ID   HYPDH_MOUSE             Reviewed;         456 AA.
AC   Q8VCZ9; Q2V058; Q9QX62;
DT   23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   04-NOV-2026, entry version 146.
DE   RecName: Full=Hydroxyproline dehydrogenase {ECO:0000250|UniProtKB:Q9UF12};
DE            Short=HYPDH {ECO:0000250|UniProtKB:Q9UF12};
DE            EC=1.5.5.3 {ECO:0000250|UniProtKB:Q9UF12};
DE   AltName: Full=Kidney and liver proline oxidase 1 {ECO:0000305};
DE   AltName: Full=MmPOX1 {ECO:0000305};
DE   AltName: Full=Probable proline dehydrogenase 2 {ECO:0000250|UniProtKB:Q9UF12};
DE            EC=1.5.5.2 {ECO:0000250|UniProtKB:Q9UF12};
DE   AltName: Full=Probable proline oxidase 2;
DE   AltName: Full=Proline oxidase-like protein;
DE            Short=PO;
DE            Short=Proline oxidase;
GN   Name=Prodh2 {ECO:0000312|MGI:MGI:1929093};
GN   Synonyms=Hypdh {ECO:0000250|UniProtKB:Q9UF12};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
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   NUCLEOTIDE SEQUENCE [MRNA].
RA   Yang Q., Tian Y., Wallner E.I., Kanwar Y.S.;
RL   Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Liver;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Liver;
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   INDUCTION BY TCF1 AND HNF4A, AND DEVELOPMENTAL STAGE.
RX   PubMed=15581617; DOI=10.1016/j.febslet.2004.10.070;
RA   Kamiya A., Inoue Y., Kodama T., Gonzalez F.J.;
RT   "Hepatocyte nuclear factors 1alpha and 4alpha control expression of proline
RT   oxidase in adult liver.";
RL   FEBS Lett. 578:63-68(2004).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney, and Liver;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [7]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-310 AND LYS-320, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA   Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA   Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT   "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT   identifies substrates of SIRT3 in metabolic pathways.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
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:0000250|UniProtKB:Q9UF12}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=trans-4-hydroxy-L-proline + a quinone = (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:0000250|UniProtKB:Q9UF12};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ubiquinone-10 + trans-4-hydroxy-L-proline = (3R,5S)-1-
CC         pyrroline-3-hydroxy-5-carboxylate + ubiquinol-10 + H(+);
CC         Xref=Rhea:RHEA:52516, ChEBI:CHEBI:15378, ChEBI:CHEBI:46245,
CC         ChEBI:CHEBI:58375, ChEBI:CHEBI:62612, ChEBI:CHEBI:64183;
CC         Evidence={ECO:0000250|UniProtKB:Q9UF12};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52517;
CC         Evidence={ECO:0000250|UniProtKB:Q9UF12};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-proline + a quinone = (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:0000250|UniProtKB:Q9UF12};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000250|UniProtKB:Q9UF12};
CC   -!- DEVELOPMENTAL STAGE: Expressed in liver at 14 dpc. Expression level
CC       increases at P5 and decreases after P21. {ECO:0000269|PubMed:15581617}.
CC   -!- INDUCTION: In liver, by TCF1 and HNF4A. {ECO:0000269|PubMed:15581617}.
CC   -!- SIMILARITY: Belongs to the proline oxidase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAF21466.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAQ13907.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; U80019; AAF21466.1; ALT_INIT; mRNA.
DR   EMBL; AF222851; AAQ13907.1; ALT_INIT; mRNA.
DR   EMBL; AK050141; BAC34090.1; -; mRNA.
DR   EMBL; BC018182; AAH18182.1; -; mRNA.
DR   CCDS; CCDS21093.1; -.
DR   RefSeq; NP_062419.2; NM_019546.6.
DR   AlphaFoldDB; Q8VCZ9; -.
DR   SMR; Q8VCZ9; -.
DR   FunCoup; Q8VCZ9; 616.
DR   STRING; 10090.ENSMUSP00000062214; -.
DR   iPTMnet; Q8VCZ9; -.
DR   PhosphoSitePlus; Q8VCZ9; -.
DR   SwissPalm; Q8VCZ9; -.
DR   jPOST; Q8VCZ9; -.
DR   PaxDb; 10090-ENSMUSP00000062214; -.
DR   ProteomicsDB; 269514; -.
DR   Antibodypedia; 44579; 87 antibodies from 19 providers.
DR   DNASU; 56189; -.
DR   Ensembl; ENSMPUT00000006082; ENSMPUP00000005977; ENSMPUG00000006028.
DR   Ensembl; ENSMUST00000058280.13; ENSMUSP00000062214.7; ENSMUSG00000036892.13.
DR   GeneID; 56189; -.
DR   KEGG; mmu:56189; -.
DR   UCSC; uc009geo.1; mouse.
DR   AGR; MGI:1929093; -.
DR   CTD; 58510; -.
DR   MGI; MGI:1929093; Prodh2.
DR   VEuPathDB; HostDB:ENSMUSG00000036892; -.
DR   eggNOG; KOG0186; Eukaryota.
DR   GeneTree; ENSGT00390000006265; -.
DR   HOGENOM; CLU_018202_3_2_1; -.
DR   InParanoid; Q8VCZ9; -.
DR   OMA; AAEETWN; -.
DR   OrthoDB; 5464at2759; -.
DR   PhylomeDB; Q8VCZ9; -.
DR   BRENDA; 1.5.5.3; 3474.
DR   Reactome; R-MMU-389661; Glyoxylate metabolism and glycine degradation.
DR   Reactome; R-MMU-70688; Proline catabolism.
DR   BioGRID-ORCS; 56189; 0 hits in 76 CRISPR screens.
DR   PRO; PR:Q8VCZ9; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; Q8VCZ9; protein.
DR   Bgee; ENSMUSG00000036892; Expressed in left lobe of liver and 53 other cell types or tissues.
DR   ExpressionAtlas; Q8VCZ9; baseline and differential.
DR   GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR   GO; GO:0005739; C:mitochondrion; IMP:MGI.
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; ISS:UniProtKB.
DR   GO; GO:0016649; F:oxidoreductase activity, acting on the CH-NH group of donors, quinone or similar compound as acceptor; IMP:MGI.
DR   GO; GO:0004657; F:proline dehydrogenase activity; ISS:UniProtKB.
DR   GO; GO:0006562; P:L-proline catabolic process; IEA:InterPro.
DR   GO; GO:0019470; P:trans-4-hydroxy-L-proline catabolic process; IMP:MGI.
DR   FunFam; 3.20.20.220:FF:000010; Proline dehydrogenase; 1.
DR   Gene3D; 3.20.20.220; -; 1.
DR   InterPro; IPR029041; FAD-linked_oxidoreductase-like.
DR   InterPro; IPR002872; Proline_DH_dom.
DR   InterPro; IPR015659; Proline_oxidase.
DR   PANTHER; PTHR13914:SF29; HYDROXYPROLINE DEHYDROGENASE; 1.
DR   PANTHER; PTHR13914; PROLINE OXIDASE; 1.
DR   Pfam; PF01619; Pro_dh; 1.
DR   SUPFAM; SSF51730; FAD-linked oxidoreductase; 1.
PE   1: Evidence at protein level;
KW   Acetylation; FAD; Flavoprotein; Oxidoreductase; Proline metabolism;
KW   Reference proteome.
FT   CHAIN           1..456
FT                   /note="Hydroxyproline dehydrogenase"
FT                   /id="PRO_0000308624"
FT   MOD_RES         310
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         320
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   CONFLICT        337
FT                   /note="R -> H (in Ref. 1; AAF21466)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        416
FT                   /note="E -> K (in Ref. 1; AAF21466)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   456 AA;  50723 MW;  CD02C1474AADBD56 CRC64;
     MIWTRLPLYG PSKPSTGGWQ PLRFDGGAFH VKGTAELARA LLVLRLCAWP PLVTHGLAFQ
     AWSQRLLGSR LSGALLRASI YGQFVAGETA EEVRNCVGQL QALGLQPLLA VPTEEEPDST
     AKTSEVWYEE NLSAMLRCVD LSRALVDAHG PARNSLMQLK VTALASTRLC KELSAWIQRP
     RGSSELSPER LAEAMDSGRN LQLSCLSTEQ NQHLQASLSR LHRVAQHARA KCVRLLVDAE
     YTFINPALSL LVAALAVRWN SPEEGGPWVW NTYQAYLKDT HQRLEQDAEA AHKAGLAFGV
     KLVRGAYLDK ERSMTQLQGK EDCTQPDYEA TSRSYSRCLE LMLRCVSNHG PPCHLMVASH
     NEESVRQATK RMWELGIPLD GPVCFGQLLG MCDHVSLALG QAGYMVYKSI PYGCLEEVIP
     YLIRRAQENR SVLQGARREQ ALLSQELWRR LLGRTA
//