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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-10-09 18:44:09 UTC
HMDB IDHMDB00162
Secondary Accession NumbersNone
Metabolite Identification
Common NameL-Proline
DescriptionL-Proline is one of the twenty amino acids used in living organisms as the building blocks of proteins. Proline is sometimes called an imino acid, although the IUPAC definition of an imine requires a carbon-nitrogen double bond. Proline is a non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons.
Structure
Thumb
Synonyms
  1. (-)-(S)-Proline
  2. (-)-2-Pyrrolidinecarboxylate
  3. (-)-2-Pyrrolidinecarboxylic acid
  4. (-)-Proline
  5. (S)-(-)-Proline
  6. (S)-(-)-Pyrrolidine-2-carboxylate
  7. (S)-(-)-Pyrrolidine-2-carboxylic acid
  8. (S)-2-Carboxypyrrolidine
  9. (S)-2-Pyrralidinecarboxylate
  10. (S)-2-Pyrralidinecarboxylic acid
  11. (S)-2-Pyrrolidinecarboxylate
  12. (S)-2-Pyrrolidinecarboxylic acid
  13. (S)-Proline
  14. 2-Pyrrolidinecarboxylate
  15. 2-Pyrrolidinecarboxylic acid
  16. Proline
Chemical FormulaC5H9NO2
Average Molecular Weight115.1305
Monoisotopic Molecular Weight115.063328537
IUPAC Name(2S)-pyrrolidine-2-carboxylic acid
Traditional NameL-proline
CAS Registry Number147-85-3
SMILES
OC(=O)[C@@H]1CCCN1
InChI Identifier
InChI=1S/C5H9NO2/c7-5(8)4-2-1-3-6-4/h4,6H,1-3H2,(H,7,8)/t4-/m0/s1
InChI KeyONIBWKKTOPOVIA-BYPYZUCNSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAmino Acids, Peptides, and Analogues
ClassAmino Acids and Derivatives
Sub ClassAlpha Amino Acids and Derivatives
Other Descriptors
  • Aliphatic Heteromonocyclic Compounds
  • Common amino acids(KEGG)
  • amino acid zwitterion(ChEBI)
Substituents
  • Carboxylic Acid
  • Pyrrolidine
  • Pyrrolidine Carboxylic Acid
  • Secondary Aliphatic Amine (Dialkylamine)
Direct ParentAlpha Amino Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Drug metabolite
  • Endogenous
Biofunction
  • Component of Arginine and proline metabolism
  • Waste products
ApplicationNot Available
Cellular locations
  • Cytoplasm
  • Extracellular
  • Mitochondria
  • Lysosome
  • Endoplasmic reticulum
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point221 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility162.0 mg/mLNot Available
LogP-2.54HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility365 g/LALOGPS
logP-2.7ALOGPS
logP-2.6ChemAxon
logS0.5ALOGPS
pKa (Strongest Acidic)1.94ChemAxon
pKa (Strongest Basic)11.33ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area49.33ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity28.06ChemAxon
Polarizability11.53ChemAxon
Spectra
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Mitochondria
  • Lysosome
  • Endoplasmic reticulum
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue Location
  • All Tissues
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Arginine and Proline MetabolismSMP00020map00330
Transcription/TranslationSMP00019Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified198.3 +/- 64.8 uMAdult (>18 years old)Not SpecifiedNormal details
BloodDetected and Quantified168.0 (108.0-228.0) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified177.5 +/- 38.6 uMAdult (>18 years old)Not SpecifiedNormal details
BloodDetected and Quantified198.0 +/- 63.0 uMChildren (1-13 years old)MaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified239.0 +/- 70.0 uMAdult (>18 years old)MaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified168.0 +/- 49.0 uMAdult (>18 years old)FemaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified230.0 +/- 75.0 uMNewborn (0-30 days old)Not SpecifiedNormal
    • Geigy Scientific ...
details
Cerebrospinal Fluid (CSF)Detected and Quantified 4.0 (0 - 8.0) uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified1.9 +/- 1.0 uMAdult (>18 years old)Not SpecifiedNormal details
SalivaDetected and Quantified158.48 +/- 122.10 uMAdult (>18 years old)BothNormal
    • Dame, ZT. et al. ...
details
SalivaDetected and Quantified>10 uMAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.86 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified<6.08-34.76 umol/mmol creatinineAdult (>18 years old)BothNormal
    • David F. Putnam C...
details
UrineDetected and Quantified3.06 /- 1.87 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified2.171 (0.0658-4.276) umol/mmol creatinineAdult (>18 years old)BothNormal
    details
    UrineDetected and Quantified1.1 (0.1-2.5) umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified1.0 (0.5-2.0) umol/mmol creatinineNewborn (0-30 days old)BothNormal
      • Geigy Scientific ...
      • West Cadwell, N.J...
      • Basel, Switzerlan...
    details
    UrineDetected and Quantified4.14 +/- 2.85 umol/mmol creatinineInfant (0-1 year old)BothNormal details
    UrineDetected and Quantified0.5 umol/mmol creatinineAdult (>18 years old)BothNormal details
    Abnormal Concentrations
    BiofluidStatusValueAgeSexConditionReferenceDetails
    BloodDetected and Quantified159.9 +/- 86.3 uMAdult (>18 years old)Not SpecifiedHeart Transplant details
    BloodDetected and Quantified201.0 +/- 149.5 uMAdult (>18 years old)Both
    Hemodialysis
    details
    BloodDetected and Quantified227.2 +/- 108.4 uMAdult (>18 years old)Both
    Hemodialysis
    details
    BloodDetected and Quantified650.00 (300.00-1000.00) uMChildren (1-13 years old)BothGlutathione synthetase deficiency details
    Cerebrospinal Fluid (CSF)Detected and Quantified0.68 +/- 0.35 uMAdult (>18 years old)BothAlzheimer's disease details
    UrineDetected and Quantified0.0068 - 0.0549 umol/mmol creatinineAdult (>18 years old)BothADPKD details
    UrineDetected and Quantified29.6 (19.7-39.47) umol/mmol creatinineChildren (1-13 years old)BothIminoglycinuria details
    Associated Disorders and Diseases
    Disease References
    Alzheimer's disease
    1. Fonteh AN, Harrington RJ, Tsai A, Liao P, Harrington MG: Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease subjects. Amino Acids. 2007 Feb;32(2):213-24. Epub 2006 Oct 10. Pubmed: 17031479
    Glutathione synthetase deficiency
    1. MetaGene
    Hemodialysis
    1. Raj DS, Ouwendyk M, Francoeur R, Pierratos A: Plasma amino acid profile on nocturnal hemodialysis. Blood Purif. 2000;18(2):97-102. Pubmed: 10838467
    Iminoglycinuria
    1. MetaGene
    Associated OMIM IDs
    DrugBank IDDB00172
    DrugBank Metabolite IDDBMET00494
    Phenol Explorer Compound IDNot Available
    Phenol Explorer Metabolite IDNot Available
    FoodDB IDFDB000570
    KNApSAcK IDC00001388
    Chemspider ID128566
    KEGG Compound IDC00148
    BioCyc IDPRO
    BiGG ID34042
    Wikipedia LinkL-Proline
    NuGOwiki LinkHMDB00162
    Metagene LinkHMDB00162
    METLIN ID29
    PubChem Compound145742
    PDB IDPRO
    ChEBI ID17203
    References
    Synthesis Reference Itoh, Tamio. Synthesis of L-proline from L-glutamine. Bulletin of the Chemical Society of Japan (1963), 36(1), 25-9
    Material Safety Data Sheet (MSDS)Download (PDF)
    General References
    1. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. Pubmed: 19212411
    2. Silwood CJ, Lynch E, Claxson AW, Grootveld MC: 1H and (13)C NMR spectroscopic analysis of human saliva. J Dent Res. 2002 Jun;81(6):422-7. Pubmed: 12097436
    3. Cynober LA: Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance. Nutrition. 2002 Sep;18(9):761-6. Pubmed: 12297216
    4. Deng C, Shang C, Hu Y, Zhang X: Rapid diagnosis of phenylketonuria and other aminoacidemias by quantitative analysis of amino acids in neonatal blood spots by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Jul 25;775(1):115-20. Pubmed: 12101068
    5. Azizi M, Junot C, Ezan E, Menard J: Angiotensin I-converting enzyme and metabolism of the haematological peptide N-acetyl-seryl-aspartyl-lysyl-proline. Clin Exp Pharmacol Physiol. 2001 Dec;28(12):1066-9. Pubmed: 11903317
    6. Roesel RA, Blankenship PR, Mobley EB, Coryell ME: Increased excretion of histidyl-L-proline diketopiperazine by infants receiving Pregestimil and Nutramigen formulas. Clin Chem. 1986 May;32(5):865-7. Pubmed: 3698278
    7. Chambers ST, Kunin CM: Osmoprotective activity for Escherichia coli in mammalian renal inner medulla and urine. Correlation of glycine and proline betaines and sorbitol with response to osmotic loads. J Clin Invest. 1987 Nov;80(5):1255-60. Pubmed: 3316273
    8. Azizi M, Ezan E, Reny JL, Wdzieczak-Bakala J, Gerineau V, Menard J: Renal and metabolic clearance of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) during angiotensin-converting enzyme inhibition in humans. Hypertension. 1999 Mar;33(3):879-86. Pubmed: 10082503
    9. Hart W, van den Hamer CJ, van der Sluys Veer J: The use of hydroxy-DL-proline-2-(14)C in the investigation of hydroxyproline metabolism in normal subjects and in patients with renal insufficiency. Clin Nephrol. 1976 Sep;6(3):379-87. Pubmed: 991465
    10. Kanwar YS, Krakower CA, Manaligod JR, Justice P, Wong PW: Biochemical, morphological and hybrid studies in hyperprolinemic mice. Biomedicine. 1975 May;22(3):209-16. Pubmed: 240452
    11. Simila S: Hydroxyproline metabolism in type II hyperprolinaemia. Ann Clin Biochem. 1979 Jul;16(4):177-81. Pubmed: 533224
    12. Lu SH, Ohshima H, Fu HM, Tian Y, Li FM, Blettner M, Wahrendorf J, Bartsch H: Urinary excretion of N-nitrosamino acids and nitrate by inhabitants of high- and low-risk areas for esophageal cancer in Northern China: endogenous formation of nitrosoproline and its inhibition by vitamin C. Cancer Res. 1986 Mar;46(3):1485-91. Pubmed: 3943105
    13. Hausmann D: [Post-traumatic imbalances of plasma amino acids--interference factors or defense mechanisms? A study of protein metabolism in severe craniocerebral trauma] Anasth Intensivther Notfallmed. 1988 Feb;23(1):14-21. Pubmed: 3364629
    14. Scriver CR, McInnes RR, Mohyuddin F: Role of epithelial architecture and intracellular metabolism in proline uptake and transtubular reclamation in PRO/re mouse kidney. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1431-5. Pubmed: 1055415
    15. Boden G, Rezvani I, Owen OE: Effects of glucagon on plasma amino acids. J Clin Invest. 1984 Mar;73(3):785-93. Pubmed: 6142902
    16. Feldman JM, Plonk JW, Admiraal J, Sidbury, JB: Plasma amino acids in patients with the carcinoid syndrome. Cancer. 1976 Nov;38(5):2127-31. Pubmed: 136295
    17. Humbertclaude V, Rivier F, Roubertie A, Echenne B, Bellet H, Vallat C, Morin D: Is hyperprolinemia type I actually a benign trait? Report of a case with severe neurologic involvement and vigabatrin intolerance. J Child Neurol. 2001 Aug;16(8):622-3. Pubmed: 11510941

    Enzymes

    General function:
    Involved in oxidoreductase activity
    Specific function:
    Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
    Gene Name:
    P4HA2
    Uniprot ID:
    O15460
    Molecular weight:
    60632.19
    Reactions
    L-Proline + Oxoglutaric acid + Oxygen → 4-Hydroxyproline + Succinic acid + Carbon dioxidedetails
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in oxidoreductase activity
    Specific function:
    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.
    Gene Name:
    PYCR1
    Uniprot ID:
    P32322
    Molecular weight:
    33360.27
    Reactions
    L-Proline + NAD(P)(+) → 1-Pyrroline-5-carboxylic acid + NAD(P)Hdetails
    L-Proline + NAD → 1-Pyrroline-5-carboxylic acid + NADH + Hydrogen Iondetails
    L-Proline + NADP → 1-Pyrroline-5-carboxylic acid + NADPH + Hydrogen Iondetails
    References
    1. Huang TC, Huang YW, Hung HJ, Ho CT, Wu ML: Delta1-pyrroline-5-carboxylic acid formed by proline dehydrogenase from the Bacillus subtilis ssp. natto expressed in Escherichia coli as a precursor for 2-acetyl-1-pyrroline. J Agric Food Chem. 2007 Jun 27;55(13):5097-102. Epub 2007 May 31. Pubmed: 17536821
    2. Hu CA, Donald SP, Yu J, Lin WW, Liu Z, Steel G, Obie C, Valle D, Phang JM: Overexpression of proline oxidase induces proline-dependent and mitochondria-mediated apoptosis. Mol Cell Biochem. 2007 Jan;295(1-2):85-92. Epub 2006 Jul 28. Pubmed: 16874462
    3. Meng Z, Lou Z, Liu Z, Hui D, Bartlam M, Rao Z: Purification, characterization, and crystallization of human pyrroline-5-carboxylate reductase. Protein Expr Purif. 2006 Sep;49(1):83-7. Epub 2006 Mar 20. Pubmed: 16600630
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
    Gene Name:
    P4HA1
    Uniprot ID:
    P13674
    Molecular weight:
    60966.645
    Reactions
    L-Proline + Oxoglutaric acid + Oxygen → 4-Hydroxyproline + Succinic acid + Carbon dioxidedetails
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in oxidoreductase activity
    Specific function:
    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.
    Gene Name:
    PYCR2
    Uniprot ID:
    Q96C36
    Molecular weight:
    25867.975
    Reactions
    L-Proline + NAD(P)(+) → 1-Pyrroline-5-carboxylic acid + NAD(P)Hdetails
    L-Proline + NAD → 1-Pyrroline-5-carboxylic acid + NADH + Hydrogen Iondetails
    L-Proline + NADP → 1-Pyrroline-5-carboxylic acid + NADPH + Hydrogen Iondetails
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    3. Murahama M, Yoshida T, Hayashi F, Ichino T, Sanada Y, Wada K: Purification and characterization of Delta(1)-pyrroline-5-carboxylate reductase isoenzymes, indicating differential distribution in spinach (Spinacia oleracea L.) leaves. Plant Cell Physiol. 2001 Jul;42(7):742-50. Pubmed: 11479381
    General function:
    Involved in nucleotide binding
    Specific function:
    Catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the multisynthetase complex and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.
    Gene Name:
    EPRS
    Uniprot ID:
    P07814
    Molecular weight:
    170589.705
    Reactions
    Adenosine triphosphate + L-Proline + tRNA(Pro) → Adenosine monophosphate + Pyrophosphate + L-prolyl-tRNA(Pro)details
    Adenosine triphosphate + L-Proline + tRNA(Pro) → Adenosine monophosphate + Pyrophosphate + L-Prolyl-tRNA(Pro)details
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in aminopeptidase activity
    Specific function:
    Presumably involved in the processing and regular turnover of intracellular proteins. Catalyzes the removal of unsubstituted N-terminal amino acids from various peptides.
    Gene Name:
    LAP3
    Uniprot ID:
    P28838
    Molecular weight:
    Not Available
    Reactions
    Peptide + Water → L-Proline + Peptidedetails
    General function:
    Involved in proline dehydrogenase activity
    Specific function:
    Converts proline to delta-1-pyrroline-5-carboxylate.
    Gene Name:
    PRODH
    Uniprot ID:
    O43272
    Molecular weight:
    56196.675
    Reactions
    L-Proline + acceptor → 1-Pyrroline-5-carboxylic acid + reduced acceptordetails
    L-Proline + Acceptor → 1-Pyrroline-5-carboxylic acid + Reduced acceptordetails
    References
    1. Huang TC, Huang YW, Hung HJ, Ho CT, Wu ML: Delta1-pyrroline-5-carboxylic acid formed by proline dehydrogenase from the Bacillus subtilis ssp. natto expressed in Escherichia coli as a precursor for 2-acetyl-1-pyrroline. J Agric Food Chem. 2007 Jun 27;55(13):5097-102. Epub 2007 May 31. Pubmed: 17536821
    2. White TA, Krishnan N, Becker DF, Tanner JJ: Structure and kinetics of monofunctional proline dehydrogenase from Thermus thermophilus. J Biol Chem. 2007 May 11;282(19):14316-27. Epub 2007 Mar 7. Pubmed: 17344208
    3. White TA, Tanner JJ: Cloning, purification and crystallization of Thermus thermophilus proline dehydrogenase. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Aug 1;61(Pt 8):737-9. Epub 2005 Jul 8. Pubmed: 16511143
    4. Phang JM, Donald SP, Pandhare J, Liu Y: The metabolism of proline, a stress substrate, modulates carcinogenic pathways. Amino Acids. 2008 Nov;35(4):681-90. Epub 2008 Apr 10. Pubmed: 18401543
    5. Phang JM, Liu W, Zabirnyk O: Proline metabolism and microenvironmental stress. Annu Rev Nutr. 2010 Aug 21;30:441-63. Pubmed: 20415579
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Not Available
    Gene Name:
    PYCRL
    Uniprot ID:
    Q53H96
    Molecular weight:
    29892.415
    Reactions
    L-Proline + NAD(P)(+) → 1-Pyrroline-5-carboxylic acid + NAD(P)Hdetails
    L-Proline + NAD → 1-Pyrroline-5-carboxylic acid + NADH + Hydrogen Iondetails
    L-Proline + NADP → 1-Pyrroline-5-carboxylic acid + NADPH + Hydrogen Iondetails
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed: 10592235
    General function:
    Not Available
    Specific function:
    Not Available
    Gene Name:
    PROSC
    Uniprot ID:
    O94903
    Molecular weight:
    30343.7
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in oxidoreductase activity
    Specific function:
    L-proline + NAD(P)(+) = 1-pyrroline-5- carboxylate + NAD(P)H
    Gene Name:
    P5CR2
    Uniprot ID:
    Q4W8W1
    Molecular weight:
    33726.4
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in neurotransmitter:sodium symporter activity
    Specific function:
    Terminates the action of proline by its high affinity sodium-dependent reuptake into presynaptic terminals.
    Gene Name:
    SLC6A7
    Uniprot ID:
    Q99884
    Molecular weight:
    70909.935
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in neurotransmitter:sodium symporter activity
    Specific function:
    Mediates the uptake of a broad range of neutral and cationic amino acids (with the exception of proline) in a Na(+)/Cl(-)-dependent manner
    Gene Name:
    SLC6A14
    Uniprot ID:
    Q9UN76
    Molecular weight:
    72152.1
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in proline dehydrogenase activity
    Specific function:
    Converts proline to delta-1-pyrroline-5-carboxylate (Probable).
    Gene Name:
    PRODH2
    Uniprot ID:
    Q9UF12
    Molecular weight:
    58870.115
    Reactions
    L-Proline + acceptor → 1-Pyrroline-5-carboxylic acid + reduced acceptordetails
    General function:
    Involved in ion channel activity
    Specific function:
    Cation channel essential for the depolarizing photoresponse of retinal ON bipolar cells. It is part of the GRM6 signaling cascade. May play a role in metastasis suppression. May act as a spontaneously active, calcium-permeable plasma membrane channel
    Gene Name:
    TRPM1
    Uniprot ID:
    Q7Z4N2
    Molecular weight:
    182177.0
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Basement membrane-associated chondroitin sulfate proteoglycan (CSPG). Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens, especially types IV and V. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts.
    Gene Name:
    LEPRE1
    Uniprot ID:
    Q32P28
    Molecular weight:
    78921.41
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Shows prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly-sequences in collagens, especially types II, IV and V (By similarity).
    Gene Name:
    LEPREL1
    Uniprot ID:
    Q8IVL5
    Molecular weight:
    60386.32
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in iron ion binding
    Specific function:
    Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly-sequences in collagens, especially types IV and V (By similarity).
    Gene Name:
    LEPREL2
    Uniprot ID:
    Q8IVL6
    Molecular weight:
    81835.705
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
    Gene Name:
    P4HA3
    Uniprot ID:
    Q7Z4N8
    Molecular weight:
    61125.675
    Reactions
    L-Proline + Oxoglutaric acid + Oxygen → 4-Hydroxyproline + Succinic acid + Carbon dioxidedetails
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality.
    Gene Name:
    EGLN1
    Uniprot ID:
    Q9GZT9
    Molecular weight:
    46020.585
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle. Also regulates susceptibility to normoxic oxidative neuronal death.
    Gene Name:
    EGLN2
    Uniprot ID:
    Q96KS0
    Molecular weight:
    43650.03
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis. Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex. In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity. Also essential for hypoxic regulation of neutrophilic inflammation. Plays a crucial role in DNA damage response (DDR) by hydroxylating TELO2, promoting its interaction with ATR which is required for activation of the ATR/CHK1/p53 pathway.
    Gene Name:
    EGLN3
    Uniprot ID:
    Q9H6Z9
    Molecular weight:
    27261.06
    General function:
    Involved in calcium ion binding
    Specific function:
    Catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates HIF1A at 'Pro-402' and 'Pro-564'. May function as a cellular oxygen sensor and, under normoxic conditions, may target HIF through the hydroxylation for proteasomal degradation via the von Hippel-Lindau ubiquitination complex.
    Gene Name:
    P4HTM
    Uniprot ID:
    Q9NXG6
    Molecular weight:
    63111.98
    General function:
    Involved in proline racemase activity
    Specific function:
    Catalyzes the dehydration of trans-3-hydroxy-L-proline to delta-1-pyrroline-2-carboxylate (Pyr2C). May be required to degrade trans-3-hydroxy-L-proline from the diet and originating from the degradation of proteins such as collagen-IV that contain it.
    Gene Name:
    L3HYPDH
    Uniprot ID:
    Q96EM0
    Molecular weight:
    38137.395
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in peptidyl-prolyl cis-trans isomerase activity
    Specific function:
    PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides
    Gene Name:
    PPIF
    Uniprot ID:
    P30405
    Molecular weight:
    22040.1
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in peptidyl-prolyl cis-trans isomerase activity
    Specific function:
    PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides
    Gene Name:
    PPIA
    Uniprot ID:
    P62937
    Molecular weight:
    18012.4
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed: 11752352
    General function:
    Involved in peptidyl-prolyl cis-trans isomerase activity
    Specific function:
    PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides
    Gene Name:
    PPIB
    Uniprot ID:
    P23284
    Molecular weight:
    23742.4
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed: 11752352
    General function:
    Involved in peptidyl-prolyl cis-trans isomerase activity
    Specific function:
    PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. May be implicated in the folding, transport, and assembly of proteins. May play an important role in the regulation of pre-mRNA splicing
    Gene Name:
    PPIG
    Uniprot ID:
    Q13427
    Molecular weight:
    88616.5
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in nucleotide binding
    Specific function:
    Not Available
    Gene Name:
    PARS2
    Uniprot ID:
    Q7L3T8
    Molecular weight:
    53262.18
    Reactions
    Adenosine triphosphate + L-Proline + tRNA(Pro) → Adenosine monophosphate + Pyrophosphate + L-prolyl-tRNA(Pro)details
    Adenosine triphosphate + L-Proline + tRNA(Pro) → Adenosine monophosphate + Pyrophosphate + L-Prolyl-tRNA(Pro)details
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    General function:
    Involved in peptidyl-prolyl cis-trans isomerase activity
    Specific function:
    PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Participates in pre-mRNA splicing. May play a role in the assembly of the U4/U5/U6 tri-snRNP complex. May act as a chaperone
    Gene Name:
    PPIH
    Uniprot ID:
    O43447
    Molecular weight:
    19208.0
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423

    Transporters

    General function:
    Involved in transmembrane transport
    Specific function:
    Sodium-independent transporter that mediates the update of aromatic acid. Can function as a net efflux pathway for aromatic amino acids in the basosolateral epithelial cells
    Gene Name:
    SLC16A10
    Uniprot ID:
    Q8TF71
    Molecular weight:
    55492.1
    References
    1. Kim DK, Kanai Y, Chairoungdua A, Matsuo H, Cha SH, Endou H: Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J Biol Chem. 2001 May 18;276(20):17221-8. Epub 2001 Feb 20. Pubmed: 11278508