KAD7_HUMAN
ID KAD7_HUMAN Reviewed; 723 AA.
AC Q96M32; Q8IYP6;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 3.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Adenylate kinase 7;
DE Short=AK 7;
DE EC=2.7.4.3 {ECO:0000269|PubMed:21080915, ECO:0000269|PubMed:23416111};
DE EC=2.7.4.6 {ECO:0000269|PubMed:23416111};
DE AltName: Full=ATP-AMP transphosphorylase 7;
GN Name=AK7;
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 [LARGE SCALE MRNA], AND VARIANTS GLN-102 AND LYS-389.
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP CATALYTIC ACTIVITY.
RX PubMed=21080915; DOI=10.1042/bj20101443;
RA Panayiotou C., Solaroli N., Xu Y., Johansson M., Karlsson A.;
RT "The characterization of human adenylate kinases 7 and 8 demonstrates
RT differences in kinetic parameters and structural organization among the
RT family of adenylate kinase isoenzymes.";
RL Biochem. J. 433:527-534(2011).
RN [4]
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 [5]
RP INVOLVEMENT IN SPGF27, VARIANT SPGF27 PRO-673, CHARACTERIZATION OF VARIANT
RP SPGF27 PRO-673, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=29365104; DOI=10.1093/hmg/ddy034;
RA Lores P., Coutton C., El Khouri E., Stouvenel L., Givelet M., Thomas L.,
RA Rode B., Schmitt A., Louis B., Sakheli Z., Chaudhry M.,
RA Fernandez-Gonzales A., Mitsialis A., Dacheux D., Wolf J.P., Papon J.F.,
RA Gacon G., Escudier E., Arnoult C., Bonhivers M., Savinov S.N., Amselem S.,
RA Ray P.F., Dulioust E., Toure A.;
RT "Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to
RT primary male infertility and multiple morphological anomalies of the
RT flagella but not to primary ciliary dyskinesia.";
RL Hum. Mol. Genet. 27:1196-1211(2018).
CC -!- FUNCTION: Nucleoside monophosphate (NMP) kinase that catalyzes the
CC reversible transfer of the terminal phosphate group between nucleoside
CC triphosphates and monophosphates. Has highest activity toward AMP, and
CC weaker activity toward dAMP, CMP and dCMP. Also displays broad
CC nucleoside diphosphate kinase activity. Involved in maintaining ciliary
CC structure and function. {ECO:0000269|PubMed:21080915,
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:21080915, ECO:0000269|PubMed:23416111};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.0 uM for AMP {ECO:0000269|PubMed:21080915};
CC KM=28 uM for dAMP {ECO:0000269|PubMed:21080915};
CC KM=1.2 uM for CMP {ECO:0000269|PubMed:21080915};
CC Vmax=1130 pmol/min/ug enzyme with AMP as substrate
CC {ECO:0000269|PubMed:21080915};
CC Vmax=860 pmol/min/ug enzyme with dAMP as substrate
CC {ECO:0000269|PubMed:21080915};
CC Vmax=150 pmol/min/ug enzyme with CMP as substrate
CC {ECO:0000269|PubMed:21080915};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:21080915}.
CC Cell projection, cilium, flagellum {ECO:0000269|PubMed:29365104}.
CC Note=Detected along the full length of sperm flagellum, where it
CC colocalizes with alpha-tubulin. {ECO:0000269|PubMed:29365104}.
CC -!- TISSUE SPECIFICITY: Expressed in sperm and airway epithelial cells (at
CC protein level). {ECO:0000269|PubMed:29365104}.
CC -!- DISEASE: Spermatogenic failure 27 (SPGF27) [MIM:617965]: An autosomal
CC recessive infertility disorder caused by spermatogenesis defects that
CC result in multiple morphologic abnormalities of the sperm flagella,
CC including short, irregular, coiled, or absent flagella.
CC {ECO:0000269|PubMed:29365104}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: In the central section; belongs to the adenylate kinase
CC family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the dpy-30 family.
CC {ECO:0000305}.
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DR EMBL; AK057426; BAB71480.1; -; mRNA.
DR EMBL; AL163051; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359240; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS9945.1; -.
DR RefSeq; NP_689540.2; NM_152327.3.
DR AlphaFoldDB; Q96M32; -.
DR BioGRID; 125773; 7.
DR IntAct; Q96M32; 4.
DR STRING; 9606.ENSP00000267584; -.
DR iPTMnet; Q96M32; -.
DR PhosphoSitePlus; Q96M32; -.
DR BioMuta; AK7; -.
DR DMDM; 269849674; -.
DR jPOST; Q96M32; -.
DR MassIVE; Q96M32; -.
DR PaxDb; Q96M32; -.
DR PeptideAtlas; Q96M32; -.
DR PRIDE; Q96M32; -.
DR ProteomicsDB; 77290; -.
DR Antibodypedia; 165; 77 antibodies from 24 providers.
DR DNASU; 122481; -.
DR Ensembl; ENST00000267584.9; ENSP00000267584.4; ENSG00000140057.9.
DR GeneID; 122481; -.
DR KEGG; hsa:122481; -.
DR MANE-Select; ENST00000267584.9; ENSP00000267584.4; NM_152327.5; NP_689540.2.
DR UCSC; uc001yfn.3; human.
DR CTD; 122481; -.
DR DisGeNET; 122481; -.
DR GeneCards; AK7; -.
DR HGNC; HGNC:20091; AK7.
DR HPA; ENSG00000140057; Tissue enhanced (fallopian).
DR MalaCards; AK7; -.
DR MIM; 615364; gene.
DR MIM; 617965; phenotype.
DR neXtProt; NX_Q96M32; -.
DR OpenTargets; ENSG00000140057; -.
DR Orphanet; 276234; Non-syndromic male infertility due to sperm motility disorder.
DR PharmGKB; PA134963502; -.
DR VEuPathDB; HostDB:ENSG00000140057; -.
DR eggNOG; KOG3078; Eukaryota.
DR GeneTree; ENSGT00390000015102; -.
DR HOGENOM; CLU_015567_1_0_1; -.
DR InParanoid; Q96M32; -.
DR OMA; NECKFRG; -.
DR OrthoDB; 572856at2759; -.
DR PhylomeDB; Q96M32; -.
DR TreeFam; TF313982; -.
DR BRENDA; 2.7.4.3; 2681.
DR PathwayCommons; Q96M32; -.
DR Reactome; R-HSA-499943; Interconversion of nucleotide di- and triphosphates.
DR SABIO-RK; Q96M32; -.
DR SignaLink; Q96M32; -.
DR BioGRID-ORCS; 122481; 9 hits in 1073 CRISPR screens.
DR ChiTaRS; AK7; human.
DR GenomeRNAi; 122481; -.
DR Pharos; Q96M32; Tbio.
DR PRO; PR:Q96M32; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q96M32; protein.
DR Bgee; ENSG00000140057; Expressed in bronchial epithelial cell and 104 other tissues.
DR ExpressionAtlas; Q96M32; baseline and differential.
DR Genevisible; Q96M32; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0004017; F:adenylate kinase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004127; F:cytidylate kinase activity; IDA:UniProtKB.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB.
DR GO; GO:0030030; P:cell projection organization; IEA:UniProtKB-KW.
DR GO; GO:0006165; P:nucleoside diphosphate phosphorylation; IDA:UniProtKB.
DR GO; GO:0009142; P:nucleoside triphosphate biosynthetic process; IDA:UniProtKB.
DR CDD; cd01428; ADK; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR000850; Adenylat/UMP-CMP_kin.
DR InterPro; IPR026867; AK7.
DR InterPro; IPR007858; Dpy-30_motif.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR23359; PTHR23359; 1.
DR PANTHER; PTHR23359:SF105; PTHR23359:SF105; 1.
DR Pfam; PF05186; Dpy-30; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell projection; Cilium; Cilium biogenesis/degradation;
KW Coiled coil; Cytoplasm; Disease variant; Flagellum; Kinase;
KW Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1..723
FT /note="Adenylate kinase 7"
FT /id="PRO_0000158952"
FT REGION 367..612
FT /note="Adenylate kinase"
FT /evidence="ECO:0000305|PubMed:21080915"
FT REGION 397..455
FT /note="NMP"
FT /evidence="ECO:0000250|UniProtKB:P69441"
FT REGION 537..547
FT /note="LID"
FT /evidence="ECO:0000250|UniProtKB:P69441"
FT REGION 679..723
FT /note="DPY-30"
FT /evidence="ECO:0000305|PubMed:21080915"
FT COILED 46..458
FT /evidence="ECO:0000255"
FT COILED 609..677
FT /evidence="ECO:0000255"
FT BINDING 377..382
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P69441"
FT BINDING 432..455
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P69441"
FT BINDING 482..485
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P69441"
FT BINDING 489
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P69441"
FT BINDING 555
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P69441"
FT BINDING 587
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P69441"
FT VARIANT 102
FT /note="R -> Q (in dbSNP:rs2275554)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_017059"
FT VARIANT 389
FT /note="N -> K (in dbSNP:rs2369679)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_057950"
FT VARIANT 673
FT /note="L -> P (in SPGF27; loss of protein expression in
FT sperm cells, no effect in airway epithelial cells;
FT dbSNP:rs116298211)"
FT /evidence="ECO:0000269|PubMed:29365104"
FT /id="VAR_080917"
FT CONFLICT 272
FT /note="P -> L (in Ref. 1; BAB71480)"
FT /evidence="ECO:0000305"
FT CONFLICT 410
FT /note="E -> G (in Ref. 1; BAB71480)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 723 AA; 82658 MW; 7A9E2BF11A4CEEF8 CRC64;
MAEEEETAAL TEKVIRTQRV FINLLDSYSS GNIGKFLSNC VVGASLEEIT EEEEEEDENK
SAMLEASSTK VKEGTFQIVG TLSKPDSPRP DFAVETYSAI SREDLLMRLL ECDVIIYNIT
ESSQQMEEAI WAVSALSEEV SHFEKRKLFI LLSTVMTWAR SKALDPEDSE VPFTEEDYRR
RKSHPNFLDH INAEKMVLKF GKKARKFAAY VVAAGLQYGA EGGMLHTFFK MAWLGEIPAL
PVFGDGTNVI PTIHVLDLAG VIQNVIDHVP KPHYLVAVDE SVHTLEDIVK CISKNTGPGK
IQKIPRENAY LTKDLTQDCL DHLLVNLRME ALFVKENFNI RWAAQTGFVE NINTILKEYK
QSRGLMPIKI CILGPPAVGK SSIAKELANY YKLHHIQLKD VISEAIAKLE AIVAPNDVGE
GEEEVEEEEE EENVEDAQEL LDGIKESMEQ NAGQLDDQYI IRFMKEKLKS MPCRNQGYIL
DGFPKTYDQA KDLFNQEDEE EEDDVRGRMF PFDKLIIPEF VCALDASDEF LKERVINLPE
SIVAGTHYSQ DRFLRALSNY RDINIDDETV FNYFDELEIH PIHIDVGKLE DAQNRLAIKQ
LIKEIGEPRN YGLTDEEKAE EERKAAEERL AREAAEEAER EHQEAVEMAE KIARWEEWNK
RLEEVKREER ELLEAQSIPL RNYLMTYVMP TLIQGLNECC NVRPEDPVDF LAEYLFKNNP
EAQ
