PDXK_HUMAN
ID PDXK_HUMAN Reviewed; 312 AA.
AC O00764; Q7Z2Y0; Q9BS02;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Pyridoxal kinase;
DE EC=2.7.1.35 {ECO:0000269|PubMed:10987144, ECO:0000269|PubMed:17766369, ECO:0000269|PubMed:19351586, ECO:0000269|PubMed:31187503, ECO:0000269|PubMed:9099727};
DE AltName: Full=Pyridoxine kinase;
GN Name=PDXK {ECO:0000312|HGNC:HGNC:8819};
GN Synonyms=C21orf124, C21orf97, PKH, PNK; ORFNames=PRED79;
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), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=9099727; DOI=10.1074/jbc.272.16.10756;
RA Hanna M.C., Turner A.J., Kirkness E.F.;
RT "Human pyridoxal kinase. cDNA cloning, expression, and modulation by
RT ligands of the benzodiazepine receptor.";
RL J. Biol. Chem. 272:10756-10760(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=15154080;
RA Fang X., Zhou Z.M., Lu L., Yin L.L., Li J.M., Zhen Y., Wang H., Sha J.H.;
RT "Expression of a novel pyridoxal kinase mRNA splice variant, PKH-T, in
RT human testis.";
RL Asian J. Androl. 6:83-91(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Eye, and Ovary;
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, BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RX PubMed=10987144;
RA Lee H.-S., Moon B.J., Choi S.Y., Kwon O.-S.;
RT "Human pyridoxal kinase: overexpression and properties of the recombinant
RT enzyme.";
RL Mol. Cells 10:452-459(2000).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213 AND SER-285, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-59; SER-164; SER-213 AND
RP SER-285, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-285, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP INDUCTION BY SP1.
RX PubMed=28716709; DOI=10.1016/j.gene.2017.07.044;
RA Huang S., Liu Z., Ma Z., Zhang J., Huang L.;
RT "Isolation and characterization of the 5'-flanking region of the human PDXK
RT gene.";
RL Gene 628:218-223(2017).
RN [12] {ECO:0007744|PDB:2AJP}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 6-312 IN COMPLEX WITH ATP ANALOG
RP AND MAGNESIUM.
RA Ismail S., Dimov S., Atanassova A., Tempel W., Arrowsmith C., Edwards A.,
RA Sundstrom M., Weigelt J., Bochkarev A., Park H.;
RT "Crystal structure of a human pyridoxal kinase.";
RL Submitted (AUG-2005) to the PDB data bank.
RN [13] {ECO:0007744|PDB:2F7K}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS).
RX PubMed=16600635; DOI=10.1016/j.jsb.2006.02.008;
RA Cao P., Gong Y., Tang L., Leung Y.C., Jiang T.;
RT "Crystal structure of human pyridoxal kinase.";
RL J. Struct. Biol. 154:327-332(2006).
RN [14] {ECO:0007744|PDB:2YXT, ECO:0007744|PDB:2YXU}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH
RP MGATP AND SODIUM, SUBUNIT, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=17766369; DOI=10.1110/ps.073022107;
RA Musayev F.N., di Salvo M.L., Ko T.P., Gandhi A.K., Goswami A., Schirch V.,
RA Safo M.K.;
RT "Crystal Structure of human pyridoxal kinase: structural basis of M(+) and
RT M(2+) activation.";
RL Protein Sci. 16:2184-2194(2007).
RN [15] {ECO:0007744|PDB:3FHX, ECO:0007744|PDB:3FHY}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF MUTANTS ALA-235 AND ASN-235 IN
RP COMPLEX WITH ATP; PYRIDOXAL PHOSPHATE; PYRIDOXAL; MAGNESIUM AND SODIUM,
RP ACTIVE SITE, MUTAGENESIS OF ASP-235, BIOPHYSICOCHEMICAL PROPERTIES,
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=19351586; DOI=10.1016/j.bbrc.2009.01.170;
RA Gandhi A.K., Ghatge M.S., Musayev F.N., Sease A., Aboagye S.O.,
RA di Salvo M.L., Schirch V., Safo M.K.;
RT "Kinetic and structural studies of the role of the active site residue
RT Asp235 of human pyridoxal kinase.";
RL Biochem. Biophys. Res. Commun. 381:12-15(2009).
RN [16] {ECO:0007744|PDB:3KEU}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH ATP; PYRIDOXAL
RP PHOSPHATE; MAGNESIUM AND SODIUM, AND COFACTOR.
RA Gandhi A.K., Musayev F.N., Safo M.K.;
RT "Crystal structure of PL kinase in complex with MgATP and PLP: Structural
RT basis of severe induced MgATP substrate inhibition of the enzyme.";
RL Submitted (OCT-2009) to the PDB data bank.
RN [17] {ECO:0007744|PDB:4EN4, ECO:0007744|PDB:4EOH}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEXES WITH ATP; MAGNESIUM;
RP SODIUM AND NEUROTOXINS, ACTIVITY REGULATION, AND COFACTOR.
RX PubMed=22879864; DOI=10.1371/journal.pone.0040954;
RA Gandhi A.K., Desai J.V., Ghatge M.S., di Salvo M.L., Di Biase S.,
RA Danso-Danquah R., Musayev F.N., Contestabile R., Schirch V., Safo M.K.;
RT "Crystal structures of human pyridoxal kinase in complex with the
RT neurotoxins, ginkgotoxin and theophylline: insights into pyridoxal kinase
RT inhibition.";
RL PLoS ONE 7:e40954-e40954(2012).
RN [18]
RP VARIANTS HMSN6C GLN-220 AND THR-228, CHARACTERIZATION OF VARIANTS HMSN6C
RP GLN-220 AND THR-228, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY,
RP FUNCTION, TISSUE SPECIFICITY, AND PATHWAY.
RX PubMed=31187503; DOI=10.1002/ana.25524;
RG Care4Rare Canada Consortium and the SYNaPS Study Group;
RA Chelban V., Wilson M.P., Warman Chardon J., Vandrovcova J., Zanetti M.N.,
RA Zamba-Papanicolaou E., Efthymiou S., Pope S., Conte M.R., Abis G.,
RA Liu Y.T., Tribollet E., Haridy N.A., Botia J.A., Ryten M., Nicolaou P.,
RA Minaidou A., Christodoulou K., Kernohan K.D., Eaton A., Osmond M., Ito Y.,
RA Bourque P., Jepson J.E.C., Bello O., Bremner F., Cordivari C., Reilly M.M.,
RA Foiani M., Heslegrave A., Zetterberg H., Heales S.J.R., Wood N.W.,
RA Rothman J.E., Boycott K.M., Mills P.B., Clayton P.T., Houlden H.;
RT "PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate
RT supplementation.";
RL Ann. Neurol. 86:225-240(2019).
CC -!- FUNCTION: Catalyzes the phosphorylation of the dietary vitamin B6
CC vitamers pyridoxal (PL), pyridoxine (PN) and pyridoxamine (PM) to form
CC pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP) and
CC pyridoxamine 5'-phosphate (PMP), respectively (PubMed:9099727,
CC PubMed:10987144, PubMed:17766369, PubMed:19351586, PubMed:31187503)
CC (Probable). PLP is the active form of vitamin B6, and acts as a
CC cofactor for over 140 different enzymatic reactions.
CC {ECO:0000269|PubMed:10987144, ECO:0000269|PubMed:17766369,
CC ECO:0000269|PubMed:19351586, ECO:0000269|PubMed:31187503,
CC ECO:0000269|PubMed:9099727, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + pyridoxal = ADP + H(+) + pyridoxal 5'-phosphate;
CC Xref=Rhea:RHEA:10224, ChEBI:CHEBI:15378, ChEBI:CHEBI:17310,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:456216, ChEBI:CHEBI:597326;
CC EC=2.7.1.35; Evidence={ECO:0000269|PubMed:10987144,
CC ECO:0000269|PubMed:17766369, ECO:0000269|PubMed:19351586,
CC ECO:0000269|PubMed:31187503, ECO:0000269|PubMed:9099727};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10225;
CC Evidence={ECO:0000269|PubMed:31187503};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + pyridoxamine = ADP + H(+) + pyridoxamine 5'-phosphate;
CC Xref=Rhea:RHEA:25104, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57761, ChEBI:CHEBI:58451, ChEBI:CHEBI:456216;
CC EC=2.7.1.35; Evidence={ECO:0000305|PubMed:17766369};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25105;
CC Evidence={ECO:0000305|PubMed:17766369};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + pyridoxine = ADP + H(+) + pyridoxine 5'-phosphate;
CC Xref=Rhea:RHEA:25108, ChEBI:CHEBI:15378, ChEBI:CHEBI:16709,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58589, ChEBI:CHEBI:456216;
CC EC=2.7.1.35; Evidence={ECO:0000305|PubMed:17766369};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25109;
CC Evidence={ECO:0000305|PubMed:17766369};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10987144, ECO:0000269|PubMed:17766369,
CC ECO:0000269|PubMed:19351586, ECO:0000269|PubMed:22879864,
CC ECO:0000269|Ref.16};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:10987144};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:10987144};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:10987144};
CC Note=Zn(2+) is the most effective divalent metal cation in vitro,
CC followed by Co(2+), Mn(2+) and Mg(2+). {ECO:0000269|PubMed:10987144};
CC -!- ACTIVITY REGULATION: Catalytic activity is inhibited competitively by
CC 4-deoxypyridoxine, and is also inhibited by the benzodiazepine receptor
CC ligands 1012S and ethyl-beta-carboline-3-carboxylate (PubMed:9099727).
CC Inhibited by ginkgotoxin, theophylline, lamotrigine, enprofylline,
CC theobromine, and caffeine (PubMed:22879864). Activity is increased in
CC the presence of K(+)or Na(+) (PubMed:17766369).
CC {ECO:0000269|PubMed:17766369, ECO:0000269|PubMed:22879864,
CC ECO:0000269|PubMed:9099727}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.3 uM for pyridoxal (in the presence of K(+))
CC {ECO:0000269|PubMed:9099727};
CC KM=14.5 uM for pyridoxal (in the presence of K(+))
CC {ECO:0000269|PubMed:31187503};
CC KM=97 uM for pyridoxal (in the presence of K(+))
CC {ECO:0000269|PubMed:10987144};
CC KM=75 uM for pyridoxal (in the presence of Na(+))
CC {ECO:0000269|PubMed:17766369};
CC KM=24 uM for pyridoxal (in the presence of Na(+))
CC {ECO:0000269|PubMed:19351586};
CC KM=58 uM for pyridoxal (in the presence of Na(+))
CC {ECO:0000269|Ref.16};
CC KM=12 uM for MgATP (in the presence of K(+))
CC {ECO:0000269|PubMed:10987144};
CC KM=500 uM for MgATP (in the presence of Na(+))
CC {ECO:0000269|PubMed:17766369};
CC KM=190 uM for MgATP (in the presence of Na(+))
CC {ECO:0000269|PubMed:19351586};
CC Note=KM is <10 uM for pyridoxal (in the presence of K(+))
CC (PubMed:17766369). KM is <25 uM for MgATP (in the presence of K(+))
CC (PubMed:17766369). kcat is 200 min(-1) for phosphorylase activity
CC using PL as substrate in the presence of Na(+). kcat is 85 min(-1)
CC for phosphorylase activity using PL as substrate in the presence of
CC K(+) (PubMed:17766369). kcat is 200 min(-1) for phosphorylase
CC activity using PL as substrate in the presence of Na(+). kcat is 85
CC min(-1) for phosphorylase activity using PL as substrate in the
CC presence of K(+) (PubMed:17766369). kcat is 29 min(-1) for
CC phosphorylase activity using PL as substrate in the presence of Na(+)
CC (PubMed:19351586). {ECO:0000269|PubMed:17766369,
CC ECO:0000269|PubMed:19351586};
CC pH dependence:
CC Optimum pH is 5.5-6.0. {ECO:0000269|PubMed:10987144};
CC -!- PATHWAY: Cofactor metabolism; pyridoxal 5'-phosphate salvage; pyridoxal
CC 5'-phosphate from pyridoxal: step 1/1. {ECO:0000269|PubMed:31187503,
CC ECO:0000305|PubMed:17766369}.
CC -!- PATHWAY: Cofactor metabolism; pyridoxal 5'-phosphate salvage;
CC pyridoxine 5'-phosphate from pyridoxine: step 1/1.
CC {ECO:0000305|PubMed:17766369}.
CC -!- PATHWAY: Cofactor metabolism; pyridoxal 5'-phosphate salvage;
CC pyridoxamine 5'-phosphate from pyridoxamine: step 1/1.
CC {ECO:0000305|PubMed:17766369}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17766369}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:9099727}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O00764-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00764-2; Sequence=VSP_004653;
CC Name=3; Synonyms=PKH-T;
CC IsoId=O00764-3; Sequence=VSP_010671;
CC -!- TISSUE SPECIFICITY: Ubiquitous (PubMed:9099727, PubMed:31187503).
CC Highly expressed in testis (PubMed:9099727).
CC {ECO:0000269|PubMed:31187503, ECO:0000269|PubMed:9099727}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: In adult testis and spermatozoa.
CC {ECO:0000269|PubMed:15154080}.
CC -!- INDUCTION: Transcriptionally regulated by Sp1 transcription factor.
CC {ECO:0000269|PubMed:28716709}.
CC -!- DISEASE: Neuropathy, hereditary motor and sensory, 6C, with optic
CC atrophy (HMSN6C) [MIM:618511]: An autosomal recessive neurologic
CC disorder characterized by childhood onset of axonal, sensorimotor
CC polyneuropathy affecting mainly the lower limbs, and adult-onset optic
CC atrophy. Clinical features include progressive distal muscle weakness
CC and atrophy, significant standing and walking difficulties, areflexia,
CC neurogenic pain and progressive visual impairment.
CC {ECO:0000269|PubMed:31187503}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the pyridoxine kinase family. {ECO:0000305}.
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DR EMBL; U89606; AAC51233.1; -; mRNA.
DR EMBL; AY303972; AAP73047.1; -; mRNA.
DR EMBL; AP001752; BAA95540.1; -; Genomic_DNA.
DR EMBL; BC000123; AAH00123.1; -; mRNA.
DR EMBL; BC005825; AAH05825.1; -; mRNA.
DR CCDS; CCDS13699.1; -. [O00764-1]
DR RefSeq; NP_003672.1; NM_003681.4. [O00764-1]
DR RefSeq; XP_005261256.1; XM_005261199.2. [O00764-3]
DR RefSeq; XP_011528062.1; XM_011529760.2. [O00764-3]
DR RefSeq; XP_011528063.1; XM_011529761.1. [O00764-3]
DR RefSeq; XP_016883972.1; XM_017028483.1. [O00764-3]
DR RefSeq; XP_016883973.1; XM_017028484.1. [O00764-3]
DR PDB; 2AJP; X-ray; 2.50 A; A/B=6-312.
DR PDB; 2F7K; X-ray; 2.80 A; A/B=1-312.
DR PDB; 2YXT; X-ray; 2.00 A; A/B=1-312.
DR PDB; 2YXU; X-ray; 2.20 A; A/B=1-312.
DR PDB; 3FHX; X-ray; 2.50 A; A/B=1-312.
DR PDB; 3FHY; X-ray; 2.30 A; A/B=1-312.
DR PDB; 3KEU; X-ray; 2.10 A; A/B=1-312.
DR PDB; 4EN4; X-ray; 2.15 A; A/B=1-312.
DR PDB; 4EOH; X-ray; 2.10 A; A/B=1-312.
DR PDBsum; 2AJP; -.
DR PDBsum; 2F7K; -.
DR PDBsum; 2YXT; -.
DR PDBsum; 2YXU; -.
DR PDBsum; 3FHX; -.
DR PDBsum; 3FHY; -.
DR PDBsum; 3KEU; -.
DR PDBsum; 4EN4; -.
DR PDBsum; 4EOH; -.
DR AlphaFoldDB; O00764; -.
DR SMR; O00764; -.
DR BioGRID; 114135; 39.
DR CORUM; O00764; -.
DR IntAct; O00764; 10.
DR MINT; O00764; -.
DR STRING; 9606.ENSP00000291565; -.
DR BindingDB; O00764; -.
DR ChEMBL; CHEMBL1075181; -.
DR DrugBank; DB04776; (2R)-2-({6-[benzyl(methyl)amino]-9-isopropyl-9H-purin-2-yl}amino)butan-1-ol.
DR DrugBank; DB03909; Adenosine-5'-[Beta, Gamma-Methylene]Triphosphate.
DR DrugBank; DB04770; O6-(R)-ROSCOVITINE, R-2-(6-BENZYLOXY-9-ISOPROPYL-9H-PURIN-2-YLAMINO)-BUTAN-1-OL.
DR DrugBank; DB00147; Pyridoxal.
DR DrugBank; DB00165; Pyridoxine.
DR DrugCentral; O00764; -.
DR GlyGen; O00764; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O00764; -.
DR MetOSite; O00764; -.
DR PhosphoSitePlus; O00764; -.
DR BioMuta; PDXK; -.
DR REPRODUCTION-2DPAGE; IPI00013004; -.
DR REPRODUCTION-2DPAGE; O00764; -.
DR EPD; O00764; -.
DR jPOST; O00764; -.
DR MassIVE; O00764; -.
DR MaxQB; O00764; -.
DR PaxDb; O00764; -.
DR PeptideAtlas; O00764; -.
DR PRIDE; O00764; -.
DR ProteomicsDB; 48024; -. [O00764-1]
DR ProteomicsDB; 48025; -. [O00764-2]
DR ProteomicsDB; 48026; -. [O00764-3]
DR Antibodypedia; 24020; 344 antibodies from 27 providers.
DR DNASU; 8566; -.
DR Ensembl; ENST00000291565.9; ENSP00000291565.4; ENSG00000160209.19. [O00764-1]
DR Ensembl; ENST00000468090.5; ENSP00000418359.1; ENSG00000160209.19. [O00764-2]
DR GeneID; 8566; -.
DR KEGG; hsa:8566; -.
DR MANE-Select; ENST00000291565.9; ENSP00000291565.4; NM_003681.5; NP_003672.1.
DR UCSC; uc002zdn.4; human. [O00764-1]
DR CTD; 8566; -.
DR DisGeNET; 8566; -.
DR GeneCards; PDXK; -.
DR HGNC; HGNC:8819; PDXK.
DR HPA; ENSG00000160209; Tissue enhanced (brain).
DR MalaCards; PDXK; -.
DR MIM; 179020; gene.
DR MIM; 618511; phenotype.
DR neXtProt; NX_O00764; -.
DR OpenTargets; ENSG00000160209; -.
DR PharmGKB; PA33162; -.
DR VEuPathDB; HostDB:ENSG00000160209; -.
DR eggNOG; KOG2599; Eukaryota.
DR GeneTree; ENSGT00390000003874; -.
DR HOGENOM; CLU_046496_1_1_1; -.
DR InParanoid; O00764; -.
DR OMA; CPNQLEL; -.
DR OrthoDB; 1091630at2759; -.
DR PhylomeDB; O00764; -.
DR TreeFam; TF315004; -.
DR BioCyc; MetaCyc:HS08466-MON; -.
DR BRENDA; 2.7.1.35; 2681.
DR PathwayCommons; O00764; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-964975; Vitamins B6 activation to pyridoxal phosphate.
DR SABIO-RK; O00764; -.
DR SignaLink; O00764; -.
DR UniPathway; UPA01068; UER00298.
DR UniPathway; UPA01068; UER00299.
DR UniPathway; UPA01068; UER00300.
DR BioGRID-ORCS; 8566; 33 hits in 1086 CRISPR screens.
DR ChiTaRS; PDXK; human.
DR EvolutionaryTrace; O00764; -.
DR GeneWiki; PDXK; -.
DR GenomeRNAi; 8566; -.
DR Pharos; O00764; Tbio.
DR PRO; PR:O00764; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; O00764; protein.
DR Bgee; ENSG00000160209; Expressed in left testis and 200 other tissues.
DR ExpressionAtlas; O00764; baseline and differential.
DR Genevisible; O00764; HS.
DR GO; GO:0005829; C:cytosol; HDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0031403; F:lithium ion binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0030955; F:potassium ion binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0008478; F:pyridoxal kinase activity; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:UniProtKB.
DR GO; GO:0031402; F:sodium ion binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0009443; P:pyridoxal 5'-phosphate salvage; IDA:UniProtKB.
DR CDD; cd01173; pyridoxal_pyridoxamine_kinase; 1.
DR Gene3D; 3.40.1190.20; -; 1.
DR InterPro; IPR013749; PM/HMP-P_kinase-1.
DR InterPro; IPR004625; PyrdxlKinase.
DR InterPro; IPR029056; Ribokinase-like.
DR PANTHER; PTHR10534; PTHR10534; 1.
DR Pfam; PF08543; Phos_pyr_kin; 1.
DR SUPFAM; SSF53613; SSF53613; 1.
DR TIGRFAMs; TIGR00687; pyridox_kin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Charcot-Marie-Tooth disease; Cobalt; Cytoplasm; Disease variant; Kinase;
KW Magnesium; Manganese; Metal-binding; Neurodegeneration; Neuropathy;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Sodium;
KW Transferase; Zinc.
FT CHAIN 1..312
FT /note="Pyridoxal kinase"
FT /id="PRO_0000213335"
FT ACT_SITE 235
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:19351586"
FT BINDING 12
FT /ligand="pyridoxal"
FT /ligand_id="ChEBI:CHEBI:17310"
FT /evidence="ECO:0000269|PubMed:19351586,
FT ECO:0007744|PDB:3FHX"
FT BINDING 47
FT /ligand="pyridoxal"
FT /ligand_id="ChEBI:CHEBI:17310"
FT /evidence="ECO:0000269|PubMed:19351586,
FT ECO:0007744|PDB:3FHX"
FT BINDING 47
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|Ref.16, ECO:0007744|PDB:3KEU"
FT BINDING 113
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:17766369,
FT ECO:0000269|PubMed:19351586, ECO:0000269|PubMed:22879864,
FT ECO:0000269|Ref.16, ECO:0007744|PDB:2YXU,
FT ECO:0007744|PDB:3FHX, ECO:0007744|PDB:3FHY,
FT ECO:0007744|PDB:3KEU, ECO:0007744|PDB:4EN4"
FT BINDING 113
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /evidence="ECO:0000269|PubMed:19351586,
FT ECO:0000269|PubMed:22879864, ECO:0007744|PDB:3FHX,
FT ECO:0007744|PDB:4EN4"
FT BINDING 118
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:17766369,
FT ECO:0000269|PubMed:19351586, ECO:0000269|PubMed:22879864,
FT ECO:0000269|Ref.16, ECO:0007744|PDB:3FHX,
FT ECO:0007744|PDB:3KEU, ECO:0007744|PDB:4EN4"
FT BINDING 148
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /evidence="ECO:0000269|PubMed:17766369,
FT ECO:0000269|PubMed:19351586, ECO:0000269|PubMed:22879864,
FT ECO:0000269|Ref.16, ECO:0007744|PDB:2YXT,
FT ECO:0007744|PDB:3FHX, ECO:0007744|PDB:3KEU,
FT ECO:0007744|PDB:4EN4"
FT BINDING 150..153
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:19351586, ECO:0000269|Ref.16,
FT ECO:0007744|PDB:3FHY, ECO:0007744|PDB:3KEU"
FT BINDING 186..187
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:17766369,
FT ECO:0000269|PubMed:19351586, ECO:0000269|PubMed:22879864,
FT ECO:0000269|Ref.16, ECO:0007744|PDB:2YXU,
FT ECO:0007744|PDB:3FHX, ECO:0007744|PDB:3FHY,
FT ECO:0007744|PDB:3KEU, ECO:0007744|PDB:4EN4"
FT BINDING 186
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /evidence="ECO:0000269|PubMed:17766369,
FT ECO:0000269|PubMed:19351586, ECO:0000269|PubMed:22879864,
FT ECO:0000269|Ref.16, ECO:0007744|PDB:2YXT,
FT ECO:0007744|PDB:3FHX, ECO:0007744|PDB:3KEU,
FT ECO:0007744|PDB:4EN4"
FT BINDING 226..228
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22879864, ECO:0000269|Ref.16,
FT ECO:0007744|PDB:3KEU, ECO:0007744|PDB:4EN4"
FT BINDING 233
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:17766369,
FT ECO:0000269|PubMed:19351586, ECO:0000269|PubMed:22879864,
FT ECO:0000269|Ref.16, ECO:0007744|PDB:2YXU,
FT ECO:0007744|PDB:3FHX, ECO:0007744|PDB:3FHY,
FT ECO:0007744|PDB:3KEU, ECO:0007744|PDB:4EN4"
FT BINDING 234..235
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:19351586, ECO:0000269|Ref.16,
FT ECO:0007744|PDB:3FHX, ECO:0007744|PDB:3KEU"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P82197"
FT MOD_RES 59
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 285
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..73
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15154080"
FT /id="VSP_010671"
FT VAR_SEQ 83..110
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004653"
FT VARIANT 220
FT /note="R -> Q (in HMSN6C; decreased pyridoxal kinase
FT activity; dbSNP:rs759333796)"
FT /evidence="ECO:0000269|PubMed:31187503"
FT /id="VAR_083156"
FT VARIANT 228
FT /note="A -> T (in HMSN6C; decreased pyridoxal kinase
FT activity; decreased affinity for ATP; decreased affinity
FT for pyridoxal 5'-phosphate; no effect on protein abundance;
FT dbSNP:rs757480516)"
FT /evidence="ECO:0000269|PubMed:31187503"
FT /id="VAR_083157"
FT MUTAGEN 235
FT /note="D->A: 15-fold decrease in pyridoxal kinase activity,
FT and a 7-fold decrease in affinity for pyridoxal."
FT /evidence="ECO:0000269|PubMed:19351586"
FT MUTAGEN 235
FT /note="D->N: 2-fold decrease in pyridoxal kinase activity
FT and pyridoxal affinity."
FT /evidence="ECO:0000269|PubMed:19351586"
FT STRAND 6..17
FT /evidence="ECO:0007829|PDB:2YXT"
FT HELIX 21..30
FT /evidence="ECO:0007829|PDB:2YXT"
FT STRAND 34..45
FT /evidence="ECO:0007829|PDB:2YXT"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:2YXT"
FT HELIX 59..71
FT /evidence="ECO:0007829|PDB:2YXT"
FT STRAND 78..82
FT /evidence="ECO:0007829|PDB:2YXT"
FT HELIX 88..104
FT /evidence="ECO:0007829|PDB:2YXT"
FT STRAND 109..112
FT /evidence="ECO:0007829|PDB:2YXT"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:3KEU"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:2AJP"
FT STRAND 125..128
FT /evidence="ECO:0007829|PDB:2YXT"
FT HELIX 132..138
FT /evidence="ECO:0007829|PDB:2YXT"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:2YXT"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:2YXT"
FT HELIX 151..158
FT /evidence="ECO:0007829|PDB:2YXT"
FT HELIX 165..178
FT /evidence="ECO:0007829|PDB:2YXT"
FT STRAND 181..185
FT /evidence="ECO:0007829|PDB:2YXT"
FT STRAND 198..208
FT /evidence="ECO:0007829|PDB:2YXT"
FT TURN 210..212
FT /evidence="ECO:0007829|PDB:2F7K"
FT STRAND 215..224
FT /evidence="ECO:0007829|PDB:2YXT"
FT HELIX 233..247
FT /evidence="ECO:0007829|PDB:2YXT"
FT HELIX 252..277
FT /evidence="ECO:0007829|PDB:2YXT"
FT TURN 286..289
FT /evidence="ECO:0007829|PDB:2YXT"
FT HELIX 294..296
FT /evidence="ECO:0007829|PDB:2YXT"
FT HELIX 297..301
FT /evidence="ECO:0007829|PDB:2YXT"
FT STRAND 310..312
FT /evidence="ECO:0007829|PDB:3KEU"
SQ SEQUENCE 312 AA; 35102 MW; 2DBDCAB5D8640569 CRC64;
MEEECRVLSI QSHVIRGYVG NRAATFPLQV LGFEIDAVNS VQFSNHTGYA HWKGQVLNSD
ELQELYEGLR LNNMNKYDYV LTGYTRDKSF LAMVVDIVQE LKQQNPRLVY VCDPVLGDKW
DGEGSMYVPE DLLPVYKEKV VPLADIITPN QFEAELLSGR KIHSQEEALR VMDMLHSMGP
DTVVITSSDL PSPQGSNYLI VLGSQRRRNP AGSVVMERIR MDIRKVDAVF VGTGDLFAAM
LLAWTHKHPN NLKVACEKTV STLHHVLQRT IQCAKAQAGE GVRPSPMQLE LRMVQSKRDI
EDPEIVVQAT VL
