KAD2_HUMAN
ID KAD2_HUMAN Reviewed; 239 AA.
AC P54819; A8K6L1; B4DHH7; B4DL64; Q16856; Q5EB54; Q5TIF7; Q8TCY2; Q8TCY3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Adenylate kinase 2, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03168};
DE Short=AK 2 {ECO:0000255|HAMAP-Rule:MF_03168};
DE EC=2.7.4.3 {ECO:0000255|HAMAP-Rule:MF_03168};
DE AltName: Full=ATP-AMP transphosphorylase 2 {ECO:0000255|HAMAP-Rule:MF_03168};
DE AltName: Full=ATP:AMP phosphotransferase {ECO:0000255|HAMAP-Rule:MF_03168};
DE AltName: Full=Adenylate monophosphate kinase {ECO:0000255|HAMAP-Rule:MF_03168};
DE Contains:
DE RecName: Full=Adenylate kinase 2, mitochondrial, N-terminally processed {ECO:0000255|HAMAP-Rule:MF_03168};
GN Name=AK2 {ECO:0000255|HAMAP-Rule:MF_03168}; Synonyms=ADK2;
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=8843353; DOI=10.1080/15216549600201931;
RA Lee Y., Kim J.W., Lee I.A., Kang H.B., Choe Y.K., Lee H.G., Lim J.S.,
RA Kim H.J., Park C., Choe I.S.;
RT "Cloning and characterization of cDNA for human adenylate kinase 2A.";
RL Biochem. Mol. Biol. Int. 39:833-842(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Fetal liver;
RX PubMed=9504408; DOI=10.1093/oxfordjournals.jbchem.a021915;
RA Lee Y., Kim J.W., Lee S.M., Kim H.J., Lee K.S., Park C., Choe I.S.;
RT "Cloning and expression of human adenylate kinase 2 isozymes: differential
RT expression of adenylate kinase 1 and 2 in human muscle tissues.";
RL J. Biochem. 123:47-54(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=9434148; DOI=10.1016/s0167-4781(97)00193-0;
RA Noma T., Song S., Yoon Y.-S., Tanaka S., Nakazawa A.;
RT "cDNA cloning and tissue-specific expression of the gene encoding human
RT adenylate kinase isozyme 2.";
RL Biochim. Biophys. Acta 1395:34-39(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
RA Guo J.;
RT "Novel isoforms of human adenylate kinase 2.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 5 AND 6).
RC TISSUE=Brain, Placenta, and Tongue;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [7]
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 [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Placenta, and Uterus;
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 [10]
RP PROTEIN SEQUENCE OF 2-14; 18-34; 73-85; 94-103; 107-117 AND 120-138,
RP CLEAVAGE OF INITIATOR METHIONINE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Heiserich L., Gottlieb E.;
RL Submitted (MAR-2008) to UniProtKB.
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-58 AND THR-195, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133, AND IDENTIFICATION BY
RP 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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [17]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH BI-SUBSTRATE ANALOG
RP AP4A, AND DISULFIDE BOND.
RA Bunkoczi G., Filippakopoulos P., Debreczeni J.E., Turnbull A.,
RA Papagrigoriou E., Savitsky P., Colebrook S., Von Delft F., Arrowsmith C.,
RA Edwards A., Sundstrom M., Weigelt J., Knapp S.;
RT "Structure of human adenylate kinase 2.";
RL Submitted (JAN-2006) to the PDB data bank.
RN [18]
RP INVOLVEMENT IN RDYS, AND TISSUE SPECIFICITY.
RX PubMed=19043417; DOI=10.1038/ng.265;
RA Pannicke U., Hoenig M., Hess I., Friesen C., Holzmann K., Rump E.-M.,
RA Barth T.F., Rojewski M.T., Schulz A., Boehm T., Friedrich W., Schwarz K.;
RT "Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene
RT encoding mitochondrial adenylate kinase 2.";
RL Nat. Genet. 41:101-105(2009).
RN [19]
RP VARIANTS RDYS TRP-103 AND GLY-165, AND FUNCTION.
RX PubMed=19043416; DOI=10.1038/ng.278;
RA Lagresle-Peyrou C., Six E.M., Picard C., Rieux-Laucat F., Michel V.,
RA Ditadi A., Chappedelaine C.D., Morillon E., Valensi F., Simon-Stoos K.L.,
RA Mullikin J.C., Noroski L.M., Besse C., Wulffraat N.M., Ferster A.,
RA Abecasis M.M., Calvo F., Petit C., Candotti F., Abel L., Fischer A.,
RA Cavazzana-Calvo M.;
RT "Human adenylate kinase 2 deficiency causes a profound hematopoietic defect
RT associated with sensorineural deafness.";
RL Nat. Genet. 41:106-111(2009).
CC -!- FUNCTION: Catalyzes the reversible transfer of the terminal phosphate
CC group between ATP and AMP. Plays an important role in cellular energy
CC homeostasis and in adenine nucleotide metabolism. Adenylate kinase
CC activity is critical for regulation of the phosphate utilization and
CC the AMP de novo biosynthesis pathways. Plays a key role in
CC hematopoiesis. {ECO:0000255|HAMAP-Rule:MF_03168,
CC ECO:0000269|PubMed:19043416}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AMP + ATP = 2 ADP; Xref=Rhea:RHEA:12973, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:456215, ChEBI:CHEBI:456216; EC=2.7.4.3;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03168};
CC -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_03168}.
CC -!- INTERACTION:
CC P54819; P54253: ATXN1; NbExp=3; IntAct=EBI-1056291, EBI-930964;
CC P54819; P16284: PECAM1; NbExp=3; IntAct=EBI-1056291, EBI-716404;
CC P54819; D3DTS7: PMP22; NbExp=3; IntAct=EBI-1056291, EBI-25882629;
CC P54819; P17612: PRKACA; NbExp=3; IntAct=EBI-1056291, EBI-476586;
CC P54819; P49810: PSEN2; NbExp=3; IntAct=EBI-1056291, EBI-2010251;
CC P54819; P50454: SERPINH1; NbExp=3; IntAct=EBI-1056291, EBI-350723;
CC P54819; P37173: TGFBR2; NbExp=3; IntAct=EBI-1056291, EBI-296151;
CC P54819; P08670: VIM; NbExp=3; IntAct=EBI-1056291, EBI-353844;
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000255|HAMAP-Rule:MF_03168}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=AK2A, AK2isoA;
CC IsoId=P54819-1; Sequence=Displayed;
CC Name=2; Synonyms=AK2B, AK2isoB;
CC IsoId=P54819-2; Sequence=VSP_002790;
CC Name=3; Synonyms=AK2C;
CC IsoId=P54819-3; Sequence=VSP_002791;
CC Name=4; Synonyms=AK2D;
CC IsoId=P54819-4; Sequence=VSP_002792, VSP_002793, VSP_002794;
CC Name=5;
CC IsoId=P54819-5; Sequence=VSP_036503, VSP_002790;
CC Name=6;
CC IsoId=P54819-6; Sequence=VSP_002792;
CC -!- TISSUE SPECIFICITY: Present in most tissues. Present at high level in
CC heart, liver and kidney, and at low level in brain, skeletal muscle and
CC skin. Present in thrombocytes but not in erythrocytes, which lack
CC mitochondria. Present in all nucleated cell populations from blood,
CC while AK1 is mostly absent. In spleen and lymph nodes, mononuclear
CC cells lack AK1, whereas AK2 is readily detectable. These results
CC indicate that leukocytes may be susceptible to defects caused by the
CC lack of AK2, as they do not express AK1 in sufficient amounts to
CC compensate for the AK2 functional deficits (at protein level).
CC {ECO:0000269|PubMed:19043417}.
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 ATP binding. Assembling and dissambling the active center
CC during each catalytic cycle provides an effective means to prevent ATP
CC hydrolysis. {ECO:0000255|HAMAP-Rule:MF_03168, ECO:0000305|Ref.17}.
CC -!- DISEASE: Reticular dysgenesis (RDYS) [MIM:267500]: A fatal form of
CC severe combined immunodeficiency, characterized by absence of
CC granulocytes, almost complete deficiency of lymphocytes in peripheral
CC blood, hypoplasia of the thymus and secondary lymphoid organs, and lack
CC of innate and adaptive humoral and cellular immunity, leading to fatal
CC septicemia within days after birth. In bone marrow of individuals with
CC reticular dysgenesis, myeloid differentiation is blocked at the
CC promyelocytic stage, whereas erythro- and megakaryocytic maturation is
CC generally normal. Inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:19043416, ECO:0000269|PubMed:19043417}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the adenylate kinase family. AK2 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03168}.
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DR EMBL; U39945; AAC52061.1; -; mRNA.
DR EMBL; U84371; AAB41790.1; -; mRNA.
DR EMBL; U54645; AAC13881.1; -; mRNA.
DR EMBL; AB005621; BAC16747.1; -; mRNA.
DR EMBL; AB005622; BAC16748.1; -; mRNA.
DR EMBL; AY080899; AAL87027.1; -; mRNA.
DR EMBL; AY080900; AAL87028.1; -; mRNA.
DR EMBL; AK291676; BAF84365.1; -; mRNA.
DR EMBL; AK295105; BAG58139.1; -; mRNA.
DR EMBL; AK296863; BAG59426.1; -; mRNA.
DR EMBL; AB451267; BAG70081.1; -; mRNA.
DR EMBL; AB451394; BAG70208.1; -; mRNA.
DR EMBL; AL020995; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07484.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07486.1; -; Genomic_DNA.
DR EMBL; BC009405; AAH09405.1; -; mRNA.
DR EMBL; BC070127; AAH70127.1; -; mRNA.
DR EMBL; BC090040; AAH90040.1; -; mRNA.
DR CCDS; CCDS373.1; -. [P54819-2]
DR CCDS; CCDS374.1; -. [P54819-1]
DR PIR; G02248; G02248.
DR PIR; JC5893; JC5893.
DR RefSeq; NP_001186128.1; NM_001199199.1. [P54819-5]
DR RefSeq; NP_001306068.1; NM_001319139.1.
DR RefSeq; NP_001306069.1; NM_001319140.1. [P54819-6]
DR RefSeq; NP_001616.1; NM_001625.3. [P54819-1]
DR RefSeq; NP_037543.1; NM_013411.4. [P54819-2]
DR PDB; 2C9Y; X-ray; 2.10 A; A=1-239.
DR PDBsum; 2C9Y; -.
DR AlphaFoldDB; P54819; -.
DR SMR; P54819; -.
DR BioGRID; 106707; 120.
DR CORUM; P54819; -.
DR IntAct; P54819; 62.
DR MINT; P54819; -.
DR STRING; 9606.ENSP00000346921; -.
DR BindingDB; P54819; -.
DR ChEMBL; CHEMBL4938; -.
DR DrugBank; DB00718; Adefovir dipivoxil.
DR DrugBank; DB01717; Bis(Adenosine)-5'-Pentaphosphate.
DR DrugBank; DB03366; Imidazole.
DR DrugBank; DB14126; Tenofovir.
DR DrugBank; DB09299; Tenofovir alafenamide.
DR DrugBank; DB00300; Tenofovir disoproxil.
DR GlyGen; P54819; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P54819; -.
DR MetOSite; P54819; -.
DR PhosphoSitePlus; P54819; -.
DR SwissPalm; P54819; -.
DR BioMuta; AK2; -.
DR DMDM; 1708596; -.
DR OGP; P54819; -.
DR REPRODUCTION-2DPAGE; IPI00218988; -.
DR UCD-2DPAGE; P54819; -.
DR EPD; P54819; -.
DR jPOST; P54819; -.
DR MassIVE; P54819; -.
DR MaxQB; P54819; -.
DR PaxDb; P54819; -.
DR PeptideAtlas; P54819; -.
DR PRIDE; P54819; -.
DR ProteomicsDB; 56726; -. [P54819-1]
DR ProteomicsDB; 56727; -. [P54819-2]
DR ProteomicsDB; 56728; -. [P54819-3]
DR ProteomicsDB; 56729; -. [P54819-4]
DR ProteomicsDB; 56730; -. [P54819-5]
DR ProteomicsDB; 56731; -. [P54819-6]
DR Antibodypedia; 17047; 464 antibodies from 33 providers.
DR DNASU; 204; -.
DR Ensembl; ENST00000373449.7; ENSP00000362548.2; ENSG00000004455.17. [P54819-2]
DR Ensembl; ENST00000672715.1; ENSP00000499935.1; ENSG00000004455.17. [P54819-1]
DR GeneID; 204; -.
DR KEGG; hsa:204; -.
DR MANE-Select; ENST00000672715.1; ENSP00000499935.1; NM_001625.4; NP_001616.1.
DR UCSC; uc001bwo.3; human. [P54819-1]
DR CTD; 204; -.
DR DisGeNET; 204; -.
DR GeneCards; AK2; -.
DR HGNC; HGNC:362; AK2.
DR HPA; ENSG00000004455; Low tissue specificity.
DR MalaCards; AK2; -.
DR MIM; 103020; gene.
DR MIM; 267500; phenotype.
DR neXtProt; NX_P54819; -.
DR OpenTargets; ENSG00000004455; -.
DR Orphanet; 33355; Reticular dysgenesis.
DR PharmGKB; PA24656; -.
DR VEuPathDB; HostDB:ENSG00000004455; -.
DR eggNOG; KOG3078; Eukaryota.
DR GeneTree; ENSGT00940000154576; -.
DR InParanoid; P54819; -.
DR OMA; FHNRMRV; -.
DR PhylomeDB; P54819; -.
DR TreeFam; TF300896; -.
DR BRENDA; 2.7.4.3; 2681.
DR PathwayCommons; P54819; -.
DR Reactome; R-HSA-499943; Interconversion of nucleotide di- and triphosphates.
DR SignaLink; P54819; -.
DR BioGRID-ORCS; 204; 94 hits in 1073 CRISPR screens.
DR ChiTaRS; AK2; human.
DR EvolutionaryTrace; P54819; -.
DR GeneWiki; AK2; -.
DR GenomeRNAi; 204; -.
DR Pharos; P54819; Tbio.
DR PRO; PR:P54819; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P54819; protein.
DR Bgee; ENSG00000004455; Expressed in rectum and 185 other tissues.
DR ExpressionAtlas; P54819; baseline and differential.
DR Genevisible; P54819; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005758; C:mitochondrial intermembrane space; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0097226; C:sperm mitochondrial sheath; IEA:Ensembl.
DR GO; GO:0004017; F:adenylate kinase activity; EXP:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0006172; P:ADP biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0046033; P:AMP metabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0046034; P:ATP metabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR CDD; cd01428; ADK; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_00235; Adenylate_kinase_Adk; 1.
DR HAMAP; MF_03168; Adenylate_kinase_AK2; 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; IPR028587; AK2.
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 TIGRFAMs; TIGR01351; adk; 1.
DR PROSITE; PS00113; ADENYLATE_KINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Direct protein sequencing; Disease variant; Disulfide bond; Kinase;
KW Mitochondrion; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW SCID; Transferase.
FT CHAIN 1..239
FT /note="Adenylate kinase 2, mitochondrial"
FT /id="PRO_0000423212"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168,
FT ECO:0000269|Ref.10, ECO:0007744|PubMed:25944712"
FT CHAIN 2..239
FT /note="Adenylate kinase 2, mitochondrial, N-terminally
FT processed"
FT /id="PRO_0000158917"
FT REGION 45..74
FT /note="NMP"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168,
FT ECO:0000269|Ref.17"
FT REGION 141..178
FT /note="LID"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168,
FT ECO:0000269|Ref.17"
FT REGION 150..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 25..30
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168,
FT ECO:0000269|Ref.17"
FT BINDING 46
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168"
FT BINDING 51
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168"
FT BINDING 72..74
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168"
FT BINDING 100..103
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168"
FT BINDING 107
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168"
FT BINDING 138
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|Ref.17"
FT BINDING 142
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168"
FT BINDING 151..152
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168,
FT ECO:0000269|Ref.17"
FT BINDING 175
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168,
FT ECO:0000269|Ref.17"
FT BINDING 186
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168"
FT BINDING 214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168,
FT ECO:0000269|Ref.17"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378, ECO:0007744|PubMed:25944712"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 62
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9WTP6"
FT MOD_RES 93
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9WTP6"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 181
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9WTP6"
FT MOD_RES 195
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT DISULFID 42..92
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168,
FT ECO:0000269|Ref.17"
FT VAR_SEQ 1..48
FT /note="Missing (in isoform 4 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.4"
FT /id="VSP_002792"
FT VAR_SEQ 135..142
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036503"
FT VAR_SEQ 177..178
FT /note="DD -> GL (in isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_002793"
FT VAR_SEQ 178..239
FT /note="DNEKALKIRLQAYHTQTTPLIEYYRKRGIHSAIDASQTPDVVFASILAAFSK
FT ATCKDLVMFI -> IGQAKRSFLRLAKISFDVLIKKALA (in isoform 3)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_002791"
FT VAR_SEQ 179..239
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_002794"
FT VAR_SEQ 232..239
FT /note="CKDLVMFI -> S (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:19054851,
FT ECO:0000303|PubMed:9434148, ECO:0000303|PubMed:9504408"
FT /id="VSP_002790"
FT VARIANT 103
FT /note="R -> W (in RDYS; dbSNP:rs267606648)"
FT /evidence="ECO:0000269|PubMed:19043416"
FT /id="VAR_054630"
FT VARIANT 165
FT /note="D -> G (in RDYS; dbSNP:rs267606643)"
FT /evidence="ECO:0000269|PubMed:19043416"
FT /id="VAR_054631"
FT VARIANT 209
FT /note="A -> T (in dbSNP:rs12116440)"
FT /id="VAR_050032"
FT STRAND 16..21
FT /evidence="ECO:0007829|PDB:2C9Y"
FT HELIX 28..39
FT /evidence="ECO:0007829|PDB:2C9Y"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:2C9Y"
FT HELIX 46..56
FT /evidence="ECO:0007829|PDB:2C9Y"
FT HELIX 59..69
FT /evidence="ECO:0007829|PDB:2C9Y"
FT HELIX 76..87
FT /evidence="ECO:0007829|PDB:2C9Y"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:2C9Y"
FT STRAND 95..100
FT /evidence="ECO:0007829|PDB:2C9Y"
FT HELIX 105..117
FT /evidence="ECO:0007829|PDB:2C9Y"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:2C9Y"
FT HELIX 132..140
FT /evidence="ECO:0007829|PDB:2C9Y"
FT TURN 146..148
FT /evidence="ECO:0007829|PDB:2C9Y"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:2C9Y"
FT TURN 154..156
FT /evidence="ECO:0007829|PDB:2C9Y"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:2C9Y"
FT HELIX 180..203
FT /evidence="ECO:0007829|PDB:2C9Y"
FT STRAND 207..211
FT /evidence="ECO:0007829|PDB:2C9Y"
FT HELIX 216..230
FT /evidence="ECO:0007829|PDB:2C9Y"
SQ SEQUENCE 239 AA; 26478 MW; 86FA94F9EE33629F CRC64;
MAPSVPAAEP EYPKGIRAVL LGPPGAGKGT QAPRLAENFC VCHLATGDML RAMVASGSEL
GKKLKATMDA GKLVSDEMVV ELIEKNLETP LCKNGFLLDG FPRTVRQAEM LDDLMEKRKE
KLDSVIEFSI PDSLLIRRIT GRLIHPKSGR SYHEEFNPPK EPMKDDITGE PLIRRSDDNE
KALKIRLQAY HTQTTPLIEY YRKRGIHSAI DASQTPDVVF ASILAAFSKA TCKDLVMFI
