KAD4_HUMAN
ID KAD4_HUMAN Reviewed; 223 AA.
AC P27144; B2R927; D3DQ62; Q6IBH4; Q6NXQ5; Q8IUU9;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Adenylate kinase 4, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03170};
DE Short=AK 4 {ECO:0000255|HAMAP-Rule:MF_03170};
DE EC=2.7.4.10 {ECO:0000255|HAMAP-Rule:MF_03170, ECO:0000269|PubMed:19766732, ECO:0000269|PubMed:23416111};
DE EC=2.7.4.6 {ECO:0000255|HAMAP-Rule:MF_03170, ECO:0000269|PubMed:19766732, ECO:0000269|PubMed:23416111};
DE AltName: Full=Adenylate kinase 3-like {ECO:0000255|HAMAP-Rule:MF_03170};
DE AltName: Full=GTP:AMP phosphotransferase AK4 {ECO:0000255|HAMAP-Rule:MF_03170};
GN Name=AK4 {ECO:0000255|HAMAP-Rule:MF_03170};
GN Synonyms=AK3, AK3L1 {ECO:0000255|HAMAP-Rule:MF_03170};
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].
RX PubMed=1639383; DOI=10.1016/0888-7543(92)90122-9;
RA Xu G., O'Connell P., Stevens J., White R.;
RT "Characterization of human adenylate kinase 3 (AK3) cDNA and mapping of the
RT AK3 pseudogene to an intron of the NF1 gene.";
RL Genomics 13:537-542(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Colon, and Lung;
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 TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=11485571; DOI=10.1042/0264-6021:3580225;
RA Noma T., Fujisawa K., Yamashiro Y., Shinohara M., Nakazawa A., Gondo T.,
RA Ishihara T., Yoshinobu K.;
RT "Structure and expression of human mitochondrial adenylate kinase targeted
RT to the mitochondrial matrix.";
RL Biochem. J. 358:225-232(2001).
RN [8]
RP FUNCTION, INTERACTION WITH SLC25A5, AND INDUCTION BY HYPOXIA.
RX PubMed=19130895; DOI=10.1016/j.biocel.2008.12.002;
RA Liu R., Stroem A.L., Zhai J., Gal J., Bao S., Gong W., Zhu H.;
RT "Enzymatically inactive adenylate kinase 4 interacts with mitochondrial
RT ADP/ATP translocase.";
RL Int. J. Biochem. Cell Biol. 41:1371-1380(2009).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF LYS-4 AND ARG-7.
RX PubMed=19766732; DOI=10.1016/j.biocel.2009.09.007;
RA Panayiotou C., Solaroli N., Johansson M., Karlsson A.;
RT "Evidence of an intact N-terminal translocation sequence of human
RT mitochondrial adenylate kinase 4.";
RL Int. J. Biochem. Cell Biol. 42:62-69(2010).
RN [10]
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 [11]
RP FUNCTION, AND INDUCTION.
RX PubMed=23474458; DOI=10.1016/j.abb.2013.02.014;
RA Kong F., Binas B., Moon J.H., Kang S.S., Kim H.J.;
RT "Differential expression of adenylate kinase 4 in the context of disparate
RT stress response strategies of HEK293 and HepG2 cells.";
RL Arch. Biochem. Biophys. 533:11-17(2013).
RN [12]
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).
RN [13]
RP FUNCTION.
RX PubMed=24767988; DOI=10.1016/j.celrep.2014.03.065;
RA Lanning N.J., Looyenga B.D., Kauffman A.L., Niemi N.M., Sudderth J.,
RA DeBerardinis R.J., MacKeigan J.P.;
RT "A mitochondrial RNAi screen defines cellular bioenergetic determinants and
RT identifies an adenylate kinase as a key regulator of ATP levels.";
RL Cell Rep. 7:907-917(2014).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
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).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=26980435; DOI=10.1186/s13046-016-0322-2;
RA Fujisawa K., Terai S., Takami T., Yamamoto N., Yamasaki T., Matsumoto T.,
RA Yamaguchi K., Owada Y., Nishina H., Noma T., Sakaida I.;
RT "Modulation of anti-cancer drug sensitivity through the regulation of
RT mitochondrial activity by adenylate kinase 4.";
RL J. Exp. Clin. Cancer Res. 35:48-48(2016).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) IN COMPLEX WITH DIGUANOSINE
RP PENTAPHOSPHATE, AND SUBUNIT.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human adenylate kinase 4 (AK4) in complex with
RT diguanosine pentaphosphate.";
RL Submitted (DEC-2005) to the PDB data bank.
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS), AND FUNCTION.
RX PubMed=19073142; DOI=10.1016/j.bbrc.2008.12.012;
RA Liu R., Xu H., Wei Z., Wang Y., Lin Y., Gong W.;
RT "Crystal structure of human adenylate kinase 4 (L171P) suggests the role of
RT hinge region in protein domain motion.";
RL Biochem. Biophys. Res. Commun. 379:92-97(2009).
CC -!- FUNCTION: Involved in maintaining the homeostasis of cellular
CC nucleotides by catalyzing the interconversion of nucleoside phosphates
CC (PubMed:19073142, PubMed:19766732, PubMed:23416111, PubMed:24767988).
CC Efficiently phosphorylates AMP and dAMP using ATP as phosphate donor,
CC but phosphorylates only AMP when using GTP as phosphate donor
CC (PubMed:19073142, PubMed:19766732, PubMed:23416111). Also displays
CC broad nucleoside diphosphate kinase activity (PubMed:19073142,
CC PubMed:19766732, PubMed:23416111). Plays a role in controlling cellular
CC ATP levels by regulating phosphorylation and activation of the energy
CC sensor protein kinase AMPK (PubMed:24767988, PubMed:26980435). Plays a
CC protective role in the cellular response to oxidative stress
CC (PubMed:19130895, PubMed:23474458, PubMed:26980435).
CC {ECO:0000255|HAMAP-Rule:MF_03170, ECO:0000269|PubMed:19073142,
CC ECO:0000269|PubMed:19130895, ECO:0000269|PubMed:19766732,
CC ECO:0000269|PubMed:23416111, ECO:0000269|PubMed:23474458,
CC ECO:0000269|PubMed:24767988, ECO:0000269|PubMed:26980435}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + AMP = a ribonucleoside 5'-
CC diphosphate + ADP; Xref=Rhea:RHEA:13749, ChEBI:CHEBI:57930,
CC ChEBI:CHEBI:61557, ChEBI:CHEBI:456215, ChEBI:CHEBI:456216;
CC EC=2.7.4.10; Evidence={ECO:0000255|HAMAP-Rule:MF_03170,
CC ECO:0000269|PubMed:19766732, 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; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03170, ECO:0000269|PubMed:19766732,
CC 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:0000255|HAMAP-Rule:MF_03170,
CC ECO:0000269|PubMed:19766732, ECO:0000269|PubMed:23416111};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.3 uM for AMP with ATP as phosphate donor
CC {ECO:0000269|PubMed:19766732};
CC KM=1.4 uM for AMP with GTP as phosphate donor
CC {ECO:0000269|PubMed:19766732};
CC KM=507 uM for dAMP with ATP as phosphate donor
CC {ECO:0000269|PubMed:19766732};
CC Vmax=90 pmol/min/ug enzyme with AMP as substrate and ATP as phosphate
CC donor {ECO:0000269|PubMed:19766732};
CC Vmax=80 pmol/min/ug enzyme with AMP as substrate and GTP as phosphate
CC donor {ECO:0000269|PubMed:19766732};
CC Vmax=88 pmol/min/ug enzyme with dAMP as substrate and ATP as
CC phosphate donor {ECO:0000269|PubMed:19766732};
CC -!- SUBUNIT: Monomer (Ref.17). Interacts with SLC25A5/ANT2
CC (PubMed:19130895). {ECO:0000255|HAMAP-Rule:MF_03170,
CC ECO:0000269|PubMed:19130895, ECO:0000269|Ref.17}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000255|HAMAP-
CC Rule:MF_03170, ECO:0000269|PubMed:11485571,
CC ECO:0000269|PubMed:19766732, ECO:0000269|PubMed:26980435}.
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney, moderately expressed in
CC heart and liver and weakly expressed in brain.
CC {ECO:0000269|PubMed:11485571}.
CC -!- INDUCTION: By hypoxia (at protein level). {ECO:0000269|PubMed:19130895,
CC ECO:0000269|PubMed:23474458, ECO:0000269|PubMed:26980435}.
CC -!- DOMAIN: Consists of three domains, a large central CORE domain and two
CC small peripheral domains, NMPbind and LID, which undergo movements
CC during catalysis. The LID domain closes over the site of phosphoryl
CC transfer upon GTP/ATP binding. Assembling and dissambling the active
CC center during each catalytic cycle provides an effective means to
CC prevent GTP/ATP hydrolysis. {ECO:0000255|HAMAP-Rule:MF_03170,
CC ECO:0000305|PubMed:19073142}.
CC -!- SIMILARITY: Belongs to the adenylate kinase family. AK3 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03170}.
CC -!- CAUTION: Some studies have failed to detect adenylate kinase activity
CC (PubMed:11485571, PubMed:19130895). However, kinase activity has been
CC demonstrated in a number of other studies (PubMed:19766732,
CC PubMed:23416111). {ECO:0000269|PubMed:11485571,
CC ECO:0000269|PubMed:19130895, ECO:0000269|PubMed:19766732,
CC ECO:0000269|PubMed:23416111}.
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DR EMBL; X60673; CAA43088.1; -; mRNA.
DR EMBL; CR456830; CAG33111.1; -; mRNA.
DR EMBL; AK313611; BAG36374.1; -; mRNA.
DR EMBL; AC099680; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356212; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06538.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06540.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06544.1; -; Genomic_DNA.
DR EMBL; BC016180; AAH16180.1; -; mRNA.
DR EMBL; BC040224; AAH40224.1; -; mRNA.
DR EMBL; BC066944; AAH66944.1; -; mRNA.
DR EMBL; BC136886; AAI36887.1; -; mRNA.
DR EMBL; BC136887; AAI36888.1; -; mRNA.
DR EMBL; BC148270; AAI48271.1; -; mRNA.
DR EMBL; BC146653; AAI46654.1; -; mRNA.
DR CCDS; CCDS629.1; -.
DR PIR; A42820; KIHUA3.
DR RefSeq; NP_001005353.1; NM_001005353.2.
DR RefSeq; NP_037542.1; NM_013410.3.
DR RefSeq; NP_982289.1; NM_203464.2.
DR PDB; 2AR7; X-ray; 2.15 A; A/B=1-223.
DR PDB; 2BBW; X-ray; 2.05 A; A/B=1-223.
DR PDB; 3NDP; X-ray; 2.30 A; A/B=1-223.
DR PDBsum; 2AR7; -.
DR PDBsum; 2BBW; -.
DR PDBsum; 3NDP; -.
DR AlphaFoldDB; P27144; -.
DR SMR; P27144; -.
DR BioGRID; 106708; 187.
DR IntAct; P27144; 22.
DR MINT; P27144; -.
DR STRING; 9606.ENSP00000378743; -.
DR BindingDB; P27144; -.
DR ChEMBL; CHEMBL4926; -.
DR DrugBank; DB00718; Adefovir dipivoxil.
DR DrugBank; DB00300; Tenofovir disoproxil.
DR iPTMnet; P27144; -.
DR PhosphoSitePlus; P27144; -.
DR BioMuta; AK4; -.
DR DMDM; 125157; -.
DR UCD-2DPAGE; P27144; -.
DR EPD; P27144; -.
DR jPOST; P27144; -.
DR MassIVE; P27144; -.
DR MaxQB; P27144; -.
DR PaxDb; P27144; -.
DR PeptideAtlas; P27144; -.
DR PRIDE; P27144; -.
DR ProteomicsDB; 54375; -.
DR TopDownProteomics; P27144; -.
DR ABCD; P27144; 10 sequenced antibodies.
DR Antibodypedia; 19540; 464 antibodies from 32 providers.
DR DNASU; 205; -.
DR Ensembl; ENST00000327299.8; ENSP00000322175.7; ENSG00000162433.15.
DR Ensembl; ENST00000395334.6; ENSP00000378743.2; ENSG00000162433.15.
DR Ensembl; ENST00000545314.5; ENSP00000445912.1; ENSG00000162433.15.
DR GeneID; 205; -.
DR KEGG; hsa:205; -.
DR MANE-Select; ENST00000327299.8; ENSP00000322175.7; NM_013410.4; NP_037542.1.
DR UCSC; uc001dby.3; human.
DR CTD; 205; -.
DR DisGeNET; 205; -.
DR GeneCards; AK4; -.
DR HGNC; HGNC:363; AK4.
DR HPA; ENSG00000162433; Tissue enhanced (kidney, liver).
DR MIM; 103030; gene.
DR neXtProt; NX_P27144; -.
DR OpenTargets; ENSG00000162433; -.
DR PharmGKB; PA165750325; -.
DR VEuPathDB; HostDB:ENSG00000162433; -.
DR eggNOG; KOG3078; Eukaryota.
DR GeneTree; ENSGT00940000154568; -.
DR HOGENOM; CLU_032354_1_1_1; -.
DR InParanoid; P27144; -.
DR OMA; IKVENTM; -.
DR OrthoDB; 1004067at2759; -.
DR PhylomeDB; P27144; -.
DR TreeFam; TF312916; -.
DR BRENDA; 2.7.4.10; 2681.
DR BRENDA; 2.7.4.3; 2681.
DR PathwayCommons; P27144; -.
DR Reactome; R-HSA-499943; Interconversion of nucleotide di- and triphosphates.
DR SABIO-RK; P27144; -.
DR SignaLink; P27144; -.
DR BioGRID-ORCS; 205; 134 hits in 1043 CRISPR screens.
DR ChiTaRS; AK4; human.
DR EvolutionaryTrace; P27144; -.
DR GeneWiki; AK3L1; -.
DR GenomeRNAi; 205; -.
DR Pharos; P27144; Tbio.
DR PRO; PR:P27144; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P27144; protein.
DR Bgee; ENSG00000162433; Expressed in adult organism and 199 other tissues.
DR ExpressionAtlas; P27144; baseline and differential.
DR Genevisible; P27144; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0004017; F:adenylate kinase activity; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB.
DR GO; GO:0050145; F:nucleoside monophosphate kinase activity; TAS:Reactome.
DR GO; GO:0046899; F:nucleoside triphosphate adenylate kinase activity; IDA:BHF-UCL.
DR GO; GO:0006172; P:ADP biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0046033; P:AMP metabolic process; IDA:BHF-UCL.
DR GO; GO:0046034; P:ATP metabolic process; IDA:BHF-UCL.
DR GO; GO:0071456; P:cellular response to hypoxia; IMP:UniProtKB.
DR GO; GO:0046039; P:GTP metabolic process; IDA:BHF-UCL.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
DR GO; GO:0006165; P:nucleoside diphosphate phosphorylation; IDA:UniProtKB.
DR GO; GO:0009142; P:nucleoside triphosphate biosynthetic process; IDA:UniProtKB.
DR GO; GO:2001169; P:regulation of ATP biosynthetic process; IMP:UniProtKB.
DR GO; GO:0002082; P:regulation of oxidative phosphorylation; IMP:UniProtKB.
DR CDD; cd01428; ADK; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_00235; Adenylate_kinase_Adk; 1.
DR HAMAP; MF_03169; Adenylate_kinase_AK3; 1.
DR HAMAP; MF_03170; Adenylate_kinase_AK4; 1.
DR InterPro; IPR006259; Adenyl_kin_sub.
DR InterPro; IPR000850; Adenylat/UMP-CMP_kin.
DR InterPro; IPR033690; Adenylat_kinase_CS.
DR InterPro; IPR007862; Adenylate_kinase_lid-dom.
DR InterPro; IPR036193; ADK_active_lid_dom_sf.
DR InterPro; IPR028586; AK3/Ak4_mitochondrial.
DR InterPro; IPR028585; AK4_mitochondrial.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR23359; PTHR23359; 1.
DR Pfam; PF05191; ADK_lid; 1.
DR PRINTS; PR00094; ADENYLTKNASE.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF57774; SSF57774; 1.
DR TIGRFAMs; TIGR01351; adk; 1.
DR PROSITE; PS00113; ADENYLATE_KINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; GTP-binding; Kinase; Mitochondrion;
KW Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1..223
FT /note="Adenylate kinase 4, mitochondrial"
FT /id="PRO_0000158926"
FT REGION 35..64
FT /note="NMP"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170,
FT ECO:0000269|PubMed:19073142"
FT REGION 125..162
FT /note="LID"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170,
FT ECO:0000269|PubMed:19073142"
FT BINDING 15..20
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170,
FT ECO:0000269|Ref.17"
FT BINDING 36
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170,
FT ECO:0000269|Ref.17"
FT BINDING 41
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170"
FT BINDING 62..64
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170,
FT ECO:0000269|Ref.17"
FT BINDING 89..92
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170,
FT ECO:0000269|Ref.17"
FT BINDING 96
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170"
FT BINDING 126
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170,
FT ECO:0000269|Ref.17"
FT BINDING 135..136
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170"
FT BINDING 170
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170,
FT ECO:0000269|Ref.17"
FT BINDING 199
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170,
FT ECO:0000269|Ref.17"
FT MOD_RES 60
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9WUR9"
FT MOD_RES 175
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9WUR9"
FT MOD_RES 179
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9WUR9"
FT MOD_RES 179
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9WUR9"
FT MOD_RES 186
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9WUR9"
FT MOD_RES 186
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9WUR9"
FT MUTAGEN 4
FT /note="K->G: Abolishes mitochondrial import; when
FT associated with G-7."
FT /evidence="ECO:0000269|PubMed:19766732"
FT MUTAGEN 7
FT /note="R->G: Abolishes mitochondrial import; when
FT associated with G-4."
FT /evidence="ECO:0000269|PubMed:19766732"
FT CONFLICT 22
FT /note="C -> S (in Ref. 6; AAH40224/AAI46654)"
FT /evidence="ECO:0000305"
FT CONFLICT 23
FT /note="Q -> R (in Ref. 6; AAH66944)"
FT /evidence="ECO:0000305"
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:2BBW"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:2BBW"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:2AR7"
FT HELIX 36..45
FT /evidence="ECO:0007829|PDB:2BBW"
FT HELIX 49..59
FT /evidence="ECO:0007829|PDB:2BBW"
FT HELIX 66..78
FT /evidence="ECO:0007829|PDB:2BBW"
FT TURN 79..82
FT /evidence="ECO:0007829|PDB:2AR7"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:2BBW"
FT HELIX 94..101
FT /evidence="ECO:0007829|PDB:2BBW"
FT STRAND 108..113
FT /evidence="ECO:0007829|PDB:2BBW"
FT HELIX 116..124
FT /evidence="ECO:0007829|PDB:2BBW"
FT STRAND 126..129
FT /evidence="ECO:0007829|PDB:2BBW"
FT TURN 130..133
FT /evidence="ECO:0007829|PDB:2BBW"
FT STRAND 134..137
FT /evidence="ECO:0007829|PDB:2BBW"
FT TURN 138..140
FT /evidence="ECO:0007829|PDB:2BBW"
FT TURN 150..152
FT /evidence="ECO:0007829|PDB:2BBW"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:2BBW"
FT HELIX 164..187
FT /evidence="ECO:0007829|PDB:2BBW"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:2BBW"
FT HELIX 199..211
FT /evidence="ECO:0007829|PDB:2BBW"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:3NDP"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:2BBW"
SQ SEQUENCE 223 AA; 25268 MW; 653341A8EB3BC723 CRC64;
MASKLLRAVI LGPPGSGKGT VCQRIAQNFG LQHLSSGHFL RENIKASTEV GEMAKQYIEK
SLLVPDHVIT RLMMSELENR RGQHWLLDGF PRTLGQAEAL DKICEVDLVI SLNIPFETLK
DRLSRRWIHP PSGRVYNLDF NPPHVHGIDD VTGEPLVQQE DDKPEAVAAR LRQYKDVAKP
VIELYKSRGV LHQFSGTETN KIWPYVYTLF SNKITPIQSK EAY
