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Protein

Pyrroline-5-carboxylate reductase 2

Gene

PYCR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Housekeeping enzyme that catalyzes the last step in proline biosynthesis. In some cell types, such as erythrocytes, its primary function may be the generation of NADP+. Can utilize both NAD and NADP. Has higher affinity for NADP, but higher catalytic efficiency with NADH (PubMed:2722838, PubMed:6894153). Involved in cellular response to oxidative stress (PubMed:25865492).3 Publications

Catalytic activityi

L-proline + NAD(P)+ = 1-pyrroline-5-carboxylate + NAD(P)H.2 Publications

Enzyme regulationi

Subject to competitive inhibition by NADP. Not inhibited by proline.2 Publications

Kineticsi

  1. KM=0.64 mM for NADH1 Publication
  2. KM=0.04 mM for NADPH1 Publication
  3. KM=1.49 mM for pyrroline-5-carboxylate (in the presence of NADH)1 Publication
  4. KM=0.23 mM for pyrroline-5-carboxylate (in the presence of NADPH)1 Publication
  1. Vmax=28.5 µmol/min/µg enzyme (in the presence of NADH)1 Publication
  2. Vmax=3.7 µmol/min/µg enzyme (in the presence of NADPH)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 (PYCRL), Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1), Pyrroline-5-carboxylate reductase 3 (PYCRL), Pyrroline-5-carboxylate reductase 2 (PYCR2), 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei34 – 341NADP; via carbonyl oxygenBy similarity
Binding sitei56 – 561NADPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi6 – 116NADPBy similarity
Nucleotide bindingi69 – 724NADPBy similarity
Nucleotide bindingi95 – 973NADPBy similarity

GO - Molecular functioni

GO - Biological processi

  • cellular amino acid biosynthetic process Source: Reactome
  • cellular response to oxidative stress Source: UniProtKB
  • L-proline biosynthetic process Source: UniProtKB-UniPathway
  • proline biosynthetic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Amino-acid biosynthesis, Proline biosynthesis

Keywords - Ligandi

NADP

Enzyme and pathway databases

ReactomeiR-HSA-70614. Amino acid synthesis and interconversion (transamination).
SABIO-RKQ96C36.
UniPathwayiUPA00098; UER00361.

Names & Taxonomyi

Protein namesi
Recommended name:
Pyrroline-5-carboxylate reductase 2 (EC:1.5.1.2)
Short name:
P5C reductase 2
Short name:
P5CR 2
Gene namesi
Name:PYCR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:30262. PYCR2.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Leukodystrophy, hypomyelinating, 10 (HLD10)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive neurologic disorder characterized by postnatal microcephaly, severely delayed psychomotor development, hypomyelination, and reduced cerebral white-matter volume.
See also OMIM:616420
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti119 – 1191R → C in HLD10; severe decrease of protein amount; does not affect mitochondrial localization. 1 Publication
Corresponds to variant rs372781135 [ dbSNP | Ensembl ].
VAR_074608
Natural varianti251 – 2511R → C in HLD10; mild decrease of homodimerization; does not affect mitochondrial localization. 1 Publication
VAR_074609

Keywords - Diseasei

Disease mutation, Leukodystrophy

Organism-specific databases

MIMi616420. phenotype.
PharmGKBiPA134881955.

Chemistry

DrugBankiDB00172. L-Proline.

Polymorphism and mutation databases

DMDMi60390642.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved1 Publication
Chaini2 – 320319Pyrroline-5-carboxylate reductase 2PRO_0000187317Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine1 Publication
Modified residuei304 – 3041PhosphoserineCombined sources

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ96C36.
MaxQBiQ96C36.
PaxDbiQ96C36.
PeptideAtlasiQ96C36.
PRIDEiQ96C36.
TopDownProteomicsiQ96C36.

PTM databases

iPTMnetiQ96C36.
PhosphoSiteiQ96C36.
SwissPalmiQ96C36.

Expressioni

Tissue specificityi

Detected in erythrocytes (at protein level) (PubMed:2722838, PubMed:6894153). Expressed in fetal brain (PubMed:25865492).3 Publications

Gene expression databases

BgeeiENSG00000143811.
CleanExiHS_PYCR2.
ExpressionAtlasiQ96C36. baseline and differential.
GenevisibleiQ96C36. HS.

Organism-specific databases

HPAiHPA056873.

Interactioni

Subunit structurei

Homodecamer; composed of 5 homodimers.1 Publication

Protein-protein interaction databases

BioGridi118962. 32 interactions.
IntActiQ96C36. 19 interactions.
MINTiMINT-1150827.
STRINGi9606.ENSP00000342502.

Structurei

3D structure databases

ProteinModelPortaliQ96C36.
SMRiQ96C36. Positions 1-275.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3124. Eukaryota.
COG0345. LUCA.
GeneTreeiENSGT00390000007443.
HOGENOMiHOG000230247.
HOVERGENiHBG053399.
InParanoidiQ96C36.
KOiK00286.
OMAiFITVKPW.
OrthoDBiEOG091G0KMI.
PhylomeDBiQ96C36.

Family and domain databases

Gene3Di1.10.3730.10. 1 hit.
3.40.50.720. 1 hit.
HAMAPiMF_01925. P5C_reductase. 1 hit.
InterProiIPR008927. 6-PGluconate_DH_C-like.
IPR016040. NAD(P)-bd_dom.
IPR029036. P5CR_dimer.
IPR028939. ProC_N.
IPR000304. Pyrroline-COOH_reductase.
[Graphical view]
PANTHERiPTHR11645. PTHR11645. 1 hit.
PfamiPF03807. F420_oxidored. 1 hit.
PF14748. P5CR_dimer. 1 hit.
[Graphical view]
PIRSFiPIRSF000193. Pyrrol-5-carb_rd. 1 hit.
SUPFAMiSSF48179. SSF48179. 1 hit.
SSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR00112. proC. 1 hit.
PROSITEiPS00521. P5CR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q96C36-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSVGFIGAGQ LAYALARGFT AAGILSAHKI IASSPEMNLP TVSALRKMGV
60 70 80 90 100
NLTRSNKETV KHSDVLFLAV KPHIIPFILD EIGADVQARH IVVSCAAGVT
110 120 130 140 150
ISSVEKKLMA FQPAPKVIRC MTNTPVVVQE GATVYATGTH ALVEDGQLLE
160 170 180 190 200
QLMSSVGFCT EVEEDLIDAV TGLSGSGPAY AFMALDALAD GGVKMGLPRR
210 220 230 240 250
LAIQLGAQAL LGAAKMLLDS EQHPCQLKDN VCSPGGATIH ALHFLESGGF
260 270 280 290 300
RSLLINAVEA SCIRTRELQS MADQEKISPA ALKKTLLDRV KLESPTVSTL
310 320
TPSSPGKLLT RSLALGGKKD
Length:320
Mass (Da):33,637
Last modified:December 1, 2001 - v1
Checksum:i9348455A64CCE722
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti13 – 131Y → N in AAP97169 (Ref. 1) Curated
Sequence conflicti23 – 242GI → AF in AAP97169 (Ref. 1) Curated
Sequence conflicti72 – 732PH → HI in AAP97169 (Ref. 1) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti119 – 1191R → C in HLD10; severe decrease of protein amount; does not affect mitochondrial localization. 1 Publication
Corresponds to variant rs372781135 [ dbSNP | Ensembl ].
VAR_074608
Natural varianti251 – 2511R → C in HLD10; mild decrease of homodimerization; does not affect mitochondrial localization. 1 Publication
VAR_074609

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF087859 mRNA. Translation: AAP97169.1.
AK291913 mRNA. Translation: BAF84602.1.
AL117348 Genomic DNA. Translation: CAI21802.1.
CH471098 Genomic DNA. Translation: EAW69762.1.
BC014868 mRNA. Translation: AAH14868.1.
BC020553 mRNA. Translation: AAH20553.1.
CCDSiCCDS31043.1.
RefSeqiNP_001258610.1. NM_001271681.1.
NP_037460.2. NM_013328.3.
UniGeneiHs.654718.

Genome annotation databases

EnsembliENST00000343818; ENSP00000342502; ENSG00000143811.
GeneIDi29920.
KEGGihsa:29920.
UCSCiuc001hpq.5. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF087859 mRNA. Translation: AAP97169.1.
AK291913 mRNA. Translation: BAF84602.1.
AL117348 Genomic DNA. Translation: CAI21802.1.
CH471098 Genomic DNA. Translation: EAW69762.1.
BC014868 mRNA. Translation: AAH14868.1.
BC020553 mRNA. Translation: AAH20553.1.
CCDSiCCDS31043.1.
RefSeqiNP_001258610.1. NM_001271681.1.
NP_037460.2. NM_013328.3.
UniGeneiHs.654718.

3D structure databases

ProteinModelPortaliQ96C36.
SMRiQ96C36. Positions 1-275.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118962. 32 interactions.
IntActiQ96C36. 19 interactions.
MINTiMINT-1150827.
STRINGi9606.ENSP00000342502.

Chemistry

DrugBankiDB00172. L-Proline.

PTM databases

iPTMnetiQ96C36.
PhosphoSiteiQ96C36.
SwissPalmiQ96C36.

Polymorphism and mutation databases

DMDMi60390642.

Proteomic databases

EPDiQ96C36.
MaxQBiQ96C36.
PaxDbiQ96C36.
PeptideAtlasiQ96C36.
PRIDEiQ96C36.
TopDownProteomicsiQ96C36.

Protocols and materials databases

DNASUi29920.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000343818; ENSP00000342502; ENSG00000143811.
GeneIDi29920.
KEGGihsa:29920.
UCSCiuc001hpq.5. human.

Organism-specific databases

CTDi29920.
GeneCardsiPYCR2.
H-InvDBHIX0200217.
HGNCiHGNC:30262. PYCR2.
HPAiHPA056873.
MIMi616406. gene.
616420. phenotype.
neXtProtiNX_Q96C36.
PharmGKBiPA134881955.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3124. Eukaryota.
COG0345. LUCA.
GeneTreeiENSGT00390000007443.
HOGENOMiHOG000230247.
HOVERGENiHBG053399.
InParanoidiQ96C36.
KOiK00286.
OMAiFITVKPW.
OrthoDBiEOG091G0KMI.
PhylomeDBiQ96C36.

Enzyme and pathway databases

UniPathwayiUPA00098; UER00361.
ReactomeiR-HSA-70614. Amino acid synthesis and interconversion (transamination).
SABIO-RKQ96C36.

Miscellaneous databases

GenomeRNAii29920.
PROiQ96C36.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000143811.
CleanExiHS_PYCR2.
ExpressionAtlasiQ96C36. baseline and differential.
GenevisibleiQ96C36. HS.

Family and domain databases

Gene3Di1.10.3730.10. 1 hit.
3.40.50.720. 1 hit.
HAMAPiMF_01925. P5C_reductase. 1 hit.
InterProiIPR008927. 6-PGluconate_DH_C-like.
IPR016040. NAD(P)-bd_dom.
IPR029036. P5CR_dimer.
IPR028939. ProC_N.
IPR000304. Pyrroline-COOH_reductase.
[Graphical view]
PANTHERiPTHR11645. PTHR11645. 1 hit.
PfamiPF03807. F420_oxidored. 1 hit.
PF14748. P5CR_dimer. 1 hit.
[Graphical view]
PIRSFiPIRSF000193. Pyrrol-5-carb_rd. 1 hit.
SUPFAMiSSF48179. SSF48179. 1 hit.
SSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR00112. proC. 1 hit.
PROSITEiPS00521. P5CR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiP5CR2_HUMAN
AccessioniPrimary (citable) accession number: Q96C36
Secondary accession number(s): A8K798, Q7Z515, Q9Y5J4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2005
Last sequence update: December 1, 2001
Last modified: September 7, 2016
This is version 129 of the entry and version 1 of the sequence. [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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.