PYCR2: Difference between revisions
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== Function == |
== Function == |
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This gene belongs to the [[pyrroline-5-carboxylate reductase]] family. The encoded [[mitochondrial]] protein catalyzes the conversion of pyrroline-5-carboxylate to [[proline]], which is the last step in proline biosynthesis.<ref name="entrez"/> Loss of PYCR2 does not lead to a gross defect in mitochondrial protein synthesis, but interestingly, loss of function of PYCR2 leads to increased apoptosis under oxidative stress.<ref name= "pmid25865492">{{cite journal|last1=Nakayama|first1=T|last2=Al-Maawali|first2=A|last3=El-Quessny|first3=M|last4=Rajab|first4=A|last5=Khalil|first5=S|last6=Stoler|first6=JM|last7=Tan|first7=WH|last8=Nasir|first8=R|last9=Schmitz-Abe|first9=K|last10=Hill|first10=RS|last11=Partlow|first11=JN|last12=Al-Saffar|first12=M|last13=Servattalab|first13=S|last14=LaCoursiere|first14=CM|last15=Tambunan|first15=DE|last16=Coulter|first16=ME|last17=Elhosary|first17=PC|last18=Gorski|first18=G|last19=Barkovich|first19=AJ|last20=Markianos|first20=K|last21=Poduri|first21=A|last22=Mochida|first22=GH|title=Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination.|journal=American journal of human genetics|date=7 May 2015|volume=96|issue=5|pages=709-19|pmid=25865492}}</ref> |
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This gene belongs to the [[pyrroline-5-carboxylate reductase]] family. The encoded [[mitochondrial]] protein catalyzes the conversion of pyrroline-5-carboxylate to [[proline]], which is the last step in proline biosynthesis.<ref name="entrez"/> |
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==Clinical significance== |
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Mutations in the PYCR2 gene have been identified as the cause of a unique syndrome characterized by postnatal microcephaly, hypomyelination, and reduced cerebral white-matter volume. Hypomyelination and the absence of wrinkly skin makes this condition distinct from that caused by previously reported mutations in the gene encoding PYCR2’s isozyme, PYCR1, suggesting a unique and indispensable role for PYCR2 in the human CNS during development. This is substantiated by the fact that PYCR2 mRNA is moderately expressed in the developing human brain, and in much higher forms than either of the other two isoforms. Although PYCR2 is an enzyme for proline biosynthesis, systemic deprivation of proline does not appear to be the pathogenetic mechanism of this condition, given that plasma amino acid analysis in two affected individuals did not show low proline levels. Furthermore, mitochondrial protein synthesis was not affected in PYCR2-deficient cells. Therefore, deficiency of proline, as a building block of proteins, might not be the major pathophysiology. However, proline has been reported as a non-enzymatic antioxidant that suppresses apoptosis, and therefore local proline biosynthesis in neurons might be important for neuronal protection against oxidative stress.<ref name= "pmid25865492" /> |
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The PYCR family also has been correlated with melanoma cells. PYCR2 as well as PYCR are abundant in melanoma cells but not detected in melanocytes.<ref>{{cite journal|last1=De Ingeniis|first1=J|last2=Ratnikov|first2=B|last3=Richardson|first3=AD|last4=Scott|first4=DA|last5=Aza-Blanc|first5=P|last6=De|first6=SK|last7=Kazanov|first7=M|last8=Pellecchia|first8=M|last9=Ronai|first9=Z|last10=Osterman|first10=AL|last11=Smith|first11=JW|title=Functional specialization in proline biosynthesis of melanoma.|journal=PloS one|date=2012|volume=7|issue=9|pages=e45190|pmid=23024808}}</ref> |
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== References == |
== References == |
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Revision as of 17:19, 20 July 2015
Template:PBB Pyrroline-5-carboxylate reductase family, member 2 is a protein that in humans is encoded by the PYCR2 gene.[1]
Function
This gene belongs to the pyrroline-5-carboxylate reductase family. The encoded mitochondrial protein catalyzes the conversion of pyrroline-5-carboxylate to proline, which is the last step in proline biosynthesis.[1] Loss of PYCR2 does not lead to a gross defect in mitochondrial protein synthesis, but interestingly, loss of function of PYCR2 leads to increased apoptosis under oxidative stress.[2]
Clinical significance
Mutations in the PYCR2 gene have been identified as the cause of a unique syndrome characterized by postnatal microcephaly, hypomyelination, and reduced cerebral white-matter volume. Hypomyelination and the absence of wrinkly skin makes this condition distinct from that caused by previously reported mutations in the gene encoding PYCR2’s isozyme, PYCR1, suggesting a unique and indispensable role for PYCR2 in the human CNS during development. This is substantiated by the fact that PYCR2 mRNA is moderately expressed in the developing human brain, and in much higher forms than either of the other two isoforms. Although PYCR2 is an enzyme for proline biosynthesis, systemic deprivation of proline does not appear to be the pathogenetic mechanism of this condition, given that plasma amino acid analysis in two affected individuals did not show low proline levels. Furthermore, mitochondrial protein synthesis was not affected in PYCR2-deficient cells. Therefore, deficiency of proline, as a building block of proteins, might not be the major pathophysiology. However, proline has been reported as a non-enzymatic antioxidant that suppresses apoptosis, and therefore local proline biosynthesis in neurons might be important for neuronal protection against oxidative stress.[2]
The PYCR family also has been correlated with melanoma cells. PYCR2 as well as PYCR are abundant in melanoma cells but not detected in melanocytes.[3]
References
- ^ a b "Entrez Gene: Pyrroline-5-carboxylate reductase family, member 2".
- ^ a b Nakayama, T; Al-Maawali, A; El-Quessny, M; Rajab, A; Khalil, S; Stoler, JM; Tan, WH; Nasir, R; Schmitz-Abe, K; Hill, RS; Partlow, JN; Al-Saffar, M; Servattalab, S; LaCoursiere, CM; Tambunan, DE; Coulter, ME; Elhosary, PC; Gorski, G; Barkovich, AJ; Markianos, K; Poduri, A; Mochida, GH (7 May 2015). "Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination". American journal of human genetics. 96 (5): 709–19. PMID 25865492.
- ^ De Ingeniis, J; Ratnikov, B; Richardson, AD; Scott, DA; Aza-Blanc, P; De, SK; Kazanov, M; Pellecchia, M; Ronai, Z; Osterman, AL; Smith, JW (2012). "Functional specialization in proline biosynthesis of melanoma". PloS one. 7 (9): e45190. PMID 23024808.
Further reading
- De Ingeniis J, Ratnikov B, Richardson AD, Scott DA, Aza-Blanc P, De SK, Kazanov M, Pellecchia M, Ronai Z, Osterman AL, Smith JW (2012). "Functional specialization in proline biosynthesis of melanoma". PloS One. 7 (9): e45190. doi:10.1371/journal.pone.0045190. PMID 23024808.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - Potapova IA, Cohen IS, Doronin SV (Sep 2007). "Voltage-gated ion channel Kv4.3 is associated with Rap guanine nucleotide exchange factors and regulates angiotensin receptor type 1 signaling to small G-protein Rap". The FEBS Journal. 274 (17): 4375–84. doi:10.1111/j.1742-4658.2007.05966.x. PMID 17725712.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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