HYPDH_HUMAN
ID HYPDH_HUMAN Reviewed; 536 AA.
AC Q9UF12;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Hydroxyproline dehydrogenase {ECO:0000303|PubMed:25697095};
DE Short=HYPDH {ECO:0000303|PubMed:25697095};
DE EC=1.5.5.3 {ECO:0000269|PubMed:25697095};
DE AltName: Full=Kidney and liver proline oxidase 1;
DE Short=HsPOX1;
DE AltName: Full=Probable proline dehydrogenase 2 {ECO:0000312|HGNC:HGNC:17325};
DE EC=1.5.5.2 {ECO:0000269|PubMed:25697095};
DE AltName: Full=Probable proline oxidase 2;
GN Name=PRODH2 {ECO:0000312|HGNC:HGNC:17325};
GN Synonyms=HSPOX1 {ECO:0000312|HGNC:HGNC:17325},
GN HYPDH {ECO:0000303|PubMed:25697095};
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 Lin W.-W., Hu C.A., Valle D.;
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, COFACTOR,
RP SUBSTRATE SPECIFICITY, AND ACTIVITY REGULATION.
RX PubMed=25697095; DOI=10.1042/bj20141159;
RA Summitt C.B., Johnson L.C., Joensson T.J., Parsonage D., Holmes R.P.,
RA Lowther W.T.;
RT "Proline dehydrogenase 2 (PRODH2) is a hydroxyproline dehydrogenase (HYPDH)
RT and molecular target for treating primary hyperoxaluria.";
RL Biochem. J. 466:273-281(2015).
CC -!- FUNCTION: Dehydrogenase that converts trans-4-L-hydroxyproline to
CC delta-1-pyrroline-3-hydroxy-5-carboxylate (Hyp) using ubiquinone-10 as
CC the terminal electron acceptor. Can also use proline as a substrate but
CC with a very much lower efficiency. Does not react with other
CC diastereomers of Hyp: trans-4-D-hydroxyproline and cis-4-L-
CC hydroxyproline. Ubiquininone analogs such as menadione, duroquinone and
CC ubiquinone-1 react more efficiently than oxygen as the terminal
CC electron acceptor during catalysis. {ECO:0000269|PubMed:25697095}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinone + trans-4-hydroxy-L-proline = (3R,5S)-1-pyrroline-3-
CC hydroxy-5-carboxylate + a quinol + H(+); Xref=Rhea:RHEA:52512,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:24646, ChEBI:CHEBI:58375,
CC ChEBI:CHEBI:62612, ChEBI:CHEBI:132124; EC=1.5.5.3;
CC Evidence={ECO:0000269|PubMed:25697095};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinone + L-proline = (S)-1-pyrroline-5-carboxylate + a
CC quinol + H(+); Xref=Rhea:RHEA:23784, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17388, ChEBI:CHEBI:24646, ChEBI:CHEBI:60039,
CC ChEBI:CHEBI:132124; EC=1.5.5.2;
CC Evidence={ECO:0000269|PubMed:25697095};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:25697095};
CC -!- ACTIVITY REGULATION: Hydroproxyproline dehydrogenase activity is
CC inhibited by THFA,(1R,3R)3-OH-cyclopentane-COOH and 5-OH-1H-pyrazole-3-
CC COOH. {ECO:0000269|PubMed:25697095}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=200 mM for trans-4-L-hydroxyproline {ECO:0000269|PubMed:25697095};
CC KM=28 mM for oxygen {ECO:0000269|PubMed:25697095};
CC KM=143 uM for duroquinone {ECO:0000269|PubMed:25697095};
CC KM=25 uM for menadione {ECO:0000269|PubMed:25697095};
CC KM=124 uM for ubiquinone-1 {ECO:0000269|PubMed:25697095};
CC Note=kcat with trans-4-L-hydroxyproline (Hyp) and ubiquinone-1 is
CC 0.19 sec(-1). Proline is unable to saturate PRODH2 at least up to
CC 750mM. kcat/KM with proline and ubiquinone-10: 0.075 M(-1)/sec. kcat
CC with oxygen, duroquinone, menadione and CoQ1 and with trans-4-L-
CC hydroxyproline are 0.002 sec(-1), 0.27 sec(-1), 0.28 sec(-1) and 0.19
CC sec(-1), respectively. {ECO:0000269|PubMed:25697095};
CC -!- SIMILARITY: Belongs to the proline oxidase family. {ECO:0000305}.
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DR EMBL; U80018; AAF21465.1; -; mRNA.
DR RefSeq; NP_067055.1; NM_021232.1.
DR AlphaFoldDB; Q9UF12; -.
DR SMR; Q9UF12; -.
DR STRING; 9606.ENSP00000301175; -.
DR ChEMBL; CHEMBL4523486; -.
DR iPTMnet; Q9UF12; -.
DR BioMuta; PRODH2; -.
DR DMDM; 74720632; -.
DR MassIVE; Q9UF12; -.
DR MaxQB; Q9UF12; -.
DR PaxDb; Q9UF12; -.
DR PeptideAtlas; Q9UF12; -.
DR PRIDE; Q9UF12; -.
DR ProteomicsDB; 84167; -.
DR Antibodypedia; 44579; 83 antibodies from 17 providers.
DR DNASU; 58510; -.
DR Ensembl; ENST00000301175.7; ENSP00000301175.3; ENSG00000250799.11.
DR GeneID; 58510; -.
DR KEGG; hsa:58510; -.
DR UCSC; uc002obx.1; human.
DR CTD; 58510; -.
DR DisGeNET; 58510; -.
DR GeneCards; PRODH2; -.
DR HGNC; HGNC:17325; PRODH2.
DR HPA; ENSG00000250799; Group enriched (kidney, liver).
DR MIM; 616377; gene.
DR neXtProt; NX_Q9UF12; -.
DR OpenTargets; ENSG00000250799; -.
DR PharmGKB; PA33802; -.
DR VEuPathDB; HostDB:ENSG00000250799; -.
DR eggNOG; KOG0186; Eukaryota.
DR GeneTree; ENSGT00390000006265; -.
DR HOGENOM; CLU_018202_3_2_1; -.
DR InParanoid; Q9UF12; -.
DR OrthoDB; 948528at2759; -.
DR PhylomeDB; Q9UF12; -.
DR TreeFam; TF313544; -.
DR BioCyc; MetaCyc:MON66-34410; -.
DR BRENDA; 1.5.5.3; 2681.
DR PathwayCommons; Q9UF12; -.
DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-HSA-70688; Proline catabolism.
DR SignaLink; Q9UF12; -.
DR BioGRID-ORCS; 58510; 64 hits in 1070 CRISPR screens.
DR GenomeRNAi; 58510; -.
DR Pharos; Q9UF12; Tbio.
DR PRO; PR:Q9UF12; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9UF12; protein.
DR Bgee; ENSG00000250799; Expressed in right lobe of liver and 87 other tissues.
DR ExpressionAtlas; Q9UF12; baseline and differential.
DR Genevisible; Q9UF12; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0071949; F:FAD binding; IBA:GO_Central.
DR GO; GO:0016645; F:oxidoreductase activity, acting on the CH-NH group of donors; IDA:UniProtKB.
DR GO; GO:0004657; F:proline dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0006562; P:proline catabolic process; TAS:Reactome.
DR GO; GO:0010133; P:proline catabolic process to glutamate; IBA:GO_Central.
DR InterPro; IPR029041; FAD-linked_oxidoreductase-like.
DR InterPro; IPR002872; Proline_DH_dom.
DR InterPro; IPR015659; Proline_oxidase.
DR PANTHER; PTHR13914; PTHR13914; 1.
DR Pfam; PF01619; Pro_dh; 1.
DR SUPFAM; SSF51730; SSF51730; 1.
PE 1: Evidence at protein level;
KW Acetylation; FAD; Flavoprotein; Oxidoreductase; Proline metabolism;
KW Reference proteome.
FT CHAIN 1..536
FT /note="Hydroxyproline dehydrogenase"
FT /id="PRO_0000308623"
FT MOD_RES 386
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCZ9"
FT VARIANT 91
FT /note="P -> R (in dbSNP:rs3848666)"
FT /id="VAR_036852"
FT VARIANT 525
FT /note="R -> Q (in dbSNP:rs3761097)"
FT /id="VAR_036853"
SQ SEQUENCE 536 AA; 58871 MW; 81EB2F4B21E39E09 CRC64;
MSPRVVSNSS VLASQSVGIT NVRTVFSNVF NNTTAFPILR GSNCHKITAP GLGKGQLVNL
LPPENLPWCG GSQGPRMLRT CYVLCSQAGP PSRGWQSLSF DGGAFHLKGT GELTRALLVL
RLCAWPPLVT HGLLLQAWSR RLLGSRLSGA FLRASVYGQF VAGETAEEVK GCVQQLRTLS
LRPLLAVPTE EEPDSAAKSG EAWYEGNLGA MLRCVDLSRG LLEPPSLAEA SLMQLKVTAL
TSTRLCKELA SWVRRPGASL ELSPERLAEA MDSGQNLQVS CLNAEQNQHL RASLSRLHRV
AQYARAQHVR LLVDAEYTSL NPALSLLVAA LAVRWNSPGE GGPWVWNTYQ ACLKDTFERL
GRDAEAAHRA GLAFGVKLVR GAYLDKERAV AQLHGMEDPT QPDYEATSQS YSRCLELMLT
HVARHGPMCH LMVASHNEES VRQATKRMWE LGIPLDGTVC FGQLLGMCDH VSLALGQAGY
VVYKSIPYGS LEEVIPYLIR RAQENRSVLQ GARREQELLS QELWRRLLPG CRRIPH
