ID P5CR1_HUMAN Reviewed; 319 AA. AC P32322; A6NFM2; B4DMU0; Q6FHI4; Q96DI6; Q9HBQ4; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2005, sequence version 2. DT 27-MAR-2024, entry version 211. DE RecName: Full=Pyrroline-5-carboxylate reductase 1, mitochondrial; DE Short=P5C reductase 1; DE Short=P5CR 1; DE EC=1.5.1.2 {ECO:0000269|PubMed:16730026}; GN Name=PYCR1; 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] (ISOFORM 1). RX PubMed=1730675; DOI=10.1016/s0021-9258(18)48364-0; RA Dougherty K.M., Brandriss M.C., Valle D.; RT "Cloning human pyrroline-5-carboxylate reductase cDNA by complementation in RT Saccharomyces cerevisiae."; RL J. Biol. Chem. 267:871-875(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Gu J.R., Wan D.F., Zhao X.T., Zhou X.M., Jiang H.Q., Zhang P.P., Qin W.X., RA Huang Y., Qiu X.K., Qian L.F., He L.P., Li H.N., Yu Y., Yu J., Han L.H.; RT "Novel Human cDNA clones with function of inhibiting cancer cell growth."; RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph, and Placenta; 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 [8] RP PROTEIN SEQUENCE OF 2-17 AND 205-215, CLEAVAGE OF INITIATOR METHIONINE, RP ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Colon carcinoma; RA Bienvenut W.V., Zebisch A., Kolch W.; RL Submitted (DEC-2008) to UniProtKB. RN [9] RP PROTEIN SEQUENCE OF 2-46; 130-147; 205-215 AND 252-264, CLEAVAGE OF RP INITIATOR METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Embryonic kidney; RA Bienvenut W.V., Waridel P., Quadroni M.; RL Submitted (MAR-2009) to UniProtKB. RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [11] RP FUNCTION, SUBCELLULAR LOCATION, VARIANTS ARCL2B GLY-119; HIS-119; THR-179; RP TRP-206 AND ARG-206, VARIANTS ARCL3B HIS-251 AND THR-257, AND VARIANT RP VAL-189. RX PubMed=19648921; DOI=10.1038/ng.413; RA Reversade B., Escande-Beillard N., Dimopoulou A., Fischer B., Chng S.C., RA Li Y., Shboul M., Tham P.-Y., Kayserili H., Al-Gazali L., Shahwan M., RA Brancati F., Lee H., O'Connor B.D., Schmidt-von Kegler M., Merriman B., RA Nelson S.F., Masri A., Alkazaleh F., Guerra D., Ferrari P., Nanda A., RA Rajab A., Markie D., Gray M., Nelson J., Grix A., Sommer A., RA Savarirayan R., Janecke A.R., Steichen E., Sillence D., Hausser I., RA Budde B., Nuernberg G., Nuernberg P., Seemann P., Kunkel D., Zambruno G., RA Dallapiccola B., Schuelke M., Robertson S., Hamamy H., Wollnik B., RA Van Maldergem L., Mundlos S., Kornak U.; RT "Mutations in PYCR1 cause cutis laxa with progeroid features."; RL Nat. Genet. 41:1016-1021(2009). RN [12] RP IDENTIFICATION BY 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 [13] 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-278 AND SER-301, AND RP IDENTIFICATION BY 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 [15] 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 [16] 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). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF APOENZYME AND IN COMPLEXES WITH RP NAD; NADP AND SUBSTRATE ANALOG GLU, CATALYTIC ACTIVITY, FUNCTION, ACTIVITY RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLU-221, AND RP SUBUNIT. RX PubMed=16730026; DOI=10.1016/j.jmb.2006.04.053; RA Meng Z., Lou Z., Liu Z., Li M., Zhao X., Bartlam M., Rao Z.; RT "Crystal structure of human pyrroline-5-carboxylate reductase."; RL J. Mol. Biol. 359:1364-1377(2006). RN [18] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1-300 IN COMPLEX WITH NAD. RG Structural genomics consortium (SGC); RT "Crystal structure of human pyrroline-5-carboxylate reductase."; RL Submitted (FEB-2009) to the PDB data bank. RN [19] RP VARIANT ARCL2B GLN-266. RX PubMed=19576563; DOI=10.1016/j.ajhg.2009.06.008; RA Guernsey D.L., Jiang H., Evans S.C., Ferguson M., Matsuoka M., RA Nightingale M., Rideout A.L., Provost S., Bedard K., Orr A., Dube M.-P., RA Ludman M., Samuels M.E.; RT "Mutation in pyrroline-5-carboxylate reductase 1 gene in families with RT cutis laxa type 2."; RL Am. J. Hum. Genet. 85:120-129(2009). RN [20] RP VARIANT ARCL3B GLU-248, AND VARIANT ARG-297. RX PubMed=22052856; DOI=10.1002/ajmg.a.34326; RA Lin D.S., Chang J.H., Liu H.L., Wei C.H., Yeung C.Y., Ho C.S., Shu C.H., RA Chiang M.F., Chuang C.K., Huang Y.W., Wu T.Y., Jian Y.R., Huang Z.D., RA Lin S.P.; RT "Compound heterozygous mutations in PYCR1 further expand the phenotypic RT spectrum of De Barsy syndrome."; RL Am. J. Med. Genet. A 155:3095-3099(2011). CC -!- FUNCTION: Housekeeping enzyme that catalyzes the last step in proline CC biosynthesis. Can utilize both NAD and NADP, but has higher affinity CC for NAD. Involved in the cellular response to oxidative stress. CC {ECO:0000269|PubMed:16730026, ECO:0000269|PubMed:19648921}. 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:16730026}; 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:16730026}; CC -!- ACTIVITY REGULATION: Subject to competitive inhibition by the reaction CC product proline. Subject to competitive inhibition by stearoyl coenzyme CC A. {ECO:0000269|PubMed:16730026}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.151 mM for NAD(+) {ECO:0000269|PubMed:16730026}; CC KM=3.06 mM for NADP(+) {ECO:0000269|PubMed:16730026}; 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 (PubMed:16730026, CC Ref.18). Interacts with LTO1 (PubMed:24930674). CC {ECO:0000269|PubMed:16730026, ECO:0000269|PubMed:24930674, CC ECO:0000269|Ref.18}. CC -!- INTERACTION: CC P32322; Q99497: PARK7; NbExp=5; IntAct=EBI-848624, EBI-1164361; CC P32322; P32322: PYCR1; NbExp=5; IntAct=EBI-848624, EBI-848624; CC P32322; O14787-2: TNPO2; NbExp=3; IntAct=EBI-848624, EBI-12076664; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:19648921}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P32322-1; Sequence=Displayed; CC Name=2; CC IsoId=P32322-2; Sequence=VSP_044507; CC Name=3; CC IsoId=P32322-3; Sequence=VSP_054616; CC -!- DISEASE: Cutis laxa, autosomal recessive, 2B (ARCL2B) [MIM:612940]: A CC disorder characterized by an excessive congenital skin wrinkling, a CC large fontanelle with delayed closure, a typical facial appearance with CC downslanting palpebral fissures, a general connective tissue weakness, CC and varying degrees of growth and developmental delay and neurological CC abnormalities. Patients do not manifest metabolic abnormalities. CC {ECO:0000269|PubMed:19576563, ECO:0000269|PubMed:19648921}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Cutis laxa, autosomal recessive, 3B (ARCL3B) [MIM:614438]: A CC disorder characterized by an aged appearance with distinctive facial CC features, sparse hair, ophthalmologic abnormalities, intrauterine CC growth retardation, and cutis laxa. {ECO:0000269|PubMed:19648921, CC ECO:0000269|PubMed:22052856}. 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 -!- SEQUENCE CAUTION: CC Sequence=AAG17242.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Mendelian genes pyrroline-5-carboxylate reductase 1 CC (PYCR1); Note=Leiden Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/PYCR1"; 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; M77836; AAA36407.1; -; mRNA. DR EMBL; AF218000; AAG17242.1; ALT_FRAME; mRNA. DR EMBL; AK297627; BAG60002.1; -; mRNA. DR EMBL; CR541769; CAG46568.1; -; mRNA. DR EMBL; AC145207; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471099; EAW89724.1; -; Genomic_DNA. DR EMBL; BC001504; AAH01504.1; -; mRNA. DR EMBL; BC071842; AAH71842.1; -; mRNA. DR CCDS; CCDS11794.1; -. [P32322-2] DR CCDS; CCDS11795.1; -. [P32322-1] DR CCDS; CCDS62366.1; -. [P32322-3] DR PIR; A41770; A41770. DR RefSeq; NP_001269209.1; NM_001282280.1. [P32322-1] DR RefSeq; NP_001269210.1; NM_001282281.1. [P32322-3] DR RefSeq; NP_008838.2; NM_006907.3. [P32322-1] DR RefSeq; NP_722546.1; NM_153824.2. [P32322-2] DR RefSeq; XP_005256438.1; XM_005256381.2. [P32322-1] DR RefSeq; XP_011521885.1; XM_011523583.2. [P32322-1] DR RefSeq; XP_011521886.1; XM_011523584.2. [P32322-1] DR PDB; 2GER; X-ray; 3.10 A; A/B/C/D/E=1-319. DR PDB; 2GR9; X-ray; 3.10 A; A/B/C/D/E=1-275. DR PDB; 2GRA; X-ray; 3.10 A; A/B/C/D/E=1-275. DR PDB; 2IZZ; X-ray; 1.95 A; A/B/C/D/E=1-300. DR PDB; 5UAT; X-ray; 1.92 A; A/B/C/D/E=1-300. DR PDB; 5UAU; X-ray; 1.90 A; A/B/C/D/E=1-300. DR PDB; 5UAV; X-ray; 1.85 A; A/B/C/D/E=1-300. DR PDB; 5UAW; X-ray; 1.85 A; A/B/C/D/E=1-300. DR PDB; 5UAX; X-ray; 1.85 A; A/B/C/D/E=1-270. DR PDB; 6XOZ; X-ray; 2.35 A; A/B/C/D/E=1-300. DR PDB; 6XP0; X-ray; 1.95 A; A/B/C/D/E=1-300. DR PDB; 6XP1; X-ray; 1.75 A; A/B/C/D/E=1-300. DR PDB; 6XP2; X-ray; 2.30 A; A/B/C/D/E=1-300. DR PDB; 6XP3; X-ray; 1.93 A; A/B/C/D/E=1-300. DR PDB; 8DKG; X-ray; 1.85 A; A/B/C/D/E=1-300. DR PDBsum; 2GER; -. DR PDBsum; 2GR9; -. DR PDBsum; 2GRA; -. DR PDBsum; 2IZZ; -. DR PDBsum; 5UAT; -. DR PDBsum; 5UAU; -. DR PDBsum; 5UAV; -. DR PDBsum; 5UAW; -. DR PDBsum; 5UAX; -. DR PDBsum; 6XOZ; -. DR PDBsum; 6XP0; -. DR PDBsum; 6XP1; -. DR PDBsum; 6XP2; -. DR PDBsum; 6XP3; -. DR PDBsum; 8DKG; -. DR AlphaFoldDB; P32322; -. DR SMR; P32322; -. DR BioGRID; 111789; 215. DR ComplexPortal; CPX-2085; Pyrroline-5-carboxylate reductase 1 complex. DR IntAct; P32322; 75. DR MINT; P32322; -. DR STRING; 9606.ENSP00000384949; -. DR BindingDB; P32322; -. DR ChEMBL; CHEMBL4296002; -. DR DrugBank; DB00157; NADH. DR DrugBank; DB00172; Proline. DR GlyGen; P32322; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; P32322; -. DR MetOSite; P32322; -. DR PhosphoSitePlus; P32322; -. DR SwissPalm; P32322; -. DR BioMuta; PYCR1; -. DR DMDM; 60416434; -. DR EPD; P32322; -. DR jPOST; P32322; -. DR MassIVE; P32322; -. DR MaxQB; P32322; -. DR PaxDb; 9606-ENSP00000384949; -. DR PeptideAtlas; P32322; -. DR ProteomicsDB; 1058; -. DR ProteomicsDB; 4639; -. DR ProteomicsDB; 54872; -. [P32322-1] DR Pumba; P32322; -. DR TopDownProteomics; P32322-1; -. [P32322-1] DR Antibodypedia; 32938; 300 antibodies from 29 providers. DR DNASU; 5831; -. DR Ensembl; ENST00000329875.13; ENSP00000328858.8; ENSG00000183010.17. [P32322-1] DR Ensembl; ENST00000337943.9; ENSP00000336579.5; ENSG00000183010.17. [P32322-2] DR Ensembl; ENST00000402252.6; ENSP00000384949.2; ENSG00000183010.17. [P32322-3] DR Ensembl; ENST00000619204.4; ENSP00000479793.1; ENSG00000183010.17. [P32322-1] DR GeneID; 5831; -. DR KEGG; hsa:5831; -. DR MANE-Select; ENST00000329875.13; ENSP00000328858.8; NM_006907.4; NP_008838.2. DR UCSC; uc002kcp.5; human. [P32322-1] DR AGR; HGNC:9721; -. DR CTD; 5831; -. DR DisGeNET; 5831; -. DR GeneCards; PYCR1; -. DR HGNC; HGNC:9721; PYCR1. DR HPA; ENSG00000183010; Tissue enhanced (pancreas, salivary gland). DR MalaCards; PYCR1; -. DR MIM; 179035; gene. DR MIM; 612940; phenotype. DR MIM; 614438; phenotype. DR neXtProt; NX_P32322; -. DR OpenTargets; ENSG00000183010; -. DR Orphanet; 357064; Autosomal recessive cutis laxa type 2B. DR Orphanet; 2078; Geroderma osteodysplastica. DR Orphanet; 293633; PYCR1-related De Barsy syndrome. DR PharmGKB; PA34064; -. DR VEuPathDB; HostDB:ENSG00000183010; -. DR eggNOG; KOG3124; Eukaryota. DR GeneTree; ENSGT00950000183044; -. DR InParanoid; P32322; -. DR OrthoDB; 196930at2759; -. DR PhylomeDB; P32322; -. DR BioCyc; MetaCyc:HS06848-MONOMER; -. DR BRENDA; 1.5.1.2; 2681. DR PathwayCommons; P32322; -. DR Reactome; R-HSA-8964539; Glutamate and glutamine metabolism. DR SABIO-RK; P32322; -. DR SignaLink; P32322; -. DR UniPathway; UPA00098; UER00361. DR BioGRID-ORCS; 5831; 24 hits in 1161 CRISPR screens. DR ChiTaRS; PYCR1; human. DR EvolutionaryTrace; P32322; -. DR GeneWiki; PYCR1; -. DR GenomeRNAi; 5831; -. DR Pharos; P32322; Tbio. DR PRO; PR:P32322; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P32322; Protein. DR Bgee; ENSG00000183010; Expressed in stromal cell of endometrium and 150 other cell types or tissues. DR ExpressionAtlas; P32322; baseline and differential. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0004735; F:pyrroline-5-carboxylate reductase activity; IDA:UniProtKB. 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:1903377; P:negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IMP:ParkinsonsUK-UCL. DR GO; GO:0006561; P:proline biosynthetic process; IDA:UniProtKB. DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IMP:ParkinsonsUK-UCL. 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:SF6; PYRROLINE-5-CARBOXYLATE REDUCTASE 1, MITOCHONDRIAL; 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; P32322; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Amino-acid biosynthesis; KW Direct protein sequencing; Disease variant; Mitochondrion; NADP; KW Oxidoreductase; Phosphoprotein; Proline biosynthesis; Reference proteome; KW Stress response. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.8, ECO:0000269|Ref.9, FT ECO:0007744|PubMed:19413330" FT CHAIN 2..319 FT /note="Pyrroline-5-carboxylate reductase 1, mitochondrial" FT /id="PRO_0000187314" FT REGION 294..319 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:0000269|Ref.18" FT BINDING 34 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|Ref.18" FT BINDING 56 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|Ref.18" FT BINDING 69..72 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|Ref.18" FT BINDING 95..97 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|Ref.18" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000269|Ref.8, ECO:0000269|Ref.9, FT ECO:0007744|PubMed:19413330" FT MOD_RES 278 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 301 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1 FT /note="M -> MVGGGRRVGRDEPVPSVGALGQGSPDSM (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054616" FT VAR_SEQ 290..319 FT /note="VKLDSPAGTALSPSGHTKLLPRSLAPAGKD -> DHLPLELGSPEGLHPLLL FT QYQLARAPS (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_044507" FT VARIANT 119 FT /note="R -> G (in ARCL2B; dbSNP:rs121918376)" FT /evidence="ECO:0000269|PubMed:19648921" FT /id="VAR_059068" FT VARIANT 119 FT /note="R -> H (in ARCL2B; dbSNP:rs121918377)" FT /evidence="ECO:0000269|PubMed:19648921" FT /id="VAR_059069" FT VARIANT 179 FT /note="A -> T (in ARCL2B; dbSNP:rs139751598)" FT /evidence="ECO:0000269|PubMed:19648921" FT /id="VAR_059070" FT VARIANT 189 FT /note="A -> V" FT /evidence="ECO:0000269|PubMed:19648921" FT /id="VAR_059071" FT VARIANT 206 FT /note="G -> R (in ARCL2B; dbSNP:rs121918375)" FT /evidence="ECO:0000269|PubMed:19648921" FT /id="VAR_059072" FT VARIANT 206 FT /note="G -> W (in ARCL2B; dbSNP:rs121918375)" FT /evidence="ECO:0000269|PubMed:19648921" FT /id="VAR_059073" FT VARIANT 248 FT /note="G -> E (in ARCL3B; results in a reduction of protein FT expression in skin fibroblasts from the patient; FT dbSNP:rs281875319)" FT /evidence="ECO:0000269|PubMed:22052856" FT /id="VAR_067600" FT VARIANT 251 FT /note="R -> H (in ARCL3B; dbSNP:rs121918378)" FT /evidence="ECO:0000269|PubMed:19648921" FT /id="VAR_059074" FT VARIANT 257 FT /note="A -> T (in ARCL3B; dbSNP:rs281875318)" FT /evidence="ECO:0000269|PubMed:19648921" FT /id="VAR_059075" FT VARIANT 266 FT /note="R -> Q (in ARCL2B; may cause skipping of exon 6; FT dbSNP:rs121918374)" FT /evidence="ECO:0000269|PubMed:19576563" FT /id="VAR_059076" FT VARIANT 297 FT /note="G -> R" FT /evidence="ECO:0000269|PubMed:22052856" FT /id="VAR_067601" FT MUTAGEN 221 FT /note="E->A: Reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:16730026" FT CONFLICT 155 FT /note="S -> T (in Ref. 1; AAA36407)" FT /evidence="ECO:0000305" FT CONFLICT 317 FT /note="G -> S (in Ref. 4; CAG46568)" FT /evidence="ECO:0000305" FT STRAND 3..6 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 10..21 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 27..29 FT /evidence="ECO:0007829|PDB:6XP1" FT STRAND 30..32 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 40..48 FT /evidence="ECO:0007829|PDB:6XP1" FT STRAND 51..54 FT /evidence="ECO:0007829|PDB:5UAV" FT HELIX 56..61 FT /evidence="ECO:0007829|PDB:6XP1" FT STRAND 64..68 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 72..74 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 75..82 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 83..85 FT /evidence="ECO:0007829|PDB:6XP1" FT STRAND 91..94 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 101..109 FT /evidence="ECO:0007829|PDB:6XP1" FT STRAND 112..114 FT /evidence="ECO:0007829|PDB:5UAW" FT STRAND 116..121 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 124..128 FT /evidence="ECO:0007829|PDB:6XP1" FT STRAND 131..137 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 143..154 FT /evidence="ECO:0007829|PDB:6XP1" FT STRAND 157..161 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 164..166 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 167..173 FT /evidence="ECO:0007829|PDB:6XP1" FT TURN 174..176 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 177..194 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 199..218 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 224..231 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 237..247 FT /evidence="ECO:0007829|PDB:6XP1" FT HELIX 250..271 FT /evidence="ECO:0007829|PDB:6XP1" SQ SEQUENCE 319 AA; 33361 MW; 9E8C4DED0638EFC5 CRC64; MSVGFIGAGQ LAFALAKGFT AAGVLAAHKI MASSPDMDLA TVSALRKMGV KLTPHNKETV QHSDVLFLAV KPHIIPFILD EIGADIEDRH IVVSCAAGVT ISSIEKKLSA FRPAPRVIRC MTNTPVVVRE GATVYATGTH AQVEDGRLME QLLSSVGFCT EVEEDLIDAV TGLSGSGPAY AFTALDALAD GGVKMGLPRR LAVRLGAQAL LGAAKMLLHS EQHPGQLKDN VSSPGGATIH ALHVLESGGF RSLLINAVEA SCIRTRELQS MADQEQVSPA AIKKTILDKV KLDSPAGTAL SPSGHTKLLP RSLAPAGKD //