OPLA_HUMAN
ID OPLA_HUMAN Reviewed; 1288 AA.
AC O14841; A5PKY8; Q75W65; Q9Y4Q0;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 3.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=5-oxoprolinase;
DE EC=3.5.2.9;
DE AltName: Full=5-oxo-L-prolinase;
DE Short=5-OPase;
DE AltName: Full=Pyroglutamase;
GN Name=OPLAH;
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].
RX PubMed=14993790; DOI=10.1248/bpb.27.288;
RA Watanabe T., Abe K., Ishikawa H., Iijima Y.;
RT "Bovine 5-oxo-L-prolinase: simple assay method, purification, cDNA cloning,
RT and detection of mRNA in the coronary artery.";
RL Biol. Pharm. Bull. 27:288-294(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [LARGE SCALE MRNA] OF 229-1288.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 901-1096.
RA Debella L.R., Wood S.;
RT "Human 5-oxo-L-prolinase partial sequence.";
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
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 INVOLVEMENT IN OPLAHD.
RX PubMed=21651516; DOI=10.1111/j.1399-0004.2011.01728.x;
RA Almaghlouth I., Mohamed J., Al-Amoudi M., Al-Ahaidib L., Al-Odaib A.,
RA Alkuraya F.;
RT "5-Oxoprolinase deficiency: report of the first human OPLAH mutation.";
RL Clin. Genet. 82:193-196(2012).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-151, 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 [8]
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).
CC -!- FUNCTION: Catalyzes the cleavage of 5-oxo-L-proline to form L-glutamate
CC coupled to the hydrolysis of ATP to ADP and inorganic phosphate.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-oxo-L-proline + ATP + 2 H2O = ADP + H(+) + L-glutamate +
CC phosphate; Xref=Rhea:RHEA:10348, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58402, ChEBI:CHEBI:456216; EC=3.5.2.9;
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- INTERACTION:
CC O14841; O14841: OPLAH; NbExp=3; IntAct=EBI-3938544, EBI-3938544;
CC O14841; P78424: POU6F2; NbExp=3; IntAct=EBI-3938544, EBI-12029004;
CC O14841; Q9H3S4: TPK1; NbExp=3; IntAct=EBI-3938544, EBI-7054500;
CC -!- DISEASE: 5-oxoprolinase deficiency (OPLAHD) [MIM:260005]: A disorder
CC characterized by calcium oxalate/carbonate urolithiasis, and excessive
CC urinary 5-oxo-L-proline. Affected individuals have recurrent episodes
CC of vomiting, diarrhea, and abdominal pain.
CC {ECO:0000269|PubMed:21651516}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the oxoprolinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB81519.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAB46426.2; Type=Frameshift; Evidence={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; AB122018; BAD13434.1; -; mRNA.
DR EMBL; BC142672; AAI42673.1; -; mRNA.
DR EMBL; AL096750; CAB46426.2; ALT_FRAME; mRNA.
DR EMBL; AH005594; AAB81519.1; ALT_FRAME; Genomic_DNA.
DR CCDS; CCDS75802.1; -.
DR PIR; T12537; T12537.
DR RefSeq; NP_060040.1; NM_017570.4.
DR AlphaFoldDB; O14841; -.
DR SMR; O14841; -.
DR BioGRID; 117922; 12.
DR IntAct; O14841; 5.
DR MINT; O14841; -.
DR STRING; 9606.ENSP00000480476; -.
DR DrugBank; DB00142; Glutamic acid.
DR GlyGen; O14841; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O14841; -.
DR MetOSite; O14841; -.
DR PhosphoSitePlus; O14841; -.
DR BioMuta; OPLAH; -.
DR EPD; O14841; -.
DR jPOST; O14841; -.
DR MassIVE; O14841; -.
DR MaxQB; O14841; -.
DR PeptideAtlas; O14841; -.
DR PRIDE; O14841; -.
DR ProteomicsDB; 48272; -.
DR Antibodypedia; 7618; 73 antibodies from 21 providers.
DR DNASU; 26873; -.
DR Ensembl; ENST00000618853.5; ENSP00000480476.1; ENSG00000178814.17.
DR GeneID; 26873; -.
DR KEGG; hsa:26873; -.
DR MANE-Select; ENST00000618853.5; ENSP00000480476.1; NM_017570.5; NP_060040.1.
DR UCSC; uc033cce.2; human.
DR CTD; 26873; -.
DR DisGeNET; 26873; -.
DR GeneCards; OPLAH; -.
DR HGNC; HGNC:8149; OPLAH.
DR HPA; ENSG00000178814; Tissue enhanced (testis).
DR MalaCards; OPLAH; -.
DR MIM; 260005; phenotype.
DR MIM; 614243; gene.
DR neXtProt; NX_O14841; -.
DR OpenTargets; ENSG00000178814; -.
DR Orphanet; 33572; 5-oxoprolinase deficiency.
DR PharmGKB; PA31935; -.
DR VEuPathDB; HostDB:ENSG00000178814; -.
DR eggNOG; KOG1939; Eukaryota.
DR GeneTree; ENSGT00390000013463; -.
DR HOGENOM; CLU_002157_0_0_1; -.
DR InParanoid; O14841; -.
DR OMA; TDCNVML; -.
DR OrthoDB; 62698at2759; -.
DR PhylomeDB; O14841; -.
DR BioCyc; MetaCyc:HS11319-MON; -.
DR BRENDA; 3.5.2.9; 2681.
DR PathwayCommons; O14841; -.
DR Reactome; R-HSA-174403; Glutathione synthesis and recycling.
DR Reactome; R-HSA-5578998; Defective OPLAH causes OPLAHD.
DR SignaLink; O14841; -.
DR BioGRID-ORCS; 26873; 10 hits in 245 CRISPR screens.
DR GenomeRNAi; 26873; -.
DR Pharos; O14841; Tbio.
DR PRO; PR:O14841; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O14841; protein.
DR Bgee; ENSG00000178814; Expressed in apex of heart and 140 other tissues.
DR ExpressionAtlas; O14841; baseline and differential.
DR Genevisible; O14841; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0017168; F:5-oxoprolinase (ATP-hydrolyzing) activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0006749; P:glutathione metabolic process; IBA:GO_Central.
DR InterPro; IPR008040; Hydant_A_N.
DR InterPro; IPR002821; Hydantoinase_A.
DR InterPro; IPR003692; Hydantoinase_B.
DR InterPro; IPR045079; Oxoprolinase_fam.
DR PANTHER; PTHR11365; PTHR11365; 1.
DR Pfam; PF05378; Hydant_A_N; 1.
DR Pfam; PF01968; Hydantoinase_A; 1.
DR Pfam; PF02538; Hydantoinase_B; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Hydrolase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1288
FT /note="5-oxoprolinase"
FT /id="PRO_0000208577"
FT REGION 1248..1272
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1255..1269
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 151
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1265
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97608"
FT VARIANT 284
FT /note="S -> R (in dbSNP:rs3935209)"
FT /id="VAR_050425"
FT CONFLICT 1084..1089
FT /note="QRVVDV -> NAWWMF (in Ref. 4; AAB81519)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1288 AA; 137457 MW; 999AC0FA497750F2 CRC64;
MGSPEGRFHF AIDRGGTFTD VFAQCPGGHV RVLKLLSEDP ANYADAPTEG IRRILEQEAG
MLLPRDQPLD SSHIASIRMG TTVATNALLE RKGERVALLV TRGFRDLLHI GTQARGDLFD
LAVPMPEVLY EEVLEVDERV VLHRGEAGTG TPVKGRTGDL LEVQQPVDLG ALRGKLEGLL
SRGIRSLAVV LMHSYTWAQH EQQVGVLARE LGFTHVSLSS EAMPMVRIVP RGHTACADAY
LTPAIQRYVQ GFCRGFQGQL KDVQVLFMRS DGGLAPMDTF SGSSAVLSGP AGGVVGYSAT
TYQQEGGQPV IGFDMGGTST DVSRYAGEFE HVFEASTAGV TLQAPQLDIN TVAAGGGSRL
FFRSGLFVVG PESAGAHPGP ACYRKGGPVT VTDANLVLGR LLPASFPCIF GPGENQPLSP
EASRKALEAV ATEVNSFLTN GPCPASPLSL EEVAMGFVRV ANEAMCRPIR ALTQARGHDP
SAHVLACFGG AGGQHACAIA RALGMDTVHI HRHSGLLSAL GLALADVVHE AQEPCSLLYA
PETFVQLDQR LSRLEEQCVD ALQAQGFPRS QISTESFLHL RYQGTDCALM VSAHQHPATA
RSPRAGDFGA AFVERYMREF GFVIPERPVV VDDVRVRGTG RSGLRLEDAP KAQTGPPRVD
KMTQCYFEGG YQETPVYLLA ELGYGHKLHG PCLIIDSNST ILVEPGCQAE VTKTGDICIS
VGAEVPGTVG PQLDPIQLSI FSHRFMSIAE QMGRILQRTA ISTNIKERLD FSCALFGPDG
GLVSNAPHIP VHLGAMQETV QFQIQHLGAD LHPGDVLLSN HPSAGGSHLP DLTVITPVFW
PGQTRPVFYV ASRGHHADIG GITPGSMPPH STMLQQEGAV FLSFKLVQGG VFQEEAVTEA
LRAPGKVPNC SGTRNLHDNL SDLRAQVAAN QKGIQLVGEL IGQYGLDVVQ AYMGHIQANA
ELAVRDMLRA FGTSRQARGL PLEVSSEDHM DDGSPIRLRV QISLSQGSAV FDFSGTGPEV
FGNLNAPRAV TLSALIYCLR CLVGRDIPLN QGCLAPVRVV IPRGSILDPS PEAAVVGGNV
LTSQRVVDVI LGAFGACAAS QGCMNNVTLG NAHMGYYETV AGGAGAGPSW HGRSGVHSHM
TNTRITDPEI LESRYPVILR RFELRRGSGG RGRFRGGDGV TRELLFREEA LLSVLTERRA
FRPYGLHGGE PGARGLNLLI RKNGRTVNLG GKTSVTVYPG DVFCLHTPGG GGYGDPEDPA
PPPGSPPQAL AFPEHGSVYE YRRAQEAV
