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Protein

Pyrroline-5-carboxylate reductase 1, mitochondrial

Gene

PYCR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Housekeeping enzyme that catalyzes the last step in proline biosynthesis. Can utilize both NAD and NADP, but has higher affinity for NAD. Involved in the cellular response to oxidative stress.2 Publications

Catalytic activityi

L-proline + NAD(P)+ = 1-pyrroline-5-carboxylate + NAD(P)H.1 Publication

Enzyme regulationi

Subject to competitive inhibition by the reaction product proline. Subject to competitive inhibition by stearoyl coenzyme A.1 Publication

Kineticsi

  1. KM=0.151 mM for NAD+1 Publication
  2. KM=3.06 mM for NADP+1 Publication

    Pathwayi: L-proline biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes L-proline from L-glutamate 5-semialdehyde.
    Proteins known to be involved in this subpathway in this organism are:
    1. Pyrroline-5-carboxylate reductase, Pyrroline-5-carboxylate reductase (P5CR2), Pyrroline-5-carboxylate reductase (PYCR2), Pyrroline-5-carboxylate reductase (PYCR1), Pyrroline-5-carboxylate reductase (PYCR3), Pyrroline-5-carboxylate reductase 3 (PYCR3), Pyrroline-5-carboxylate reductase 2 (PYCR2), Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1), Pyrroline-5-carboxylate reductase (PYCR1), Pyrroline-5-carboxylate reductase (PYCR2), Pyrroline-5-carboxylate reductase (PYCRL), Pyrroline-5-carboxylate reductase (PYCR2), Pyrroline-5-carboxylate reductase (PYCR1), Pyrroline-5-carboxylate reductase (PYCR1), Pyrroline-5-carboxylate reductase
    This subpathway is part of the pathway L-proline biosynthesis, which is itself part of Amino-acid biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-proline from L-glutamate 5-semialdehyde, the pathway L-proline biosynthesis and in Amino-acid biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei34NADP; via carbonyl oxygen1 Publication1
    Binding sitei56NADP1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi6 – 11NADP1 Publication6
    Nucleotide bindingi69 – 72NADP1 Publication4
    Nucleotide bindingi95 – 97NADP1 Publication3

    GO - Molecular functioni

    • identical protein binding Source: IntAct
    • pyrroline-5-carboxylate reductase activity Source: UniProtKB

    GO - Biological processi

    • cellular amino acid biosynthetic process Source: Reactome
    • cellular response to oxidative stress Source: UniProtKB
    • L-proline biosynthetic process Source: UniProtKB-UniPathway
    • negative regulation of hydrogen peroxide-induced cell death Source: ParkinsonsUK-UCL
    • proline biosynthetic process Source: UniProtKB
    • regulation of mitochondrial membrane potential Source: ParkinsonsUK-UCL

    Keywordsi

    Molecular functionOxidoreductase
    Biological processAmino-acid biosynthesis, Proline biosynthesis, Stress response
    LigandNADP

    Enzyme and pathway databases

    BioCyciMetaCyc:HS06848-MONOMER
    BRENDAi1.5.1.2 2681
    ReactomeiR-HSA-70614 Amino acid synthesis and interconversion (transamination)
    SABIO-RKiP32322
    UniPathwayiUPA00098; UER00361

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pyrroline-5-carboxylate reductase 1, mitochondrial (EC:1.5.1.2)
    Short name:
    P5C reductase 1
    Short name:
    P5CR 1
    Gene namesi
    Name:PYCR1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 17

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000183010.16
    HGNCiHGNC:9721 PYCR1
    MIMi179035 gene
    neXtProtiNX_P32322

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    Cutis laxa, autosomal recessive, 2B (ARCL2B)2 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, a general connective tissue weakness, and varying degrees of growth and developmental delay and neurological abnormalities. Patients do not manifest metabolic abnormalities.
    See also OMIM:612940
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_059068119R → G in ARCL2B. 1 PublicationCorresponds to variant dbSNP:rs121918376EnsemblClinVar.1
    Natural variantiVAR_059069119R → H in ARCL2B. 1 PublicationCorresponds to variant dbSNP:rs121918377EnsemblClinVar.1
    Natural variantiVAR_059070179A → T in ARCL2B. 1 PublicationCorresponds to variant dbSNP:rs139751598EnsemblClinVar.1
    Natural variantiVAR_059072206G → R in ARCL2B. 1 PublicationCorresponds to variant dbSNP:rs121918375EnsemblClinVar.1
    Natural variantiVAR_059073206G → W in ARCL2B. 1 PublicationCorresponds to variant dbSNP:rs121918375EnsemblClinVar.1
    Natural variantiVAR_059076266R → Q in ARCL2B; may cause skipping of exon 6. 1 PublicationCorresponds to variant dbSNP:rs121918374EnsemblClinVar.1
    Cutis laxa, autosomal recessive, 3B (ARCL3B)2 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA disorder characterized by an aged appearance with distinctive facial features, sparse hair, ophthalmologic abnormalities, intrauterine growth retardation, and cutis laxa.
    See also OMIM:614438
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_067600248G → E in ARCL3B; results in a reduction of protein expression in skin fibroblasts from the patient. 1 PublicationCorresponds to variant dbSNP:rs281875319EnsemblClinVar.1
    Natural variantiVAR_059074251R → H in ARCL3B. 1 PublicationCorresponds to variant dbSNP:rs121918378EnsemblClinVar.1
    Natural variantiVAR_059075257A → T in ARCL3B. 1 PublicationCorresponds to variant dbSNP:rs281875318EnsemblClinVar.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi221E → A: Reduced enzyme activity. 1 Publication1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi5831
    MalaCardsiPYCR1
    MIMi612940 phenotype
    614438 phenotype
    OpenTargetsiENSG00000183010
    Orphaneti357064 Autosomal recessive cutis laxa type 2B
    2078 Geroderma osteodysplastica
    293633 PYCR1-related De Barsy syndrome
    PharmGKBiPA34064

    Chemistry databases

    DrugBankiDB00172 L-Proline
    DB00157 NADH

    Polymorphism and mutation databases

    BioMutaiPYCR1
    DMDMi60416434

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedCombined sources2 Publications
    ChainiPRO_00001873142 – 319Pyrroline-5-carboxylate reductase 1, mitochondrialAdd BLAST318

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylserineCombined sources2 Publications1
    Modified residuei278PhosphoserineCombined sources1
    Modified residuei301PhosphoserineCombined sources1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiP32322
    MaxQBiP32322
    PaxDbiP32322
    PeptideAtlasiP32322
    PRIDEiP32322
    ProteomicsDBi54872
    TopDownProteomicsiP32322-1 [P32322-1]

    PTM databases

    iPTMnetiP32322
    PhosphoSitePlusiP32322
    SwissPalmiP32322

    Expressioni

    Gene expression databases

    BgeeiENSG00000183010
    CleanExiHS_PYCR1
    ExpressionAtlasiP32322 baseline and differential
    GenevisibleiP32322 HS

    Organism-specific databases

    HPAiHPA047660

    Interactioni

    Subunit structurei

    Homodecamer; composed of 5 homodimers.2 Publications

    Binary interactionsi

    Show more details

    GO - Molecular functioni

    • identical protein binding Source: IntAct

    Protein-protein interaction databases

    BioGridi111789, 33 interactors
    ComplexPortaliCPX-2085 Pyrroline-5-carboxylate reductase 1 complex
    IntActiP32322, 31 interactors
    MINTiP32322
    STRINGi9606.ENSP00000328858

    Structurei

    Secondary structure

    1319
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi3 – 7Combined sources5
    Helixi10 – 21Combined sources12
    Helixi27 – 29Combined sources3
    Beta strandi30 – 33Combined sources4
    Helixi40 – 48Combined sources9
    Beta strandi51 – 54Combined sources4
    Helixi56 – 62Combined sources7
    Beta strandi64 – 68Combined sources5
    Helixi72 – 74Combined sources3
    Helixi75 – 82Combined sources8
    Helixi83 – 85Combined sources3
    Beta strandi91 – 94Combined sources4
    Helixi101 – 109Combined sources9
    Beta strandi112 – 114Combined sources3
    Beta strandi116 – 121Combined sources6
    Helixi124 – 128Combined sources5
    Beta strandi131 – 137Combined sources7
    Helixi143 – 154Combined sources12
    Beta strandi157 – 161Combined sources5
    Helixi164 – 166Combined sources3
    Helixi167 – 173Combined sources7
    Turni174 – 176Combined sources3
    Helixi177 – 194Combined sources18
    Helixi199 – 218Combined sources20
    Helixi224 – 230Combined sources7
    Helixi237 – 247Combined sources11
    Helixi250 – 273Combined sources24

    3D structure databases

    ProteinModelPortaliP32322
    SMRiP32322
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP32322

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG3124 Eukaryota
    COG0345 LUCA
    GeneTreeiENSGT00390000007443
    HOGENOMiHOG000230247
    HOVERGENiHBG053399
    InParanoidiP32322
    KOiK00286
    OMAiRVMTNTP
    OrthoDBiEOG091G0KMI
    PhylomeDBiP32322

    Family and domain databases

    HAMAPiMF_01925 P5C_reductase, 1 hit
    InterProiView protein in InterPro
    IPR008927 6-PGluconate_DH-like_C_sf
    IPR036291 NAD(P)-bd_dom_sf
    IPR028939 P5C_Rdtase_cat_N
    IPR029036 P5CR_dimer
    IPR000304 Pyrroline-COOH_reductase
    PfamiView protein in Pfam
    PF03807 F420_oxidored, 1 hit
    PF14748 P5CR_dimer, 1 hit
    PIRSFiPIRSF000193 Pyrrol-5-carb_rd, 1 hit
    SUPFAMiSSF48179 SSF48179, 1 hit
    SSF51735 SSF51735, 1 hit
    TIGRFAMsiTIGR00112 proC, 1 hit
    PROSITEiView protein in PROSITE
    PS00521 P5CR, 1 hit

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P32322-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MSVGFIGAGQ LAFALAKGFT AAGVLAAHKI MASSPDMDLA TVSALRKMGV
    60 70 80 90 100
    KLTPHNKETV QHSDVLFLAV KPHIIPFILD EIGADIEDRH IVVSCAAGVT
    110 120 130 140 150
    ISSIEKKLSA FRPAPRVIRC MTNTPVVVRE GATVYATGTH AQVEDGRLME
    160 170 180 190 200
    QLLSSVGFCT EVEEDLIDAV TGLSGSGPAY AFTALDALAD GGVKMGLPRR
    210 220 230 240 250
    LAVRLGAQAL LGAAKMLLHS EQHPGQLKDN VSSPGGATIH ALHVLESGGF
    260 270 280 290 300
    RSLLINAVEA SCIRTRELQS MADQEQVSPA AIKKTILDKV KLDSPAGTAL
    310
    SPSGHTKLLP RSLAPAGKD
    Length:319
    Mass (Da):33,361
    Last modified:March 1, 2005 - v2
    Checksum:i9E8C4DED0638EFC5
    GO
    Isoform 2 (identifier: P32322-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         290-319: VKLDSPAGTALSPSGHTKLLPRSLAPAGKD → DHLPLELGSPEGLHPLLLQYQLARAPS

    Show »
    Length:316
    Mass (Da):33,341
    Checksum:i65C247E391225ED6
    GO
    Isoform 3 (identifier: P32322-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MVGGGRRVGRDEPVPSVGALGQGSPDSM

    Note: No experimental confirmation available.
    Show »
    Length:346
    Mass (Da):35,981
    Checksum:i25E6A7FEBBB34A3E
    GO

    Sequence cautioni

    The sequence AAG17242 differs from that shown. Reason: Frameshift at position 214.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti155S → T in AAA36407 (PubMed:1730675).Curated1
    Sequence conflicti317G → S in CAG46568 (Ref. 4) Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_059068119R → G in ARCL2B. 1 PublicationCorresponds to variant dbSNP:rs121918376EnsemblClinVar.1
    Natural variantiVAR_059069119R → H in ARCL2B. 1 PublicationCorresponds to variant dbSNP:rs121918377EnsemblClinVar.1
    Natural variantiVAR_059070179A → T in ARCL2B. 1 PublicationCorresponds to variant dbSNP:rs139751598EnsemblClinVar.1
    Natural variantiVAR_059071189A → V1 Publication1
    Natural variantiVAR_059072206G → R in ARCL2B. 1 PublicationCorresponds to variant dbSNP:rs121918375EnsemblClinVar.1
    Natural variantiVAR_059073206G → W in ARCL2B. 1 PublicationCorresponds to variant dbSNP:rs121918375EnsemblClinVar.1
    Natural variantiVAR_067600248G → E in ARCL3B; results in a reduction of protein expression in skin fibroblasts from the patient. 1 PublicationCorresponds to variant dbSNP:rs281875319EnsemblClinVar.1
    Natural variantiVAR_059074251R → H in ARCL3B. 1 PublicationCorresponds to variant dbSNP:rs121918378EnsemblClinVar.1
    Natural variantiVAR_059075257A → T in ARCL3B. 1 PublicationCorresponds to variant dbSNP:rs281875318EnsemblClinVar.1
    Natural variantiVAR_059076266R → Q in ARCL2B; may cause skipping of exon 6. 1 PublicationCorresponds to variant dbSNP:rs121918374EnsemblClinVar.1
    Natural variantiVAR_067601297G → R1 Publication1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0546161M → MVGGGRRVGRDEPVPSVGAL GQGSPDSM in isoform 3. 1 Publication1
    Alternative sequenceiVSP_044507290 – 319VKLDS…PAGKD → DHLPLELGSPEGLHPLLLQY QLARAPS in isoform 2. 1 PublicationAdd BLAST30

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M77836 mRNA Translation: AAA36407.1
    AF218000 mRNA Translation: AAG17242.1 Frameshift.
    AK297627 mRNA Translation: BAG60002.1
    CR541769 mRNA Translation: CAG46568.1
    AC145207 Genomic DNA No translation available.
    CH471099 Genomic DNA Translation: EAW89724.1
    BC001504 mRNA Translation: AAH01504.1
    BC071842 mRNA Translation: AAH71842.1
    CCDSiCCDS11794.1 [P32322-2]
    CCDS11795.1 [P32322-1]
    CCDS62366.1 [P32322-3]
    PIRiA41770
    RefSeqiNP_001269209.1, NM_001282280.1 [P32322-1]
    NP_001269210.1, NM_001282281.1 [P32322-3]
    NP_008838.2, NM_006907.3 [P32322-1]
    NP_722546.1, NM_153824.2 [P32322-2]
    XP_005256438.1, XM_005256381.2 [P32322-1]
    XP_011521885.1, XM_011523583.2 [P32322-1]
    XP_011521886.1, XM_011523584.2 [P32322-1]
    UniGeneiHs.163451

    Genome annotation databases

    EnsembliENST00000329875; ENSP00000328858; ENSG00000183010 [P32322-1]
    ENST00000337943; ENSP00000336579; ENSG00000183010 [P32322-2]
    ENST00000402252; ENSP00000384949; ENSG00000183010 [P32322-3]
    ENST00000619204; ENSP00000479793; ENSG00000183010 [P32322-1]
    GeneIDi5831
    KEGGihsa:5831
    UCSCiuc002kcp.5 human [P32322-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiP5CR1_HUMAN
    AccessioniPrimary (citable) accession number: P32322
    Secondary accession number(s): A6NFM2
    , B4DMU0, Q6FHI4, Q96DI6, Q9HBQ4
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1993
    Last sequence update: March 1, 2005
    Last modified: June 20, 2018
    This is version 175 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

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