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Protein

Proline dehydrogenase 1, mitochondrial

Gene

PRODH

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

Functioni

Converts proline to delta-1-pyrroline-5-carboxylate.

Catalytic activityi

L-proline + a quinone = (S)-1-pyrroline-5-carboxylate + a quinol.1 Publication

Cofactori

FAD1 Publication

Pathwayi: L-proline degradation into L-glutamate

This protein is involved in step 1 of the subpathway that synthesizes L-glutamate from L-proline.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Proline dehydrogenase 1, mitochondrial (PRODH)
  2. Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial (ALDH4A1)
This subpathway is part of the pathway L-proline degradation into L-glutamate, which is itself part of Amino-acid degradation.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-glutamate from L-proline, the pathway L-proline degradation into L-glutamate and in Amino-acid degradation.

GO - Molecular functioni

  • FAD binding Source: UniProtKB
  • proline dehydrogenase activity Source: UniProtKB

GO - Biological processi

  • 4-hydroxyproline catabolic process Source: BHF-UCL
  • intrinsic apoptotic signaling pathway in response to oxidative stress Source: UniProtKB
  • positive regulation of cell death Source: ParkinsonsUK-UCL
  • proline catabolic process Source: Reactome
  • proline catabolic process to glutamate Source: GO_Central
  • proline metabolic process Source: ProtInc

Keywordsi

Molecular functionOxidoreductase
Biological processProline metabolism
LigandFAD, Flavoprotein

Enzyme and pathway databases

BioCyciMetaCyc:HS01958-MONOMER
BRENDAi1.5.99.B2 2681
ReactomeiR-HSA-70688 Proline catabolism
SIGNORiO43272
UniPathwayi
UPA00261;UER00373

Names & Taxonomyi

Protein namesi
Recommended name:
Proline dehydrogenase 1, mitochondrialCurated (EC:1.5.5.21 Publication)
Alternative name(s):
Proline oxidase
Proline oxidase 2
p53-induced gene 6 protein
Gene namesi
Name:PRODHImported
Synonyms:PIG6, POX2, PRODH21 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100033.16
HGNCiHGNC:9453 PRODH
MIMi606810 gene
neXtProtiNX_O43272

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

Hyperprolinemia 1 (HYRPRO1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn inborn error of proline metabolism resulting in elevated levels of proline in the plasma and urine. The disorder is generally benign and most affected individuals are clinically asymptomatic. Some patients, however, have neurologic manifestations, including epilepsy and mental retardation. Association with certain forms of schizophrenia have been reported.
See also OMIM:239500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029566289L → M in HYRPRO1; mild decrease of enzymatic activity. 2 Publications1
Natural variantiVAR_029568426D → N in HYRPRO1; moderate reduction of enzymatic activity. 1 Publication1
Natural variantiVAR_029570431R → H in HYRPRO1; moderate reduction of enzymatic activity. 3 PublicationsCorresponds to variant dbSNP:rs2904552EnsemblClinVar.1
Natural variantiVAR_029573455A → S in HYRPRO1; mild decrease of enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs1807467EnsemblClinVar.1
Schizophrenia 4 (SCZD4)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder.
See also OMIM:600850
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029567406P → L in SCZD4; may be associated with disease susceptibility; strongly reduced enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs3970555Ensembl.1
Natural variantiVAR_029574466T → M in SCZD4; may be associated with disease susceptibility; strongly reduced affinity for FAD; strongly reduced enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs2870984EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Schizophrenia

Organism-specific databases

DisGeNETi5625
MalaCardsiPRODH
MIMi181500 phenotype
239500 phenotype
600850 phenotype
Orphaneti419 Hyperprolinemia type 1
PharmGKBiPA33801

Chemistry databases

DrugBankiDB06756 Glycine betaine
DB00172 L-Proline

Polymorphism and mutation databases

BioMutaiPRODH

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000025800? – 600Proline dehydrogenase 1, mitochondrial
Transit peptidei1 – ?MitochondrionSequence analysis

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei368N6-acetyllysineBy similarity1
Modified residuei486N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiO43272
PaxDbiO43272
PeptideAtlasiO43272
PRIDEiO43272
ProteomicsDBi48843
48844 [O43272-1]
48845 [O43272-2]

PTM databases

iPTMnetiO43272
PhosphoSitePlusiO43272

Expressioni

Tissue specificityi

Expressed in lung, skeletal muscle and brain, to a lesser extent in heart and kidney, and weakly in liver, placenta and pancreas.

Inductioni

During p53/TP53-induced apoptosis.1 Publication

Gene expression databases

BgeeiENSG00000100033 Expressed in 89 organ(s), highest expression level in right lung
ExpressionAtlasiO43272 baseline and differential
GenevisibleiO43272 HS

Organism-specific databases

HPAiHPA020361

Interactioni

Protein-protein interaction databases

BioGridi111609, 9 interactors
STRINGi9606.ENSP00000349577

Structurei

3D structure databases

ProteinModelPortaliO43272
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the proline oxidase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0186 Eukaryota
COG0506 LUCA
HOVERGENiHBG008262
InParanoidiO43272
KOiK00318
PhylomeDBiO43272
TreeFamiTF313544

Family and domain databases

InterProiView protein in InterPro
IPR029041 FAD-linked_oxidoreductase-like
IPR002872 Proline_DH_dom
IPR015659 Proline_oxidase
PANTHERiPTHR13914 PTHR13914, 1 hit
PfamiView protein in Pfam
PF01619 Pro_dh, 1 hit
SUPFAMiSSF51730 SSF51730, 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

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O43272-4) [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
MALRRALPAL RPCIPRFVQL STAPASREQP AAGPAAVPGG GSATAVRPPV
60 70 80 90 100
PAVDFGNAQE AYRSRRTWEL ARSLLVLRLC AWPALLARHE QLLYVSRKLL
110 120 130 140 150
GQRLFNKLMK MTFYGHFVAG EDQESIQPLL RHYRAFGVSA ILDYGVEEDL
160 170 180 190 200
SPEEAEHKEM ESCTSAAERD GSGTNKRDKQ YQAHRAFGDR RNGVISARTY
210 220 230 240 250
FYANEAKCDS HMETFLRCIE ASGRVSDDGF IAIKLTALGR PQFLLQFSEV
260 270 280 290 300
LAKWRCFFHQ MAVEQGQAGL AAMDTKLEVA VLQESVAKLG IASRAEIEDW
310 320 330 340 350
FTAETLGVSG TMDLLDWSSL IDSRTKLSKH LVVPNAQTGQ LEPLLSRFTE
360 370 380 390 400
EEELQMTRML QRMDVLAKKA TEMGVRLMVD AEQTYFQPAI SRLTLEMQRK
410 420 430 440 450
FNVEKPLIFN TYQCYLKDAY DNVTLDVELA RREGWCFGAK LVRGAYLAQE
460 470 480 490 500
RARAAEIGYE DPINPTYEAT NAMYHRCLDY VLEELKHNAK AKVMVASHNE
510 520 530 540 550
DTVRFALRRM EELGLHPADH QVYFGQLLGM CDQISFPLGQ AGYPVYKYVP
560 570 580 590 600
YGPVMEVLPY LSRRALENSS LMKGTHRERQ LLWLELLRRL RTGNLFHRPA
Length:600
Mass (Da):68,002
Last modified:April 5, 2011 - v3
Checksum:i249E98A0A5BB8027
GO
Isoform 2 (identifier: O43272-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.

Show »
Length:492
Mass (Da):56,197
Checksum:iBE51A3277E264431
GO
Isoform 3 (identifier: O43272-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-84: Missing.
     85-95: LLARHEQLLYV → MLEFVMREWKK

Show »
Length:516
Mass (Da):59,231
Checksum:iE5E72B3C595B4596
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WWM6A0A087WWM6_HUMAN
Proline dehydrogenase
PRODH
600Annotation score:
C9JIW4C9JIW4_HUMAN
Proline dehydrogenase
PRODH
135Annotation score:
E7EQL6E7EQL6_HUMAN
Proline dehydrogenase
PRODH
492Annotation score:
H7C363H7C363_HUMAN
Proline dehydrogenase 1, mitochondr...
PRODH
185Annotation score:
H7C3U9H7C3U9_HUMAN
Proline dehydrogenase 1, mitochondr...
PRODH
164Annotation score:

Sequence cautioni

The sequence AAC39529 differs from that shown. Reason: Frameshift at positions 540, 563, 568, 577, 580 and 582.Curated
The sequence AAH68260 differs from that shown. Reason: Frameshift at position 123.Curated
The sequence AAH94736 differs from that shown. Artifact. Missing internal sequence that doesn't correspond to an exon-intron boundary.Curated
The sequence AAH94736 differs from that shown. Reason: Frameshift at position 40.Curated
The sequence BAD92709 differs from that shown. Intron retention. Includes intronic sequence at the 5' end.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti144Y → F in AAH94736 (PubMed:15489334).Curated1
Sequence conflicti164T → S in AAB88789 (PubMed:9385373).Curated1
Sequence conflicti343P → H in AAH68260 (PubMed:15489334).Curated1
Sequence conflicti347R → G in AAF21464 (PubMed:15662599).Curated1
Sequence conflicti455 – 456AE → Q in AAC39529 (PubMed:9305847).Curated2
Sequence conflicti571L → F in BAD92709 (Ref. 6) Curated1
Sequence conflicti588R → K in AAC39529 (PubMed:9305847).Curated1
Sequence conflicti596F → L in AAH68260 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0648838P → L. 1
Natural variantiVAR_06488419Q → P Polymorphism; moderate reduction of enzymatic activity. Corresponds to variant dbSNP:rs2008720Ensembl.1
Natural variantiVAR_06488530P → S. 1
Natural variantiVAR_06488658A → T. 1
Natural variantiVAR_029563167A → V Polymorphism; may be a risk factor for schizophrenia; moderate reduction of enzymatic activity. 1 Publication1
Natural variantiVAR_029564185R → Q Polymorphism; mild decrease of enzymatic activity. 1 Publication1
Natural variantiVAR_029565185R → W Polymorphism; moderate reduction of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs4819756EnsemblClinVar.1
Natural variantiVAR_029874275T → N1 Publication1
Natural variantiVAR_029566289L → M in HYRPRO1; mild decrease of enzymatic activity. 2 Publications1
Natural variantiVAR_029567406P → L in SCZD4; may be associated with disease susceptibility; strongly reduced enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs3970555Ensembl.1
Natural variantiVAR_029568426D → N in HYRPRO1; moderate reduction of enzymatic activity. 1 Publication1
Natural variantiVAR_029569427V → M in HYRPRO1 and SCZD4; may be associated with disease susceptibility; moderate reduction of enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs2238731EnsemblClinVar.1
Natural variantiVAR_029570431R → H in HYRPRO1; moderate reduction of enzymatic activity. 3 PublicationsCorresponds to variant dbSNP:rs2904552EnsemblClinVar.1
Natural variantiVAR_029571441L → P in HYRPRO1 and SCZD4; may be associated with disease susceptibility; strongly reduced enzymatic activity. 3 PublicationsCorresponds to variant dbSNP:rs2904551EnsemblClinVar.1
Natural variantiVAR_029875444G → D1 Publication1
Natural variantiVAR_029572453R → C in HYRPRO1 and SCZD4; may be associated with disease susceptibility; strongly reduced enzymatic activity. 3 PublicationsCorresponds to variant dbSNP:rs3970559EnsemblClinVar.1
Natural variantiVAR_029573455A → S in HYRPRO1; mild decrease of enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs1807467EnsemblClinVar.1
Natural variantiVAR_029574466T → M in SCZD4; may be associated with disease susceptibility; strongly reduced affinity for FAD; strongly reduced enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs2870984EnsemblClinVar.1
Natural variantiVAR_029575472A → T in HYRPRO1 and SCZD4; associated with disease susceptibility; mild decrease of enzymatic activity. 3 PublicationsCorresponds to variant dbSNP:rs2870983Ensembl.1
Natural variantiVAR_036566488N → S in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_029576521Q → E Strongly reduced enzymatic activity. 1 Publication1
Natural variantiVAR_029577521Q → R in HYRPRO1 and SCZD4; may be associated with disease susceptibility; enhanced enzymatic activity. 4 PublicationsCorresponds to variant dbSNP:rs450046EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0218481 – 108Missing in isoform 2. 1 PublicationAdd BLAST108
Alternative sequenceiVSP_0408481 – 84Missing in isoform 3. 2 PublicationsAdd BLAST84
Alternative sequenceiVSP_04084985 – 95LLARHEQLLYV → MLEFVMREWKK in isoform 3. 2 PublicationsAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82381 mRNA Translation: AAB88789.1
AF120278 mRNA Translation: AAD24775.1
U79754 mRNA Translation: AAF21464.1
AC007326 Genomic DNA No translation available.
BC068260 mRNA Translation: AAH68260.1 Frameshift.
BC094736 mRNA Translation: AAH94736.1 Sequence problems.
BC118597 mRNA Translation: AAI18598.1
BC121809 mRNA Translation: AAI21810.1
AB209472 mRNA Translation: BAD92709.1 Sequence problems.
AF010310 mRNA Translation: AAC39529.1 Frameshift.
CCDSiCCDS13754.1 [O43272-4]
CCDS56223.1 [O43272-2]
RefSeqiNP_001182155.1, NM_001195226.1 [O43272-2]
NP_057419.4, NM_016335.4
UniGeneiHs.517352

Genome annotation databases

EnsembliENST00000357068; ENSP00000349577; ENSG00000100033
GeneIDi5625
KEGGihsa:5625
UCSCiuc062bjw.1 human [O43272-4]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82381 mRNA Translation: AAB88789.1
AF120278 mRNA Translation: AAD24775.1
U79754 mRNA Translation: AAF21464.1
AC007326 Genomic DNA No translation available.
BC068260 mRNA Translation: AAH68260.1 Frameshift.
BC094736 mRNA Translation: AAH94736.1 Sequence problems.
BC118597 mRNA Translation: AAI18598.1
BC121809 mRNA Translation: AAI21810.1
AB209472 mRNA Translation: BAD92709.1 Sequence problems.
AF010310 mRNA Translation: AAC39529.1 Frameshift.
CCDSiCCDS13754.1 [O43272-4]
CCDS56223.1 [O43272-2]
RefSeqiNP_001182155.1, NM_001195226.1 [O43272-2]
NP_057419.4, NM_016335.4
UniGeneiHs.517352

3D structure databases

ProteinModelPortaliO43272
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111609, 9 interactors
STRINGi9606.ENSP00000349577

Chemistry databases

DrugBankiDB06756 Glycine betaine
DB00172 L-Proline

PTM databases

iPTMnetiO43272
PhosphoSitePlusiO43272

Polymorphism and mutation databases

BioMutaiPRODH

Proteomic databases

EPDiO43272
PaxDbiO43272
PeptideAtlasiO43272
PRIDEiO43272
ProteomicsDBi48843
48844 [O43272-1]
48845 [O43272-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357068; ENSP00000349577; ENSG00000100033
GeneIDi5625
KEGGihsa:5625
UCSCiuc062bjw.1 human [O43272-4]

Organism-specific databases

CTDi5625
DisGeNETi5625
EuPathDBiHostDB:ENSG00000100033.16
GeneCardsiPRODH
HGNCiHGNC:9453 PRODH
HPAiHPA020361
MalaCardsiPRODH
MIMi181500 phenotype
239500 phenotype
600850 phenotype
606810 gene
neXtProtiNX_O43272
Orphaneti419 Hyperprolinemia type 1
PharmGKBiPA33801
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0186 Eukaryota
COG0506 LUCA
HOVERGENiHBG008262
InParanoidiO43272
KOiK00318
PhylomeDBiO43272
TreeFamiTF313544

Enzyme and pathway databases

UniPathwayi
UPA00261;UER00373

BioCyciMetaCyc:HS01958-MONOMER
BRENDAi1.5.99.B2 2681
ReactomeiR-HSA-70688 Proline catabolism
SIGNORiO43272

Miscellaneous databases

ChiTaRSiPRODH human
GeneWikiiProline_oxidase
GenomeRNAii5625
PROiPR:O43272
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100033 Expressed in 89 organ(s), highest expression level in right lung
ExpressionAtlasiO43272 baseline and differential
GenevisibleiO43272 HS

Family and domain databases

InterProiView protein in InterPro
IPR029041 FAD-linked_oxidoreductase-like
IPR002872 Proline_DH_dom
IPR015659 Proline_oxidase
PANTHERiPTHR13914 PTHR13914, 1 hit
PfamiView protein in Pfam
PF01619 Pro_dh, 1 hit
SUPFAMiSSF51730 SSF51730, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPROD_HUMAN
AccessioniPrimary (citable) accession number: O43272
Secondary accession number(s): A6NF53
, O14680, Q0P507, Q147W8, Q504W1, Q59FI8, Q6NV86, Q9UF13
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: April 5, 2011
Last modified: November 7, 2018
This is version 171 of the entry and version 3 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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