NDK6_HUMAN
ID NDK6_HUMAN Reviewed; 186 AA.
AC O75414; B4DGW7; B4DM99; Q53HM5; Q96E73; Q9BQ63;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Nucleoside diphosphate kinase 6;
DE Short=NDK 6;
DE Short=NDP kinase 6;
DE EC=2.7.4.6;
DE AltName: Full=Inhibitor of p53-induced apoptosis-alpha;
DE Short=IPIA-alpha;
DE AltName: Full=nm23-H6;
GN Name=NME6;
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).
RC TISSUE=Liver;
RX PubMed=10453732; DOI=10.1007/s004390050987;
RA Mehus J.G., Deloukas P., Lambeth D.O.;
RT "NME6: a new member of the nm23/nucleoside diphosphate kinase gene family
RT located on human chromosome 3p21.3.";
RL Hum. Genet. 104:454-459(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Nakamura H., Tsuiki H., Honda Y., Sasaki J., Masuko N., Akagi K., Saya H.;
RT "Identification of a gene that inhibits p53-induced apoptosis.";
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Coronary artery;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 [7]
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Major role in the synthesis of nucleoside triphosphates other
CC than ATP. The ATP gamma phosphate is transferred to the NDP beta
CC phosphate via a ping-pong mechanism, using a phosphorylated active-site
CC intermediate. Inhibitor of p53-induced apoptosis.
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; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10030};
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:0000255|PROSITE-ProRule:PRU10030};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- INTERACTION:
CC O75414; Q96I51: RCC1L; NbExp=5; IntAct=EBI-3941531, EBI-2117080;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O75414-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75414-2; Sequence=VSP_036882;
CC Name=3;
CC IsoId=O75414-3; Sequence=VSP_036883;
CC -!- TISSUE SPECIFICITY: Expressed at a moderately low level in many
CC tissues. Most abundant in kidney, prostate, ovary, intestine, and
CC spleen.
CC -!- SIMILARITY: Belongs to the NDK family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC69439.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH01808.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH12828.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAD96275.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF051941; AAC78463.1; -; mRNA.
DR EMBL; U90449; AAC69439.1; ALT_INIT; mRNA.
DR EMBL; AK294809; BAG57928.1; -; mRNA.
DR EMBL; AK297364; BAG59811.1; -; mRNA.
DR EMBL; AK222555; BAD96275.1; ALT_INIT; mRNA.
DR EMBL; AC105267; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001808; AAH01808.1; ALT_INIT; mRNA.
DR EMBL; BC012828; AAH12828.1; ALT_INIT; mRNA.
DR CCDS; CCDS77733.1; -. [O75414-3]
DR CCDS; CCDS77734.1; -. [O75414-1]
DR CCDS; CCDS82768.1; -. [O75414-2]
DR RefSeq; NP_001295355.1; NM_001308426.1. [O75414-1]
DR RefSeq; NP_001295356.1; NM_001308427.1. [O75414-1]
DR RefSeq; NP_001295357.1; NM_001308428.1. [O75414-1]
DR RefSeq; NP_001295360.1; NM_001308431.1. [O75414-3]
DR RefSeq; NP_001295362.1; NM_001308433.1. [O75414-3]
DR RefSeq; NP_001295364.1; NM_001308435.1. [O75414-2]
DR RefSeq; NP_005784.1; NM_005793.4.
DR RefSeq; XP_016861003.1; XM_017005514.1. [O75414-1]
DR RefSeq; XP_016861004.1; XM_017005515.1. [O75414-3]
DR AlphaFoldDB; O75414; -.
DR SMR; O75414; -.
DR BioGRID; 115496; 16.
DR IntAct; O75414; 10.
DR MINT; O75414; -.
DR STRING; 9606.ENSP00000416658; -.
DR GlyGen; O75414; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75414; -.
DR PhosphoSitePlus; O75414; -.
DR BioMuta; NME6; -.
DR EPD; O75414; -.
DR jPOST; O75414; -.
DR MassIVE; O75414; -.
DR MaxQB; O75414; -.
DR PaxDb; O75414; -.
DR PeptideAtlas; O75414; -.
DR PRIDE; O75414; -.
DR ProteomicsDB; 49985; -. [O75414-1]
DR ProteomicsDB; 49986; -. [O75414-2]
DR ProteomicsDB; 49987; -. [O75414-3]
DR Antibodypedia; 13081; 196 antibodies from 23 providers.
DR DNASU; 10201; -.
DR Ensembl; ENST00000415053.5; ENSP00000399582.1; ENSG00000172113.10. [O75414-1]
DR Ensembl; ENST00000415644.5; ENSP00000394232.1; ENSG00000172113.10. [O75414-2]
DR Ensembl; ENST00000426689.6; ENSP00000440286.1; ENSG00000172113.10. [O75414-1]
DR Ensembl; ENST00000435684.5; ENSP00000393261.1; ENSG00000172113.10. [O75414-3]
DR Ensembl; ENST00000442597.6; ENSP00000406642.1; ENSG00000172113.10. [O75414-1]
DR Ensembl; ENST00000451657.6; ENSP00000407933.1; ENSG00000172113.10. [O75414-3]
DR Ensembl; ENST00000452211.5; ENSP00000392352.1; ENSG00000172113.10. [O75414-1]
DR Ensembl; ENST00000643457.1; ENSP00000495130.1; ENSG00000172113.10. [O75414-1]
DR GeneID; 10201; -.
DR KEGG; hsa:10201; -.
DR MANE-Select; ENST00000442597.6; ENSP00000406642.1; NM_001308426.2; NP_001295355.1.
DR UCSC; uc003cso.4; human. [O75414-1]
DR CTD; 10201; -.
DR DisGeNET; 10201; -.
DR GeneCards; NME6; -.
DR HGNC; HGNC:20567; NME6.
DR HPA; ENSG00000172113; Low tissue specificity.
DR MIM; 608294; gene.
DR neXtProt; NX_O75414; -.
DR OpenTargets; ENSG00000172113; -.
DR PharmGKB; PA134873104; -.
DR VEuPathDB; HostDB:ENSG00000172113; -.
DR eggNOG; KOG0888; Eukaryota.
DR GeneTree; ENSGT00940000160284; -.
DR HOGENOM; CLU_2060685_0_0_1; -.
DR InParanoid; O75414; -.
DR OrthoDB; 1395365at2759; -.
DR PhylomeDB; O75414; -.
DR TreeFam; TF354225; -.
DR PathwayCommons; O75414; -.
DR SignaLink; O75414; -.
DR BioGRID-ORCS; 10201; 103 hits in 1087 CRISPR screens.
DR ChiTaRS; NME6; human.
DR GenomeRNAi; 10201; -.
DR Pharos; O75414; Tbio.
DR PRO; PR:O75414; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; O75414; protein.
DR Bgee; ENSG00000172113; Expressed in ventricular zone and 150 other tissues.
DR ExpressionAtlas; O75414; baseline and differential.
DR Genevisible; O75414; HS.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006241; P:CTP biosynthetic process; IEA:InterPro.
DR GO; GO:0006183; P:GTP biosynthetic process; IEA:InterPro.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0045839; P:negative regulation of mitotic nuclear division; IDA:UniProtKB.
DR GO; GO:0006165; P:nucleoside diphosphate phosphorylation; IEA:InterPro.
DR GO; GO:0006228; P:UTP biosynthetic process; IEA:InterPro.
DR CDD; cd04414; NDPk6; 1.
DR Gene3D; 3.30.70.141; -; 1.
DR InterPro; IPR034907; NDK-like_dom.
DR InterPro; IPR036850; NDK-like_dom_sf.
DR InterPro; IPR037994; NDPk6.
DR InterPro; IPR001564; Nucleoside_diP_kinase.
DR InterPro; IPR023005; Nucleoside_diP_kinase_AS.
DR PANTHER; PTHR46956; PTHR46956; 1.
DR Pfam; PF00334; NDK; 1.
DR PRINTS; PR01243; NUCDPKINASE.
DR SMART; SM00562; NDK; 1.
DR SUPFAM; SSF54919; SSF54919; 1.
DR PROSITE; PS00469; NDP_KINASES; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; ATP-binding; Kinase; Magnesium;
KW Metal-binding; Nucleotide metabolism; Nucleotide-binding;
KW Reference proteome; Transferase.
FT CHAIN 1..186
FT /note="Nucleoside diphosphate kinase 6"
FT /id="PRO_0000137127"
FT ACT_SITE 129
FT /note="Pros-phosphohistidine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10030"
FT BINDING 19
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 68
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 96
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 102
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 116
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 126
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT VAR_SEQ 65..186
FT /note="GRFFYQRLVEFMASGPIRAYILAHKDAIQLWRTLMGPTRVFRARHVAPDSIR
FT GSFGLTDTRNTTHGSDSVVSASREIAAFFPDFSEQRWYEEEEPQLRCGPVCYSPEGGVH
FT YVAGTGGLGPA -> AGQSEPTSLPTRMPSSSGGRSWDPPECSEHAMWPQILSVGVSAS
FT LTPATPPMVRTLWFQPAERLQPSSLTSVNSAGMRRKSPSCAVALCAIAQREVSTM (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036883"
FT VAR_SEQ 65..131
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036882"
FT CONFLICT 182
FT /note="G -> S (in Ref. 3; BAD96275)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 186 AA; 21142 MW; DB8C5E046FACD143 CRC64;
MASILRSPQA LQLTLALIKP DAVAHPLILE AVHQQILSNK FLIVRMRELL WRKEDCQRFY
REHEGRFFYQ RLVEFMASGP IRAYILAHKD AIQLWRTLMG PTRVFRARHV APDSIRGSFG
LTDTRNTTHG SDSVVSASRE IAAFFPDFSE QRWYEEEEPQ LRCGPVCYSP EGGVHYVAGT
GGLGPA
