KAD2_MOUSE
ID KAD2_MOUSE Reviewed; 239 AA.
AC Q9WTP6; A2A820; Q3THT3; Q3TI11; Q3TKI6; Q8C7I9; Q9CY37;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 5.
DT 03-AUG-2022, entry version 177.
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};
GN Name=Ak2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Noma T.;
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=BALB/cJ, and C57BL/6J; TISSUE=Embryonic liver, and Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [5]
RP PROTEIN SEQUENCE OF 94-103.
RC TISSUE=Brain;
RA Lubec G., Yang J.W., Zigmond M.;
RL Submitted (JUL-2007) to UniProtKB.
RN [6]
RP TISSUE SPECIFICITY.
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).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-91, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-62 AND LYS-93, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-181, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
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 -!- 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 -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000255|HAMAP-Rule:MF_03168}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9WTP6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9WTP6-2; Sequence=VSP_036504;
CC -!- TISSUE SPECIFICITY: Present in the inner ear. Not detected in the
CC vestibule at any developmental stage. Present at high level in the
CC cochlea uniquely in the stria vascularis at postnatal day 7 but not at
CC birth. Present within the lumen of the stria vascularis capillaries.
CC Not detected in the capillaries or vessels of the adjacent connective
CC tissue (at protein level). {ECO:0000269|PubMed:19043416}.
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}.
CC -!- SIMILARITY: Belongs to the adenylate kinase family. AK2 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03168}.
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DR EMBL; AB020202; BAA77359.1; -; mRNA.
DR EMBL; AK010951; BAB27286.1; -; mRNA.
DR EMBL; AK050133; BAC34085.1; -; mRNA.
DR EMBL; AK166976; BAE39159.1; -; mRNA.
DR EMBL; AK168056; BAE40035.1; -; mRNA.
DR EMBL; AK168148; BAE40113.1; -; mRNA.
DR EMBL; AL607086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU210866; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008610; AAH08610.1; -; mRNA.
DR CCDS; CCDS18679.1; -. [Q9WTP6-2]
DR CCDS; CCDS18680.1; -. [Q9WTP6-1]
DR RefSeq; NP_001029138.1; NM_001033966.4. [Q9WTP6-1]
DR RefSeq; NP_058591.2; NM_016895.4. [Q9WTP6-2]
DR AlphaFoldDB; Q9WTP6; -.
DR SMR; Q9WTP6; -.
DR BioGRID; 198046; 3.
DR STRING; 10090.ENSMUSP00000030583; -.
DR iPTMnet; Q9WTP6; -.
DR PhosphoSitePlus; Q9WTP6; -.
DR SwissPalm; Q9WTP6; -.
DR REPRODUCTION-2DPAGE; Q9WTP6; -.
DR CPTAC; non-CPTAC-3717; -.
DR EPD; Q9WTP6; -.
DR jPOST; Q9WTP6; -.
DR MaxQB; Q9WTP6; -.
DR PaxDb; Q9WTP6; -.
DR PeptideAtlas; Q9WTP6; -.
DR PRIDE; Q9WTP6; -.
DR ProteomicsDB; 269236; -. [Q9WTP6-1]
DR ProteomicsDB; 269237; -. [Q9WTP6-2]
DR Antibodypedia; 17047; 464 antibodies from 33 providers.
DR DNASU; 11637; -.
DR Ensembl; ENSMUST00000030583; ENSMUSP00000030583; ENSMUSG00000028792. [Q9WTP6-1]
DR Ensembl; ENSMUST00000102604; ENSMUSP00000099664; ENSMUSG00000028792. [Q9WTP6-2]
DR GeneID; 11637; -.
DR KEGG; mmu:11637; -.
DR UCSC; uc008uvt.2; mouse. [Q9WTP6-1]
DR UCSC; uc008uvu.2; mouse. [Q9WTP6-2]
DR CTD; 204; -.
DR MGI; MGI:87978; Ak2.
DR VEuPathDB; HostDB:ENSMUSG00000028792; -.
DR eggNOG; KOG3078; Eukaryota.
DR GeneTree; ENSGT00940000154576; -.
DR HOGENOM; CLU_032354_1_0_1; -.
DR InParanoid; Q9WTP6; -.
DR OMA; FHNRMRV; -.
DR OrthoDB; 1004067at2759; -.
DR PhylomeDB; Q9WTP6; -.
DR TreeFam; TF300896; -.
DR BRENDA; 2.7.4.3; 3474.
DR Reactome; R-MMU-499943; Interconversion of nucleotide di- and triphosphates.
DR BioGRID-ORCS; 11637; 16 hits in 77 CRISPR screens.
DR ChiTaRS; Ak2; mouse.
DR PRO; PR:Q9WTP6; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9WTP6; protein.
DR Bgee; ENSMUSG00000028792; Expressed in small intestine Peyer's patch and 278 other tissues.
DR ExpressionAtlas; Q9WTP6; baseline and differential.
DR Genevisible; Q9WTP6; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0036126; C:sperm flagellum; IDA:MGI.
DR GO; GO:0097226; C:sperm mitochondrial sheath; IDA:MGI.
DR GO; GO:0004017; F:adenylate kinase activity; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019205; F:nucleobase-containing compound kinase activity; ISO:MGI.
DR GO; GO:0006172; P:ADP biosynthetic process; ISO:MGI.
DR GO; GO:0046033; P:AMP metabolic process; ISO:MGI.
DR GO; GO:0046034; P:ATP metabolic process; ISO:MGI.
DR GO; GO:0046060; P:dATP metabolic process; ISO:MGI.
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 Acetylation; Alternative splicing; ATP-binding; Direct protein sequencing;
KW Disulfide bond; Kinase; Mitochondrion; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..239
FT /note="Adenylate kinase 2, mitochondrial"
FT /id="PRO_0000158918"
FT REGION 45..74
FT /note="NMP"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168"
FT REGION 141..178
FT /note="LID"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168"
FT BINDING 25..30
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168"
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 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 BINDING 175
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168"
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 MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P54819"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54819"
FT MOD_RES 62
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 93
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54819"
FT MOD_RES 181
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 195
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P54819"
FT DISULFID 42..92
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03168"
FT VAR_SEQ 232..239
FT /note="CKDLVMFI -> S (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|Ref.1"
FT /id="VSP_036504"
FT CONFLICT 61
FT /note="G -> R (in Ref. 1; BAA77359)"
FT /evidence="ECO:0000305"
FT CONFLICT 110
FT /note="M -> V (in Ref. 2; BAE40113)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="D -> E (in Ref. 1; BAA77359)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="K -> E (in Ref. 1; BAA77359)"
FT /evidence="ECO:0000305"
FT CONFLICT 145
FT /note="H -> R (in Ref. 1; BAA77359)"
FT /evidence="ECO:0000305"
FT CONFLICT 146
FT /note="P -> R (in Ref. 2; BAE40113)"
FT /evidence="ECO:0000305"
FT CONFLICT 151
FT /note="S -> F (in Ref. 1; BAA77359)"
FT /evidence="ECO:0000305"
FT CONFLICT 191
FT /note="H -> Y (in Ref. 1; BAA77359)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="R -> H (in Ref. 2; BAE40035)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 239 AA; 26469 MW; CAFF06F053CECE36 CRC64;
MAPNVLASEP EIPKGIRAVL LGPPGAGKGT QAPKLAENFC VCHLATGDML RAMVASGSEL
GKKLKATMDA GKLVSDEMVV ELIEKNLETP SCKNGFLLDG FPRTVRQAEM LDDLMEKRKE
KLDSVIEFSI QDSLLIRRIT GRLIHPKSGR SYHEEFNPPK EPMKDDITGE PLIRRSDDNE
KALKTRLEAY HTQTTPLVEY YRKRGIHCAI DASQTPDIVF ASILAAFSKA TCKDLVMFI
