Q5EBM0 (CMPK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
UMP-CMP kinase 2, mitochondrial
EC=2.7.4.14

Gene names

Name:

CMPK2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	449 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May participate in dUTP and dCTP synthesis in mitochondria. Is able to phosphorylate dUMP, dCMP, CMP, UMP and monophosphates of the pyrimidine nucleoside analogs ddC, dFdC, araC, BVDU and FdUrd with ATP as phosphate donor. Efficacy is highest for dUMP followed by dCMP; CMP and UMP are poor substrates. May be involved in mtDNA depletion caused by long term treatment with ddC or other pyrimidine analogs. Ref.1
Catalytic activity	ATP + (d)CMP = ADP + (d)CDP.
Subcellular location	Mitochondrion Ref.1.
Tissue specificity	Among all investigated tumors, leukemia cells show the most abundant expression. Ref.1
Sequence similarities	Belongs to the thymidylate kinase family.
Biophysicochemical properties	Kinetic parameters: KM=3.09 mM for CMP KM=6.3 mM for UMP KM=1.31 mM for dCMP KM=0.1 mM for dUMP Vmax=1.64 µmol/min/mg enzyme towards CMP Vmax=0.19 µmol/min/mg enzyme towards UMP Vmax=1.77 µmol/min/mg enzyme towards dCMP Vmax=0.48 µmol/min/mg enzyme towards dUMP

Ontologies

Keywords
Biological process	Pyrimidine biosynthesis
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	dTDP biosynthetic process Inferred from electronic annotation. Source: InterPro
Cellular component	mitochondrion Inferred from direct assay Ref.1. Source: MGI nucleus Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW UMP kinase activity Inferred from direct assay Ref.1. Source: MGI cytidylate kinase activity Inferred from direct assay Ref.1. Source: MGI thymidylate kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q5EBM0-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q5EBM0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     280-303: LLKSPPSCIGQWRKIFDDEPTIIR → PQPITLCTSGQRTCSNLTLSCCSL
     304-449: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q5EBM0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     332-449: YWHSTATYAI...SLIQNSFSEP → SQLGGTLYHPSLHLLGSEVCGTGILDSSHSSQGLE

Note: No experimental confirmation available.

Isoform 4 (identifier: Q5EBM0-4)

The sequence of this isoform differs from the canonical sequence as follows:
     410-449: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 98	98	Mitochondrion Potential
	Chain	99 – 449	351	UMP-CMP kinase 2, mitochondrial		PRO_0000331524
Regions
	Nucleotide binding	259 – 266	8	ATP Potential
	Coiled coil	380 – 412	33	Potential
Natural variations
	Alternative sequence	280 – 303	24	LLKSP…PTIIR → PQPITLCTSGQRTCSNLTLS CCSL in isoform 2.		VSP_033238
	Alternative sequence	304 – 449	146	Missing in isoform 2.		VSP_033239
	Alternative sequence	332 – 449	118	YWHST…SFSEP → SQLGGTLYHPSLHLLGSEVC GTGILDSSHSSQGLE in isoform 3.		VSP_033240
	Alternative sequence	410 – 449	40	Missing in isoform 4.		VSP_033241
	Natural variant	433	1	K → R. Corresponds to variant rs6712141 [ dbSNP | Ensembl ].		VAR_055997
Experimental info
	Sequence conflict	448	1	E → G in AAH89425. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: 99F382E34332B6DE	FASTA	449	49,448
	10 20 30 40 50 60 MAFARRLLRG PLSGPLLGRR GVCAGAMAPP RRFVLELPDC TLAHFALGAD APGDADAPDP 70 80 90 100 110 120 RLAALLGPPE RSYSLCVPVT PDAGCGARVR AARLHQRLLH QLRRGPFQRC QLLRLLCYCP 130 140 150 160 170 180 GGQAGGAQQG FLLRDPLDDP DTRQALLELL GACQEAPRPH LGEFEADPRG QLWQRLWEVQ 190 200 210 220 230 240 DGRRLQVGCA QVVPVPEPPL HPVVPDLPSS VVFPDREAAR AVLEECTSFI PEARAVLDLV 250 260 270 280 290 300 DQCPKQIQKG KFQVVAIEGL DATGKTTVTQ SVADSLKAVL LKSPPSCIGQ WRKIFDDEPT 310 320 330 340 350 360 IIRRAFYSLG NYIVASEIAK ESAKSPVIVD RYWHSTATYA IATEVSGGLQ HLPPAHHPVY 370 380 390 400 410 420 QWPEDLLKPD LILLLTVSPE ERLQRLQGRG MEKTREEAEL EANSVFRQKV EMSYQRMENP 430 440 GCHVVDASPS REKVLQTVLS LIQNSFSEP
	Isoform 2 [UniParc]. Checksum: 4C7D0715B7B970C6	FASTA	303	32,646
	10 20 30 40 50 60 MAFARRLLRG PLSGPLLGRR GVCAGAMAPP RRFVLELPDC TLAHFALGAD APGDADAPDP 70 80 90 100 110 120 RLAALLGPPE RSYSLCVPVT PDAGCGARVR AARLHQRLLH QLRRGPFQRC QLLRLLCYCP 130 140 150 160 170 180 GGQAGGAQQG FLLRDPLDDP DTRQALLELL GACQEAPRPH LGEFEADPRG QLWQRLWEVQ 190 200 210 220 230 240 DGRRLQVGCA QVVPVPEPPL HPVVPDLPSS VVFPDREAAR AVLEECTSFI PEARAVLDLV 250 260 270 280 290 300 DQCPKQIQKG KFQVVAIEGL DATGKTTVTQ SVADSLKAVP QPITLCTSGQ RTCSNLTLSC CSL
	Isoform 3 [UniParc]. Checksum: CE09AA2A0A6E6DB3	FASTA	366	39,562
	10 20 30 40 50 60 MAFARRLLRG PLSGPLLGRR GVCAGAMAPP RRFVLELPDC TLAHFALGAD APGDADAPDP 70 80 90 100 110 120 RLAALLGPPE RSYSLCVPVT PDAGCGARVR AARLHQRLLH QLRRGPFQRC QLLRLLCYCP 130 140 150 160 170 180 GGQAGGAQQG FLLRDPLDDP DTRQALLELL GACQEAPRPH LGEFEADPRG QLWQRLWEVQ 190 200 210 220 230 240 DGRRLQVGCA QVVPVPEPPL HPVVPDLPSS VVFPDREAAR AVLEECTSFI PEARAVLDLV 250 260 270 280 290 300 DQCPKQIQKG KFQVVAIEGL DATGKTTVTQ SVADSLKAVL LKSPPSCIGQ WRKIFDDEPT 310 320 330 340 350 360 IIRRAFYSLG NYIVASEIAK ESAKSPVIVD RSQLGGTLYH PSLHLLGSEV CGTGILDSSH SSQGLE
	Isoform 4 [UniParc]. Checksum: A102FAA659D793D0	FASTA	409	44,959
	10 20 30 40 50 60 MAFARRLLRG PLSGPLLGRR GVCAGAMAPP RRFVLELPDC TLAHFALGAD APGDADAPDP 70 80 90 100 110 120 RLAALLGPPE RSYSLCVPVT PDAGCGARVR AARLHQRLLH QLRRGPFQRC QLLRLLCYCP 130 140 150 160 170 180 GGQAGGAQQG FLLRDPLDDP DTRQALLELL GACQEAPRPH LGEFEADPRG QLWQRLWEVQ 190 200 210 220 230 240 DGRRLQVGCA QVVPVPEPPL HPVVPDLPSS VVFPDREAAR AVLEECTSFI PEARAVLDLV 250 260 270 280 290 300 DQCPKQIQKG KFQVVAIEGL DATGKTTVTQ SVADSLKAVL LKSPPSCIGQ WRKIFDDEPT 310 320 330 340 350 360 IIRRAFYSLG NYIVASEIAK ESAKSPVIVD RYWHSTATYA IATEVSGGLQ HLPPAHHPVY 370 380 390 400 QWPEDLLKPD LILLLTVSPE ERLQRLQGRG MEKTREEAEL EANSVFRQK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human UMP-CMP kinase 2, a novel nucleoside monophosphate kinase localized in mitochondria." Xu Y., Johansson M., Karlsson A. J. Biol. Chem. 283:1563-1571(2008) [PubMed: 17999954] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-449 (ISOFORM 1). Tissue: Lymph and Prostate.
[4]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK127983 mRNA. Translation: BAC87217.1. BC016969 mRNA. Translation: AAH16969.1. BC141802 mRNA. Translation: AAI41803.1. BC132821 mRNA. Translation: AAI32822.1. BC089425 mRNA. Translation: AAH89425.1. BC144202 mRNA. Translation: AAI44203.1.
IPI	IPI00410404. IPI00830006. IPI00884425. IPI00890710.
RefSeq	NP_997198.2. NM_207315.2.
UniGene	Hs.7155.
3D structure databases
HSSP	HSSP built from PDB template 1TMK based on UniProtKB P00572.
ProteinModelPortal	Q5EBM0.
SMR	Q5EBM0. Positions 247-448.
ModBase	Search...
Protein-protein interaction databases
STRING	Q5EBM0.
Polymorphism databases
DMDM	296439392.
Proteomic databases
PRIDE	Q5EBM0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000256722; ENSP00000256722; ENSG00000134326. ENST00000458098; ENSP00000396385; ENSG00000134326.
GeneID	129607.
KEGG	hsa:129607.
UCSC	uc002qyo.1. human.
Organism-specific databases
CTD	129607.
GeneCards	GC02M006980.
H-InvDB	HIX0023970.
HGNC	HGNC:27015. CMPK2.
HPA	HPA041430.
MIM	611787. gene.
neXtProt	NX_Q5EBM0.
PharmGKB	PA162382556.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04718.
GeneTree	ENSGT00390000014266.
HOGENOM	HBG713134.
HOVERGEN	HBG088202.
InParanoid	Q5EBM0.
OMA	CTLAHFA.
OrthoDB	EOG40K803.
Gene expression databases
ArrayExpress	Q5EBM0.
Bgee	Q5EBM0.
CleanEx	HS_CMPK2.
Genevestigator	Q5EBM0.
Family and domain databases
InterPro	IPR018094. Thymidylate_kinase. IPR014505. UMP-CMP_kinase_mit. [Graphical view]
KO	K13809.
PANTHER	PTHR10344. Thymidylate_kin. 1 hit.
Pfam	PF02223. Thymidylate_kin. 1 hit. [Graphical view]
PIRSF	PIRSF019736. dTMP_TKRP1. 1 hit.
PROSITE	PS01331. THYMIDYLATE_KINASE. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	82613.
SOURCE	Search...

Entry information

Entry name

CMPK2_HUMAN

Accession

Primary (citable) accession number: Q5EBM0
Secondary accession number(s): A2RUB0 , A5D8T2, B7ZM18, Q6ZRU2, Q96AL8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 29, 2008
Last sequence update:	May 18, 2010
Last modified:	January 25, 2012
This is version 57 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.