DHCR7

Pretraga
PMC	članci
PubMed	članci
NCBI	proteini

7-Dehidroholesterol-reduktaza
7-Dehidroholesterol-reduktaza
Identifikatori
EC broj	1.3.1.21
CAS broj	9080-21-1
Baze podataka
IntEnz	IntEnz pregled
BRENDA	BRENDA unos
ExPASy	NiceZyme pregled
KEGG	KEGG unos
MetaCyc	metabolički put
PRIAM	profil
PDB strukture	RCSB PDB PDBj PDBe PDBsum
Ontologija gena	AmiGO / QuickGO
PMC
Pretraga
PMC	članci
PubMed	članci
NCBI	proteini

DHCR7
Identifikatori
Aliasi	DHCR7
Vanjski ID-jevi	OMIM: 602858 MGI: 1298378 HomoloGene: 1042 GeneCards: DHCR7
EC broj	1.3.1.21
Lokacija gena (čovjek)
Hrom.	Hromosom 11 (čovjek)
Kraj	71,452,868 bp
Lokacija gena (miš)
Hrom.	Hromosom 7 (miš)
Kraj	143,402,147 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor; • oxidoreductase activity; • NADP binding; • 7-dehydrocholesterol reductase activity; • sterol delta7 reductase activity;
Ćelijska komponenta	• integral component of membrane; • endoplasmic reticulum membrane; • membrana; • intracellular membrane-bounded organelle; • integral component of endoplasmic reticulum membrane; • Endoplazmatski retikulum; • nuclear outer membrane; • citosol;
Biološki proces	• Ćelijska diferencijacija; • steroid metabolic process; • sterol biosynthetic process; • multicellular organism growth; • lung development; • lipid metabolism; • cholesterol metabolic process; • post-embryonic development; • blood vessel development; • regulation of cell population proliferation; • cholesterol biosynthetic process via lathosterol; • cholesterol biosynthetic process via desmosterol; • steroid biosynthetic process; • cholesterol biosynthetic process; • brassinosteroid biosynthetic process; • regulation of cholesterol biosynthetic process;
	Izvori:Amigo / QuickGO
Ortolozi
	1717
	13360
	ENSG00000172893
	ENSMUSG00000058454
	Q9UBM7
	O88455
	NM_001163817; NM_001360
NM_007856; NM_001382498; NM_001382499; NM_001382500; NM_001382501;
	NM_001382502; NM_001382503
	NP_001157289; NP_001351
NP_031882; NP_001369427; NP_001369428; NP_001369429; NP_001369430;
	NP_001369431; NP_001369432
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

7-Dehidroholesterol-reduktaza, znana kao DHCR7, je proteinski enzim koji je kod ljudi kodiran genom DHCR7.^[5]^[6]^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 475 aminokiselina, a molekulska težina 54.489 Da.^[8]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MAAKSQPNIP	KAKSLDGVTN	DRTASQGQWG	RAWEVDWFSL	ASVIFLLLFA
PFIVYYFIMA	CDQYSCALTG	PVVDIVTGHA	RLSDIWAKTP	PITRKAAQLY
TLWVTFQVLL	YTSLPDFCHK	FLPGYVGGIQ	EGAVTPAGVV	NKYQINGLQA
WLLTHLLWFA	NAHLLSWFSP	TIIFDNWIPL	LWCANILGYA	VSTFAMVKGY
FFPTSARDCK	FTGNFFYNYM	MGIEFNPRIG	KWFDFKLFFN	GRPGIVAWTL
INLSFAAKQR	ELHSHVTNAM	VLVNVLQAIY	VIDFFWNETW	YLKTIDICHD
HFGWYLGWGD	CVWLPYLYTL	QGLYLVYHPV	QLSTPHAVGV	LLLGLVGYYI
FRVANHQKDL	FRRTDGRCLI	WGRKPKVIEC	SYTSADGQRH	HSKLLVSGFW
GVARHFNYVG	DLMGSLAYCL	ACGGGHLLPY	FYIIYMAILL	THRCLRDEHR
CASKYGRDWE	RYTAAVPYRL	LPGIF

Funkcija

Protein kodiran ovim genom je enzim koji katalizira proizvodnju holesterola iz 7-dehidroholesterola, pomoću NADPH.

Gen DHCR7 kodira delta-7-sterol reduktazu (EC 1.3.1.21), vrhunski enzim biosinteze sisarskog sterola kojeg pretvara iz 7-dehidroholesterola (7-DHC) u holesterol. Ovaj enzim uklanja C (7-8) dvostruku vezu koju uvode sterol delta8-delta7 izomeraze. Osim toga, poznata je njegova uloga u malformacijama uzrokovanim lijekovima: inhibitori posljednjeg koraka biosinteze holesterola poput AY9944 i BM15766 ozbiljno narušavaju razvoj mozga.^[5]

Patologija

Nedostatak je povezan sa Smith-Lemli-Opitzovim sindromom.^[9]

Sve kućne mačke i psi imaju veću aktivnost ovog enzima od uobičajene, uzrokujući nemogućnost sinteze vitamina D zbog nedostatka 7-dehidroholesterola.^[10]

Interaktivna mapa puta

Šablon:VitaminDSynthesis WP1531

Također pogledajta

Steroidogeni enzim

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000172893 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000058454 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: DHCR7 7-dehydrocholesterol reductase".
^ Moebius FF, Fitzky BU, Lee JN, Paik YK, Glossmann H (Feb 1998). "Molecular cloning and expression of the human delta7-sterol reductase". Proceedings of the National Academy of Sciences of the United States of America. 95 (4): 1899–902. doi:10.1073/pnas.95.4.1899. PMC 19210. PMID 9465114.
^ Wassif CA, Maslen C, Kachilele-Linjewile S, Lin D, Linck LM, Connor WE, Steiner RD, Porter FD (Jul 1998). "Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome". American Journal of Human Genetics. 63 (1): 55–62. doi:10.1086/301936. PMC 1377256. PMID 9634533.
^ "UniProt, Q9UBM7". Pristupljeno 20. 8. 2021.
^ Yu H, Patel SB (Nov 2005). "Recent insights into the Smith-Lemli-Opitz syndrome". Clinical Genetics. 68 (5): 383–91. doi:10.1111/j.1399-0004.2005.00515.x. PMC 1350989. PMID 16207203.
^ Zafalon, Rafael V. A.; Risolia, Larissa W.; Pedrinelli, Vivian; Vendramini, Thiago H. A.; Rodrigues, Roberta B. A.; Amaral, Andressa R.; Kogika, Marcia M.; Brunetto, Marcio A. (januar 2020). "Vitamin D metabolism in dogs and cats and its relation to diseases not associated with bone metabolism". Journal of Animal Physiology and Animal Nutrition. 104 (1): 322–342. doi:10.1111/jpn.13259. PMID 31803981.

Dopunska literatura

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Nowaczyk MJ, Nakamura LM, Waye JS (Dec 2001). "DHCR7 and Smith-Lemli-Opitz syndrome". Clinical and Investigative Medicine. 24 (6): 311–7. PMID 11767235.
Shefer S, Salen G, Batta AK, Honda A, Tint GS, Irons M, Elias ER, Chen TC, Holick MF (Oct 1995). "Markedly inhibited 7-dehydrocholesterol-delta 7-reductase activity in liver microsomes from Smith-Lemli-Opitz homozygotes". The Journal of Clinical Investigation. 96 (4): 1779–85. doi:10.1172/JCI118223. PMC 185814. PMID 7560069.
Moebius FF, Fitzky BU, Lee JN, Paik YK, Glossmann H (Feb 1998). "Molecular cloning and expression of the human delta7-sterol reductase". Proceedings of the National Academy of Sciences of the United States of America. 95 (4): 1899–902. doi:10.1073/pnas.95.4.1899. PMC 19210. PMID 9465114.
Wassif CA, Maslen C, Kachilele-Linjewile S, Lin D, Linck LM, Connor WE, Steiner RD, Porter FD (Jul 1998). "Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome". American Journal of Human Genetics. 63 (1): 55–62. doi:10.1086/301936. PMC 1377256. PMID 9634533.
Fitzky BU, Witsch-Baumgartner M, Erdel M, Lee JN, Paik YK, Glossmann H, Utermann G, Moebius FF (Jul 1998). "Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome". Proceedings of the National Academy of Sciences of the United States of America. 95 (14): 8181–6. doi:10.1073/pnas.95.14.8181. PMC 20950. PMID 9653161.
Waterham HR, Wijburg FA, Hennekam RC, Vreken P, Poll-The BT, Dorland L, Duran M, Jira PE, Smeitink JA, Wevers RA, Wanders RJ (Aug 1998). "Smith-Lemli-Opitz syndrome is caused by mutations in the 7-dehydrocholesterol reductase gene". American Journal of Human Genetics. 63 (2): 329–38. doi:10.1086/301982. PMC 1377322. PMID 9683613.
Holmer L, Pezhman A, Worman HJ (Dec 1998). "The human lamin B receptor/sterol reductase multigene family". Genomics. 54 (3): 469–76. doi:10.1006/geno.1998.5615. PMID 9878250.
De Brasi D, Esposito T, Rossi M, Parenti G, Sperandeo MP, Zuppaldi A, Bardaro T, Ambruzzi MA, Zelante L, Ciccodicola A, Sebastio G, D'Urso M, Andria G (Dec 1999). "Smith-Lemli-Opitz syndrome: evidence of T93M as a common mutation of delta7-sterol reductase in Italy and report of three novel mutations". European Journal of Human Genetics. 7 (8): 937–40. doi:10.1038/sj.ejhg.5200390. PMID 10602371. S2CID 20399957.
Witsch-Baumgartner M, Fitzky BU, Ogorelkova M, Kraft HG, Moebius FF, Glossmann H, Seedorf U, Gillessen-Kaesbach G, Hoffmann GF, Clayton P, Kelley RI, Utermann G (Feb 2000). "Mutational spectrum in the Delta7-sterol reductase gene and genotype-phenotype correlation in 84 patients with Smith-Lemli-Opitz syndrome". American Journal of Human Genetics. 66 (2): 402–12. doi:10.1086/302760. PMC 1288092. PMID 10677299.
Linck LM, Hayflick SJ, Lin DS, Battaile KP, Ginat S, Burlingame T, Gibson KM, Honda M, Honda A, Salen G, Tint GS, Connor WE, Steiner RD (Mar 2000). "Fetal demise with Smith-Lemli-Opitz syndrome confirmed by tissue sterol analysis and the absence of measurable 7-dehydrocholesterol Delta(7)-reductase activity in chorionic villi". Prenatal Diagnosis. 20 (3): 238–40. doi:10.1002/(SICI)1097-0223(200003)20:3<238::AID-PD792>3.0.CO;2-W. PMID 10719329.
Yu H, Lee MH, Starck L, Elias ER, Irons M, Salen G, Patel SB, Tint GS (maj 2000). "Spectrum of Delta(7)-dehydrocholesterol reductase mutations in patients with the Smith-Lemli-Opitz (RSH) syndrome". Human Molecular Genetics. 9 (9): 1385–91. doi:10.1093/hmg/9.9.1385. PMID 10814720.
Krakowiak PA, Nwokoro NA, Wassif CA, Battaile KP, Nowaczyk MJ, Connor WE, Maslen C, Steiner RD, Porter FD (Sep 2000). "Mutation analysis and description of sixteen RSH/Smith-Lemli-Opitz syndrome patients: polymerase chain reaction-based assays to simplify genotyping". American Journal of Medical Genetics. 94 (3): 214–27. doi:10.1002/1096-8628(20000918)94:3<214::AID-AJMG7>3.0.CO;2-R. PMID 10995508.
Löffler J, Trojovsky A, Casati B, Kroisel PM, Utermann G (Nov 2000). "Homozygosity for the W151X stop mutation in the delta7-sterol reductase gene (DHCR7) causing a lethal form of Smith-Lemli-Opitz syndrome: retrospective molecular diagnosis". American Journal of Medical Genetics. 95 (2): 174–7. doi:10.1002/1096-8628(20001113)95:2<174::AID-AJMG16>3.0.CO;2-9. PMID 11078571.
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Nowaczyk MJ, Heshka T, Eng B, Feigenbaum AJ, Waye JS (Apr 2001). "DHCR7 genotypes of cousins with Smith-Lemli-Opitz syndrome". American Journal of Medical Genetics. 100 (2): 162–3. doi:10.1002/ajmg.1227. PMID 11298379.
Jira PE, Wanders RJ, Smeitink JA, De Jong J, Wevers RA, Oostheim W, Tuerlings JH, Hennekam RC, Sengers RC, Waterham HR (maj 2001). "Novel mutations in the 7-dehydrocholesterol reductase gene of 13 patients with Smith--Lemli--Opitz syndrome". Annals of Human Genetics. 65 (Pt 3): 229–36. doi:10.1017/S0003480001008600. PMID 11427181.
Nowaczyk MJ, Farrell SA, Sirkin WL, Velsher L, Krakowiak PA, Waye JS, Porter FD (Sep 2001). "Smith-Lemli-Opitz (RHS) syndrome: holoprosencephaly and homozygous IVS8-1G-->C genotype". American Journal of Medical Genetics. 103 (1): 75–80. doi:10.1002/1096-8628(20010915)103:1<75::AID-AJMG1502>3.0.CO;2-R. PMID 11562938.