CYP2R1: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Robot: Automated text replacement (-{{WikiDoc Cardiology Network Infobox}} +, -<references /> +{{reflist|2}}, -{{reflist}} +{{reflist|2}}))
m (Bot: HTTP→HTTPS)
 
Line 1: Line 1:
{{PBB|geneid=120227}}
{{Infobox_gene}}
{{SI}}
'''Vitamin D 25-hydroxylase''' also known as '''cytochrome P450 2R1''' is an [[enzyme]] that in humans is encoded by the ''CYP2R1'' [[gene]].<ref name="pmid12464240">{{cite journal | author = Nelson DR | title = Comparison of P450s from human and fugu: 420 million years of vertebrate P450 evolution | journal = Arch Biochem Biophys | volume = 409 | issue = 1 | pages = 18–24 |date=Dec 2002 | pmid = 12464240 | pmc =  | doi =10.1016/S0003-9861(02)00553-2  }}</ref><ref name="pmid12867411">{{cite journal | doi = 10.1073/pnas.0402490101 | vauthors = Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW | title = Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase | journal = Proc Natl Acad Sci U S A | volume = 101 | issue = 20 | pages = 7711–7715 | date = 2004-05-18 | pmid = 15128933 | pmc = 419671 | bibcode=2004PNAS..101.7711C}}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CYP2R1 cytochrome P450, family 2, subfamily R, polypeptide 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=120227| accessdate = }}</ref>


== Function ==


'''Cytochrome P450, family 2, subfamily R, polypeptide 1''', also known as '''CYP2R1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CYP2R1 cytochrome P450, family 2, subfamily R, polypeptide 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=120227| accessdate = }}</ref>
Vitamin D 25-hydroxylase is a member of the [[cytochrome P450]] superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. Found in the liver, this enzyme is a [[microsome|microsomal]] vitamin D hydroxylase that converts [[vitamin D]] into [[calcifediol|25-hydroxyvitamin D]] (calcidiol), which is the major circulatory form of the vitamin.


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
== Clinical significance ==
{{PBB_Summary
 
| section_title =  
An inherited [[mutation]] in the ''CYP2R1'' gene which results in the substitution of a [[proline]] for a [[leucine]] residue at [[codon]] 99 eliminates the enzyme activity and is associated with low circulating levels of 25-hydroxyvitamin D and classic symptoms of [[vitamin D deficiency]].<ref name="pmid12867411"/> The gene product which it encodes, vitamin D 25-hydroxylase, has therefore been proposed as the key enzyme in the conversion of [[cholecalciferol]] (vitamin D<sub>3</sub>) to [[calcidiol]]. Calcidiol is subsequently converted by the action of [[25-hydroxyvitamin D3 1-alpha-hydroxylase]] to [[calcitriol]], the active form of vitamin D<sub>3</sub> that binds to the [[calcitriol receptor|vitamin D receptor]] (VDR) which mediates most of the physiological actions of the vitamin.<ref name="pmid12867411"/>
| summary_text = This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This enzyme is a microsomal vitamin D hydroxylase that converts vitamin D into the active ligand for the vitamin D receptor. A mutation in this gene has been associated with selective 25-hydroxyvitamin D deficiency.<ref name="entrez">{{cite web | title = Entrez Gene: CYP2R1 cytochrome P450, family 2, subfamily R, polypeptide 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=120227| accessdate = }}</ref>
 
}}
{|
|[[File:Reaction - cholecalciferol to calcidiol (vertical).png|thumb|300px|Conversion of cholecalciferol to calcidiol as catalyzed by CYP2R1.]]
|}
 
===Interactive pathway map===
{{VitaminDSynthesis_WP1531|highlight=CYP2R1}}
 
==Model organisms==
[[Model organism]]s have been used in the study of CYP2R1 function. A conditional [[knockout mouse]] line called ''Cyp2r1<sup>tm1b(EUCOMM)Wtsi</sup>'' was generated at the [[Wellcome Trust Sanger Institute]].<ref name="mgp_reference">{{cite journal |title=The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice |author=Gerdin AK |year=2010 |journal=Acta Ophthalmologica|volume=88 |pages=925–7|doi=10.1111/j.1755-3768.2010.4142.x }}</ref> Male and female animals underwent a standardized [[phenotypic screen]]<ref name="IMPCsearch_ref">{{cite web |url=http://www.mousephenotype.org/data/search?q=Cyp2r1#fq=*:*&facet=gene |title=International Mouse Phenotyping Consortium}}</ref> to determine the effects of deletion.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref><ref name="pmid23870131">{{cite journal | vauthors = White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, ((Sanger Institute Mouse Genetics Project)), Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP | title = Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes | journal = Cell | volume = 154 | issue = 2 | pages = 452–64 | year = 2013 | pmid = 23870131 | doi = 10.1016/j.cell.2013.06.022 | pmc=3717207}}</ref> Additional screens performed:  - In-depth immunological phenotyping<ref name="iii_ref">{{cite web |url= http://www.immunophenotyping.org/data/search?keys=Cyp2r1&field_gene_construct_tid=All |title=Infection and Immunity Immunophenotyping (3i) Consortium}}</ref>  
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: left;" |
|+ ''Cyp2r1'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
|-
| colspan=2; style="text-align: center;" | All data available at.<ref name="IMPCsearch_ref"/><ref name="iii_ref" />
|-
| Insulin || bgcolor="#488ED3"|Normal
 
|-
| Homozygous viability at P14 || bgcolor="#488ED3"|Normal
 
|-
| Homozygous Fertility || bgcolor="#488ED3"|Normal
 
|-
| Body weight || bgcolor="#488ED3"|Normal
 
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
 
|-
| Grip strength || bgcolor="#488ED3"|Normal
 
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
 
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
 
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
 
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
 
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
 
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
 
|-
| Eye morphology || bgcolor="#488ED3"|Normal
 
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
 
|-
| ''[[Haematology]]'' 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Peripheral blood leukocytes 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Heart weight || bgcolor="#488ED3"|Normal
 
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal
 
|-
| Spleen Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Mesenteric Lymph Node Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Epidermal Immune Composition || bgcolor="#488ED3"|Normal
 
|-
| Influenza Challenge || bgcolor="#488ED3"|Normal
 
|-
|}


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{Refbegin| 2}}
{{PBB_Further_reading  
{{PBB_Further_reading
| citations =  
| citations =
*{{cite journal  | author=Ramos-Lopez E, Brück P, Jansen T, ''et al.'' |title=CYP2R1 (vitamin D 25-hydroxylase) gene is associated with susceptibility to type 1 diabetes and vitamin D levels in Germans. |journal=Diabetes Metab. Res. Rev. |volume=23 |issue= 8 |pages= 631–6 |year= 2008 |pmid= 17607662 |doi= 10.1002/dmrr.719 }}
*{{Cite journal  | vauthors=Ramos-Lopez E, Brück P, Jansen T |title=CYP2R1 (vitamin D 25-hydroxylase) gene is associated with susceptibility to type 1 diabetes and vitamin D levels in Germans. |journal=Diabetes Metab. Res. Rev. |volume=23 |issue= 8 |pages= 631–6 |year= 2008 |pmid= 17607662 |doi= 10.1002/dmrr.719 |display-authors=etal}}
*{{cite journal  | author=Ramos-Lopez E, Brück P, Jansen T, ''et al.'' |title=CYP2R1-, CYP27B1- and CYP24-mRNA expression in German type 1 diabetes patients. |journal=J. Steroid Biochem. Mol. Biol. |volume=103 |issue= 3-5 |pages= 807–10 |year= 2007 |pmid= 17223345 |doi= 10.1016/j.jsbmb.2006.12.056 }}
*{{Cite journal  | vauthors=Ramos-Lopez E, Brück P, Jansen T |title=CYP2R1-, CYP27B1- and CYP24-mRNA expression in German type 1 diabetes patients. |journal=J. Steroid Biochem. Mol. Biol. |volume=103 |issue= 3–5 |pages= 807–10 |year= 2007 |pmid= 17223345 |doi= 10.1016/j.jsbmb.2006.12.056 |display-authors=etal}}
*{{cite journal  | author=Wjst M, Altmüller J, Faus-Kessler T, ''et al.'' |title=Asthma families show transmission disequilibrium of gene variants in the vitamin D metabolism and signalling pathway. |journal=Respir. Res. |volume=7 |issue=  |pages= 60 |year= 2006 |pmid= 16600026 |doi= 10.1186/1465-9921-7-60 }}
*{{Cite journal  | vauthors=Wjst M, Altmüller J, Faus-Kessler T |title=Asthma families show transmission disequilibrium of gene variants in the vitamin D metabolism and signalling pathway |journal=Respir. Res. |volume=7 |issue=  |pages= 60 |year= 2006 |pmid= 16600026 |doi= 10.1186/1465-9921-7-60 | pmc=1508148 |display-authors=etal}}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{Cite journal  | vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 |display-authors=etal}}
*{{cite journal  | author=Shinkyo R, Sakaki T, Kamakura M, ''et al.'' |title=Metabolism of vitamin D by human microsomal CYP2R1. |journal=Biochem. Biophys. Res. Commun. |volume=324 |issue= 1 |pages= 451–7 |year= 2004 |pmid= 15465040 |doi= 10.1016/j.bbrc.2004.09.073 }}
*{{Cite journal  | vauthors=Shinkyo R, Sakaki T, Kamakura M |title=Metabolism of vitamin D by human microsomal CYP2R1 |journal=Biochem. Biophys. Res. Commun. |volume=324 |issue= 1 |pages= 451–7 |year= 2004 |pmid= 15465040 |doi= 10.1016/j.bbrc.2004.09.073 |display-authors=etal}}
*{{cite journal  | author=Cheng JB, Levine MA, Bell NH, ''et al.'' |title=Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 20 |pages= 7711–5 |year= 2004 |pmid= 15128933 |doi= 10.1073/pnas.0402490101 }}
*{{Cite journal  | vauthors=Ota T, Suzuki Y, Nishikawa T |title=Complete sequencing and characterization of 21,243 full-length human cDNAs |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 |display-authors=etal}}
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{Cite journal  | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 |bibcode = 2002PNAS...9916899M |display-authors=etal}}
*{{cite journal  | author=Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW |title=De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. |journal=J. Biol. Chem. |volume=278 |issue= 39 |pages= 38084–93 |year= 2003 |pmid= 12867411 |doi= 10.1074/jbc.M307028200 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal | author=Nelson DR |title=Comparison of P450s from human and fugu: 420 million years of vertebrate P450 evolution. |journal=Arch. Biochem. Biophys. |volume=409 |issue= 1 |pages= 18–24 |year= 2003 |pmid= 12464240 |doi= }}
}}
}}
{{refend}}
{{Refend}}
 


==External links==
* {{UCSC gene info|CYP2R1}}
{{PDB Gallery|geneid=120227}}
{{Cytochrome P450}}
{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}


<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{PBB_Controls
{{PBB_Controls
| update_page = yes  
| update_page = yes
| require_manual_inspection = no  
| require_manual_inspection = no
| update_protein_box = yes
| update_protein_box = yes
| update_summary = yes
| update_summary = no
| update_citations = yes
| update_citations = yes
}}
}}


{{WH}}
[[Category:EC 1.14.13]]
{{WS}}
 
 
{{gene-11-stub}}

Latest revision as of 10:15, 30 August 2017

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Vitamin D 25-hydroxylase also known as cytochrome P450 2R1 is an enzyme that in humans is encoded by the CYP2R1 gene.[1][2][3]

Function

Vitamin D 25-hydroxylase is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. Found in the liver, this enzyme is a microsomal vitamin D hydroxylase that converts vitamin D into 25-hydroxyvitamin D (calcidiol), which is the major circulatory form of the vitamin.

Clinical significance

An inherited mutation in the CYP2R1 gene which results in the substitution of a proline for a leucine residue at codon 99 eliminates the enzyme activity and is associated with low circulating levels of 25-hydroxyvitamin D and classic symptoms of vitamin D deficiency.[2] The gene product which it encodes, vitamin D 25-hydroxylase, has therefore been proposed as the key enzyme in the conversion of cholecalciferol (vitamin D3) to calcidiol. Calcidiol is subsequently converted by the action of 25-hydroxyvitamin D3 1-alpha-hydroxylase to calcitriol, the active form of vitamin D3 that binds to the vitamin D receptor (VDR) which mediates most of the physiological actions of the vitamin.[2]

File:Reaction - cholecalciferol to calcidiol (vertical).png
Conversion of cholecalciferol to calcidiol as catalyzed by CYP2R1.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

[[File:
<imagemap> Image:VitaminDSynthesis WP1531.png
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
<imagemap> Image:VitaminDSynthesis WP1531.png
|{{{bSize}}}px|alt=Vitamin D Synthesis Pathway (view / edit)]]
Vitamin D Synthesis Pathway (view / edit)
  1. ↑ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".

Model organisms

Model organisms have been used in the study of CYP2R1 function. A conditional knockout mouse line called Cyp2r1tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[4] Male and female animals underwent a standardized phenotypic screen[5] to determine the effects of deletion.[6][7][8][9] Additional screens performed: - In-depth immunological phenotyping[10]

References

  1. ↑ Nelson DR (Dec 2002). "Comparison of P450s from human and fugu: 420 million years of vertebrate P450 evolution". Arch Biochem Biophys. 409 (1): 18–24. doi:10.1016/S0003-9861(02)00553-2. PMID 12464240.
  2. ↑ 2.0 2.1 2.2 Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW (2004-05-18). "Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase". Proc Natl Acad Sci U S A. 101 (20): 7711–7715. Bibcode:2004PNAS..101.7711C. doi:10.1073/pnas.0402490101. PMC 419671. PMID 15128933.
  3. ↑ "Entrez Gene: CYP2R1 cytochrome P450, family 2, subfamily R, polypeptide 1".
  4. ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  5. ↑ 5.0 5.1 "International Mouse Phenotyping Consortium".
  6. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  7. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  8. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  9. ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  10. ↑ 10.0 10.1 "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

External links


Retrieved from "https://www.wikidoc.org/index.php?title=CYP2R1&oldid=1415281"