P5CR1_HUMAN
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 03-AUG-2022, entry version 202.
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";
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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 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 AlphaFoldDB; P32322; -.
DR SMR; P32322; -.
DR BioGRID; 111789; 173.
DR ComplexPortal; CPX-2085; Pyrroline-5-carboxylate reductase 1 complex.
DR IntAct; P32322; 69.
DR MINT; P32322; -.
DR STRING; 9606.ENSP00000384949; -.
DR BindingDB; P32322; -.
DR ChEMBL; CHEMBL4296002; -.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB00172; Proline.
DR GlyGen; P32322; 1 site, 1 O-linked glycan (1 site).
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; P32322; -.
DR PeptideAtlas; P32322; -.
DR PRIDE; P32322; -.
DR ProteomicsDB; 1058; -.
DR ProteomicsDB; 4639; -.
DR ProteomicsDB; 54872; -. [P32322-1]
DR TopDownProteomics; P32322-1; -. [P32322-1]
DR Antibodypedia; 32938; 260 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 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; 952695at2759; -.
DR PhylomeDB; P32322; -.
DR BioCyc; MetaCyc:HS06848-MON; -.
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; 23 hits in 1080 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 148 other tissues.
DR ExpressionAtlas; P32322; baseline and differential.
DR Genevisible; P32322; HS.
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:1903206; P:negative regulation of hydrogen peroxide-induced cell death; 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 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; 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
