KAD4_MOUSE
ID KAD4_MOUSE Reviewed; 223 AA.
AC Q9WUR9; Q9R1X7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 167.
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};
DE EC=2.7.4.6 {ECO:0000255|HAMAP-Rule:MF_03170};
DE AltName: Full=Adenylate kinase 3-like {ECO:0000255|HAMAP-Rule:MF_03170};
DE AltName: Full=Adenylate kinase isoenzyme 4;
DE AltName: Full=GTP:AMP phosphotransferase AK4 {ECO:0000255|HAMAP-Rule:MF_03170};
GN Name=Ak4; Synonyms=Ak-4, Ak3b, Ak3l1;
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], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Brain;
RX PubMed=9813319; DOI=10.1016/s0169-328x(98)00249-6;
RA Yoneda T., Sato M., Maeda M., Takagi H.;
RT "Identification of a novel adenylate kinase system in the brain: cloning of
RT the fourth adenylate kinase.";
RL Brain Res. Mol. Brain Res. 62:187-195(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Noma T.;
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=19492028; DOI=10.1267/ahc.08012;
RA Miyoshi K., Akazawa Y., Horiguchi T., Noma T.;
RT "Localization of adenylate kinase 4 in mouse tissues.";
RL Acta Histochem. Cytochem. 42:55-64(2009).
RN [5]
RP TISSUE SPECIFICITY.
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, 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 [7]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-60; LYS-179 AND LYS-186, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast, and 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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-175; LYS-179 AND LYS-186, AND
RP IDENTIFICATION BY MASS 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: Involved in maintaining the homeostasis of cellular
CC nucleotides by catalyzing the interconversion of nucleoside phosphates
CC (By similarity). Efficiently phosphorylates AMP and dAMP using ATP as
CC phosphate donor, but phosphorylates only AMP when using GTP as
CC phosphate donor (By similarity). Also displays broad nucleoside
CC diphosphate kinase activity (By similarity). Plays a role in
CC controlling cellular ATP levels by regulating phosphorylation and
CC activation of the energy sensor protein kinase AMPK (By similarity).
CC Plays a protective role in the cellular response to oxidative stress
CC (By similarity). {ECO:0000250|UniProtKB:P27144, ECO:0000255|HAMAP-
CC Rule:MF_03170}.
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 -!- 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};
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 -!- SUBUNIT: Monomer (By similarity). Interacts with SLC25A5/ANT2 (By
CC similarity). {ECO:0000250|UniProtKB:P27144, ECO:0000255|HAMAP-
CC Rule:MF_03170}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000255|HAMAP-
CC Rule:MF_03170}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney, liver, stomach, brain, spinal
CC cord, heart, ovary, oviduct, colon, jejunum, ileum and testis (at
CC protein level) (PubMed:19492028, PubMed:19130895). In the brain,
CC expressed in the pyramidal cells of the cerebrum and glial cells in the
CC cerebellum (at protein level) (PubMed:19492028). In the heart,
CC expressed by myocytes (at protein level) (PubMed:19492028). In the
CC kidney, expressed in the proximal to distal tubule in the cortex and
CC the outer and inner zones of the medulla (at protein level)
CC (PubMed:19492028). In the stomach, expressed in stratified squamous
CC epithelia in the forestomach and in the gastric pit and mucus producing
CC cells of the glandular stomach (at protein level) (PubMed:19492028).
CC Expressed in epithelial cells of the jejunum, ileum, and colon (at
CC protein level) (PubMed:19492028). In the testis, expressed by
CC spermatocytes (at protein level) (PubMed:19492028). In the ovaries,
CC expressed by oocytes, follicular epithelial cells, and corpus luteum
CC cells (at protein level) (PubMed:19492028). In the oviduct, expressed
CC in the epithelia of the isthmus and the ciliated cells of the ampulla
CC (at protein level) (PubMed:19492028). Expressed in the pyramidal cells
CC in the hippocampus (PubMed:9813319). {ECO:0000269|PubMed:19130895,
CC ECO:0000269|PubMed:19492028, ECO:0000269|PubMed:9813319}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the central nervous system in a
CC region-specific manner from the middle stage of embryogenesis to the
CC adulthood in the rodent. {ECO:0000269|PubMed:9813319}.
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 -!- SIMILARITY: Belongs to the adenylate kinase family. AK3 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03170}.
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DR EMBL; D85036; BAA77760.1; -; mRNA.
DR EMBL; AB020239; BAA77363.1; -; mRNA.
DR EMBL; BC086663; AAH86663.1; -; mRNA.
DR CCDS; CCDS18394.1; -.
DR RefSeq; NP_001171073.1; NM_001177602.1.
DR RefSeq; NP_001171075.1; NM_001177604.1.
DR RefSeq; NP_001171076.1; NM_001177605.1.
DR RefSeq; NP_033777.1; NM_009647.5.
DR AlphaFoldDB; Q9WUR9; -.
DR SMR; Q9WUR9; -.
DR BioGRID; 198047; 1.
DR STRING; 10090.ENSMUSP00000102559; -.
DR iPTMnet; Q9WUR9; -.
DR PhosphoSitePlus; Q9WUR9; -.
DR SwissPalm; Q9WUR9; -.
DR REPRODUCTION-2DPAGE; Q9WUR9; -.
DR EPD; Q9WUR9; -.
DR jPOST; Q9WUR9; -.
DR MaxQB; Q9WUR9; -.
DR PaxDb; Q9WUR9; -.
DR PRIDE; Q9WUR9; -.
DR ProteomicsDB; 269171; -.
DR Antibodypedia; 19540; 464 antibodies from 32 providers.
DR DNASU; 11639; -.
DR Ensembl; ENSMUST00000102780; ENSMUSP00000099841; ENSMUSG00000028527.
DR Ensembl; ENSMUST00000106945; ENSMUSP00000102558; ENSMUSG00000028527.
DR Ensembl; ENSMUST00000106946; ENSMUSP00000102559; ENSMUSG00000028527.
DR GeneID; 11639; -.
DR KEGG; mmu:11639; -.
DR UCSC; uc008tvn.2; mouse.
DR CTD; 205; -.
DR MGI; MGI:87979; Ak4.
DR VEuPathDB; HostDB:ENSMUSG00000028527; -.
DR eggNOG; KOG3078; Eukaryota.
DR GeneTree; ENSGT00940000154568; -.
DR InParanoid; Q9WUR9; -.
DR OMA; IKVENTM; -.
DR OrthoDB; 1004067at2759; -.
DR PhylomeDB; Q9WUR9; -.
DR TreeFam; TF312916; -.
DR Reactome; R-MMU-499943; Interconversion of nucleotide di- and triphosphates.
DR BioGRID-ORCS; 11639; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Ak4; mouse.
DR PRO; PR:Q9WUR9; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9WUR9; protein.
DR Bgee; ENSMUSG00000028527; Expressed in cumulus cell and 267 other tissues.
DR ExpressionAtlas; Q9WUR9; baseline and differential.
DR Genevisible; Q9WUR9; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0004017; F:adenylate kinase activity; IEA:InterPro.
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; ISS:UniProtKB.
DR GO; GO:0046899; F:nucleoside triphosphate adenylate kinase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0006172; P:ADP biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0046033; P:AMP metabolic process; ISO:MGI.
DR GO; GO:0046034; P:ATP metabolic process; ISO:MGI.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0046039; P:GTP metabolic process; ISO:MGI.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0006165; P:nucleoside diphosphate phosphorylation; ISS:UniProtKB.
DR GO; GO:0009142; P:nucleoside triphosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:2001169; P:regulation of ATP biosynthetic process; ISS:UniProtKB.
DR GO; GO:0002082; P:regulation of oxidative phosphorylation; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
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; 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 TIGRFAMs; TIGR01351; adk; 1.
DR PROSITE; PS00113; ADENYLATE_KINASE; 1.
PE 1: Evidence at protein level;
KW 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_0000158927"
FT REGION 35..64
FT /note="NMP"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170"
FT REGION 125..162
FT /note="LID"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170"
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 BINDING 36
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170"
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 BINDING 89..92
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170"
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 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 BINDING 199
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03170"
FT MOD_RES 60
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 175
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 179
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 179
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 186
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 186
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 68
FT /note="V -> A (in Ref. 2; BAA77363)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="S -> N (in Ref. 2; BAA77363)"
FT /evidence="ECO:0000305"
FT CONFLICT 190
FT /note="V -> M (in Ref. 2; BAA77363)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 223 AA; 25062 MW; 50552294971515EC CRC64;
MASKLLRAVI LGPPGSGKGT VCERIAQNFG LQHLSSGHLL RENLKTGTEV GDVAKQYLEK
GLLVPDHVIT RLMMSELETR SAQHWLLDGF PRTLVQAEAL DGICDVDLVI SLNIPFETLK
DRLSRRWIHP SSGRVYNLDF NPPQVQGIDD ITGEPLVQQE DDKPEAVAAR LRRYKDAAKP
VIELYKSRGV LHQFSGTETN RIWPYVYTLF SNKITPIQSK EAY
