HYKK_HUMAN
ID HYKK_HUMAN Reviewed; 373 AA.
AC A2RU49; B7ZMA5; F8W6X5; Q6ZTN0;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Hydroxylysine kinase;
DE Short=5-hydroxy-L-lysine kinase;
DE EC=2.7.1.81;
DE AltName: Full=Aminoglycoside phosphotransferase domain-containing protein 1;
GN Name=HYKK; Synonyms=AGPHD1;
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] (ISOFORM 2).
RC TISSUE=Uterus;
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=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [3]
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 (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22241472; DOI=10.1074/jbc.m111.323485;
RA Veiga-da-Cunha M., Hadi F., Balligand T., Stroobant V., Van Schaftingen E.;
RT "Molecular identification of hydroxylysine kinase and of
RT ammoniophospholyases acting on 5-phosphohydroxy-L-lysine and
RT phosphoethanolamine.";
RL J. Biol. Chem. 287:7246-7255(2012).
CC -!- FUNCTION: Catalyzes the GTP-dependent phosphorylation of 5-hydroxy-L-
CC lysine. {ECO:0000269|PubMed:22241472}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5R)-5-hydroxy-L-lysine + GTP = (5R)-5-phosphooxy-L-lysine +
CC GDP + H(+); Xref=Rhea:RHEA:19049, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:57882, ChEBI:CHEBI:58189,
CC ChEBI:CHEBI:58357; EC=2.7.1.81;
CC Evidence={ECO:0000269|PubMed:22241472};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=280 uM for (5R)-5-hydroxy-L-lysine (in the presence of 2 mM ATP)
CC {ECO:0000269|PubMed:22241472};
CC KM=7.6 uM for (5R)-5-hydroxy-L-lysine (in the presence of 0.2 mM GTP)
CC {ECO:0000269|PubMed:22241472};
CC KM=810 uM for ATP (in the presence of 0.5 mM (5R)-5-hydroxy-L-lysine)
CC {ECO:0000269|PubMed:22241472};
CC KM=3.5 uM for GTP (in the presence of 0.5 mM (5R)-5-hydroxy-L-lysine)
CC {ECO:0000269|PubMed:22241472};
CC Vmax=4.95 umol/min/mg enzyme toward (5R)-5-hydroxy-L-lysine (in the
CC presence of 2 mM ATP) {ECO:0000269|PubMed:22241472};
CC Vmax=0.49 umol/min/mg enzyme toward (5R)-5-hydroxy-L-lysine (in the
CC presence of 0.2 mM GTP) {ECO:0000269|PubMed:22241472};
CC Vmax=5.28 umol/min/mg enzyme toward ATP (in the presence of 0.5 mM
CC (5R)-5-hydroxy-L-lysine) {ECO:0000269|PubMed:22241472};
CC Vmax=0.57 umol/min/mg enzyme toward GTP (in the presence of 0.5 mM
CC (5R)-5-hydroxy-L-lysine) {ECO:0000269|PubMed:22241472};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A2RU49-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A2RU49-2; Sequence=VSP_032517, VSP_032518;
CC Name=3;
CC IsoId=A2RU49-3; Sequence=VSP_032520;
CC -!- SIMILARITY: Belongs to the aminoglycoside phosphotransferase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK126453; BAC86556.1; -; mRNA.
DR EMBL; AC027228; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471136; EAW99167.1; -; Genomic_DNA.
DR EMBL; BC132753; AAI32754.1; -; mRNA.
DR EMBL; BC144383; AAI44384.1; -; mRNA.
DR CCDS; CCDS42063.1; -. [A2RU49-1]
DR CCDS; CCDS45318.1; -. [A2RU49-3]
DR RefSeq; NP_001013641.2; NM_001013619.3. [A2RU49-1]
DR RefSeq; NP_001077081.1; NM_001083612.1. [A2RU49-3]
DR AlphaFoldDB; A2RU49; -.
DR SMR; A2RU49; -.
DR BioGRID; 125829; 8.
DR IntAct; A2RU49; 3.
DR STRING; 9606.ENSP00000455459; -.
DR iPTMnet; A2RU49; -.
DR PhosphoSitePlus; A2RU49; -.
DR BioMuta; HYKK; -.
DR EPD; A2RU49; -.
DR MassIVE; A2RU49; -.
DR MaxQB; A2RU49; -.
DR PaxDb; A2RU49; -.
DR PeptideAtlas; A2RU49; -.
DR PRIDE; A2RU49; -.
DR ProteomicsDB; 29851; -.
DR ProteomicsDB; 497; -. [A2RU49-1]
DR ProteomicsDB; 498; -. [A2RU49-2]
DR ProteomicsDB; 499; -. [A2RU49-3]
DR Antibodypedia; 51728; 42 antibodies from 14 providers.
DR DNASU; 123688; -.
DR Ensembl; ENST00000388988.9; ENSP00000373640.4; ENSG00000188266.14. [A2RU49-1]
DR Ensembl; ENST00000408962.6; ENSP00000386197.2; ENSG00000188266.14. [A2RU49-3]
DR Ensembl; ENST00000563233.2; ENSP00000454850.1; ENSG00000188266.14. [A2RU49-3]
DR Ensembl; ENST00000566289.5; ENSP00000456614.1; ENSG00000188266.14. [A2RU49-2]
DR Ensembl; ENST00000569878.5; ENSP00000455459.1; ENSG00000188266.14. [A2RU49-1]
DR GeneID; 123688; -.
DR KEGG; hsa:123688; -.
DR MANE-Select; ENST00000388988.9; ENSP00000373640.4; NM_001013619.4; NP_001013641.2.
DR UCSC; uc002bdt.4; human. [A2RU49-1]
DR CTD; 123688; -.
DR DisGeNET; 123688; -.
DR GeneCards; HYKK; -.
DR HGNC; HGNC:34403; HYKK.
DR HPA; ENSG00000188266; Low tissue specificity.
DR MIM; 614681; gene.
DR neXtProt; NX_A2RU49; -.
DR OpenTargets; ENSG00000188266; -.
DR PharmGKB; PA165478483; -.
DR VEuPathDB; HostDB:ENSG00000188266; -.
DR eggNOG; ENOG502QT7T; Eukaryota.
DR GeneTree; ENSGT00390000011314; -.
DR HOGENOM; CLU_042971_1_1_1; -.
DR InParanoid; A2RU49; -.
DR OMA; QNFHVHI; -.
DR OrthoDB; 1519192at2759; -.
DR PhylomeDB; A2RU49; -.
DR TreeFam; TF324471; -.
DR BRENDA; 2.7.1.81; 2681.
DR PathwayCommons; A2RU49; -.
DR Reactome; R-HSA-71064; Lysine catabolism.
DR SignaLink; A2RU49; -.
DR BioGRID-ORCS; 123688; 8 hits in 1037 CRISPR screens.
DR ChiTaRS; HYKK; human.
DR GenomeRNAi; 123688; -.
DR Pharos; A2RU49; Tbio.
DR PRO; PR:A2RU49; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; A2RU49; protein.
DR Bgee; ENSG00000188266; Expressed in olfactory segment of nasal mucosa and 101 other tissues.
DR ExpressionAtlas; A2RU49; baseline and differential.
DR Genevisible; A2RU49; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0019202; F:amino acid kinase activity; IBA:GO_Central.
DR GO; GO:0047992; F:hydroxylysine kinase activity; IDA:FlyBase.
DR GO; GO:0006554; P:lysine catabolic process; TAS:Reactome.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR InterPro; IPR002575; Aminoglycoside_PTrfase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR Pfam; PF01636; APH; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Kinase; Reference proteome; Transferase.
FT CHAIN 1..373
FT /note="Hydroxylysine kinase"
FT /id="PRO_0000326044"
FT ACT_SITE 226
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT VAR_SEQ 160..172
FT /note="RFHHPKLSSLHRE -> EGKPRVTPLLAKN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_032517"
FT VAR_SEQ 173..373
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_032518"
FT VAR_SEQ 221..373
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_032520"
FT VARIANT A2RU49-2:165
FT /note="V -> I (in dbSNP:4380026)"
FT /evidence="ECO:0000305"
FT /id="VAR_082892"
SQ SEQUENCE 373 AA; 41933 MW; C8BF3521D8D980A2 CRC64;
MSSGNYQQSE ALSKPTFSEE QASALVESVF GLKVSKVRPL PSYDDQNFHV YVSKTKDGPT
EYVLKISNTK ASKNPDLIEV QNHIIMFLKA AGFPTASVCH TKGDNTASLV SVDSGSEIKS
YLVRLLTYLP GRPIAELPVS PQLLYEIGKL AAKLDKTLQR FHHPKLSSLH RENFIWNLKN
VPLLEKYLYA LGQNRNREIV EHVIHLFKEE VMTKLSHFRE CINHGDLNDH NILIESSKSA
SGNAEYQVSG ILDFGDMSYG YYVFEVAITI MYMMIESKSP IQVGGHVLAG FESITPLTAV
EKGALFLLVC SRFCQSLVMA AYSCQLYPEN KDYLMVTAKT GWKHLQQMFD MGQKAVEEIW
FETAKSYESG ISM
