; A=1-196.
DR PDBsum; 1TEV; -.
DR ProteinModelPortal; P30085; -.
DR SMR; P30085; 3-196.
DR IntAct; P30085; 1.
DR MINT; MINT-5000978; -.
DR STRING; 9606.ENSP00000360939; -.
DR ChEMBL; CHEMBL5681; -.
DR DrugBank; DB00441; Gemcitabine.
DR PhosphoSite; P30085; -.
DR DMDM; 12644008; -.
DR OGP; P30085; -.
DR SWISS-2DPAGE; P30085; -.
DR PaxDb; P30085; -.
DR PRIDE; P30085; -.
DR DNASU; 51727; -.
DR Ensembl; ENST00000371873; ENSP00000360939; ENSG00000162368.
DR Ensembl; ENST00000450808; ENSP00000398192; ENSG00000162368.
DR GeneID; 51727; -.
DR KEGG; hsa:51727; -.
DR UCSC; uc010omp.2; human.
DR CTD; 51727; -.
DR GeneCards; GC01P047799; -.
DR HGNC; HGNC:18170; CMPK1.
DR MIM; 191710; gene.
DR neXtProt; NX_P30085; -.
DR PharmGKB; PA162382539; -.
DR eggNOG; COG0563; -.
DR HOVERGEN; HBG108060; -.
DR InParanoid; P30085; -.
DR KO; K13800; -.
DR OrthoDB; EOG7X0VJ0; -.
DR BioCyc; MetaCyc:HS08663-MONOMER; -.
DR BRENDA; 2.7.4.14; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P30085; -.
DR EvolutionaryTrace; P30085; -.
DR GeneWiki; CMPK; -.
DR GenomeRNAi; 51727; -.
DR NextBio; 35473968; -.
DR PRO; PR:P30085; -.
DR ArrayExpress; P30085; -.
DR Bgee; P30085; -.
DR CleanEx; HS_CMPK1; -.
DR Genevestigator; P30085; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004127; F:cytidylate kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB.
DR GO; GO:0033862; F:UMP kinase activity; IEA:Ensembl.
DR GO; GO:0004849; F:uridine kinase activity; TAS:ProtInc.
DR GO; GO:0046705; P:CDP biosynthetic process; IEA:Ensembl.
DR GO; GO:0006240; P:dCDP biosynthetic process; IEA:Ensembl.
DR GO; GO:0006227; P:dUDP biosynthetic process; IEA:Ensembl.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
DR GO; GO:0009142; P:nucleoside triphosphate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0022602; P:ovulation cycle process; IEA:Ensembl.
DR GO; GO:0018963; P:phthalate metabolic process; IEA:Ensembl.
DR GO; GO:0006225; P:UDP biosynthetic process; IEA:Ensembl.
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; 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; Acetylation; Alternative splicing; ATP-binding;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Kinase;
KW Nucleotide-binding; Nucleus; Pyrimidine biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1 196 UMP-CMP kinase.
FT /FTId=PRO_0000158949.
FT NP_BIND 13 18 ATP (By similarity).
FT NP_BIND 61 63 NMP (By similarity).
FT NP_BIND 93 96 NMP (By similarity).
FT REGION 33 63 NMPbind.
FT REGION 133 143 LID.
FT BINDING 39 39 NMP (By similarity).
FT BINDING 100 100 CMP (By similarity).
FT BINDING 134 134 ATP (By similarity).
FT BINDING 140 140 NMP (By similarity).
FT BINDING 151 151 NMP (By similarity).
FT BINDING 179 179 ATP; via carbonyl oxygen (By similarity).
FT SITE 1 1 Not acetylated.
FT MOD_RES 55 55 N6-acetyllysine.
FT VAR_SEQ 26 74 Missing (in isoform 2).
FT /FTId=VSP_046683.
FT CONFLICT 27 27 Y -> I (in Ref. 11; AA sequence).
FT STRAND 4 9
FT HELIX 16 27
FT STRAND 30 33
FT HELIX 34 43
FT HELIX 50 58
FT HELIX 65 82
FT STRAND 88 93
FT HELIX 98 108
FT TURN 109 111
FT STRAND 113 121
FT HELIX 124 136
FT HELIX 145 168
FT STRAND 172 176
FT HELIX 181 194
SQ SEQUENCE 196 AA; 22222 MW; 6837B1E6D7543768 CRC64;
MKPLVVFVLG GPGAGKGTQC ARIVEKYGYT HLSAGELLRD ERKNPDSQYG ELIEKYIKEG
KIVPVEITIS LLKREMDQTM AANAQKNKFL IDGFPRNQDN LQGWNKTMDG KADVSFVLFF
DCNNEICIER CLERGKSSGR SDDNRESLEK RIQTYLQSTK PIIDLYEEMG KVKKIDASKS
VDEVFDEVVQ IFDKEG
//
MIM
191710
*RECORD*
*FIELD* NO
191710
*FIELD* TI
*191710 CYTIDINE MONOPHOSPHATE (UMP-CMP) KINASE 1, CYTOSOLIC; CMPK1
;;CYTIDINE MONOPHOSPHATE KINASE; CMPK;;
read moreCYTIDYLATE KINASE; CMK;;
URIDINE MONOPHOSPHATE/CYTIDINE MONOPHOSPHATE KINASE;;
UMP/CMP KINASE;;
UMP/CMPK;;
URIDINE MONOPHOSPHATE KINASE; UMPK; UMK
*FIELD* TX
DESCRIPTION
Uridine monophosphate (UMP)/cytidine monophosphate (CMP) kinase (EC
2.7.4.4) catalyzes the phosphoryl transfer from ATP to UMP, CMP, and
deoxy-CMP (dCMP), resulting in the formation of ADP and the
corresponding nucleoside diphosphate. These nucleoside diphosphates are
required for cellular nucleic acid synthesis (Liou et al., 2002).
CLONING
By searching an EST database for sequences similar to pig UMP/CMP
kinase, Van Rompay et al. (1999) identified and cloned human UMP/CMP
kinase. The longest deduced protein contains 228 amino acids and has a
calculated molecular mass of 26 kD. However, translation likely begins
at the second initiation methionine, resulting in a protein of 196 amino
acids. UMP/CMP kinase has a glycine-rich nucleoside triphosphate-binding
region followed by a nucleoside monophosphate-binding site in its
N-terminal half and a lid domain in its C-terminal half. Northern blot
analysis detected a 3.9-kb transcript expressed in all tissues examined,
with highest expression in pancreas, skeletal muscle, and liver.
Fluorescence-tagged UMP/CMP kinase localized to both the cytosol and
nucleus of transfected Chinese hamster ovary cells.
By EST database analysis and PCR of a human epidermoid carcinoma cell
line cDNA library, Liou et al. (2002) cloned UMP/CMP kinase. Western
blot analysis detected UMP/CMP kinase in all human cell lines examined.
The endogenous enzyme appeared as a single protein that comigrated with
the 196-amino acid form expressed in transfected HeLa cells. Liou et al.
(2002) concluded that the shorter form is the endogenously translated
protein.
GENE FUNCTION
Van Rompay et al. (1999) characterized the enzymatic activity of
recombinant UMP/CMP kinase. The ribonucleotides UMP and CMP were both
efficiently phosphorylated, and lower activity was detected for dCMP,
dUMP, AMP, and dAMP. UMP/CMP kinase did not phosphorylate other
nucleotide monophosphates. The addition of a reducing agent increased
phosphorylation of dCMP 21-fold, but it had no effect on other
substrates. Overall, CMP was the best substrate. Monophosphate
derivatives of several anticancer nucleosides were also substrates for
UMP/CMP kinase.
Liou et al. (2002) found that the 228- and 196-amino acid forms of
UMP/CMP kinase showed identical enzymatic activity. By examining the
kinetics of the phosphorylation of D- and L-forms of dideoxyCMP, they
determined that UMP/CMP kinase lacks stereoselectivity. Reducing agents
activated UMP/CMP kinase in a dose-dependent manner. ATP and dATP were
the best phosphate donors, whereas CTP was the poorest. dGTP and TTP
were efficient phosphate donors for UMP and dCMP substrates, but not for
CMP. There was strong feedback inhibition, with CTP inhibiting UMP
phosphorylation by 80% and dCMP phosphorylation by 60%.
BIOCHEMICAL FEATURES
Segura-Pena et al. (2004) reported the crystal structure of the
substrate-free open form of UMP/CMP kinase and compared it to the closed
state previously reported for the similar D. discoideum UMP/CMP kinase.
They observed a classic example of induced fit, where substrate-induced
conformational changes in hinge residues result in rigid body movements
of functional domains to form the catalytically competent state. The lid
domain undergoes closure upon binding of substrates, bringing several
catalytic residues in close proximity with the phosphate groups of both
substrates.
MAPPING
Giblett et al. (1975) showed that UMPK and Rh (111700) are linked (lod
score of 2.313 at theta 0.05 on the basis of 4 families). (Rh is located
on 1p36.2-p34. Cook and Hamerton (1979) gave 1p32 as the SRO of UMPK.)
Satlin et al. (1975) assigned UMPK to chromosome 1 by study of somatic
cell hybrids. The Goss-Harris method of mapping combined features of
recombinational study in families and synteny tests in hybrid cells. As
applied to chromosome 1, the method showed that AK2 and UMPK are distal
to PGM1 and that the order of the loci is PGM1: UMPK: (AK2, alpha-FUC):
ENO1 (Goss and Harris, 1977).
By radiation hybrid analysis, Van Rompay et al. (1999) mapped the
UMP/CMPK gene to chromosome 1p34.1-p33.
MOLECULAR GENETICS
Giblett et al. (1974) found genetic polymorphism of UMPK by means of
starch gel electrophoresis. Family studies provided evidence for 3
alleles--UMPK1, UMPK2, and UMPK3--at an autosomal locus. The UMPK1
allele was associated with about 3 times the catalytic activity of the
UMPK2 allele, so that UMPK2 homozygotes are relatively deficient of the
enzyme. Two of 3 UMPK2 homozygotes were children with prolonged
respiratory infection. This suggested to Giblett et al. (1974) that the
ability of immunocompetent lymphocytes to respond to appropriate stimuli
is impaired in the UMPK2 homozygote in a manner similar to the immune
defect resulting from adenosine deaminase deficiency. Alaskan Eskimos
have the highest known prevalence of invasive Hemophilus influenzae type
B disease, primarily meningitis: in 1 to 5% of all children in the first
2 years of life. In this population a polymorphic variant of UMPK,
UMPK3, is positively associated with invasive HIB disease (relative risk
3.3). No difference in levels of naturally acquired HIB anticapsular
antibodies between persons with HIB disease and health controls was
found. Thus, the UMPK3 allele may have a role in mediating nonhumoral
immunity to HIB (Petersen et al., 1985).
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
NOMENCLATURE
Uridine kinase, or UK (see UCK2; 609329), has sometimes been used as an
alias for UMPK. Such usage, however, is inaccurate, since the 2 enzymes
catalyze different steps in nucleoside triphosphate synthesis. Uridine
kinase catalyzes the addition of the first phosphate to uridine to form
UMP, whereas UMPK catalyzes the addition of the second phosphate to form
UDP.
*FIELD* SA
Gallango et al. (1978); Gallango and Suinaga (1978); Ranzani et al.
(1977)
*FIELD* RF
1. Cook, P. J. L.; Hamerton, J. L.: Report of the committee on the
genetic constitution of chromosome 1. Cytogenet. Cell Genet. 25:
9-20, 1979.
2. Gallango, M. L.; Muller, A.; Suinaga, R.: Biochemical characterization
of a red cell UMP kinase variant found in the Warao Indians of Venezuela. Biochem.
Genet. 16: 1085-1093, 1978.
3. Gallango, M. L.; Suinaga, R.: Uridine monophosphate kinase polymorphism
in two Venezuelan populations. Am. J. Hum. Genet. 30: 215-218, 1978.
4. Giblett, E. R.; Anderson, J. E.; Chen, S.-H.; Teng, Y.-S.; Cohen,
F.: Uridine monophosphate kinase: a new genetic polymorphism with
possible clinical implications. Am. J. Hum. Genet. 26: 627-635,
1974.
5. Giblett, E. R.; Anderson, J. E.; Lewis, M.; Kaita, H.: A new polymorphic
enzyme, uridine monophosphate kinase: gene frequencies and a linkage
analysis. Birth Defects Orig. Art. Ser. 11(3): 159-161, 1975. Note:
Alternate: Cytogenet. Cell Genet. 14: 329-331, 1975.
6. Goss, S. J.; Harris, H.: Gene transfer by means of cell fusion.
II. The mapping of 8 loci on human chromosome 1 by statistical analysis
of gene assortment in somatic cell hybrids. J. Cell Sci. 25: 39-57,
1977.
7. Liou, J.-Y.; Dutschman, G. E.; Lam, W.; Jiang, Z.; Cheng, Y.-C.
: Characterization of human UMP/CMP kinase and its phosphorylation
of D- and L-form deoxycytidine analogue monophosphates. Cancer Res. 62:
1624-1631, 2002.
8. Petersen, G. M.; Silimperi, D. R.; Scott, E. M.; Hall, D. B.; Rotter,
J. I.; Ward, J. I.: Uridine monophosphate kinase 3: a genetic marker
for susceptibility to Haemophilus influenzae type B disease. Lancet 326:
417-418, 1985. Note: Originally Volume II.
9. Ranzani, G.; Bertolotti, E.; Santachiara-Benerecetti, A. S.: The
polymorphism of the red cell uridine monophosphate kinase in two samples
of the Italian population. Hum. Hered. 27: 332-335, 1977.
10. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
11. Satlin, A.; Kucherlapati, R. S.; Ruddle, F. H.: Assignment of
the gene for human uridine monophosphate kinase to chromosome 1 using
somatic cell hybrid clone panels. Cytogenet. Cell Genet. 15: 146-152,
1975.
12. Segura-Pena, D.; Sekulic, N.; Ort, S.; Konrad, M.; Lavie, A.:
Substrate-induced conformational changes in human UMP/CMP kinase. J.
Biol. Chem. 279: 33882-33889, 2004.
13. Van Rompay, A. R.; Johansson, M.; Karlsson, A.: Phosphorylation
of deoxycytidine analog monophosphates by UMP-CMP kinase: molecular
characterization of the human enzyme. Molec. Pharm. 56: 562-569,
1999.
*FIELD* CN
Patricia A. Hartz - updated: 4/19/2005
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
terry: 02/10/2009
carol: 2/12/2008
mgross: 5/17/2005
mgross: 4/22/2005
terry: 4/19/2005
carol: 2/22/2001
mimadm: 6/7/1995
warfield: 3/29/1994
carol: 4/21/1992
supermim: 3/16/1992
carol: 2/26/1991
carol: 2/8/1991
*RECORD*
*FIELD* NO
191710
*FIELD* TI
*191710 CYTIDINE MONOPHOSPHATE (UMP-CMP) KINASE 1, CYTOSOLIC; CMPK1
;;CYTIDINE MONOPHOSPHATE KINASE; CMPK;;
read moreCYTIDYLATE KINASE; CMK;;
URIDINE MONOPHOSPHATE/CYTIDINE MONOPHOSPHATE KINASE;;
UMP/CMP KINASE;;
UMP/CMPK;;
URIDINE MONOPHOSPHATE KINASE; UMPK; UMK
*FIELD* TX
DESCRIPTION
Uridine monophosphate (UMP)/cytidine monophosphate (CMP) kinase (EC
2.7.4.4) catalyzes the phosphoryl transfer from ATP to UMP, CMP, and
deoxy-CMP (dCMP), resulting in the formation of ADP and the
corresponding nucleoside diphosphate. These nucleoside diphosphates are
required for cellular nucleic acid synthesis (Liou et al., 2002).
CLONING
By searching an EST database for sequences similar to pig UMP/CMP
kinase, Van Rompay et al. (1999) identified and cloned human UMP/CMP
kinase. The longest deduced protein contains 228 amino acids and has a
calculated molecular mass of 26 kD. However, translation likely begins
at the second initiation methionine, resulting in a protein of 196 amino
acids. UMP/CMP kinase has a glycine-rich nucleoside triphosphate-binding
region followed by a nucleoside monophosphate-binding site in its
N-terminal half and a lid domain in its C-terminal half. Northern blot
analysis detected a 3.9-kb transcript expressed in all tissues examined,
with highest expression in pancreas, skeletal muscle, and liver.
Fluorescence-tagged UMP/CMP kinase localized to both the cytosol and
nucleus of transfected Chinese hamster ovary cells.
By EST database analysis and PCR of a human epidermoid carcinoma cell
line cDNA library, Liou et al. (2002) cloned UMP/CMP kinase. Western
blot analysis detected UMP/CMP kinase in all human cell lines examined.
The endogenous enzyme appeared as a single protein that comigrated with
the 196-amino acid form expressed in transfected HeLa cells. Liou et al.
(2002) concluded that the shorter form is the endogenously translated
protein.
GENE FUNCTION
Van Rompay et al. (1999) characterized the enzymatic activity of
recombinant UMP/CMP kinase. The ribonucleotides UMP and CMP were both
efficiently phosphorylated, and lower activity was detected for dCMP,
dUMP, AMP, and dAMP. UMP/CMP kinase did not phosphorylate other
nucleotide monophosphates. The addition of a reducing agent increased
phosphorylation of dCMP 21-fold, but it had no effect on other
substrates. Overall, CMP was the best substrate. Monophosphate
derivatives of several anticancer nucleosides were also substrates for
UMP/CMP kinase.
Liou et al. (2002) found that the 228- and 196-amino acid forms of
UMP/CMP kinase showed identical enzymatic activity. By examining the
kinetics of the phosphorylation of D- and L-forms of dideoxyCMP, they
determined that UMP/CMP kinase lacks stereoselectivity. Reducing agents
activated UMP/CMP kinase in a dose-dependent manner. ATP and dATP were
the best phosphate donors, whereas CTP was the poorest. dGTP and TTP
were efficient phosphate donors for UMP and dCMP substrates, but not for
CMP. There was strong feedback inhibition, with CTP inhibiting UMP
phosphorylation by 80% and dCMP phosphorylation by 60%.
BIOCHEMICAL FEATURES
Segura-Pena et al. (2004) reported the crystal structure of the
substrate-free open form of UMP/CMP kinase and compared it to the closed
state previously reported for the similar D. discoideum UMP/CMP kinase.
They observed a classic example of induced fit, where substrate-induced
conformational changes in hinge residues result in rigid body movements
of functional domains to form the catalytically competent state. The lid
domain undergoes closure upon binding of substrates, bringing several
catalytic residues in close proximity with the phosphate groups of both
substrates.
MAPPING
Giblett et al. (1975) showed that UMPK and Rh (111700) are linked (lod
score of 2.313 at theta 0.05 on the basis of 4 families). (Rh is located
on 1p36.2-p34. Cook and Hamerton (1979) gave 1p32 as the SRO of UMPK.)
Satlin et al. (1975) assigned UMPK to chromosome 1 by study of somatic
cell hybrids. The Goss-Harris method of mapping combined features of
recombinational study in families and synteny tests in hybrid cells. As
applied to chromosome 1, the method showed that AK2 and UMPK are distal
to PGM1 and that the order of the loci is PGM1: UMPK: (AK2, alpha-FUC):
ENO1 (Goss and Harris, 1977).
By radiation hybrid analysis, Van Rompay et al. (1999) mapped the
UMP/CMPK gene to chromosome 1p34.1-p33.
MOLECULAR GENETICS
Giblett et al. (1974) found genetic polymorphism of UMPK by means of
starch gel electrophoresis. Family studies provided evidence for 3
alleles--UMPK1, UMPK2, and UMPK3--at an autosomal locus. The UMPK1
allele was associated with about 3 times the catalytic activity of the
UMPK2 allele, so that UMPK2 homozygotes are relatively deficient of the
enzyme. Two of 3 UMPK2 homozygotes were children with prolonged
respiratory infection. This suggested to Giblett et al. (1974) that the
ability of immunocompetent lymphocytes to respond to appropriate stimuli
is impaired in the UMPK2 homozygote in a manner similar to the immune
defect resulting from adenosine deaminase deficiency. Alaskan Eskimos
have the highest known prevalence of invasive Hemophilus influenzae type
B disease, primarily meningitis: in 1 to 5% of all children in the first
2 years of life. In this population a polymorphic variant of UMPK,
UMPK3, is positively associated with invasive HIB disease (relative risk
3.3). No difference in levels of naturally acquired HIB anticapsular
antibodies between persons with HIB disease and health controls was
found. Thus, the UMPK3 allele may have a role in mediating nonhumoral
immunity to HIB (Petersen et al., 1985).
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
NOMENCLATURE
Uridine kinase, or UK (see UCK2; 609329), has sometimes been used as an
alias for UMPK. Such usage, however, is inaccurate, since the 2 enzymes
catalyze different steps in nucleoside triphosphate synthesis. Uridine
kinase catalyzes the addition of the first phosphate to uridine to form
UMP, whereas UMPK catalyzes the addition of the second phosphate to form
UDP.
*FIELD* SA
Gallango et al. (1978); Gallango and Suinaga (1978); Ranzani et al.
(1977)
*FIELD* RF
1. Cook, P. J. L.; Hamerton, J. L.: Report of the committee on the
genetic constitution of chromosome 1. Cytogenet. Cell Genet. 25:
9-20, 1979.
2. Gallango, M. L.; Muller, A.; Suinaga, R.: Biochemical characterization
of a red cell UMP kinase variant found in the Warao Indians of Venezuela. Biochem.
Genet. 16: 1085-1093, 1978.
3. Gallango, M. L.; Suinaga, R.: Uridine monophosphate kinase polymorphism
in two Venezuelan populations. Am. J. Hum. Genet. 30: 215-218, 1978.
4. Giblett, E. R.; Anderson, J. E.; Chen, S.-H.; Teng, Y.-S.; Cohen,
F.: Uridine monophosphate kinase: a new genetic polymorphism with
possible clinical implications. Am. J. Hum. Genet. 26: 627-635,
1974.
5. Giblett, E. R.; Anderson, J. E.; Lewis, M.; Kaita, H.: A new polymorphic
enzyme, uridine monophosphate kinase: gene frequencies and a linkage
analysis. Birth Defects Orig. Art. Ser. 11(3): 159-161, 1975. Note:
Alternate: Cytogenet. Cell Genet. 14: 329-331, 1975.
6. Goss, S. J.; Harris, H.: Gene transfer by means of cell fusion.
II. The mapping of 8 loci on human chromosome 1 by statistical analysis
of gene assortment in somatic cell hybrids. J. Cell Sci. 25: 39-57,
1977.
7. Liou, J.-Y.; Dutschman, G. E.; Lam, W.; Jiang, Z.; Cheng, Y.-C.
: Characterization of human UMP/CMP kinase and its phosphorylation
of D- and L-form deoxycytidine analogue monophosphates. Cancer Res. 62:
1624-1631, 2002.
8. Petersen, G. M.; Silimperi, D. R.; Scott, E. M.; Hall, D. B.; Rotter,
J. I.; Ward, J. I.: Uridine monophosphate kinase 3: a genetic marker
for susceptibility to Haemophilus influenzae type B disease. Lancet 326:
417-418, 1985. Note: Originally Volume II.
9. Ranzani, G.; Bertolotti, E.; Santachiara-Benerecetti, A. S.: The
polymorphism of the red cell uridine monophosphate kinase in two samples
of the Italian population. Hum. Hered. 27: 332-335, 1977.
10. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
11. Satlin, A.; Kucherlapati, R. S.; Ruddle, F. H.: Assignment of
the gene for human uridine monophosphate kinase to chromosome 1 using
somatic cell hybrid clone panels. Cytogenet. Cell Genet. 15: 146-152,
1975.
12. Segura-Pena, D.; Sekulic, N.; Ort, S.; Konrad, M.; Lavie, A.:
Substrate-induced conformational changes in human UMP/CMP kinase. J.
Biol. Chem. 279: 33882-33889, 2004.
13. Van Rompay, A. R.; Johansson, M.; Karlsson, A.: Phosphorylation
of deoxycytidine analog monophosphates by UMP-CMP kinase: molecular
characterization of the human enzyme. Molec. Pharm. 56: 562-569,
1999.
*FIELD* CN
Patricia A. Hartz - updated: 4/19/2005
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
terry: 02/10/2009
carol: 2/12/2008
mgross: 5/17/2005
mgross: 4/22/2005
terry: 4/19/2005
carol: 2/22/2001
mimadm: 6/7/1995
warfield: 3/29/1994
carol: 4/21/1992
supermim: 3/16/1992
carol: 2/26/1991
carol: 2/8/1991