GGPS1

Geranylgeranyl pyrophosphate synthase is an enzyme that in humans is encoded by the GGPS1 gene.[5][6][7]

GGPS1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2Q80
Identifiers
Aliases	GGPS1, GGPPS, GGPPS1, geranylgeranyl diphosphate synthase 1
External IDs	OMIM: 606982 MGI: 1341724 HomoloGene: 31267 GeneCards: GGPS1
EC number	2.5.1.1
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q42.3 Start 235,327,350 bp[1] End 235,344,532 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13 A1|13 5.29 cM Start 14,050,659 bp[2] End 14,063,488 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transferase activity • farnesyltranstransferase activity • GO:0001948 protein binding • metal ion binding • dimethylallyltranstransferase activity • geranyltranstransferase activity • identical protein binding Cellular component • cytoplasm • cytosol Biological process • cholesterol biosynthetic process • farnesyl diphosphate biosynthetic process • geranyl diphosphate biosynthetic process • geranylgeranyl diphosphate biosynthetic process • isoprenoid biosynthetic process • isoprenoid metabolic process • regulation of cholesterol biosynthetic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	9453	14593
Ensembl	ENSG00000152904	ENSMUSG00000021302
UniProt	O95749	Q9WTN0
RefSeq (mRNA)	NM_001037277 NM_001037278 NM_004837 NM_001371477 NM_001371478	NM_010282 NM_001331119 NM_001331176 NM_001331177 NM_001331178 NM_001331180
RefSeq (protein)	NP_001032354 NP_001032355 NP_001358406 NP_001358407 NP_004828 NP_001032354.1	NP_001318048 NP_001318105 NP_001318106 NP_001318107 NP_001318109 NP_034412
Location (UCSC)	Chr 1: 235.33 – 235.34 Mb	Chr 13: 14.05 – 14.06 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene is a member of the prenyltransferase family and encodes a protein with geranylgeranyl diphosphate (GGPP) synthase activity. The enzyme catalyzes the synthesis of GGPP from farnesyl diphosphate and isopentenyl diphosphate. GGPP is an important molecule responsible for the C20-prenylation of proteins and for the regulation of a nuclear hormone receptor. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[7]

Much like its homolog farnesyl diphosphate synthase, GGPS1 is inhibited by bisphosphonate compounds.[8]

Clinical

Mutations in both copies of this gene have been associated with a syndrome of muscular dystrophy, hearing loss and ovarian insufficiency.[9]

References

1. GRCh38: Ensembl release 89: ENSG00000152904 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021302 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Ericsson J, Greene JM, Carter KC, Shell BK, Duan DR, Florence C, Edwards PA (September 1998). "Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression". Journal of Lipid Research. 39 (9): 1731–9. PMID 9741684.
6. Kainou T, Kawamura K, Tanaka K, Matsuda H, Kawamukai M (March 1999). "Identification of the GGPS1 genes encoding geranylgeranyl diphosphate synthases from mouse and human". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1437 (3): 333–40. doi:10.1016/S1388-1981(99)00028-1. PMID 10101267.
7. "Entrez Gene: GGPS1 geranylgeranyl diphosphate synthase 1".
8. Wiemer AJ, Wiemer DF, Hohl RJ (December 2011). "Geranylgeranyl diphosphate synthase: an emerging therapeutic target". Clinical Pharmacology and Therapeutics. 90 (6): 804–12. doi:10.1038/clpt.2011.215. PMID 22048229.
9. Foley AR, Zou Y, Dunford JE, Rooney J, Chandra G, Xiong H, Straub V, Voit T, Romero N, Donkervoort S, Hu Y, Markello T, Horn A, Qebibo L, Dastgir J, Meilleur K, Finkel RS, Fan Y, Mamchaoui K, Duguez S, Nelson I, Laporte J, Santi M, Malfatti E, Maisonobe T, Touraine P, Hirano M, Hughes I, Bushby K, Oppermann U, Böhm J, Jaiswal JK, Stojkovic T, Bönnemann CG (2020) GGPS1 mutations cause muscular dystrophy/hearing loss/ovarian insufficiency syndrome. Ann Neurol

Further reading

• Ericsson J, Runquist M, Thelin A, Andersson M, Chojnacki T, Dallner G (January 1993). "Distribution of prenyltransferases in rat tissues. Evidence for a cytosolic all-trans-geranylgeranyl diphosphate synthase". The Journal of Biological Chemistry. 268 (2): 832–8. PMID 8419360.
• Kuzuguchi T, Morita Y, Sagami I, Sagami H, Ogura K (February 1999). "Human geranylgeranyl diphosphate synthase. cDNA cloning and expression". The Journal of Biological Chemistry. 274 (9): 5888–94. doi:10.1074/jbc.274.9.5888. PMID 10026212.
• Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL (August 2000). "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning". Proceedings of the National Academy of Sciences of the United States of America. 97 (17): 9543–8. doi:10.1073/pnas.160270997. PMC 16901. PMID 10931946.
• Bommel H, Xie G, Rossoll W, Wiese S, Jablonka S, Boehm T, Sendtner M (November 2002). "Missense mutation in the tubulin-specific chaperone E (Tbce) gene in the mouse mutant progressive motor neuronopathy, a model of human motoneuron disease". The Journal of Cell Biology. 159 (4): 563–9. doi:10.1083/jcb.200208001. PMC 2173089. PMID 12446740.
• Kavanagh KL, Dunford JE, Bunkoczi G, Russell RG, Oppermann U (August 2006). "The crystal structure of human geranylgeranyl pyrophosphate synthase reveals a novel hexameric arrangement and inhibitory product binding". The Journal of Biological Chemistry. 281 (31): 22004–12. doi:10.1074/jbc.M602603200. PMID 16698791.
• Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC (March 2007). "Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects". Atherosclerosis. 191 (1): 63–72. doi:10.1016/j.atherosclerosis.2006.05.032. PMID 16806233.
• Raz T, Nardi V, Azam M, Cortes J, Daley GQ (September 2007). "Farnesyl transferase inhibitor resistance probed by target mutagenesis". Blood. 110 (6): 2102–9. doi:10.1182/blood-2006-12-064907. PMC 1976354. PMID 17536018.