ID   RPIA_HUMAN              Reviewed;         311 AA.
AC   P49247; Q541P9; Q96BJ6;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   24-JUL-2007, sequence version 3.
DT   02-SEP-2026, entry version 210.
DE   RecName: Full=Ribose-5-phosphate isomerase {ECO:0000305};
DE            EC=5.3.1.6 {ECO:0000269|PubMed:14988808};
DE   AltName: Full=Phosphoriboisomerase;
GN   Name=RPIA {ECO:0000312|HGNC:HGNC:10297}; Synonyms=RPI;
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].
RA   Guo J.H., Yu L.;
RT   "Cloning and characterization of human ribose 5-phosphate isomerase (RPI)
RT   gene.";
RL   Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pancreas;
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   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 186-311.
RC   TISSUE=B-cell;
RX   PubMed=7758956; DOI=10.1016/0378-1119(94)00901-4;
RA   Apel T.W., Scherer A., Adachi T., Auch D., Ayane M., Reth M.;
RT   "The ribose 5-phosphate isomerase-encoding gene is located immediately
RT   downstream from that encoding murine immunoglobulin kappa.";
RL   Gene 156:191-197(1995).
RN   [4]
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   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-106, 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   [6]
RP   METHYLATION [LARGE SCALE ANALYSIS] AT ARG-52, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Colon carcinoma;
RX   PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA   Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA   Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA   Bedford M.T., Comb M.J.;
RT   "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT   methylation.";
RL   Mol. Cell. Proteomics 13:372-387(2014).
RN   [7]
RP   VARIANT RPIAD VAL-135, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=14988808; DOI=10.1086/383204;
RA   Huck J.H.J., Verhoeven N.M., Struys E.A., Salomons G.S., Jakobs C.,
RA   van der Knaap M.S.;
RT   "Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose
RT   phosphate pathway associated with a slowly progressive
RT   leukoencephalopathy.";
RL   Am. J. Hum. Genet. 74:745-751(2004).
CC   -!- FUNCTION: Catalyzes the reversible conversion of ribose-5-phosphate to
CC       ribulose 5-phosphate and participates in the first step of the non-
CC       oxidative branch of the pentose phosphate pathway.
CC       {ECO:0000269|PubMed:14988808}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=aldehydo-D-ribose 5-phosphate = D-ribulose 5-phosphate;
CC         Xref=Rhea:RHEA:14657, ChEBI:CHEBI:58121, ChEBI:CHEBI:58273;
CC         EC=5.3.1.6; Evidence={ECO:0000269|PubMed:14988808};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14658;
CC         Evidence={ECO:0000305|PubMed:14988808};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14659;
CC         Evidence={ECO:0000305|PubMed:14988808};
CC   -!- PATHWAY: Carbohydrate degradation; pentose phosphate pathway; D-ribose
CC       5-phosphate from D-ribulose 5-phosphate (non-oxidative stage): step
CC       1/1. {ECO:0000269|PubMed:14988808}.
CC   -!- INTERACTION:
CC       P49247; Q8N5M1: ATPAF2; NbExp=12; IntAct=EBI-744831, EBI-1166928;
CC       P49247; Q9NWQ9: C14orf119; NbExp=3; IntAct=EBI-744831, EBI-725606;
CC       P49247; Q6IPU0: CENPP; NbExp=8; IntAct=EBI-744831, EBI-10250303;
CC       P49247; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-744831, EBI-742054;
CC       P49247; Q75MZ5: FOXP2; NbExp=4; IntAct=EBI-744831, EBI-10255915;
CC       P49247; Q9H8Y8: GORASP2; NbExp=8; IntAct=EBI-744831, EBI-739467;
CC       P49247; Q9UJY1: HSPB8; NbExp=3; IntAct=EBI-744831, EBI-739074;
CC       P49247; Q8TBB1: LNX1; NbExp=5; IntAct=EBI-744831, EBI-739832;
CC       P49247; Q96HA8: NTAQ1; NbExp=8; IntAct=EBI-744831, EBI-741158;
CC       P49247; P22061: PCMT1; NbExp=4; IntAct=EBI-744831, EBI-353343;
CC       P49247; P22061-2: PCMT1; NbExp=4; IntAct=EBI-744831, EBI-12386584;
CC       P49247; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-744831, EBI-79165;
CC       P49247; Q06124: PTPN11; NbExp=4; IntAct=EBI-744831, EBI-297779;
CC       P49247; Q9H0X6: RNF208; NbExp=3; IntAct=EBI-744831, EBI-751555;
CC       P49247; P49247: RPIA; NbExp=4; IntAct=EBI-744831, EBI-744831;
CC       P49247; O00560: SDCBP; NbExp=3; IntAct=EBI-744831, EBI-727004;
CC       P49247; O75716: STK16; NbExp=4; IntAct=EBI-744831, EBI-749295;
CC       P49247; Q99757: TXN2; NbExp=6; IntAct=EBI-744831, EBI-2932492;
CC   -!- DISEASE: Ribose 5-phosphate isomerase deficiency (RPIAD) [MIM:608611]:
CC       An autosomal recessive inborn error of polyols metabolism characterized
CC       by highly elevated level of ribitol and arabitol in brain and body
CC       fluids. Clinical features include leukoencephalopathy, psychomotor
CC       retardation from early life, neurologic regression, and a mild
CC       sensorimotor neuropathy. {ECO:0000269|PubMed:14988808}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the ribose 5-phosphate isomerase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAK95569.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AY050633; AAK95569.1; ALT_FRAME; mRNA.
DR   EMBL; BC015529; AAH15529.2; -; mRNA.
DR   EMBL; L35035; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS2004.2; -.
DR   RefSeq; NP_653164.2; NM_144563.3.
DR   AlphaFoldDB; P49247; -.
DR   SMR; P49247; -.
DR   BioGRID; 116594; 78.
DR   FunCoup; P49247; 3075.
DR   IntAct; P49247; 44.
DR   MINT; P49247; -.
DR   NDEx; IQUERY-CP-RPIA; 5 NDEx IQuery Curated Pathways.
DR   STRING; 9606.ENSP00000283646; -.
DR   BindingDB; P49247; -.
DR   ChEMBL; CHEMBL5725137; -.
DR   DrugBank; DB01756; 4-phospho-L-threonic acid.
DR   GlyGen; P49247; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; P49247; -.
DR   PhosphoSitePlus; P49247; -.
DR   BioMuta; RPIA; -.
DR   DMDM; 156637353; -.
DR   jPOST; P49247; -.
DR   MassIVE; P49247; -.
DR   PaxDb; 9606-ENSP00000283646; -.
DR   PeptideAtlas; P49247; -.
DR   ProteomicsDB; 55976; -.
DR   Pumba; P49247; -.
DR   Antibodypedia; 32248; 166 antibodies from 27 providers.
DR   DNASU; 22934; -.
DR   Ensembl; ENST00000283646.5; ENSP00000283646.3; ENSG00000153574.10.
DR   GeneID; 22934; -.
DR   KEGG; hsa:22934; -.
DR   MANE-Select; ENST00000283646.5; ENSP00000283646.3; NM_144563.3; NP_653164.2.
DR   UCSC; uc002ste.4; human.
DR   AGR; HGNC:10297; -.
DR   ClinPGx; PA34659; -.
DR   CTD; 22934; -.
DR   DisGeNET; 22934; -.
DR   GeneCards; RPIA; -.
DR   HGNC; HGNC:10297; RPIA.
DR   HPA; ENSG00000153574; Tissue enhanced (bone).
DR   MalaCards; RPIA; -.
DR   MIM; 180430; gene.
DR   MIM; 608611; phenotype.
DR   OpenTargets; ENSG00000153574; -.
DR   Orphanet; 440706; Ribose-5-P isomerase deficiency.
DR   VEuPathDB; HostDB:ENSG00000153574; -.
DR   eggNOG; KOG3075; Eukaryota.
DR   GeneTree; ENSGT00390000004352; -.
DR   HOGENOM; CLU_056590_0_2_1; -.
DR   InParanoid; P49247; -.
DR   OMA; ACHVQEK; -.
DR   OrthoDB; 1555531at2759; -.
DR   PAN-GO; P49247; 3 GO annotations based on evolutionary models.
DR   PhylomeDB; P49247; -.
DR   BRENDA; 5.3.1.6; 2681.
DR   PathwayCommons; P49247; -.
DR   Reactome; R-HSA-5659996; RPIA deficiency: failed conversion of R5P to RU5P.
DR   Reactome; R-HSA-6791461; RPIA deficiency: failed conversion of RU5P to R5P.
DR   Reactome; R-HSA-71336; Pentose phosphate pathway.
DR   SignaLink; P49247; -.
DR   SIGNOR; P49247; -.
DR   UniPathway; UPA00115; UER00412.
DR   Agora; ENSG00000153574; -.
DR   BioGRID-ORCS; 22934; 250 hits in 1174 CRISPR screens.
DR   ChiTaRS; RPIA; human.
DR   GenomeRNAi; 22934; -.
DR   Pharos; P49247; Tbio.
DR   PRO; PR:P49247; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; P49247; protein.
DR   Bgee; ENSG00000153574; Expressed in secondary oocyte and 205 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; HTP:FlyBase.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0048029; F:monosaccharide binding; IEA:Ensembl.
DR   GO; GO:0004751; F:ribose-5-phosphate isomerase activity; EXP:Reactome.
DR   GO; GO:0006014; P:D-ribose metabolic process; IBA:GO_Central.
DR   GO; GO:0006098; P:pentose-phosphate shunt; TAS:Reactome.
DR   GO; GO:0009052; P:pentose-phosphate shunt, non-oxidative branch; IBA:GO_Central.
DR   CDD; cd01398; RPI_A; 1.
DR   FunFam; 3.40.50.1360:FF:000013; Ribose 5-phosphate isomerase A; 1.
DR   FunFam; 3.30.70.260:FF:000018; Ribose-5-phosphate isomerase A; 1.
DR   Gene3D; 3.30.70.260; -; 1.
DR   Gene3D; 3.40.50.1360; -; 1.
DR   HAMAP; MF_00170; Rib_5P_isom_A; 1.
DR   InterPro; IPR037171; NagB/RpiA_transferase-like.
DR   InterPro; IPR020672; Ribose5P_isomerase_typA_subgr.
DR   InterPro; IPR004788; Ribose5P_isomerase_type_A.
DR   NCBIfam; NF001924; PRK00702.1; 1.
DR   NCBIfam; TIGR00021; rpiA; 1.
DR   PANTHER; PTHR11934; RIBOSE-5-PHOSPHATE ISOMERASE; 1.
DR   PANTHER; PTHR11934:SF0; RIBOSE-5-PHOSPHATE ISOMERASE; 1.
DR   Pfam; PF06026; Rib_5-P_isom_A; 1.
DR   SUPFAM; SSF75445; D-ribose-5-phosphate isomerase (RpiA), lid domain; 1.
DR   SUPFAM; SSF100950; NagB/RpiA/CoA transferase-like; 1.
PE   1: Evidence at protein level;
KW   Disease variant; Isomerase; Methylation; Neuropathy; Phosphoprotein;
KW   Proteomics identification; Reference proteome.
FT   CHAIN           1..311
FT                   /note="Ribose-5-phosphate isomerase"
FT                   /id="PRO_0000158521"
FT   REGION          22..67
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        22..32
FT                   /note="Gly residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        57..67
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         52
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0007744|PubMed:24129315"
FT   MOD_RES         106
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VARIANT         135
FT                   /note="A -> V (in RPIAD; dbSNP:rs121918591)"
FT                   /evidence="ECO:0000269|PubMed:14988808"
FT                   /id="VAR_019122"
FT   CONFLICT        207
FT                   /note="D -> V (in Ref. 3; L35035)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        239
FT                   /note="L -> V (in Ref. 3; L35035)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   311 AA;  33269 MW;  4ED587A40F10223D CRC64;
     MQRPGPFSTL YGRVLAPLPG RAGGAASGGG GNSWDLPGSH VRLPGRAQSG TRGGAGNTST
     SCGDSNSICP APSTMSKAEE AKKLAGRAAV ENHVRNNQVL GIGSGSTIVH AVQRIAERVK
     QENLNLVCIP TSFQARQLIL QYGLTLSDLD RHPEIDLAID GADEVDADLN LIKGGGGCLT
     QEKIVAGYAS RFIVIADFRK DSKNLGDQWH KGIPIEVIPM AYVPVSRAVS QKFGGVVELR
     MAVNKAGPVV TDNGNFILDW KFDRVHKWSE VNTAIKMIPG VVDTGLFINM AERVYFGMQD
     GSVNMREKPF C
//