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 27-MAR-2024, entry version 182. 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}. 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; 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; 227. DR IntAct; Q96C36; 78. DR MINT; Q96C36; -. DR STRING; 9606.ENSP00000342502; -. DR ChEMBL; CHEMBL4295923; -. DR DrugBank; DB00157; NADH. DR DrugBank; DB00172; Proline. DR GlyGen; Q96C36; 4 sites, 1 O-linked glycan (4 sites). 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; 9606-ENSP00000342502; -. DR PeptideAtlas; Q96C36; -. DR ProteomicsDB; 76158; -. DR Pumba; Q96C36; -. DR TopDownProteomics; Q96C36; -. DR Antibodypedia; 34774; 375 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 AGR; HGNC:30262; -. 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; EGTPVAW; -. DR OrthoDB; 196930at2759; -. 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; 16 hits in 1145 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 179 other cell types or tissues. DR ExpressionAtlas; Q96C36; baseline and differential. 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 Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR Gene3D; 1.10.3730.10; ProC C-terminal domain-like; 1. 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 NCBIfam; TIGR00112; proC; 1. DR PANTHER; PTHR11645; PYRROLINE-5-CARBOXYLATE REDUCTASE; 1. DR PANTHER; PTHR11645:SF61; PYRROLINE-5-CARBOXYLATE REDUCTASE 2; 1. DR Pfam; PF03807; F420_oxidored; 1. DR Pfam; PF14748; P5CR_dimer; 1. DR PIRSF; PIRSF000193; Pyrrol-5-carb_rd; 1. DR SUPFAM; SSF48179; 6-phosphogluconate dehydrogenase C-terminal domain-like; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR PROSITE; PS00521; P5CR; 1. DR Genevisible; Q96C36; HS. 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 //