PLPHP_HUMAN
ID PLPHP_HUMAN Reviewed; 275 AA.
AC O94903; Q6FI94;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Pyridoxal phosphate homeostasis protein {ECO:0000255|HAMAP-Rule:MF_03225};
DE Short=PLP homeostasis protein {ECO:0000255|HAMAP-Rule:MF_03225};
DE AltName: Full=Proline synthase co-transcribed bacterial homolog protein {ECO:0000255|HAMAP-Rule:MF_03225};
DE AltName: Full=Pyridoxal phosphate-binding protein {ECO:0000312|HGNC:HGNC:9457};
GN Name=PLPBP {ECO:0000255|HAMAP-Rule:MF_03225, ECO:0000312|HGNC:HGNC:9457};
GN Synonyms=PROSC {ECO:0000255|HAMAP-Rule:MF_03225,
GN ECO:0000312|HGNC:HGNC:9457};
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 [GENOMIC DNA].
RX PubMed=10496079; DOI=10.1007/s100380050172;
RA Ikegawa S., Isomura M., Koshizuka Y., Nakamura Y.;
RT "Cloning and characterization of human and mouse PROSC (proline synthetase
RT co-transcribed) genes.";
RL J. Hum. Genet. 44:337-342(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6 AND SER-244, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226 AND SER-244, AND
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [9]
RP INVOLVEMENT IN EPVB6D, FUNCTION, VARIANTS EPVB6D 71-GLN--HIS-275 DEL;
RP 78-SER--HIS-275 DEL; LEU-87; PRO-175 AND GLN-241, AND CHARACTERIZATION OF
RP VARIANTS EPVB6D 78-SER--HIS-275 DEL AND PRO-175.
RX PubMed=27912044; DOI=10.1016/j.ajhg.2016.10.011;
RA Darin N., Reid E., Prunetti L., Samuelsson L., Husain R.A., Wilson M.,
RA El Yacoubi B., Footitt E., Chong W.K., Wilson L.C., Prunty H., Pope S.,
RA Heales S., Lascelles K., Champion M., Wassmer E., Veggiotti P.,
RA de Crecy-Lagard V., Mills P.B., Clayton P.T.;
RT "Mutations in PROSC disrupt cellular pyridoxal phosphate homeostasis and
RT cause vitamin-B6-dependent epilepsy.";
RL Am. J. Hum. Genet. 99:1325-1337(2016).
CC -!- FUNCTION: Pyridoxal 5'-phosphate (PLP)-binding protein, which may be
CC involved in intracellular homeostatic regulation of pyridoxal 5'-
CC phosphate (PLP), the active form of vitamin B6. {ECO:0000255|HAMAP-
CC Rule:MF_03225, ECO:0000269|PubMed:27912044}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DISEASE: Epilepsy, early-onset, vitamin B6-dependent (EPVB6D)
CC [MIM:617290]: An autosomal recessive neurologic disorder characterized
CC by seizures responsive to treatment with activated vitamin B6 and/or
CC pyridoxine. Most patients show delayed psychomotor development,
CC intellectual disability and learning disability. Seizures onset is in
CC the first days or months of life. {ECO:0000269|PubMed:27912044}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the pyridoxal phosphate-binding protein
CC YggS/PROSC family. {ECO:0000255|HAMAP-Rule:MF_03225}.
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DR EMBL; AB018566; BAA36842.1; -; Genomic_DNA.
DR EMBL; AL136616; CAB66551.1; -; mRNA.
DR EMBL; CR533532; CAG38563.1; -; mRNA.
DR EMBL; BC012334; AAH12334.1; -; mRNA.
DR CCDS; CCDS6096.1; -.
DR RefSeq; NP_009129.1; NM_007198.3.
DR AlphaFoldDB; O94903; -.
DR SMR; O94903; -.
DR BioGRID; 116381; 109.
DR IntAct; O94903; 29.
DR MINT; O94903; -.
DR STRING; 9606.ENSP00000333551; -.
DR DrugBank; DB00172; Proline.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR GlyGen; O94903; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O94903; -.
DR MetOSite; O94903; -.
DR PhosphoSitePlus; O94903; -.
DR BioMuta; PLPBP; -.
DR UCD-2DPAGE; O94903; -.
DR EPD; O94903; -.
DR jPOST; O94903; -.
DR MassIVE; O94903; -.
DR MaxQB; O94903; -.
DR PaxDb; O94903; -.
DR PeptideAtlas; O94903; -.
DR PRIDE; O94903; -.
DR ProteomicsDB; 50537; -.
DR Antibodypedia; 4465; 294 antibodies from 24 providers.
DR DNASU; 11212; -.
DR Ensembl; ENST00000328195.8; ENSP00000333551.3; ENSG00000147471.12.
DR GeneID; 11212; -.
DR KEGG; hsa:11212; -.
DR MANE-Select; ENST00000328195.8; ENSP00000333551.3; NM_007198.4; NP_009129.1.
DR UCSC; uc003xkh.4; human.
DR CTD; 11212; -.
DR DisGeNET; 11212; -.
DR GeneCards; PLPBP; -.
DR HGNC; HGNC:9457; PLPBP.
DR HPA; ENSG00000147471; Low tissue specificity.
DR MalaCards; PLPBP; -.
DR MIM; 604436; gene.
DR MIM; 617290; phenotype.
DR neXtProt; NX_O94903; -.
DR OpenTargets; ENSG00000147471; -.
DR Orphanet; 3006; Pyridoxine-dependent epilepsy.
DR PharmGKB; PA33810; -.
DR VEuPathDB; HostDB:ENSG00000147471; -.
DR eggNOG; KOG3157; Eukaryota.
DR GeneTree; ENSGT00390000004928; -.
DR HOGENOM; CLU_059988_2_1_1; -.
DR InParanoid; O94903; -.
DR OMA; IEWHMIG; -.
DR OrthoDB; 1423577at2759; -.
DR PhylomeDB; O94903; -.
DR TreeFam; TF314637; -.
DR PathwayCommons; O94903; -.
DR SignaLink; O94903; -.
DR BioGRID-ORCS; 11212; 15 hits in 1082 CRISPR screens.
DR ChiTaRS; PROSC; human.
DR GeneWiki; PROSC; -.
DR GenomeRNAi; 11212; -.
DR Pharos; O94903; Tbio.
DR PRO; PR:O94903; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O94903; protein.
DR Bgee; ENSG00000147471; Expressed in cardia of stomach and 217 other tissues.
DR ExpressionAtlas; O94903; baseline and differential.
DR Genevisible; O94903; HS.
DR GO; GO:0005737; C:cytoplasm; NAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IBA:GO_Central.
DR Gene3D; 3.20.20.10; -; 1.
DR HAMAP; MF_02087; PLP_homeostasis; 1.
DR InterPro; IPR001608; Ala_racemase_N.
DR InterPro; IPR029066; PLP-binding_barrel.
DR InterPro; IPR011078; PyrdxlP_homeostasis.
DR PANTHER; PTHR10146; PTHR10146; 1.
DR Pfam; PF01168; Ala_racemase_N; 1.
DR PIRSF; PIRSF004848; YBL036c_PLPDEIII; 1.
DR SUPFAM; SSF51419; SSF51419; 1.
DR TIGRFAMs; TIGR00044; TIGR00044; 1.
DR PROSITE; PS01211; UPF0001; 1.
PE 1: Evidence at protein level;
KW Disease variant; Epilepsy; Phosphoprotein; Pyridoxal phosphate;
KW Reference proteome.
FT CHAIN 1..275
FT /note="Pyridoxal phosphate homeostasis protein"
FT /id="PRO_0000163210"
FT REGION 251..275
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 6
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 47
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03225"
FT MOD_RES 69
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2Y8"
FT MOD_RES 125
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2Y8"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 244
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VARIANT 24
FT /note="V -> M (in dbSNP:rs35423325)"
FT /id="VAR_052476"
FT VARIANT 71..275
FT /note="Missing (in EPVB6D)"
FT /evidence="ECO:0000269|PubMed:27912044"
FT /id="VAR_078004"
FT VARIANT 78..275
FT /note="Missing (in EPVB6D; decreased expression at the mRNA
FT level; undetectable at the protein level in patient's
FT fibroblasts)"
FT /evidence="ECO:0000269|PubMed:27912044"
FT /id="VAR_078005"
FT VARIANT 87
FT /note="P -> L (in EPVB6D; dbSNP:rs755946598)"
FT /evidence="ECO:0000269|PubMed:27912044"
FT /id="VAR_078006"
FT VARIANT 175
FT /note="L -> P (in EPVB6D; decreased expression at the mRNA
FT level; undetectable at the protein level in patient's
FT fibroblasts; dbSNP:rs752753379)"
FT /evidence="ECO:0000269|PubMed:27912044"
FT /id="VAR_078007"
FT VARIANT 241
FT /note="R -> Q (in EPVB6D; dbSNP:rs760609867)"
FT /evidence="ECO:0000269|PubMed:27912044"
FT /id="VAR_078008"
SQ SEQUENCE 275 AA; 30344 MW; A81049432B1A8732 CRC64;
MWRAGSMSAE LGVGCALRAV NERVQQAVAR RPRDLPAIQP RLVAVSKTKP ADMVIEAYGH
GQRTFGENYV QELLEKASNP KILSLCPEIK WHFIGHLQKQ NVNKLMAVPN LFMLETVDSV
KLADKVNSSW QRKGSPERLK VMVQINTSGE ESKHGLPPSE TIAIVEHINA KCPNLEFVGL
MTIGSFGHDL SQGPNPDFQL LLSLREELCK KLNIPADQVE LSMGMSADFQ HAVEVGSTNV
RIGSTIFGER DYSKKPTPDK CAADVKAPLE VAQEH
