P5CR3_HUMAN
ID P5CR3_HUMAN Reviewed; 274 AA.
AC Q53H96; B3KMB5; B4DVT6; H0Y6C3; Q8N3N9; Q96HX4; Q9H896;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-NOV-2014, sequence version 3.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Pyrroline-5-carboxylate reductase 3 {ECO:0000312|HGNC:HGNC:25846};
DE Short=P5C reductase 3;
DE Short=P5CR 3;
DE EC=1.5.1.2 {ECO:0000269|PubMed:23024808};
DE AltName: Full=Pyrroline-5-carboxylate reductase-like protein;
GN Name=PYCR3 {ECO:0000312|HGNC:HGNC:25846};
GN Synonyms=PYCRL {ECO:0000312|HGNC:HGNC:25846};
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Spleen, and Thyroid;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASN-150.
RC TISSUE=Lung;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-264 (ISOFORM 1), AND VARIANT
RP ASN-150.
RC TISSUE=Brain;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 31-274 (ISOFORM 1), AND VARIANT
RP ASN-150.
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
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 [7]
RP SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY,
RP FUNCTION, AND ACTIVITY REGULATION.
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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Enzyme that catalyzes the last step in proline biosynthesis.
CC Proline is synthesized from either glutamate or ornithine; both are
CC converted to pyrroline-5-carboxylate (P5C), and then to proline via
CC pyrroline-5-carboxylate reductases (PYCRs). PYCRL is exclusively linked
CC to the conversion of ornithine to proline.
CC {ECO:0000269|PubMed:23024808}.
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:23024808};
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:23024808};
CC -!- ACTIVITY REGULATION: Not inhibited by proline.
CC {ECO:0000269|PubMed:23024808}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.42 mM for NADH {ECO:0000269|PubMed:23024808};
CC KM=0.37 mM for NADPH {ECO:0000269|PubMed:23024808};
CC KM=4.64 mM for pyrroline-5-carboxylate (in the presence of NADH)
CC {ECO:0000269|PubMed:23024808};
CC KM=0.38 mM for pyrroline-5-carboxylate (in the presence of NADPH)
CC {ECO:0000269|PubMed:23024808};
CC Note=kcat is 197 sec(-1) for the NADH-dependent reduction of
CC pyrroline-5-carboxylate. kcat is 35 sec(-1) for the NADPH-dependent
CC reduction of pyrroline-5-carboxylate. {ECO:0000269|PubMed:23024808};
CC -!- PATHWAY: Amino-acid biosynthesis; L-proline biosynthesis; L-proline
CC from L-glutamate 5-semialdehyde: step 1/1.
CC {ECO:0000269|PubMed:23024808}.
CC -!- SUBUNIT: Homodecamer; composed of 5 homodimers.
CC {ECO:0000250|UniProtKB:P32322}.
CC -!- INTERACTION:
CC Q53H96; O95429: BAG4; NbExp=3; IntAct=EBI-2959680, EBI-2949658;
CC Q53H96; P42772: CDKN2B; NbExp=3; IntAct=EBI-2959680, EBI-711280;
CC Q53H96; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-2959680, EBI-741158;
CC Q53H96; P20618: PSMB1; NbExp=3; IntAct=EBI-2959680, EBI-372273;
CC Q53H96; O00560: SDCBP; NbExp=8; IntAct=EBI-2959680, EBI-727004;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23024808}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q53H96-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q53H96-2; Sequence=VSP_057219;
CC -!- SIMILARITY: Belongs to the pyrroline-5-carboxylate reductase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD96405.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD96405.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={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; AK001500; BAG50927.1; -; mRNA.
DR EMBL; AK023914; BAB14721.1; -; mRNA.
DR EMBL; AK301225; BAG62798.1; -; mRNA.
DR EMBL; AC067930; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007993; AAH07993.1; -; mRNA.
DR EMBL; AK222685; BAD96405.1; ALT_SEQ; mRNA.
DR EMBL; AL833857; CAD38716.1; -; mRNA.
DR CCDS; CCDS6407.2; -. [Q53H96-1]
DR RefSeq; NP_001316795.1; NM_001329866.1. [Q53H96-2]
DR RefSeq; NP_075566.2; NM_023078.4. [Q53H96-1]
DR AlphaFoldDB; Q53H96; -.
DR SMR; Q53H96; -.
DR BioGRID; 122418; 115.
DR IntAct; Q53H96; 25.
DR MINT; Q53H96; -.
DR STRING; 9606.ENSP00000220966; -.
DR DrugBank; DB00172; Proline.
DR iPTMnet; Q53H96; -.
DR PhosphoSitePlus; Q53H96; -.
DR BioMuta; PYCR3; -.
DR DMDM; 172046829; -.
DR EPD; Q53H96; -.
DR jPOST; Q53H96; -.
DR MassIVE; Q53H96; -.
DR MaxQB; Q53H96; -.
DR PaxDb; Q53H96; -.
DR PeptideAtlas; Q53H96; -.
DR PRIDE; Q53H96; -.
DR ProteomicsDB; 35179; -.
DR ProteomicsDB; 62502; -. [Q53H96-1]
DR Antibodypedia; 28003; 207 antibodies from 20 providers.
DR DNASU; 65263; -.
DR Ensembl; ENST00000433751.5; ENSP00000404493.2; ENSG00000104524.14. [Q53H96-2]
DR Ensembl; ENST00000495276.6; ENSP00000480945.1; ENSG00000104524.14. [Q53H96-1]
DR Ensembl; ENST00000631620.1; ENSP00000488877.1; ENSG00000276657.2. [Q53H96-2]
DR Ensembl; ENST00000632107.1; ENSP00000488371.1; ENSG00000276657.2. [Q53H96-1]
DR GeneID; 65263; -.
DR KEGG; hsa:65263; -.
DR MANE-Select; ENST00000495276.6; ENSP00000480945.1; NM_023078.6; NP_075566.3.
DR UCSC; uc064rcg.1; human. [Q53H96-1]
DR CTD; 65263; -.
DR DisGeNET; 65263; -.
DR GeneCards; PYCR3; -.
DR HGNC; HGNC:25846; PYCR3.
DR HPA; ENSG00000104524; Low tissue specificity.
DR MIM; 616408; gene.
DR neXtProt; NX_Q53H96; -.
DR OpenTargets; ENSG00000104524; -.
DR PharmGKB; PA134889043; -.
DR VEuPathDB; HostDB:ENSG00000104524; -.
DR eggNOG; KOG3124; Eukaryota.
DR GeneTree; ENSGT00950000183044; -.
DR HOGENOM; CLU_042344_3_0_1; -.
DR InParanoid; Q53H96; -.
DR OrthoDB; 952695at2759; -.
DR PathwayCommons; Q53H96; -.
DR Reactome; R-HSA-8964539; Glutamate and glutamine metabolism.
DR SignaLink; Q53H96; -.
DR UniPathway; UPA00098; UER00361.
DR BioGRID-ORCS; 65263; 15 hits in 1076 CRISPR screens.
DR ChiTaRS; PYCRL; human.
DR GenomeRNAi; 65263; -.
DR Pharos; Q53H96; Tbio.
DR PRO; PR:Q53H96; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q53H96; protein.
DR Bgee; ENSG00000104524; Expressed in prefrontal cortex and 95 other tissues.
DR ExpressionAtlas; Q53H96; baseline and differential.
DR Genevisible; Q53H96; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0072686; C:mitotic spindle; IDA:HPA.
DR GO; GO:0004735; F:pyrroline-5-carboxylate reductase activity; IDA:UniProtKB.
DR GO; GO:0055129; P:L-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 Acetylation; Alternative splicing; Amino-acid biosynthesis; Cytoplasm;
KW NADP; Oxidoreductase; Proline biosynthesis; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..274
FT /note="Pyrroline-5-carboxylate reductase 3"
FT /id="PRO_0000324561"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 113..132
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057219"
FT VARIANT 57
FT /note="R -> Q (in dbSNP:rs11549789)"
FT /id="VAR_039828"
FT VARIANT 105
FT /note="V -> M (in dbSNP:rs2242089)"
FT /id="VAR_039829"
FT VARIANT 150
FT /note="K -> N (in dbSNP:rs2242090)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005, ECO:0000269|Ref.4"
FT /id="VAR_039830"
SQ SEQUENCE 274 AA; 28663 MW; 846FDEC603F3B548 CRC64;
MAAAEPSPRR VGFVGAGRMA GAIAQGLIRA GKVEAQHILA SAPTDRNLCH FQALGCRTTH
SNQEVLQSCL LVIFATKPHV LPAVLAEVAP VVTTEHILVS VAAGVSLSTL EELLPPNTRV
LRVLPNLPCV VQEGAIVMAR GRHVGSSETK LLQHLLEACG RCEEVPEAYV DIHTGLSGSG
VAFVCAFSEA LAEGAVKMGM PSSLAHRIAA QTLLGTAKML LHEGQHPAQL RSDVCTPGGT
TIYGLHALEQ GGLRAATMSA VEAATCRAKE LSRK
