KAD6_HUMAN
ID KAD6_HUMAN Reviewed; 172 AA.
AC Q9Y3D8; A8MSZ6; Q5F2S9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Adenylate kinase isoenzyme 6 {ECO:0000255|HAMAP-Rule:MF_03173};
DE Short=AK6 {ECO:0000255|HAMAP-Rule:MF_03173};
DE EC=2.7.4.3 {ECO:0000255|HAMAP-Rule:MF_03173};
DE AltName: Full=Adrenal gland protein AD-004;
DE AltName: Full=Coilin-interacting nuclear ATPase protein {ECO:0000255|HAMAP-Rule:MF_03173};
DE Short=hCINAP;
DE AltName: Full=Dual activity adenylate kinase/ATPase {ECO:0000255|HAMAP-Rule:MF_03173};
DE Short=AK/ATPase {ECO:0000255|HAMAP-Rule:MF_03173};
GN Name=AK6 {ECO:0000255|HAMAP-Rule:MF_03173};
GN Synonyms=CINAP {ECO:0000255|HAMAP-Rule:MF_03173}; ORFNames=AD-004, CGI-137;
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), BIOPHYSICOCHEMICAL PROPERTIES,
RP INTERACTION WITH COIL, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP ALTERNATIVE SPLICING.
RC TISSUE=Cervix carcinoma, and Placenta;
RX PubMed=16079131; DOI=10.1074/jbc.m501982200;
RA Santama N., Ogg S.C., Malekkou A., Zographos S.E., Weis K., Lamond A.I.;
RT "Characterization of hCINAP, a novel coilin-interacting protein encoded by
RT a transcript from the transcription factor TAFIID32 locus.";
RL J. Biol. Chem. 280:36429-36441(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
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] (ISOFORM 1).
RC TISSUE=Lymph;
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 SUBUNIT.
RX PubMed=15213396; DOI=10.1107/s0907444904010467;
RA Ren H., Liang Y., Li R., Ding H., Qiu S., Lu S., An J., Li L., Luo M.,
RA Zheng X., Su X.D.;
RT "Protein preparation, crystallization and preliminary X-ray analysis of
RT human adrenal gland protein AD-004.";
RL Acta Crystallogr. D 60:1292-1294(2004).
RN [8]
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 [9]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RX PubMed=15630091; DOI=10.1073/pnas.0407459102;
RA Ren H., Wang L., Bennett M., Liang Y., Zheng X., Lu F., Li L., Nan J.,
RA Luo M., Eriksson S., Zhang C., Su X.-D.;
RT "The crystal structure of human adenylate kinase 6: an adenylate kinase
RT localized to the cell nucleus.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:303-308(2005).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) IN COMPLEX WITH ADP AND DADP,
RP MUTAGENESIS OF HIS-79, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22038794; DOI=10.1002/prot.23186;
RA Drakou C.E., Malekkou A., Hayes J.M., Lederer C.W., Leonidas D.D.,
RA Oikonomakos N.G., Lamond A.I., Santama N., Zographos S.E.;
RT "hCINAP is an atypical mammalian nuclear adenylate kinase with an ATPase
RT motif: structural and functional studies.";
RL Proteins 80:206-220(2012).
CC -!- FUNCTION: Broad-specificity nucleoside monophosphate (NMP) kinase that
CC catalyzes the reversible transfer of the terminal phosphate group
CC between nucleoside triphosphates and monophosphates. AMP and dAMP are
CC the preferred substrates, but CMP and dCMP are also good substrates.
CC IMP is phosphorylated to a much lesser extent. All nucleoside
CC triphosphates ATP, GTP, UTP, CTP, dATP, dCTP, dGTP, and TTP are
CC accepted as phosphate donors. CTP is the best phosphate donor, followed
CC by UTP, ATP, GTP and dCTP. May have a role in nuclear energy
CC homeostasis. Has also ATPase activity. May be involved in regulation of
CC Cajal body (CB) formation. {ECO:0000269|PubMed:15630091}.
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_03173,
CC ECO:0000269|PubMed:15630091};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=192 uM for AMP {ECO:0000269|PubMed:15630091,
CC ECO:0000269|PubMed:16079131, ECO:0000269|PubMed:22038794};
CC KM=45 uM for ATP (for adenylate kinase activity)
CC {ECO:0000269|PubMed:15630091, ECO:0000269|PubMed:16079131,
CC ECO:0000269|PubMed:22038794};
CC KM=332 uM for ATP (for ATPase activity) {ECO:0000269|PubMed:15630091,
CC ECO:0000269|PubMed:16079131, ECO:0000269|PubMed:22038794};
CC Vmax=1.27 umol/min/mg enzyme for ATPase activity
CC {ECO:0000269|PubMed:15630091, ECO:0000269|PubMed:16079131,
CC ECO:0000269|PubMed:22038794};
CC Vmax=982 nmol/min/mg enzyme for the forward adenylate kinase reaction
CC {ECO:0000269|PubMed:15630091, ECO:0000269|PubMed:16079131,
CC ECO:0000269|PubMed:22038794};
CC Vmax=955 nmol/min/mg enzyme for the reverse adenylate kinase reaction
CC {ECO:0000269|PubMed:15630091, ECO:0000269|PubMed:16079131,
CC ECO:0000269|PubMed:22038794};
CC Note=kcat is 6.3 sec(-1) for adenylate kinase activity. kcat is 4.8
CC sec(-1) for ATPase activity.;
CC -!- SUBUNIT: Monomer and homodimer (By similarity). Interacts with COIL
CC (via C-terminus). {ECO:0000255|HAMAP-Rule:MF_03173,
CC ECO:0000269|PubMed:15213396, ECO:0000269|PubMed:16079131,
CC ECO:0000269|PubMed:22038794}.
CC -!- INTERACTION:
CC Q9Y3D8; P38432: COIL; NbExp=5; IntAct=EBI-2896123, EBI-945751;
CC Q9Y3D8; A0A0C4DGV4: LAMTOR5; NbExp=3; IntAct=EBI-2896123, EBI-10173304;
CC Q9Y3D8; Q92597-3: NDRG1; NbExp=3; IntAct=EBI-2896123, EBI-10278703;
CC Q9Y3D8; P62263: RPS14; NbExp=4; IntAct=EBI-2896123, EBI-352783;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm. Nucleus, Cajal body.
CC Note=Displays widespread diffuse nucleoplasmic distribution but not
CC detected in nucleoli. Detected in Cajal bodies but not in all cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=AK6;
CC IsoId=Q9Y3D8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y3D8-2; Sequence=VSP_039714;
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, placenta, lung, liver,
CC skeletal muscle, kidney, pancreas, chorionic villi and the central
CC nervous system. {ECO:0000269|PubMed:16079131}.
CC -!- SIMILARITY: Belongs to the adenylate kinase family. AK6 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03173}.
CC -!- CAUTION: AK6 and TAF9 were initially considered as products of the same
CC gene since they share two exons. However, they are translated from
CC different initiation codons and reading frames and encode unrelated
CC proteins. This arrangement is conserved in some mammalian species.
CC {ECO:0000305}.
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DR EMBL; AJ878880; CAI48030.1; -; mRNA.
DR EMBL; AJ878881; CAI48031.1; -; mRNA.
DR EMBL; AF151895; AAD34132.1; -; mRNA.
DR EMBL; AF110777; AAF14860.1; -; mRNA.
DR EMBL; AC145132; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471137; EAW51290.1; -; Genomic_DNA.
DR EMBL; CH471137; EAW51291.1; -; Genomic_DNA.
DR EMBL; CH471137; EAW51292.1; -; Genomic_DNA.
DR EMBL; CH471137; EAW51297.1; -; Genomic_DNA.
DR EMBL; BC007349; AAH07349.1; -; mRNA.
DR EMBL; BC007426; AAH07426.1; -; mRNA.
DR CCDS; CCDS4001.1; -. [Q9Y3D8-1]
DR CCDS; CCDS43324.1; -. [Q9Y3D8-2]
DR RefSeq; NP_001015891.1; NM_001015891.1. [Q9Y3D8-2]
DR RefSeq; NP_057367.1; NM_016283.4. [Q9Y3D8-1]
DR PDB; 1RKB; X-ray; 2.00 A; A=1-172.
DR PDB; 3IIJ; X-ray; 1.76 A; A=1-172.
DR PDB; 3IIK; X-ray; 1.95 A; A=1-172.
DR PDB; 3IIL; X-ray; 2.00 A; A=1-172.
DR PDB; 3IIM; X-ray; 2.00 A; A=1-172.
DR PDB; 5JZV; X-ray; 2.07 A; A=1-172.
DR PDBsum; 1RKB; -.
DR PDBsum; 3IIJ; -.
DR PDBsum; 3IIK; -.
DR PDBsum; 3IIL; -.
DR PDBsum; 3IIM; -.
DR PDBsum; 5JZV; -.
DR AlphaFoldDB; Q9Y3D8; -.
DR SMR; Q9Y3D8; -.
DR BioGRID; 3194050; 11.
DR IntAct; Q9Y3D8; 20.
DR MINT; Q9Y3D8; -.
DR STRING; 9606.ENSP00000370201; -.
DR iPTMnet; Q9Y3D8; -.
DR PhosphoSitePlus; Q9Y3D8; -.
DR BioMuta; AK6; -.
DR DMDM; 6831735; -.
DR EPD; Q9Y3D8; -.
DR jPOST; Q9Y3D8; -.
DR MassIVE; Q9Y3D8; -.
DR MaxQB; Q9Y3D8; -.
DR PeptideAtlas; Q9Y3D8; -.
DR PRIDE; Q9Y3D8; -.
DR ProteomicsDB; 86024; -. [Q9Y3D8-1]
DR ProteomicsDB; 86025; -. [Q9Y3D8-2]
DR Antibodypedia; 3945; 110 antibodies from 21 providers.
DR DNASU; 6880; -.
DR Ensembl; ENST00000380818.7; ENSP00000370197.3; ENSG00000085231.14. [Q9Y3D8-2]
DR Ensembl; ENST00000380822.9; ENSP00000370201.4; ENSG00000085231.14. [Q9Y3D8-1]
DR Ensembl; ENST00000612207.4; ENSP00000484679.1; ENSG00000279247.3. [Q9Y3D8-1]
DR Ensembl; ENST00000620269.4; ENSP00000480829.1; ENSG00000279247.3. [Q9Y3D8-2]
DR GeneID; 102157402; -.
DR KEGG; hsa:102157402; -.
DR MANE-Select; ENST00000380822.9; ENSP00000370201.4; NM_016283.5; NP_057367.1.
DR UCSC; uc003jwa.4; human. [Q9Y3D8-1]
DR CTD; 102157402; -.
DR DisGeNET; 102157402; -.
DR GeneCards; AK6; -.
DR HGNC; HGNC:49151; AK6.
DR HPA; ENSG00000085231; Low tissue specificity.
DR MIM; 619357; gene.
DR neXtProt; NX_Q9Y3D8; -.
DR OpenTargets; ENSG00000085231; -.
DR PharmGKB; PA36317; -.
DR VEuPathDB; HostDB:ENSG00000085231; -.
DR eggNOG; KOG3347; Eukaryota.
DR GeneTree; ENSGT00390000015930; -.
DR HOGENOM; CLU_079096_3_3_1; -.
DR OMA; QCEIFGT; -.
DR OrthoDB; 1488235at2759; -.
DR BRENDA; 2.7.4.3; 2681.
DR PathwayCommons; Q9Y3D8; -.
DR Reactome; R-HSA-499943; Interconversion of nucleotide di- and triphosphates.
DR SignaLink; Q9Y3D8; -.
DR BioGRID-ORCS; 102157402; 604 hits in 948 CRISPR screens.
DR ChiTaRS; AK6; human.
DR EvolutionaryTrace; Q9Y3D8; -.
DR GenomeRNAi; 102157402; -.
DR Pharos; Q9Y3D8; Tbio.
DR PRO; PR:Q9Y3D8; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9Y3D8; protein.
DR Bgee; ENSG00000085231; Expressed in calcaneal tendon and 98 other tissues.
DR ExpressionAtlas; Q9Y3D8; baseline and differential.
DR Genevisible; Q9Y3D8; HS.
DR GO; GO:0015030; C:Cajal body; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004017; F:adenylate kinase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:UniProtKB-UniRule.
DR GO; GO:0050145; F:nucleoside monophosphate kinase activity; TAS:Reactome.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_00039; Adenylate_kinase_AK6; 1.
DR InterPro; IPR020618; Adenyl_kinase_AK6.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR12595; PTHR12595; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Kinase;
KW Nucleotide-binding; Nucleus; Reference proteome; Transferase.
FT CHAIN 1..172
FT /note="Adenylate kinase isoenzyme 6"
FT /id="PRO_0000153896"
FT REGION 33..56
FT /note="NMP"
FT REGION 108..118
FT /note="LID"
FT BINDING 13..18
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 39
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000305"
FT BINDING 79
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 105
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 109
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 148..149
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT VAR_SEQ 2..9
FT /note="LLPNILLT -> CHRKP (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_039714"
FT MUTAGEN 79
FT /note="H->G: Induces homodimerization. Reduces adenylate
FT kinase activity by 72% and ATPase activity by 76%.
FT Significantly changes Cajal body organization in the
FT nucleus, resulting in enhanced apoptosis and reduced
FT proliferation."
FT /evidence="ECO:0000269|PubMed:22038794"
FT STRAND 6..9
FT /evidence="ECO:0007829|PDB:3IIJ"
FT HELIX 16..27
FT /evidence="ECO:0007829|PDB:3IIJ"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:3IIJ"
FT HELIX 34..41
FT /evidence="ECO:0007829|PDB:3IIJ"
FT STRAND 44..48
FT /evidence="ECO:0007829|PDB:3IIJ"
FT TURN 49..52
FT /evidence="ECO:0007829|PDB:3IIJ"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:3IIJ"
FT HELIX 58..71
FT /evidence="ECO:0007829|PDB:3IIJ"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:3IIJ"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:3IIJ"
FT STRAND 90..96
FT /evidence="ECO:0007829|PDB:3IIJ"
FT HELIX 99..108
FT /evidence="ECO:0007829|PDB:3IIJ"
FT HELIX 113..124
FT /evidence="ECO:0007829|PDB:3IIJ"
FT HELIX 127..135
FT /evidence="ECO:0007829|PDB:3IIJ"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:3IIJ"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:3IIJ"
FT HELIX 149..169
FT /evidence="ECO:0007829|PDB:3IIJ"
SQ SEQUENCE 172 AA; 20061 MW; 33F62318FB434301 CRC64;
MLLPNILLTG TPGVGKTTLG KELASKSGLK YINVGDLARE EQLYDGYDEE YDCPILDEDR
VVDELDNQMR EGGVIVDYHG CDFFPERWFH IVFVLRTDTN VLYERLETRG YNEKKLTDNI
QCEIFQVLYE EATASYKEEI VHQLPSNKPE ELENNVDQIL KWIEQWIKDH NS
