P5CR2_HUMAN
ID P5CR2_HUMAN Reviewed; 320 AA.
AC Q96C36; A8K798; Q7Z515; Q9Y5J4;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Pyrroline-5-carboxylate reductase 2;
DE Short=P5C reductase 2;
DE Short=P5CR 2;
DE EC=1.5.1.2;
GN Name=PYCR2;
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 Yue P., Yu L., Zhao S.Y.;
RT "Cloning of a new human cDNA homologous to human pyrroline 5-carboxylate
RT reductase mRNA.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix, and Skin;
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 [6]
RP PROTEIN SEQUENCE OF 2-17, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT
RP SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Heiserich L., Gottlieb E., Zebisch A., Kolch W.;
RL Submitted (OCT-2008) to UniProtKB.
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=6894153; DOI=10.1172/jci110115;
RA Yeh G.C., Harris S.C., Phang J.M.;
RT "Pyrroline-5-carboxylate reductase in human erythrocytes.";
RL J. Clin. Invest. 67:1042-1046(1981).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RX PubMed=2722838; DOI=10.1016/s0021-9258(18)60538-1;
RA Merrill M.J., Yeh G.C., Phang J.M.;
RT "Purified human erythrocyte pyrroline-5-carboxylate reductase. Preferential
RT oxidation of NADPH.";
RL J. Biol. Chem. 264:9352-9358(1989).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=23024808; DOI=10.1371/journal.pone.0045190;
RA De Ingeniis J., Ratnikov B., Richardson A.D., Scott D.A., Aza-Blanc P.,
RA De S.K., Kazanov M., Pellecchia M., Ronai Z., Osterman A.L., Smith J.W.;
RT "Functional specialization in proline biosynthesis of melanoma.";
RL PLoS ONE 7:E45190-E45190(2012).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304, AND IDENTIFICATION BY
RP 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 [18]
RP INTERACTION WITH LTO1.
RX PubMed=24930674; DOI=10.18632/oncotarget.1561;
RA Togashi Y., Arao T., Kato H., Matsumoto K., Terashima M., Hayashi H.,
RA de Velasco M.A., Fujita Y., Kimura H., Yasuda T., Shiozaki H., Nishio K.;
RT "Frequent amplification of ORAOV1 gene in esophageal squamous cell cancer
RT promotes an aggressive phenotype via proline metabolism and ROS
RT production.";
RL Oncotarget 5:2962-2973(2014).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INVOLVEMENT IN HLD10,
RP VARIANTS HLD10 CYS-119 AND CYS-251, AND CHARACTERIZATION OF VARIANTS HLD10
RP CYS-119 AND CYS-251.
RX PubMed=25865492; DOI=10.1016/j.ajhg.2015.03.003;
RA Nakayama T., Al-Maawali A., El-Quessny M., Rajab A., Khalil S.,
RA Stoler J.M., Tan W.H., Nasir R., Schmitz-Abe K., Hill R.S., Partlow J.N.,
RA Al-Saffar M., Servattalab S., LaCoursiere C.M., Tambunan D.E.,
RA Coulter M.E., Elhosary P.C., Gorski G., Barkovich A.J., Markianos K.,
RA Poduri A., Mochida G.H.;
RT "Mutations in PYCR2, encoding pyrroline-5-carboxylate reductase 2, cause
RT microcephaly and hypomyelination.";
RL Am. J. Hum. Genet. 96:709-719(2015).
RN [20]
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).
CC -!- FUNCTION: Housekeeping enzyme that catalyzes the last step in proline
CC biosynthesis. In some cell types, such as erythrocytes, its primary
CC function may be the generation of NADP(+). Can utilize both NAD and
CC NADP. Has higher affinity for NADP, but higher catalytic efficiency
CC with NADH (PubMed:2722838, PubMed:6894153). Involved in cellular
CC response to oxidative stress (PubMed:25865492).
CC {ECO:0000269|PubMed:25865492, ECO:0000269|PubMed:2722838,
CC ECO:0000269|PubMed:6894153}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-proline + NADP(+) = 1-pyrroline-5-carboxylate + 2 H(+) +
CC NADPH; Xref=Rhea:RHEA:14109, ChEBI:CHEBI:15378, ChEBI:CHEBI:15893,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:60039; EC=1.5.1.2;
CC Evidence={ECO:0000269|PubMed:2722838, ECO:0000269|PubMed:6894153};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-proline + NAD(+) = 1-pyrroline-5-carboxylate + 2 H(+) +
CC NADH; Xref=Rhea:RHEA:14105, ChEBI:CHEBI:15378, ChEBI:CHEBI:15893,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:60039; EC=1.5.1.2;
CC Evidence={ECO:0000269|PubMed:2722838, ECO:0000269|PubMed:6894153};
CC -!- ACTIVITY REGULATION: Subject to competitive inhibition by NADP. Not
CC inhibited by proline. {ECO:0000269|PubMed:2722838,
CC ECO:0000269|PubMed:6894153}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.64 mM for NADH {ECO:0000269|PubMed:2722838};
CC KM=0.04 mM for NADPH {ECO:0000269|PubMed:2722838};
CC KM=1.49 mM for pyrroline-5-carboxylate (in the presence of NADH)
CC {ECO:0000269|PubMed:2722838};
CC KM=0.23 mM for pyrroline-5-carboxylate (in the presence of NADPH)
CC {ECO:0000269|PubMed:2722838};
CC Vmax=28.5 umol/min/ug enzyme (in the presence of NADH)
CC {ECO:0000269|PubMed:2722838};
CC Vmax=3.7 umol/min/ug enzyme (in the presence of NADPH)
CC {ECO:0000269|PubMed:2722838};
CC -!- PATHWAY: Amino-acid biosynthesis; L-proline biosynthesis; L-proline
CC from L-glutamate 5-semialdehyde: step 1/1.
CC -!- SUBUNIT: Homodecamer; composed of 5 homodimers (Probable). Interacts
CC with LTO1 (PubMed:24930674). {ECO:0000269|PubMed:24930674,
CC ECO:0000305|PubMed:2722838}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:2722838}.
CC Mitochondrion {ECO:0000269|PubMed:23024808,
CC ECO:0000269|PubMed:25865492}.
CC -!- TISSUE SPECIFICITY: Detected in erythrocytes (at protein level)
CC (PubMed:2722838, PubMed:6894153). Expressed in fetal brain
CC (PubMed:25865492). {ECO:0000269|PubMed:25865492,
CC ECO:0000269|PubMed:2722838, ECO:0000269|PubMed:6894153}.
CC -!- DISEASE: Leukodystrophy, hypomyelinating, 10 (HLD10) [MIM:616420]: An
CC autosomal recessive neurologic disorder characterized by postnatal
CC microcephaly, severely delayed psychomotor development,
CC hypomyelination, and reduced cerebral white-matter volume.
CC {ECO:0000269|PubMed:25865492}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the pyrroline-5-carboxylate reductase family.
CC {ECO:0000305}.
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DR EMBL; AF087859; AAP97169.1; -; mRNA.
DR EMBL; AK291913; BAF84602.1; -; mRNA.
DR EMBL; AL117348; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471098; EAW69762.1; -; Genomic_DNA.
DR EMBL; BC014868; AAH14868.1; -; mRNA.
DR EMBL; BC020553; AAH20553.1; -; mRNA.
DR CCDS; CCDS31043.1; -.
DR RefSeq; NP_001258610.1; NM_001271681.1.
DR RefSeq; NP_037460.2; NM_013328.3.
DR PDB; 6LHM; X-ray; 3.40 A; A/B/C/D/E=1-300.
DR PDBsum; 6LHM; -.
DR AlphaFoldDB; Q96C36; -.
DR PCDDB; Q96C36; -.
DR SMR; Q96C36; -.
DR BioGRID; 118962; 190.
DR IntAct; Q96C36; 69.
DR MINT; Q96C36; -.
DR STRING; 9606.ENSP00000342502; -.
DR ChEMBL; CHEMBL4295923; -.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB00172; Proline.
DR GlyGen; Q96C36; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96C36; -.
DR MetOSite; Q96C36; -.
DR PhosphoSitePlus; Q96C36; -.
DR SwissPalm; Q96C36; -.
DR BioMuta; PYCR2; -.
DR DMDM; 60390642; -.
DR EPD; Q96C36; -.
DR jPOST; Q96C36; -.
DR MassIVE; Q96C36; -.
DR MaxQB; Q96C36; -.
DR PaxDb; Q96C36; -.
DR PeptideAtlas; Q96C36; -.
DR PRIDE; Q96C36; -.
DR ProteomicsDB; 76158; -.
DR TopDownProteomics; Q96C36; -.
DR Antibodypedia; 34774; 329 antibodies from 26 providers.
DR DNASU; 29920; -.
DR Ensembl; ENST00000343818.11; ENSP00000342502.6; ENSG00000143811.20.
DR GeneID; 29920; -.
DR KEGG; hsa:29920; -.
DR MANE-Select; ENST00000343818.11; ENSP00000342502.6; NM_013328.4; NP_037460.2.
DR UCSC; uc001hpq.5; human.
DR CTD; 29920; -.
DR DisGeNET; 29920; -.
DR GeneCards; PYCR2; -.
DR HGNC; HGNC:30262; PYCR2.
DR HPA; ENSG00000143811; Low tissue specificity.
DR MalaCards; PYCR2; -.
DR MIM; 616406; gene.
DR MIM; 616420; phenotype.
DR neXtProt; NX_Q96C36; -.
DR OpenTargets; ENSG00000143811; -.
DR Orphanet; 2512; Autosomal recessive primary microcephaly.
DR Orphanet; 481152; PYCR2-related microcephaly-progressive leukoencephalopathy.
DR PharmGKB; PA134881955; -.
DR VEuPathDB; HostDB:ENSG00000143811; -.
DR eggNOG; KOG3124; Eukaryota.
DR GeneTree; ENSGT00950000183044; -.
DR HOGENOM; CLU_042344_3_0_1; -.
DR InParanoid; Q96C36; -.
DR OMA; TSHNEPW; -.
DR OrthoDB; 952695at2759; -.
DR PhylomeDB; Q96C36; -.
DR PathwayCommons; Q96C36; -.
DR Reactome; R-HSA-8964539; Glutamate and glutamine metabolism.
DR SABIO-RK; Q96C36; -.
DR SignaLink; Q96C36; -.
DR UniPathway; UPA00098; UER00361.
DR BioGRID-ORCS; 29920; 9 hits in 1064 CRISPR screens.
DR ChiTaRS; PYCR2; human.
DR GenomeRNAi; 29920; -.
DR Pharos; Q96C36; Tbio.
DR PRO; PR:Q96C36; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96C36; protein.
DR Bgee; ENSG00000143811; Expressed in cardiac muscle of right atrium and 177 other tissues.
DR ExpressionAtlas; Q96C36; baseline and differential.
DR Genevisible; Q96C36; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0004735; F:pyrroline-5-carboxylate reductase activity; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0055129; P:L-proline biosynthetic process; IBA:GO_Central.
DR GO; GO:0006561; P:proline biosynthetic process; IDA:UniProtKB.
DR HAMAP; MF_01925; P5C_reductase; 1.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR028939; P5C_Rdtase_cat_N.
DR InterPro; IPR029036; P5CR_dimer.
DR InterPro; IPR000304; Pyrroline-COOH_reductase.
DR PANTHER; PTHR11645; PTHR11645; 1.
DR Pfam; PF03807; F420_oxidored; 1.
DR Pfam; PF14748; P5CR_dimer; 1.
DR PIRSF; PIRSF000193; Pyrrol-5-carb_rd; 1.
DR SUPFAM; SSF48179; SSF48179; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR00112; proC; 1.
DR PROSITE; PS00521; P5CR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Amino-acid biosynthesis; Cytoplasm;
KW Direct protein sequencing; Disease variant; Leukodystrophy; Mitochondrion;
KW NADP; Oxidoreductase; Phosphoprotein; Proline biosynthesis;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.6"
FT CHAIN 2..320
FT /note="Pyrroline-5-carboxylate reductase 2"
FT /id="PRO_0000187317"
FT REGION 295..320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 6..11
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 34
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 56
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 69..72
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 95..97
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.6"
FT MOD_RES 304
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT VARIANT 119
FT /note="R -> C (in HLD10; severe decrease of protein amount;
FT does not affect mitochondrial localization;
FT dbSNP:rs372781135)"
FT /evidence="ECO:0000269|PubMed:25865492"
FT /id="VAR_074608"
FT VARIANT 251
FT /note="R -> C (in HLD10; mild decrease of homodimerization;
FT does not affect mitochondrial localization;
FT dbSNP:rs876657403)"
FT /evidence="ECO:0000269|PubMed:25865492"
FT /id="VAR_074609"
FT CONFLICT 13
FT /note="Y -> N (in Ref. 1; AAP97169)"
FT /evidence="ECO:0000305"
FT CONFLICT 23..24
FT /note="GI -> AF (in Ref. 1; AAP97169)"
FT /evidence="ECO:0000305"
FT CONFLICT 72..73
FT /note="PH -> HI (in Ref. 1; AAP97169)"
FT /evidence="ECO:0000305"
FT STRAND 3..6
FT /evidence="ECO:0007829|PDB:6LHM"
FT HELIX 10..22
FT /evidence="ECO:0007829|PDB:6LHM"
FT STRAND 27..31
FT /evidence="ECO:0007829|PDB:6LHM"
FT HELIX 40..48
FT /evidence="ECO:0007829|PDB:6LHM"
FT HELIX 57..60
FT /evidence="ECO:0007829|PDB:6LHM"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:6LHM"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:6LHM"
FT HELIX 75..82
FT /evidence="ECO:0007829|PDB:6LHM"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:6LHM"
FT STRAND 91..94
FT /evidence="ECO:0007829|PDB:6LHM"
FT HELIX 101..111
FT /evidence="ECO:0007829|PDB:6LHM"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:6LHM"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:6LHM"
FT TURN 125..129
FT /evidence="ECO:0007829|PDB:6LHM"
FT STRAND 131..137
FT /evidence="ECO:0007829|PDB:6LHM"
FT HELIX 143..154
FT /evidence="ECO:0007829|PDB:6LHM"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:6LHM"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:6LHM"
FT HELIX 167..174
FT /evidence="ECO:0007829|PDB:6LHM"
FT HELIX 177..195
FT /evidence="ECO:0007829|PDB:6LHM"
FT HELIX 199..219
FT /evidence="ECO:0007829|PDB:6LHM"
FT HELIX 224..231
FT /evidence="ECO:0007829|PDB:6LHM"
FT HELIX 237..247
FT /evidence="ECO:0007829|PDB:6LHM"
FT HELIX 250..269
FT /evidence="ECO:0007829|PDB:6LHM"
SQ SEQUENCE 320 AA; 33637 MW; 9348455A64CCE722 CRC64;
MSVGFIGAGQ LAYALARGFT AAGILSAHKI IASSPEMNLP TVSALRKMGV NLTRSNKETV
KHSDVLFLAV KPHIIPFILD EIGADVQARH IVVSCAAGVT ISSVEKKLMA FQPAPKVIRC
MTNTPVVVQE GATVYATGTH ALVEDGQLLE QLMSSVGFCT EVEEDLIDAV TGLSGSGPAY
AFMALDALAD GGVKMGLPRR LAIQLGAQAL LGAAKMLLDS EQHPCQLKDN VCSPGGATIH
ALHFLESGGF RSLLINAVEA SCIRTRELQS MADQEKISPA ALKKTLLDRV KLESPTVSTL
TPSSPGKLLT RSLALGGKKD
