P3H1

Summary

Gene Symbol: P3H1
Description: prolyl 3-hydroxylase 1
Alias: GROS1, LEPRE1, OI8, prolyl 3-hydroxylase 1, growth suppressor 1, leprecan, leucine proline-enriched proteoglycan (leprecan) 1, leucine- and proline-enriched proteoglycan 1, procollagen-proline 3-dioxygenase
Species: human
Products:     P3H1

Top Publications

  1. Vranka J, Sakai L, Bachinger H. Prolyl 3-hydroxylase 1, enzyme characterization and identification of a novel family of enzymes. J Biol Chem. 2004;279:23615-21 pubmed
    ..P3H1 is the chick homologue of mammalian leprecan or growth suppressor 1. Two other P3H family members are the genes previously called MLAT4 and GRCB...
  2. Cabral W, Chang W, Barnes A, Weis M, Scott M, Leikin S, et al. Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. Nat Genet. 2007;39:359-65 pubmed
    ..CRTAP forms a complex with cyclophilin B and prolyl 3-hydroxylase 1, which is encoded by LEPRE1 and hydroxylates one residue in type I collagen, alpha1(I)Pro986...
  3. Willaert A, Malfait F, Symoens S, Gevaert K, Kayserili H, Megarbane A, et al. Recessive osteogenesis imperfecta caused by LEPRE1 mutations: clinical documentation and identification of the splice form responsible for prolyl 3-hydroxylation. J Med Genet. 2009;46:233-41 pubmed publisher
    Recessive forms of osteogenesis imperfecta (OI) may be caused by mutations in LEPRE1, encoding prolyl 3-hydroxylase-1 (P3H1) or in CRTAP, encoding cartilage associated protein...
  4. Baldridge D, Schwarze U, Morello R, Lennington J, Bertin T, Pace J, et al. CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. Hum Mutat. 2008;29:1435-42 pubmed publisher
    ..Two proteins, cartilage-associated protein (CRTAP) and prolyl-3-hydroxylase-1 (P3H1, encoded by the LEPRE1 gene) form a complex that performs the hydroxylation and brings the prolyl cis-trans isomerase cyclophilin-B (CYPB)..
  5. Chang W, Barnes A, Cabral W, Bodurtha J, Marini J. Prolyl 3-hydroxylase 1 and CRTAP are mutually stabilizing in the endoplasmic reticulum collagen prolyl 3-hydroxylation complex. Hum Mol Genet. 2010;19:223-34 pubmed publisher
    Null mutations in cartilage-associated protein (CRTAP) and prolyl 3-hydroxylase 1 (P3H1/LEPRE1) cause types VII and VIII OI, respectively, two novel recessive forms of osteogenesis imperfecta (OI) with severe to lethal bone dysplasia and ..
  6. Barnes A, Carter E, Cabral W, Weis M, Chang W, Makareeva E, et al. Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding. N Engl J Med. 2010;362:521-8 pubmed publisher
    ..of the collagen prolyl 3-hydroxylation complex (cartilage-associated protein [CRTAP] and prolyl 3-hydroxylase 1 [P3H1]) cause autosomal recessive osteogenesis imperfecta with rhizomelia (shortening of proximal segments of upper and ..
  7. van Dijk F, Nikkels P, Den Hollander N, Nesbitt I, van Rijn R, Cobben J, et al. Lethal/severe osteogenesis imperfecta in a large family: a novel homozygous LEPRE1 mutation and bone histological findings. Pediatr Dev Pathol. 2011;14:228-34 pubmed publisher
    ..are affected with autosomal recessive lethal or severe osteogenesis imperfecta (OI) due to a novel homozygous LEPRE1 mutation...
  8. Wu J, Zhang W, Xia L, Feng L, Shu Z, Zhang J, et al. Characterization of PPIB interaction in the P3H1 ternary complex and implications for its pathological mutations. Cell Mol Life Sci. 2019;: pubmed publisher
    The P3H1/CRTAP/PPIB complex is essential for prolyl 3-hydroxylation and folding of procollagens in the endoplasmic reticulum (ER)...
  9. Zhang Y, Dallner O, Nakadai T, Fayzikhodjaeva G, Lu Y, Lazar M, et al. A noncanonical PPAR?/RXR?-binding sequence regulates leptin expression in response to changes in adipose tissue mass. Proc Natl Acad Sci U S A. 2018;115:E6039-E6047 pubmed publisher
    ..receptor gamma (PPAR?)/retinoid X receptor alpha (RXR?)-binding site, leptin regulatory element 1 (LepRE1), within LE1, and show that it is necessary for the fat-regulated quantitative control of reporter (luciferase) ..

More Information

Publications33

  1. Hudson D, Joeng K, Werther R, Rajagopal A, Weis M, Lee B, et al. Post-translationally abnormal collagens of prolyl 3-hydroxylase-2 null mice offer a pathobiological mechanism for the high myopia linked to human LEPREL1 mutations. J Biol Chem. 2015;290:8613-22 pubmed publisher
    ..P3H2 is a member of a family of genes that includes three isoenzymes of prolyl 3-hydroxylase (P3H), P3H1, P3H2, and P3H3...
  2. Mohd Nawawi N, Selveindran N, Rasat R, Chow Y, Abdul Latiff Z, Syed Zakaria S, et al. Genotype-phenotype correlation among Malaysian patients with osteogenesis imperfecta. Clin Chim Acta. 2018;484:141-147 pubmed publisher
    ..Furthermore, a few patients (28%, n = 8) had mutations in IFITM5, BMP1, P3H1 and SERPINF1...
  3. Séguéla Arnaud M, Crismani W, Larchevêque C, Mazel J, Froger N, Choinard S, et al. Multiple mechanisms limit meiotic crossovers: TOP3α and two BLM homologs antagonize crossovers in parallel to FANCM. Proc Natl Acad Sci U S A. 2015;112:4713-8 pubmed publisher
    ..Here we identified Topoisomerase3α (TOP3α) and the RECQ4 helicases--the Arabidopsis slow growth suppressor 1 (Sgs1)/Bloom syndrome protein (BLM) homologs--as major barriers to meiotic CO formation...
  4. Marini J, Reich A, Smith S. Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation. Curr Opin Pediatr. 2014;26:500-7 pubmed publisher
    ..via defective bone mineralization, while defects in cartilage-associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1), and cyclophilin B (CYPB) cause types VII-IX osteogenesis imperfecta via defective collagen post-translational ..
  5. Panigrahi I, Didel S, Kirpal H, Bellampalli R, Miyanath S, Mullapudi N, et al. Novel mutation in a family with WNT1-related osteoporosis. Eur J Med Genet. 2018;61:369-371 pubmed publisher
    ..NGS)done for the child didn't show any variations in other OI genes including COL1A1, COL1A2, SERPINH1, CRTAP, LEPRE1, PP1B, 1F1TM5 and BMP1 genes...
  6. Succoio M, Comegna M, D Ambrosio C, Scaloni A, Cimino F, Faraonio R. Proteomic analysis reveals novel common genes modulated in both replicative and stress-induced senescence. J Proteomics. 2015;128:18-29 pubmed publisher
    ..by silencing nine of these genes in young cells, which demonstrated that RNA interference-mediated knockdown of LEPRE1, LIMA1/EPLIN, MAGOHA and MAGOHB induces a premature senescent phenotype in IMR90 cells...
  7. Heard M, Besio R, Weis M, Rai J, Hudson D, Dimori M, et al. Sc65-Null Mice Provide Evidence for a Novel Endoplasmic Reticulum Complex Regulating Collagen Lysyl Hydroxylation. PLoS Genet. 2016;12:e1006002 pubmed publisher
    ..Here we describe the critical role of SC65 (Synaptonemal Complex 65, P3H4), a leprecan-family member, as part of an endoplasmic reticulum (ER) complex with prolyl 3-hydroxylase 3...
  8. Scollo P, Snead M, Richards A, Pollitt R, Devile C. Bilateral giant retinal tears in Osteogenesis Imperfecta. BMC Med Genet. 2018;19:8 pubmed publisher
    ..the first case of a child with a rare recessive type of OI, subtype VIII, resulting from a P3H1 (also known as LEPRE1) gene mutation presenting with bilateral giant retinal tears and the surgical challenges encountered in performing ..
  9. Fratzl Zelman N, Bächinger H, Vranka J, Roschger P, Klaushofer K, Rauch F. Bone matrix hypermineralization in prolyl-3 hydroxylase 1 deficient mice. Bone. 2016;85:15-22 pubmed publisher
    Lack of prolyl 3-hydroxylase 1 (P3H1) due to mutations in P3H1 results in severe forms of recessive osteogenesis imperfecta. In the present study, we investigated the bone tissue characteristics of P3H1 null mice...
  10. Mrosk J, Bhavani G, Shah H, Hecht J, Krüger U, Shukla A, et al. Diagnostic strategies and genotype-phenotype correlation in a large Indian cohort of osteogenesis imperfecta. Bone. 2018;110:368-377 pubmed publisher
    ..The percentage of autosomal recessive forms due to mutations in BMP1, FKBP10, LEPRE1, SERPINF1, and WNT1 was unusually high (48%)...
  11. Hudson D, Weis M, Rai J, Joeng K, Dimori M, Lee B, et al. P3h3-null and Sc65-null Mice Phenocopy the Collagen Lysine Under-hydroxylation and Cross-linking Abnormality of Ehlers-Danlos Syndrome Type VIA. J Biol Chem. 2017;292:3877-3887 pubmed publisher
    ..Previous studies revealed that P3h1 preferentially 3-hydroxylates proline at a single site in collagen type I chains, whereas P3h2 is responsible for 3-..
  12. Kaul S, Sugihara T, Yoshida A, Nomura H, Wadhwa R. Gros1, a potential growth suppressor on chromosome 1: its identity to basement membrane-associated proteoglycan, leprecan. Oncogene. 2000;19:3576-83 pubmed
    ..characterized its rat-homolog as a leucine proline-enriched novel basement membrane-associated proteoglycan leprecan. We describe here cloning, expression and biological activity analysis implying that this novel proteoglycan is a ..
  13. Wassenhove McCarthy D, McCarthy K. Molecular characterization of a novel basement membrane-associated proteoglycan, leprecan. J Biol Chem. 1999;274:25004-17 pubmed
  14. Zhang Z, Zhang H, Ke Y, Yue H, Xiao W, Yu J, et al. The identification of novel mutations in COL1A1, COL1A2, and LEPRE1 genes in Chinese patients with osteogenesis imperfecta. J Bone Miner Metab. 2012;30:69-77 pubmed publisher
    ..imperfecta (OI) is caused by mutations in COL1A1 or COL1A2, the genes that encode type I collagen, and CRTAP, LEPRE1, PPIB, FKBP10, SERPINH1, and SP7 mutations were recently detected in a minority of patients with autosomal ..
  15. Takagi M, Ishii T, Barnes A, Weis M, Amano N, Tanaka M, et al. A novel mutation in LEPRE1 that eliminates only the KDEL ER- retrieval sequence causes non-lethal osteogenesis imperfecta. PLoS ONE. 2012;7:e36809 pubmed publisher
    Prolyl 3-hydroxylase 1 (P3H1), encoded by the LEPRE1 gene, forms a molecular complex with cartilage-associated protein (CRTAP) and cyclophilin B (encoded by PPIB) in the endoplasmic reticulum (ER)...
  16. Marini J, Cabral W, Barnes A. Null mutations in LEPRE1 and CRTAP cause severe recessive osteogenesis imperfecta. Cell Tissue Res. 2010;339:59-70 pubmed publisher
    ..lies in defects in the genes encoding cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1 (P3H1/LEPRE1)...
  17. Gagliardi A, Besio R, Carnemolla C, Landi C, Armini A, Aglan M, et al. Cytoskeleton and nuclear lamina affection in recessive osteogenesis imperfecta: A functional proteomics perspective. J Proteomics. 2017;167:46-59 pubmed publisher
    ..Among the recessive forms, OI types VII, VIII, and IX are due to mutations in CRTAP, P3H1, and PPIB genes, respectively...
  18. Barbirato C, Trancozo M, Almeida M, Almeida L, Santos T, Duarte J, et al. Mutational characterization of the P3H1/CRTAP/CypB complex in recessive osteogenesis imperfecta. Genet Mol Res. 2015;14:15848-58 pubmed publisher
    ..The LEPRE1, CRTAP, and PPIB genes encode proteins that form the P3H1/CRTAP/CypB complex, which is responsible for ..
  19. Quist E, Doan R, Pool R, Porter B, Bannasch D, Dindot S. Identification of a candidate mutation in the COL1A2 gene of a Chow Chow with osteogenesis imperfecta. J Hered. 2017;: pubmed publisher
    ..Targeted next-generation sequencing of genes associated with OI in humans (COL1A1, COL1A2, LEPRE1, SERPINH1, and CRTAP) revealed a G>A heterozygous mutation in the splice donor site of exon 18 of the COL1A2 ..
  20. Huang Y, Mei L, Lv W, Li H, Zhang R, Pan Q, et al. Targeted exome sequencing identifies novel compound heterozygous mutations in P3H1 in a fetus with osteogenesis imperfecta type VIII. Clin Chim Acta. 2017;464:170-175 pubmed publisher
    ..genes known to be involved in skeletal system diseases, we identified novel compound heterozygous mutation in the P3H1 gene in the fetus with OI type VIII: c.105_120del (p.D36Rfs*16) and c.2164C>T (p.Q722*)...
  21. Fratzl Zelman N, Barnes A, Weis M, Carter E, Hefferan T, Perino G, et al. Non-Lethal Type VIII Osteogenesis Imperfecta Has Elevated Bone Matrix Mineralization. J Clin Endocrinol Metab. 2016;101:3516-25 pubmed publisher
    ..osteogenesis imperfecta (OI; OMIM 601915) is a recessive form of lethal or severe OI caused by null mutations in P3H1, which encodes prolyl 3-hydroxylase 1. Clinical and bone material description of non-lethal type VIII OI...
  22. Ishikawa Y, Bachinger H. An additional function of the rough endoplasmic reticulum protein complex prolyl 3-hydroxylase 1·cartilage-associated protein·cyclophilin B: the CXXXC motif reveals disulfide isomerase activity in vitro. J Biol Chem. 2013;288:31437-46 pubmed publisher
    ..Prolyl 3-hydroxylase 1 (P3H1) forms a hetero-trimeric complex with cartilage-associated protein and cyclophilin B (CypB)...
  23. Bodian D, Chan T, Poon A, Schwarze U, Yang K, Byers P, et al. Mutation and polymorphism spectrum in osteogenesis imperfecta type II: implications for genotype-phenotype relationships. Hum Mol Genet. 2009;18:463-71 pubmed publisher
    ..In three samples without collagen mutations, we found inactivating mutations in CRTAP and LEPRE1, suggesting a frequency of these recessive mutations of approximately 5% in OI type II...
  24. Cabral W, Barnes A, Adeyemo A, Cushing K, Chitayat D, Porter F, et al. A founder mutation in LEPRE1 carried by 1.5% of West Africans and 0.4% of African Americans causes lethal recessive osteogenesis imperfecta. Genet Med. 2012;14:543-51 pubmed publisher
    Deficiency of prolyl 3-hydroxylase 1, encoded by LEPRE1, causes recessive osteogenesis imperfecta (OI). We previously identified a LEPRE1 mutation exclusively in African Americans and contemporary West Africans...