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Protein

UMP-CMP kinase 2, mitochondrial

Gene

CMPK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Also displays broad nucleoside diphosphate kinase activity.2 Publications

Catalytic activityi

ATP + (d)CMP = ADP + (d)CDP.1 Publication
ATP + nucleoside diphosphate = ADP + nucleoside triphosphate.1 Publication

Kineticsi

  1. KM=3.09 mM for CMP
  2. KM=6.3 mM for UMP
  3. KM=1.31 mM for dCMP
  4. KM=0.1 mM for dUMP
  1. Vmax=1.64 µmol/min/mg enzyme towards CMP
  2. Vmax=0.19 µmol/min/mg enzyme towards UMP
  3. Vmax=1.77 µmol/min/mg enzyme towards dCMP
  4. Vmax=0.48 µmol/min/mg enzyme towards dUMP

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi259 – 2668ATPSequence Analysis

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cytidylate kinase activity Source: MGI
  • nucleoside diphosphate kinase activity Source: UniProtKB
  • thymidylate kinase activity Source: GO_Central
  • UMP kinase activity Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Pyrimidine biosynthesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.4.14. 2681.
SABIO-RKQ5EBM0.

Names & Taxonomyi

Protein namesi
Recommended name:
UMP-CMP kinase 2, mitochondrial (EC:2.7.4.14)
Alternative name(s):
Nucleoside-diphosphate kinase (EC:2.7.4.6)
Gene namesi
Name:CMPK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:27015. CMPK2.

Subcellular locationi

  • Mitochondrion 1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA162382556.

Polymorphism and mutation databases

BioMutaiCMPK2.
DMDMi296439392.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 9898MitochondrionSequence AnalysisAdd
BLAST
Chaini99 – 449351UMP-CMP kinase 2, mitochondrialPRO_0000331524Add
BLAST

Proteomic databases

MaxQBiQ5EBM0.
PaxDbiQ5EBM0.
PRIDEiQ5EBM0.

Expressioni

Tissue specificityi

Among all investigated tumors, leukemia cells show the most abundant expression.1 Publication

Gene expression databases

BgeeiQ5EBM0.
CleanExiHS_CMPK2.
GenevisibleiQ5EBM0. HS.

Organism-specific databases

HPAiHPA041430.

Interactioni

Protein-protein interaction databases

BioGridi126200. 1 interaction.
STRINGi9606.ENSP00000256722.

Structurei

3D structure databases

ProteinModelPortaliQ5EBM0.
SMRiQ5EBM0. Positions 248-447.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili380 – 41233Sequence AnalysisAdd
BLAST

Sequence similaritiesi

Belongs to the thymidylate kinase family.Curated

Keywords - Domaini

Coiled coil, Transit peptide

Phylogenomic databases

eggNOGiNOG259135.
GeneTreeiENSGT00640000091577.
HOGENOMiHOG000082499.
HOVERGENiHBG088202.
InParanoidiQ5EBM0.
KOiK13809.
OMAiHPVYQWP.
OrthoDBiEOG73NG3S.
PhylomeDBiQ5EBM0.
TreeFamiTF328875.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR014505. UMP-CMP_kinase_mit.
[Graphical view]
PIRSFiPIRSF019736. dTMP_TKRP1. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5EBM0-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAFARRLLRG PLSGPLLGRR GVCAGAMAPP RRFVLELPDC TLAHFALGAD
60 70 80 90 100
APGDADAPDP RLAALLGPPE RSYSLCVPVT PDAGCGARVR AARLHQRLLH
110 120 130 140 150
QLRRGPFQRC QLLRLLCYCP GGQAGGAQQG FLLRDPLDDP DTRQALLELL
160 170 180 190 200
GACQEAPRPH LGEFEADPRG QLWQRLWEVQ DGRRLQVGCA QVVPVPEPPL
210 220 230 240 250
HPVVPDLPSS VVFPDREAAR AVLEECTSFI PEARAVLDLV DQCPKQIQKG
260 270 280 290 300
KFQVVAIEGL DATGKTTVTQ SVADSLKAVL LKSPPSCIGQ WRKIFDDEPT
310 320 330 340 350
IIRRAFYSLG NYIVASEIAK ESAKSPVIVD RYWHSTATYA IATEVSGGLQ
360 370 380 390 400
HLPPAHHPVY QWPEDLLKPD LILLLTVSPE ERLQRLQGRG MEKTREEAEL
410 420 430 440
EANSVFRQKV EMSYQRMENP GCHVVDASPS REKVLQTVLS LIQNSFSEP
Length:449
Mass (Da):49,448
Last modified:May 18, 2010 - v3
Checksum:i99F382E34332B6DE
GO
Isoform 2 (identifier: Q5EBM0-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:303
Mass (Da):32,646
Checksum:i4C7D0715B7B970C6
GO
Isoform 3 (identifier: Q5EBM0-3) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:366
Mass (Da):39,562
Checksum:iCE09AA2A0A6E6DB3
GO
Isoform 4 (identifier: Q5EBM0-4) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:409
Mass (Da):44,959
Checksum:iA102FAA659D793D0
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti448 – 4481E → G in AAH89425 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti433 – 4331K → R.
Corresponds to variant rs6712141 [ dbSNP | Ensembl ].
VAR_055997

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei280 – 30324LLKSP…PTIIR → PQPITLCTSGQRTCSNLTLS CCSL in isoform 2. 1 PublicationVSP_033238Add
BLAST
Alternative sequencei304 – 449146Missing in isoform 2. 1 PublicationVSP_033239Add
BLAST
Alternative sequencei332 – 449118YWHST…SFSEP → SQLGGTLYHPSLHLLGSEVC GTGILDSSHSSQGLE in isoform 3. 1 PublicationVSP_033240Add
BLAST
Alternative sequencei410 – 44940Missing in isoform 4. 1 PublicationVSP_033241Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS42648.1. [Q5EBM0-1]
CCDS58695.1. [Q5EBM0-3]
CCDS58696.1. [Q5EBM0-4]
RefSeqiNP_001243406.1. NM_001256477.1. [Q5EBM0-4]
NP_001243407.1. NM_001256478.1. [Q5EBM0-3]
NP_997198.2. NM_207315.3. [Q5EBM0-1]
UniGeneiHs.7155.

Genome annotation databases

EnsembliENST00000256722; ENSP00000256722; ENSG00000134326. [Q5EBM0-1]
ENST00000404168; ENSP00000384915; ENSG00000134326. [Q5EBM0-4]
ENST00000458098; ENSP00000396385; ENSG00000134326. [Q5EBM0-3]
GeneIDi129607.
KEGGihsa:129607.
UCSCiuc002qyo.4. human. [Q5EBM0-1]
uc010yis.2. human. [Q5EBM0-3]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS42648.1. [Q5EBM0-1]
CCDS58695.1. [Q5EBM0-3]
CCDS58696.1. [Q5EBM0-4]
RefSeqiNP_001243406.1. NM_001256477.1. [Q5EBM0-4]
NP_001243407.1. NM_001256478.1. [Q5EBM0-3]
NP_997198.2. NM_207315.3. [Q5EBM0-1]
UniGeneiHs.7155.

3D structure databases

ProteinModelPortaliQ5EBM0.
SMRiQ5EBM0. Positions 248-447.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126200. 1 interaction.
STRINGi9606.ENSP00000256722.

Polymorphism and mutation databases

BioMutaiCMPK2.
DMDMi296439392.

Proteomic databases

MaxQBiQ5EBM0.
PaxDbiQ5EBM0.
PRIDEiQ5EBM0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000256722; ENSP00000256722; ENSG00000134326. [Q5EBM0-1]
ENST00000404168; ENSP00000384915; ENSG00000134326. [Q5EBM0-4]
ENST00000458098; ENSP00000396385; ENSG00000134326. [Q5EBM0-3]
GeneIDi129607.
KEGGihsa:129607.
UCSCiuc002qyo.4. human. [Q5EBM0-1]
uc010yis.2. human. [Q5EBM0-3]

Organism-specific databases

CTDi129607.
GeneCardsiGC02M006980.
H-InvDBHIX0023970.
HGNCiHGNC:27015. CMPK2.
HPAiHPA041430.
MIMi611787. gene.
neXtProtiNX_Q5EBM0.
PharmGKBiPA162382556.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG259135.
GeneTreeiENSGT00640000091577.
HOGENOMiHOG000082499.
HOVERGENiHBG088202.
InParanoidiQ5EBM0.
KOiK13809.
OMAiHPVYQWP.
OrthoDBiEOG73NG3S.
PhylomeDBiQ5EBM0.
TreeFamiTF328875.

Enzyme and pathway databases

BRENDAi2.7.4.14. 2681.
SABIO-RKQ5EBM0.

Miscellaneous databases

GenomeRNAii129607.
NextBioi82613.
PROiQ5EBM0.
SOURCEiSearch...

Gene expression databases

BgeeiQ5EBM0.
CleanExiHS_CMPK2.
GenevisibleiQ5EBM0. HS.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR014505. UMP-CMP_kinase_mit.
[Graphical view]
PIRSFiPIRSF019736. dTMP_TKRP1. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  5. "The human adenylate kinase 9 is a nucleoside mono- and diphosphate kinase."
    Amiri M., Conserva F., Panayiotou C., Karlsson A., Solaroli N.
    Int. J. Biochem. Cell Biol. 45:925-931(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY.

Entry informationi

Entry nameiCMPK2_HUMAN
AccessioniPrimary (citable) accession number: Q5EBM0
Secondary accession number(s): A2RUB0
, A5D8T2, B7ZM18, Q6ZRU2, Q96AL8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 29, 2008
Last sequence update: May 18, 2010
Last modified: June 24, 2015
This is version 90 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.