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 27-MAR-2024, entry version 190. 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. DR RefSeq; XP_016861004.1; XM_017005515.1. [O75414-3] DR AlphaFoldDB; O75414; -. DR SMR; O75414; -. DR BioGRID; 115496; 20. DR IntAct; O75414; 11. 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; 9606-ENSP00000416658; -. DR PeptideAtlas; O75414; -. DR ProteomicsDB; 49985; -. [O75414-1] DR ProteomicsDB; 49986; -. [O75414-2] DR ProteomicsDB; 49987; -. [O75414-3] DR Pumba; O75414; -. DR Antibodypedia; 13081; 203 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 AGR; HGNC:20567; -. 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; 4638at2759; -. DR PhylomeDB; O75414; -. DR TreeFam; TF354225; -. DR PathwayCommons; O75414; -. DR SignaLink; O75414; -. DR BioGRID-ORCS; 10201; 115 hits in 1171 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 primordial germ cell in gonad and 152 other cell types or tissues. DR ExpressionAtlas; O75414; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB. 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:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0006228; P:UTP biosynthetic process; IEA:InterPro. DR CDD; cd04414; NDPk6; 1. DR Gene3D; 3.30.70.141; Nucleoside diphosphate kinase-like domain; 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; NUCLEOSIDE DIPHOSPHATE KINASE 6; 1. DR PANTHER; PTHR46956:SF1; NUCLEOSIDE DIPHOSPHATE KINASE 6; 1. DR Pfam; PF00334; NDK; 1. DR PRINTS; PR01243; NUCDPKINASE. DR SMART; SM00562; NDK; 1. DR SUPFAM; SSF54919; Nucleoside diphosphate kinase, NDK; 1. DR PROSITE; PS00469; NDPK; 1. DR PROSITE; PS51374; NDPK_LIKE; 1. DR Genevisible; O75414; HS. 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 //