ID   ADCK2_HUMAN             Reviewed;         626 AA.
AC   Q7Z695; Q96CN6; Q9Y6T5;
DT   09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2003, sequence version 1.
DT   27-MAR-2024, entry version 146.
DE   RecName: Full=Uncharacterized aarF domain-containing protein kinase 2;
DE            EC=2.7.11.-;
GN   Name=ADCK2; Synonyms=AARF;
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].
RA   Huang C.Q., Shan Y.X., Cheng Z.;
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-388.
RC   TISSUE=Muscle;
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   FUNCTION, VARIANT 333-ARG--PRO-626 DEL, AND CHARACTERIZATION OF VARIANT
RP   333-ARG--PRO-626 DEL.
RX   PubMed=31480808; DOI=10.3390/jcm8091374;
RA   Vazquez-Fonseca L., Schaefer J., Navas-Enamorado I., Santos-Ocana C.,
RA   Hernandez-Camacho J.D., Guerra I., Cascajo M.V., Sanchez-Cuesta A.,
RA   Horvath Z., Siendones E., Jou C., Casado M., Gutierrez P., Brea-Calvo G.,
RA   Lopez-Lluch G., Fernandez-Ayala D.J.M., Cortes-Rodriguez A.B.,
RA   Rodriguez-Aguilera J.C., Matte C., Ribes A., Prieto-Soler S.Y.,
RA   Dominguez-Del-Toro E., Francesco A.D., Aon M.A., Bernier M., Salviati L.,
RA   Artuch R., Cabo R., Jackson S., Navas P.;
RT   "ADCK2 Haploinsufficiency Reduces Mitochondrial Lipid Oxidation and Causes
RT   Myopathy Associated with CoQ Deficiency.";
RL   J. Clin. Med. 8:0-0(2019).
RN   [5]
RP   SUBCELLULAR LOCATION.
RX   PubMed=33988507; DOI=10.7554/elife.64943;
RA   Zhang H., Cao X., Tang M., Zhong G., Si Y., Li H., Zhu F., Liao Q., Li L.,
RA   Zhao J., Feng J., Li S., Wang C., Kaulich M., Wang F., Chen L., Li L.,
RA   Xia Z., Liang T., Lu H., Feng X.H., Zhao B.;
RT   "A subcellular map of the human kinome.";
RL   Elife 10:0-0(2021).
RN   [6]
RP   VARIANTS [LARGE SCALE ANALYSIS] PRO-307; LEU-418; LEU-622 AND LEU-626.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
CC   -!- FUNCTION: The function of this protein is not yet clear. It is not
CC       known if it has protein kinase activity and what type of substrate it
CC       would phosphorylate (Ser, Thr or Tyr) (Probable). Involved in the
CC       mitochondrial import of CoQ precursors, plays a role in muscle
CC       mitochondrial function and fatty acid beta-oxidation (PubMed:31480808).
CC       {ECO:0000269|PubMed:31480808, ECO:0000305}.
CC   -!- INTERACTION:
CC       Q7Z695; P05141: SLC25A5; NbExp=4; IntAct=EBI-21505425, EBI-355133;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:33988507}.
CC       Membrane {ECO:0000255}; Single-pass membrane protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. ADCK protein
CC       kinase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH14107.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR   EMBL; AY302592; AAP60021.1; -; mRNA.
DR   EMBL; AC006344; AAD43192.1; -; Genomic_DNA.
DR   EMBL; AC006452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC014107; AAH14107.1; ALT_SEQ; mRNA.
DR   CCDS; CCDS5861.1; -.
DR   RefSeq; NP_443085.2; NM_052853.3.
DR   AlphaFoldDB; Q7Z695; -.
DR   BioGRID; 124782; 82.
DR   IntAct; Q7Z695; 59.
DR   MINT; Q7Z695; -.
DR   STRING; 9606.ENSP00000072869; -.
DR   iPTMnet; Q7Z695; -.
DR   PhosphoSitePlus; Q7Z695; -.
DR   SwissPalm; Q7Z695; -.
DR   BioMuta; ADCK2; -.
DR   DMDM; 74723374; -.
DR   EPD; Q7Z695; -.
DR   jPOST; Q7Z695; -.
DR   MassIVE; Q7Z695; -.
DR   PaxDb; 9606-ENSP00000072869; -.
DR   PeptideAtlas; Q7Z695; -.
DR   ProteomicsDB; 69383; -.
DR   Antibodypedia; 32457; 187 antibodies from 25 providers.
DR   DNASU; 90956; -.
DR   Ensembl; ENST00000072869.9; ENSP00000072869.4; ENSG00000133597.11.
DR   GeneID; 90956; -.
DR   KEGG; hsa:90956; -.
DR   MANE-Select; ENST00000072869.9; ENSP00000072869.4; NM_052853.4; NP_443085.2.
DR   UCSC; uc003vvy.2; human.
DR   AGR; HGNC:19039; -.
DR   CTD; 90956; -.
DR   DisGeNET; 90956; -.
DR   GeneCards; ADCK2; -.
DR   HGNC; HGNC:19039; ADCK2.
DR   HPA; ENSG00000133597; Low tissue specificity.
DR   neXtProt; NX_Q7Z695; -.
DR   OpenTargets; ENSG00000133597; -.
DR   PharmGKB; PA134902329; -.
DR   VEuPathDB; HostDB:ENSG00000133597; -.
DR   eggNOG; KOG1236; Eukaryota.
DR   GeneTree; ENSGT00390000001536; -.
DR   HOGENOM; CLU_006533_6_1_1; -.
DR   InParanoid; Q7Z695; -.
DR   OMA; LSMVRTH; -.
DR   OrthoDB; 120989at2759; -.
DR   PhylomeDB; Q7Z695; -.
DR   TreeFam; TF315018; -.
DR   PathwayCommons; Q7Z695; -.
DR   SignaLink; Q7Z695; -.
DR   BioGRID-ORCS; 90956; 31 hits in 1189 CRISPR screens.
DR   ChiTaRS; ADCK2; human.
DR   GenomeRNAi; 90956; -.
DR   Pharos; Q7Z695; Tbio.
DR   PRO; PR:Q7Z695; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; Q7Z695; Protein.
DR   Bgee; ENSG00000133597; Expressed in buccal mucosa cell and 207 other cell types or tissues.
DR   ExpressionAtlas; Q7Z695; baseline and differential.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0010795; P:regulation of ubiquinone biosynthetic process; IDA:UniProtKB.
DR   CDD; cd13971; ADCK2-like; 1.
DR   InterPro; IPR004147; ABC1_dom.
DR   InterPro; IPR044095; ADCK2_dom.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   PANTHER; PTHR45890; AARF DOMAIN CONTAINING KINASE 2 (PREDICTED); 1.
DR   PANTHER; PTHR45890:SF25; AARF DOMAIN-CONTAINING KINASE 2; 1.
DR   Pfam; PF03109; ABC1; 2.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   Genevisible; Q7Z695; HS.
PE   1: Evidence at protein level;
KW   ATP-binding; Kinase; Membrane; Mitochondrion; Nucleotide-binding;
KW   Reference proteome; Serine/threonine-protein kinase; Transferase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..626
FT                   /note="Uncharacterized aarF domain-containing protein
FT                   kinase 2"
FT                   /id="PRO_0000271792"
FT   TRANSMEM        103..123
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          200..618
FT                   /note="Protein kinase"
FT   ACT_SITE        445
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         206..214
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         311
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   VARIANT         66
FT                   /note="S -> G (in dbSNP:rs2968558)"
FT                   /id="VAR_060990"
FT   VARIANT         307
FT                   /note="S -> P (in dbSNP:rs1140034)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_029992"
FT   VARIANT         333..626
FT                   /note="Missing (found in a patient with slow and
FT                   progressive proximal muscle weakness with permanent myalgia
FT                   both at rest and during muscular exertion which results in
FT                   permanent disability; uncertain significance; decreased
FT                   levels of coenzyme Q10)"
FT                   /evidence="ECO:0000269|PubMed:31480808"
FT                   /id="VAR_088468"
FT   VARIANT         418
FT                   /note="V -> L (in dbSNP:rs3748092)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041418"
FT   VARIANT         418
FT                   /note="V -> M (in dbSNP:rs3748092)"
FT                   /id="VAR_029993"
FT   VARIANT         622
FT                   /note="P -> L (in dbSNP:rs1046515)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_029994"
FT   VARIANT         626
FT                   /note="P -> L (in dbSNP:rs55922126)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041419"
SQ   SEQUENCE   626 AA;  68982 MW;  F8E25DB672017AF4 CRC64;
     MVAPWRVSVR VCLSHLRCFE LRQGLSLLRP SECPRDARLC WLLLGTLPKV VSLCGDVGEG
     APDVLSRRRV RCSGAAGAGP AESLPRAGPL GGVFLHLRLW LRAGALLVKF FPLLLLYPLT
     YLAPSVSTLW LHLLLKATET SGPTYIKLGQ WASTRRDLFS EAFCAQFSKL HVRVTPHPWT
     HTERFLRQAF GDDWGSILSF ENREPVGSGC VAQVYKAYAN TAFLETDSVQ RLGRASCLPP
     FSHTGAVGGL RELFGYLGNG RKPPENLADQ SFLERLLLPK ADLVGSNAGV SRAQVPGHQP
     EATNLISVAV KVLHPGLLAQ VHMDLLLMKI GSRVLGVLPG IKWLSLPEIV EEFEKLMVQQ
     IDLRYEAQNL EHFQVNFRNV KAVKFPTPLR PFVTREVLVE TYEESVPVSS YQQAGIPVDL
     KRKIARLGIN MLLKMIFVDN FVHADLHPGN ILVQGANGLS SSQEAQLQQA DICDTLVVAV
     PSSLCPLRLV LLDAGIVAEL QAPDLRNFRA VFMAVVMGQG QRVAELILHH ARASECRDVE
     GFKTEMAMLV TQARKNTITL EKLHVSSLLS SVFKLLMTHK VKLESNFASI VFAIMVLEGL
     GRSLDPKLDI LEAARPFLLT GPVCPP
//