KAD5_HUMAN
ID KAD5_HUMAN Reviewed; 562 AA.
AC Q9Y6K8; Q5U622; Q6FH66; Q7Z4T5; Q86YS0; Q8N464; Q96EC9;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Adenylate kinase isoenzyme 5;
DE Short=AK 5;
DE EC=2.7.4.3;
DE EC=2.7.4.6;
DE AltName: Full=ATP-AMP transphosphorylase 5;
GN Name=AK5;
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 2), AND TISSUE SPECIFICITY.
RX PubMed=10215863; DOI=10.1046/j.1432-1327.1999.00294.x;
RA Van Rompay A.R., Johansson M., Karlsson A.;
RT "Identification of a novel human adenylate kinase. cDNA cloning, expression
RT analysis, chromosome localization and characterization of the recombinant
RT protein.";
RL Eur. J. Biochem. 261:509-517(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Li J., Ji C., Xie Y., Mao Y.;
RT "Cloning and characterization of a novel human gene, adenylate kinase 6.";
RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Guo J.H., Yu L., Li D.;
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain, and Liver;
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 [6]
RP INTERACTION WITH YWHAZ.
RX PubMed=16959763; DOI=10.1074/mcp.m600147-mcp200;
RA Angrand P.O., Segura I., Voelkel P., Ghidelli S., Terry R., Brajenovic M.,
RA Vintersten K., Klein R., Superti-Furga G., Drewes G., Kuster B.,
RA Bouwmeester T., Acker-Palmer A.;
RT "Transgenic mouse proteomics identifies new 14-3-3-associated proteins
RT involved in cytoskeletal rearrangements and cell signaling.";
RL Mol. Cell. Proteomics 5:2211-2227(2006).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=19647735; DOI=10.1016/j.febslet.2009.07.047;
RA Solaroli N., Panayiotou C., Johansson M., Karlsson A.;
RT "Identification of two active functional domains of human adenylate kinase
RT 5.";
RL FEBS Lett. 583:2872-2876(2009).
RN [8]
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 [9]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 366-562 IN COMPLEX WITH AMP.
RG Structural genomics consortium (SGC);
RT "Crystal structure of adenylate kinase 5.";
RL Submitted (JUL-2005) to the PDB data bank.
CC -!- FUNCTION: Nucleoside monophosphate (NMP) kinase that catalyzes the
CC reversible transfer of the terminal phosphate group between nucleoside
CC triphosphates and monophosphates. Active on AMP and dAMP with ATP as a
CC donor. When GTP is used as phosphate donor, the enzyme phosphorylates
CC AMP, CMP, and to a small extent dCMP. Also displays broad nucleoside
CC diphosphate kinase activity. {ECO:0000269|PubMed:19647735,
CC ECO:0000269|PubMed:23416111}.
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:0000269|PubMed:19647735};
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;
CC Evidence={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:0000269|PubMed:23416111};
CC -!- SUBUNIT: Monomer. Interacts with YWHAZ (PubMed:16959763).
CC {ECO:0000250|UniProtKB:P00568, ECO:0000269|PubMed:16959763}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19647735}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y6K8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y6K8-2; Sequence=VSP_037878;
CC Name=3; Synonyms=Adenylate kinase 6;
CC IsoId=Q9Y6K8-3; Sequence=VSP_037879;
CC -!- TISSUE SPECIFICITY: Brain specific. {ECO:0000269|PubMed:10215863}.
CC -!- MISCELLANEOUS: [Isoform 2]: It is unsure whether Met-1 or Met-5 is the
CC initiator. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the adenylate kinase family. {ECO:0000305}.
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DR EMBL; AF062595; AAD27956.1; -; mRNA.
DR EMBL; AY171600; AAO16520.2; -; mRNA.
DR EMBL; AF445193; AAP97322.1; -; mRNA.
DR EMBL; CR541890; CAG46688.1; -; mRNA.
DR EMBL; BC033896; AAH33896.1; -; mRNA.
DR EMBL; BC036666; AAH36666.1; -; mRNA.
DR EMBL; BC012467; AAH12467.2; -; mRNA.
DR CCDS; CCDS675.1; -. [Q9Y6K8-1]
DR CCDS; CCDS676.1; -. [Q9Y6K8-3]
DR RefSeq; NP_036225.2; NM_012093.3. [Q9Y6K8-3]
DR RefSeq; NP_777283.1; NM_174858.2. [Q9Y6K8-1]
DR RefSeq; XP_006710635.1; XM_006710572.3. [Q9Y6K8-3]
DR RefSeq; XP_016856497.1; XM_017001008.1. [Q9Y6K8-3]
DR RefSeq; XP_016856498.1; XM_017001009.1. [Q9Y6K8-3]
DR PDB; 2BWJ; X-ray; 2.30 A; A/B/C/D/E/F=366-562.
DR PDBsum; 2BWJ; -.
DR AlphaFoldDB; Q9Y6K8; -.
DR SMR; Q9Y6K8; -.
DR BioGRID; 117670; 9.
DR IntAct; Q9Y6K8; 9.
DR STRING; 9606.ENSP00000346577; -.
DR iPTMnet; Q9Y6K8; -.
DR PhosphoSitePlus; Q9Y6K8; -.
DR BioMuta; AK5; -.
DR DMDM; 257051028; -.
DR EPD; Q9Y6K8; -.
DR jPOST; Q9Y6K8; -.
DR MassIVE; Q9Y6K8; -.
DR MaxQB; Q9Y6K8; -.
DR PaxDb; Q9Y6K8; -.
DR PeptideAtlas; Q9Y6K8; -.
DR PRIDE; Q9Y6K8; -.
DR ProteomicsDB; 86713; -. [Q9Y6K8-1]
DR ProteomicsDB; 86714; -. [Q9Y6K8-2]
DR ProteomicsDB; 86715; -. [Q9Y6K8-3]
DR Antibodypedia; 19726; 378 antibodies from 28 providers.
DR DNASU; 26289; -.
DR Ensembl; ENST00000344720.9; ENSP00000341430.5; ENSG00000154027.19. [Q9Y6K8-3]
DR Ensembl; ENST00000354567.7; ENSP00000346577.2; ENSG00000154027.19. [Q9Y6K8-1]
DR GeneID; 26289; -.
DR KEGG; hsa:26289; -.
DR MANE-Select; ENST00000354567.7; ENSP00000346577.2; NM_174858.3; NP_777283.1.
DR UCSC; uc001dhn.4; human. [Q9Y6K8-1]
DR CTD; 26289; -.
DR DisGeNET; 26289; -.
DR GeneCards; AK5; -.
DR HGNC; HGNC:365; AK5.
DR HPA; ENSG00000154027; Tissue enriched (brain).
DR MIM; 608009; gene.
DR neXtProt; NX_Q9Y6K8; -.
DR OpenTargets; ENSG00000154027; -.
DR PharmGKB; PA24659; -.
DR VEuPathDB; HostDB:ENSG00000154027; -.
DR eggNOG; KOG3079; Eukaryota.
DR GeneTree; ENSGT00940000155917; -.
DR HOGENOM; CLU_034712_1_0_1; -.
DR InParanoid; Q9Y6K8; -.
DR OMA; TGEQGND; -.
DR OrthoDB; 1378291at2759; -.
DR PhylomeDB; Q9Y6K8; -.
DR TreeFam; TF313747; -.
DR BioCyc; MetaCyc:HS07943-MON; -.
DR BRENDA; 2.7.4.3; 2681.
DR PathwayCommons; Q9Y6K8; -.
DR Reactome; R-HSA-499943; Interconversion of nucleotide di- and triphosphates.
DR SignaLink; Q9Y6K8; -.
DR BioGRID-ORCS; 26289; 10 hits in 1072 CRISPR screens.
DR ChiTaRS; AK5; human.
DR EvolutionaryTrace; Q9Y6K8; -.
DR GenomeRNAi; 26289; -.
DR Pharos; Q9Y6K8; Tbio.
DR PRO; PR:Q9Y6K8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9Y6K8; protein.
DR Bgee; ENSG00000154027; Expressed in middle temporal gyrus and 129 other tissues.
DR ExpressionAtlas; Q9Y6K8; baseline and differential.
DR Genevisible; Q9Y6K8; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0004017; F:adenylate kinase activity; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB.
DR GO; GO:0006172; P:ADP biosynthetic process; TAS:ProtInc.
DR GO; GO:0046034; P:ATP metabolic process; IEA:InterPro.
DR GO; GO:0006173; P:dADP biosynthetic process; TAS:ProtInc.
DR GO; GO:0006165; P:nucleoside diphosphate phosphorylation; IDA:UniProtKB.
DR GO; GO:0009142; P:nucleoside triphosphate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0009220; P:pyrimidine ribonucleotide biosynthetic process; TAS:ProtInc.
DR CDD; cd01428; ADK; 2.
DR Gene3D; 3.40.50.300; -; 2.
DR HAMAP; MF_00235; Adenylate_kinase_Adk; 2.
DR InterPro; IPR000850; Adenylat/UMP-CMP_kin.
DR InterPro; IPR033690; Adenylat_kinase_CS.
DR InterPro; IPR006267; AK1/5.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR23359; PTHR23359; 3.
DR PRINTS; PR00094; ADENYLTKNASE.
DR SUPFAM; SSF52540; SSF52540; 2.
DR TIGRFAMs; TIGR01360; aden_kin_iso1; 1.
DR PROSITE; PS00113; ADENYLATE_KINASE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Kinase;
KW Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1..562
FT /note="Adenylate kinase isoenzyme 5"
FT /id="PRO_0000158930"
FT REGION 133..316
FT /note="Adenylate kinase 1"
FT /evidence="ECO:0000305|PubMed:19647735"
FT REGION 162..193
FT /note="NMP 1"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT REGION 256..266
FT /note="LID 1"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT REGION 377..559
FT /note="Adenylate kinase 2"
FT /evidence="ECO:0000305|PubMed:19647735"
FT REGION 406..435
FT /note="NMP 2"
FT /evidence="ECO:0000269|Ref.9"
FT REGION 499..509
FT /note="LID 2"
FT /evidence="ECO:0000269|Ref.9"
FT BINDING 142..147
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 168
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 191..193
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 219..222
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 226
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 257
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 263
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 274
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 386..391
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 407
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 412
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 433..435
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 462..465
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 469
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 500
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 517
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT BINDING 545
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P00568"
FT VAR_SEQ 1..365
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10215863,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4"
FT /id="VSP_037878"
FT VAR_SEQ 1..26
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_037879"
FT VARIANT 465
FT /note="R -> Q (in dbSNP:rs2803140)"
FT /id="VAR_059435"
FT CONFLICT 10
FT /note="L -> M (in Ref. 5; AAH36666)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="E -> G (in Ref. 5; AAH36666)"
FT /evidence="ECO:0000305"
FT CONFLICT 182
FT /note="L -> P (in Ref. 2; AAO16520 and 5; AAH33896)"
FT /evidence="ECO:0000305"
FT CONFLICT 321
FT /note="P -> S (in Ref. 2; AAO16520)"
FT /evidence="ECO:0000305"
FT CONFLICT 343
FT /note="I -> T (in Ref. 2; AAO16520)"
FT /evidence="ECO:0000305"
FT CONFLICT 348
FT /note="S -> Y (in Ref. 5; AAH33896)"
FT /evidence="ECO:0000305"
FT CONFLICT 385
FT /note="P -> T (in Ref. 5; AAH33896)"
FT /evidence="ECO:0000305"
FT CONFLICT 561
FT /note="Missing (in Ref. 2; AAP97322 and 5; AAH33896/
FT AAH12467)"
FT /evidence="ECO:0000305"
FT HELIX 369..375
FT /evidence="ECO:0007829|PDB:2BWJ"
FT STRAND 378..383
FT /evidence="ECO:0007829|PDB:2BWJ"
FT HELIX 389..400
FT /evidence="ECO:0007829|PDB:2BWJ"
FT STRAND 403..406
FT /evidence="ECO:0007829|PDB:2BWJ"
FT HELIX 407..417
FT /evidence="ECO:0007829|PDB:2BWJ"
FT HELIX 420..430
FT /evidence="ECO:0007829|PDB:2BWJ"
FT HELIX 437..451
FT /evidence="ECO:0007829|PDB:2BWJ"
FT STRAND 458..461
FT /evidence="ECO:0007829|PDB:2BWJ"
FT HELIX 467..476
FT /evidence="ECO:0007829|PDB:2BWJ"
FT STRAND 481..487
FT /evidence="ECO:0007829|PDB:2BWJ"
FT HELIX 490..499
FT /evidence="ECO:0007829|PDB:2BWJ"
FT HELIX 507..535
FT /evidence="ECO:0007829|PDB:2BWJ"
FT STRAND 536..542
FT /evidence="ECO:0007829|PDB:2BWJ"
FT HELIX 547..561
FT /evidence="ECO:0007829|PDB:2BWJ"
SQ SEQUENCE 562 AA; 63333 MW; CF7DB084924A782F CRC64;
MNTNDAKEYL ARREIPQLFE SLLNGLMCSK PEDPVEYLES CLQKVKELGG CDKVKWDTFV
SQEKKTLPPL NGGQSRRSFL RNVMPENSNF PYRRYDRLPP IHQFSIESDT DLSETAELIE
EYEVFDPTRP RPKIILVIGG PGSGKGTQSL KIAERYGFQY ISVGELLRKK IHSTSSNRKW
SLIAKIITTG ELAPQETTIT EIKQKLMQIP DEEGIVIDGF PRDVAQALSF EDQICTPDLV
VFLACANQRL KERLLKRAEQ QGRPDDNVKA TQRRLMNFKQ NAAPLVKYFQ EKGLIMTFDA
DRDEDEVFYD ISMAVDNKLF PNKEAAAGSS DLDPSMILDT GEIIDTGSDY EDQGDDQLNV
FGEDTMGGFM EDLRKCKIIF IIGGPGSGKG TQCEKLVEKY GFTHLSTGEL LREELASESE
RSKLIRDIME RGDLVPSGIV LELLKEAMVA SLGDTRGFLI DGYPREVKQG EEFGRRIGDP
QLVICMDCSA DTMTNRLLQR SRSSLPVDDT TKTIAKRLEA YYRASIPVIA YYETKTQLHK
INAEGTPEDV FLQLCTAIDS IF
