LOCUS       NP_009129                275 aa            linear   PRI 27-APR-2025
DEFINITION  pyridoxal phosphate homeostasis protein isoform 2 [Homo sapiens].
ACCESSION   NP_009129
VERSION     NP_009129.1
DBSOURCE    REFSEQ: accession NM_007198.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 275)
  AUTHORS   Ciapaite,J., van Roermund,C.W.T., Bosma,M., Gerrits,J.,
            Houten,S.M., IJlst,L., Waterham,H.R., van Karnebeek,C.D.M.,
            Wanders,R.J.A., Zwartkruis,F.J.T., Jans,J.J. and
            Verhoeven-Duif,N.M.
  TITLE     Maintenance of cellular vitamin B6 levels and mitochondrial
            oxidative function depend on pyridoxal 5'-phosphate homeostasis
            protein
  JOURNAL   J Biol Chem 299 (9), 105047 (2023)
   PUBMED   37451483
  REMARK    GeneRIF: Maintenance of cellular vitamin B6 levels and
            mitochondrial oxidative function depend on pyridoxal 5'-phosphate
            homeostasis protein.
REFERENCE   2  (residues 1 to 275)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   3  (residues 1 to 275)
  AUTHORS   Plecko,B., Zweier,M., Begemann,A., Mathis,D., Schmitt,B.,
            Striano,P., Baethmann,M., Vari,M.S., Beccaria,F., Zara,F.,
            Crowther,L.M., Joset,P., Sticht,H., Papuc,S.M. and Rauch,A.
  TITLE     Confirmation of mutations in PROSC as a novel cause of vitamin B 6
            -dependent epilepsy
  JOURNAL   J Med Genet 54 (12), 809-814 (2017)
   PUBMED   28391250
  REMARK    GeneRIF: We therefore confirm PROSC as a novel gene for
            vitamin-B6-dependent epilepsy and delineate a non-specific plasma
            vitamin B6 profile under pyridoxine treatment.
REFERENCE   4  (residues 1 to 275)
  AUTHORS   Tremino,L., Forcada-Nadal,A., Contreras,A. and Rubio,V.
  TITLE     Studies on cyanobacterial protein PipY shed light on structure,
            potential functions, and vitamin B6 -dependent epilepsy
  JOURNAL   FEBS Lett 591 (20), 3431-3442 (2017)
   PUBMED   28914444
  REMARK    GeneRIF: Exploiting the universality of the Synechococcus elongatus
            COG0325 (PiPY) functions, it has been used in site-directed
            mutagenesis studies to shed light on disease causation by
            epilepsy-associated mutations in the human COG0325 gene PROSC.
REFERENCE   5  (residues 1 to 275)
  AUTHORS   Darin,N., Reid,E., Prunetti,L., Samuelsson,L., Husain,R.A.,
            Wilson,M., El Yacoubi,B., Footitt,E., Chong,W.K., Wilson,L.C.,
            Prunty,H., Pope,S., Heales,S., Lascelles,K., Champion,M.,
            Wassmer,E., Veggiotti,P., de Crecy-Lagard,V., Mills,P.B. and
            Clayton,P.T.
  TITLE     Mutations in PROSC Disrupt Cellular Pyridoxal Phosphate Homeostasis
            and Cause Vitamin-B6-Dependent Epilepsy
  JOURNAL   Am J Hum Genet 99 (6), 1325-1337 (2016)
   PUBMED   27912044
  REMARK    GeneRIF: studies suggest that PROSC is involved in intracellular
            homeostatic regulation of pyridoxal 5'-phosphate, supplying this
            cofactor to apoenzymes while minimizing any toxic side reactions
REFERENCE   6  (residues 1 to 275)
  AUTHORS   Roessler,S., Long,E.L., Budhu,A., Chen,Y., Zhao,X., Ji,J.,
            Walker,R., Jia,H.L., Ye,Q.H., Qin,L.X., Tang,Z.Y., He,P.,
            Hunter,K.W., Thorgeirsson,S.S., Meltzer,P.S. and Wang,X.W.
  TITLE     Integrative genomic identification of genes on 8p associated with
            hepatocellular carcinoma progression and patient survival
  JOURNAL   Gastroenterology 142 (4), 957-966 (2012)
   PUBMED   22202459
REFERENCE   7  (residues 1 to 275)
  AUTHORS   Bowling,F.G.
  TITLE     Pyridoxine supply in human development
  JOURNAL   Semin Cell Dev Biol 22 (6), 611-618 (2011)
   PUBMED   21664474
  REMARK    Review article
REFERENCE   8  (residues 1 to 275)
  AUTHORS   Ikegawa,S., Isomura,M., Koshizuka,Y. and Nakamura,Y.
  TITLE     Cloning and characterization of human and mouse PROSC (proline
            synthetase co-transcribed) genes
  JOURNAL   J Hum Genet 44 (5), 337-342 (1999)
   PUBMED   10496079
REFERENCE   9  (residues 1 to 275)
  AUTHORS   Al-Shekaili,H., Ciapaite,J., van Karnebeek,C. and Pena,I.
  TITLE     PLPBP Deficiency
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   36795901
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC012334.1, AL136616.1 and
            BM984988.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            Summary: This gene encodes a pyridoxal 5'-phosphate binding protein
            involved in the homeostatic regulation of intracellular pyridoxal
            5'-phosphate. This gene has a tumor suppressive effect on
            hepatocellular carcinoma and other solid tumors of epithelial
            origin. Naturally occurring mutations in this gene are associated
            with a pyridoxine-dependent epilepsy. [provided by RefSeq, Mar
            2017].
            
            Transcript Variant: This variant (2) uses an alternate splice site
            in the 3' coding region compared to variant 1. The encoded isoform
            (2) is shorter than isoform 1.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC012334.1, AK291135.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000328195.8/ ENSP00000333551.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..275
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="8"
                     /map="8p11.23"
     Protein         1..275
                     /product="pyridoxal phosphate homeostasis protein isoform
                     2"
                     /note="proline synthetase co-transcribed bacterial homolog
                     protein; proline synthase co-transcribed bacterial homolog
                     protein; PLP homeostasis protein; pyridoxal phosphate
                     homeostasis protein"
                     /calculated_mol_wt=30213
     Site            6
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (O94903.1)"
     Region          17..248
                     /region_name="PLPDE_III_YBL036c_euk"
                     /note="Pyridoxal 5-phosphate (PLP)-binding TIM barrel
                     domain of Type III PLP-Dependent Enzymes, Eukaryotic
                     YBL036c-like proteins; cd06822"
                     /db_xref="CDD:143496"
     Site            order(45,47,68,94,181,183,225..226,241..244)
                     /site_type="other"
                     /note="pyridoxal 5'-phosphate (PLP) binding site [chemical
                     binding]"
                     /db_xref="CDD:143496"
     Site            47
                     /site_type="active"
                     /note="catalytic residue [active]"
                     /db_xref="CDD:143496"
     Site            69
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine.
                     /evidence=ECO:0000250|UniProtKB:Q9Z2Y8; propagated from
                     UniProtKB/Swiss-Prot (O94903.1)"
     Site            226
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:24275569; propagated from
                     UniProtKB/Swiss-Prot (O94903.1)"
     Site            244
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163,
                     ECO:0007744|PubMed:24275569; propagated from
                     UniProtKB/Swiss-Prot (O94903.1)"
     Region          251..275
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (O94903.1)"
     CDS             1..275
                     /gene="PLPBP"
                     /gene_synonym="EPEO1; EPVB6D; PROSC"
                     /coded_by="NM_007198.4:16..843"
                     /note="isoform 2 is encoded by transcript variant 2"
                     /db_xref="CCDS:CCDS6096.1"
                     /db_xref="GeneID:11212"
                     /db_xref="HGNC:HGNC:9457"
                     /db_xref="MIM:604436"
ORIGIN      
        1 mwragsmsae lgvgcalrav nervqqavar rprdlpaiqp rlvavsktkp admvieaygh
       61 gqrtfgenyv qellekasnp kilslcpeik whfighlqkq nvnklmavpn lfmletvdsv
      121 kladkvnssw qrkgsperlk vmvqintsge eskhglppse tiaivehina kcpnlefvgl
      181 mtigsfghdl sqgpnpdfql llslreelck klnipadqve lsmgmsadfq havevgstnv
      241 rigstifger dyskkptpdk caadvkaple vaqeh
//
