CMPK2_HUMAN
ID CMPK2_HUMAN Reviewed; 449 AA.
AC Q5EBM0; A2RUB0; A5D8T2; B7ZM18; Q6ZRU2; Q96AL8;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=UMP-CMP kinase 2, mitochondrial;
DE EC=2.7.4.14;
DE AltName: Full=Nucleoside-diphosphate kinase;
DE EC=2.7.4.6;
DE Flags: Precursor;
GN Name=CMPK2;
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), FUNCTION, TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=17999954; DOI=10.1074/jbc.m707997200;
RA Xu Y., Johansson M., Karlsson A.;
RT "Human UMP-CMP kinase 2, a novel nucleoside monophosphate kinase localized
RT in mitochondria.";
RL J. Biol. Chem. 283:1563-1571(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 9-449 (ISOFORM 1).
RC TISSUE=Lymph, and Prostate;
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 [4]
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 [5]
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).
CC -!- FUNCTION: May participate in dUTP and dCTP synthesis in mitochondria.
CC Is able to phosphorylate dUMP, dCMP, CMP, UMP and monophosphates of the
CC pyrimidine nucleoside analogs ddC, dFdC, araC, BVDU and FdUrd with ATP
CC as phosphate donor. Efficacy is highest for dUMP followed by dCMP; CMP
CC and UMP are poor substrates. May be involved in mtDNA depletion caused
CC by long term treatment with ddC or other pyrimidine analogs. Also
CC displays broad nucleoside diphosphate kinase activity.
CC {ECO:0000269|PubMed:17999954, ECO:0000269|PubMed:23416111}.
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;
CC Evidence={ECO:0000269|PubMed:23416111};
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;
CC Evidence={ECO:0000269|PubMed:23416111};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-diphosphate + ATP = a 2'-
CC deoxyribonucleoside 5'-triphosphate + ADP; Xref=Rhea:RHEA:44640,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61560, ChEBI:CHEBI:73316,
CC ChEBI:CHEBI:456216; EC=2.7.4.6;
CC Evidence={ECO:0000269|PubMed:23416111};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-diphosphate + ATP = a ribonucleoside 5'-
CC triphosphate + ADP; Xref=Rhea:RHEA:18113, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557, ChEBI:CHEBI:456216; EC=2.7.4.6;
CC Evidence={ECO:0000269|PubMed:23416111};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.09 mM for CMP;
CC KM=6.3 mM for UMP;
CC KM=1.31 mM for dCMP;
CC KM=0.1 mM for dUMP;
CC Vmax=1.64 umol/min/mg enzyme towards CMP;
CC Vmax=0.19 umol/min/mg enzyme towards UMP;
CC Vmax=1.77 umol/min/mg enzyme towards dCMP;
CC Vmax=0.48 umol/min/mg enzyme towards dUMP;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:17999954}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q5EBM0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5EBM0-2; Sequence=VSP_033238, VSP_033239;
CC Name=3;
CC IsoId=Q5EBM0-3; Sequence=VSP_033240;
CC Name=4;
CC IsoId=Q5EBM0-4; Sequence=VSP_033241;
CC -!- TISSUE SPECIFICITY: Among all investigated tumors, leukemia cells show
CC the most abundant expression. {ECO:0000269|PubMed:17999954}.
CC -!- SIMILARITY: Belongs to the thymidylate kinase family. {ECO:0000305}.
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DR EMBL; AK127983; BAC87217.1; -; mRNA.
DR EMBL; BC016969; AAH16969.1; -; mRNA.
DR EMBL; BC141802; AAI41803.1; -; mRNA.
DR EMBL; BC132821; AAI32822.1; -; mRNA.
DR EMBL; BC089425; AAH89425.1; -; mRNA.
DR EMBL; BC144202; AAI44203.1; -; mRNA.
DR CCDS; CCDS42648.1; -. [Q5EBM0-1]
DR CCDS; CCDS58695.1; -. [Q5EBM0-3]
DR CCDS; CCDS58696.1; -. [Q5EBM0-4]
DR RefSeq; NP_001243406.1; NM_001256477.1. [Q5EBM0-4]
DR RefSeq; NP_001243407.1; NM_001256478.1. [Q5EBM0-3]
DR RefSeq; NP_997198.2; NM_207315.3. [Q5EBM0-1]
DR AlphaFoldDB; Q5EBM0; -.
DR SMR; Q5EBM0; -.
DR STRING; 9606.ENSP00000256722; -.
DR iPTMnet; Q5EBM0; -.
DR PhosphoSitePlus; Q5EBM0; -.
DR BioMuta; CMPK2; -.
DR DMDM; 296439392; -.
DR EPD; Q5EBM0; -.
DR jPOST; Q5EBM0; -.
DR MassIVE; Q5EBM0; -.
DR MaxQB; Q5EBM0; -.
DR PaxDb; Q5EBM0; -.
DR PeptideAtlas; Q5EBM0; -.
DR PRIDE; Q5EBM0; -.
DR ProteomicsDB; 62766; -. [Q5EBM0-1]
DR ProteomicsDB; 62767; -. [Q5EBM0-2]
DR ProteomicsDB; 62768; -. [Q5EBM0-3]
DR ProteomicsDB; 62769; -. [Q5EBM0-4]
DR Antibodypedia; 26409; 87 antibodies from 21 providers.
DR DNASU; 129607; -.
DR Ensembl; ENST00000256722.10; ENSP00000256722.5; ENSG00000134326.12. [Q5EBM0-1]
DR Ensembl; ENST00000404168.1; ENSP00000384915.1; ENSG00000134326.12. [Q5EBM0-4]
DR Ensembl; ENST00000458098.5; ENSP00000396385.1; ENSG00000134326.12. [Q5EBM0-3]
DR GeneID; 129607; -.
DR KEGG; hsa:129607; -.
DR MANE-Select; ENST00000256722.10; ENSP00000256722.5; NM_207315.4; NP_997198.2.
DR UCSC; uc002qyo.5; human. [Q5EBM0-1]
DR CTD; 129607; -.
DR DisGeNET; 129607; -.
DR GeneCards; CMPK2; -.
DR HGNC; HGNC:27015; CMPK2.
DR HPA; ENSG00000134326; Tissue enhanced (brain, salivary gland).
DR MIM; 611787; gene.
DR neXtProt; NX_Q5EBM0; -.
DR OpenTargets; ENSG00000134326; -.
DR PharmGKB; PA162382556; -.
DR VEuPathDB; HostDB:ENSG00000134326; -.
DR eggNOG; KOG3327; Eukaryota.
DR GeneTree; ENSGT00940000154030; -.
DR HOGENOM; CLU_049896_0_0_1; -.
DR InParanoid; Q5EBM0; -.
DR OMA; MAPPRCF; -.
DR OrthoDB; 1450196at2759; -.
DR PhylomeDB; Q5EBM0; -.
DR TreeFam; TF328875; -.
DR BRENDA; 2.7.4.14; 2681.
DR PathwayCommons; Q5EBM0; -.
DR SABIO-RK; Q5EBM0; -.
DR BioGRID-ORCS; 129607; 16 hits in 1084 CRISPR screens.
DR GenomeRNAi; 129607; -.
DR Pharos; Q5EBM0; Tbio.
DR PRO; PR:Q5EBM0; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q5EBM0; protein.
DR Bgee; ENSG00000134326; Expressed in palpebral conjunctiva and 182 other tissues.
DR Genevisible; Q5EBM0; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0036430; F:CMP kinase activity; IEA:RHEA.
DR GO; GO:0004127; F:cytidylate kinase activity; IDA:MGI.
DR GO; GO:0036431; F:dCMP kinase activity; IEA:RHEA.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB.
DR GO; GO:0004798; F:thymidylate kinase activity; IBA:GO_Central.
DR GO; GO:0033862; F:UMP kinase activity; IDA:MGI.
DR GO; GO:0009041; F:uridylate kinase activity; IBA:GO_Central.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0006233; P:dTDP biosynthetic process; IBA:GO_Central.
DR GO; GO:0006235; P:dTTP biosynthetic process; IBA:GO_Central.
DR GO; GO:0006227; P:dUDP biosynthetic process; IBA:GO_Central.
DR GO; GO:0006165; P:nucleoside diphosphate phosphorylation; IDA:UniProtKB.
DR GO; GO:0009142; P:nucleoside triphosphate biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039430; Thymidylate_kin-like_dom.
DR InterPro; IPR014505; UMP-CMP_kinase_2.
DR Pfam; PF02223; Thymidylate_kin; 1.
DR PIRSF; PIRSF019736; dTMP_TKRP1; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Coiled coil; Kinase; Mitochondrion;
KW Nucleotide-binding; Pyrimidine biosynthesis; Reference proteome;
KW Transferase; Transit peptide.
FT TRANSIT 1..98
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 99..449
FT /note="UMP-CMP kinase 2, mitochondrial"
FT /id="PRO_0000331524"
FT COILED 380..412
FT /evidence="ECO:0000255"
FT BINDING 259..266
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT VAR_SEQ 280..303
FT /note="LLKSPPSCIGQWRKIFDDEPTIIR -> PQPITLCTSGQRTCSNLTLSCCSL
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033238"
FT VAR_SEQ 304..449
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033239"
FT VAR_SEQ 332..449
FT /note="YWHSTATYAIATEVSGGLQHLPPAHHPVYQWPEDLLKPDLILLLTVSPEERL
FT QRLQGRGMEKTREEAELEANSVFRQKVEMSYQRMENPGCHVVDASPSREKVLQTVLSLI
FT QNSFSEP -> SQLGGTLYHPSLHLLGSEVCGTGILDSSHSSQGLE (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033240"
FT VAR_SEQ 410..449
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033241"
FT VARIANT 433
FT /note="K -> R (in dbSNP:rs6712141)"
FT /id="VAR_055997"
FT CONFLICT 448
FT /note="E -> G (in Ref. 3; AAH89425)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 449 AA; 49448 MW; 99F382E34332B6DE CRC64;
MAFARRLLRG PLSGPLLGRR GVCAGAMAPP RRFVLELPDC TLAHFALGAD APGDADAPDP
RLAALLGPPE RSYSLCVPVT PDAGCGARVR AARLHQRLLH QLRRGPFQRC QLLRLLCYCP
GGQAGGAQQG FLLRDPLDDP DTRQALLELL GACQEAPRPH LGEFEADPRG QLWQRLWEVQ
DGRRLQVGCA QVVPVPEPPL HPVVPDLPSS VVFPDREAAR AVLEECTSFI PEARAVLDLV
DQCPKQIQKG KFQVVAIEGL DATGKTTVTQ SVADSLKAVL LKSPPSCIGQ WRKIFDDEPT
IIRRAFYSLG NYIVASEIAK ESAKSPVIVD RYWHSTATYA IATEVSGGLQ HLPPAHHPVY
QWPEDLLKPD LILLLTVSPE ERLQRLQGRG MEKTREEAEL EANSVFRQKV EMSYQRMENP
GCHVVDASPS REKVLQTVLS LIQNSFSEP
