Ask about this productRelated genes to: LEPREL2 antibody
- Gene:
- P3H3 NIH gene
- Name:
- prolyl 3-hydroxylase 3
- Previous symbol:
- LEPREL2
- Synonyms:
- GRCB, HSU47926
- Chromosome:
- 12p13.31
- Locus Type:
- gene with protein product
- Date approved:
- 2004-05-12
- Date modifiied:
- 2015-12-04
Related products to: LEPREL2 antibody
Related articles to: LEPREL2 antibody
- Type I collagen is the main structural protein in vertebrates and undergoes extensive post-translational modification (PTM) during biosynthesis. Prolyl-3-hydroxylase 1 (P3H1) catalyzes collagen prolyl-3-hydroxylation and functions as a collagen chaperone. Loss of P3H1 causes osteogenesis imperfecta, and P3H1 is consistently upregulated in idiopathic pulmonary fibrosis. However, the full impact of P3H1 deficiency on the collagen biosynthesis machinery, including PTMs, is not known. Here, we comprehensively investigated the consequences of P3H1 deficiency in two independent models: type I collagen from P3H1 KO mouse tail tendon and type I collagen from primary human lung fibroblasts following P3H1 knockdown. Using amino acid analysis, high-resolution tandem mass spectrometry for site-specific PTM and quantification, and gene expression analysis, we show that P3H1 deficiency profoundly disrupts the collagen PTM network. Amino acid analysis revealed global overmodification of prolines and lysines. Site-resolved tandem mass spectrometry analysis confirmed the P3H1-dependent 3-hydroxyproline site COL1A1-P1153 and demonstrated widespread increases in prolyl-3-hydroxylation, prolyl-4-hydroxylation, and lysyl modification in P3H1-deficient tendon. In both models, prolyl-4-hydroxylation frequency was increased at multiple sites, indicating that loss of P3H1 alters local modification kinetics and/or collagen chain accessibility, thereby rapidly promoting prolyl-4-hydroxylation. P3H1 deficiency also led to compensatory increases of P3H2 and P3H3 protein levels. Gene expression analyses revealed selective upregulation of collagen biosynthetic enzymes at the transcript level, including P4ha2 and Lh2 in mouse tendon and P3H2 in human fibroblasts, suggesting feedback mechanisms linking perturbation of collagen biosynthesis to nuclear transcriptional control. Taken together, this study emphasizes the essential role of P3H1 in collagen quality control. - Source: PubMed
Publication date: 2026/04/01
Staab-Weijnitz Claudia AMerl-Pham JulianeHennen ElisabethOnursal CeylanCabeza-Boeddinghaus NataliaKandhari KushalStremlau MarleenBehr JürgenHilgendorff AnneBächinger Hans PeterHauck Stefanie MVanacore RobertoHansen Kirk CBasak Trayambak - Thyroid hormones are central to regulating metabolism, growth, and development, yet their complex interactions with socioeconomic, metabolic, and genetic factors remain understudied in diverse populations. We compared thyroid profiles - free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) in Indian adolescents with anthropometric traits, metabolic markers, and socioeconomic status (SES). We observed that adolescents from higher SES backgrounds exhibited greater metabolic dysregulation, altered thyroid profiles, and abnormalities in lipid and adipokine levels. Subclinical (16.1%) and clinical hypothyroidism (1.1%) were found to be prevalent in this population but were not associated with obesity. Instead, they showed links with dyslipidemia and altered adipokine profiles. To investigate the genetic basis of thyroid traits, we conducted an exome-wide association study (ExWAS, N = 4324), and a two-staged genome-wide association study (GWAS, N = 4854). The ExWAS revealed two novel loci for TSH (GYS2 and CEP162) and fifteen novel loci for FT4, including ZNF467, P3H3, CRLF3, SPATA2L, MEFV, THNSL2, COL27A1, COL28A1, IGSF3, ZNF732, MOG, GABBR1, HPF1, LOC440563, and SPEG. The GWAS identified novel associations at near-genome-wide significance for TSH (ACTL7B) and FT4 (LINC00648, YTHDC1, and C2CD4B). We also replicated established associations in FOXE1 and IGFBP5. Our findings suggest that SES, metabolic health, and genetics jointly influence thyroid function in Indian adolescents. The identification of population-specific loci emphasizes the importance of ancestry-informed genetic studies and supports the development of precision interventions to enhance pediatric thyroid health. - Source: PubMed
Publication date: 2025/11/17
Nair Janaki MBandesh KhushdeepK Giri AnilMarwaha Raman KBasu AnalabhaTandon NikhilChakraborty ShraddhaBharadwaj Dwaipayan - Excessive deposition of fibrillar collagen in the interstitial extracellular matrix (ECM) of human lung tissue causes fibrosis, which can ultimately lead to organ failure. Despite our understanding of the molecular mechanisms underlying the disease, no cure for pulmonary fibrosis has yet been found. We screened a drug library and found that dextromethorphan (DXM), a cough expectorant, reduced the amount of excess fibrillar collagen deposited in the ECM in cultured primary human lung fibroblasts, a bleomycin mouse model, and a cultured human precision-cut lung slice model of lung fibrosis. The reduced extracellular fibrillar collagen upon DXM treatment was due to reversible trafficking inhibition of collagen type I (COL1) in the endoplasmic reticulum (ER) in TANGO1- and HSP47-positive structures. Mass spectrometric analysis showed that DXM promoted hyperhydroxylation of proline and lysine residues on various collagens (COL1, COL3, COL4, COL5, COL7, and COL12) and latent transforming growth factor-β-binding protein (LTBP1 and LTBP2) peptides, coinciding with their secretion block. Additionally, proteome profiling of DXM-treated cells showed increased thermal stability of prolyl-hydroxylases P3H2, P3H3, P3H4, P4HA1, and P4HA2, suggesting a change in their activity. Transcriptome analysis of profibrotic stimulated primary human lung fibroblasts and human ex vivo lung slices after DXM treatment showed activation of an antifibrotic program through regulation of multiple pathways, including the MMP-ADAMTS axis, WNT signaling, and fibroblast-to-myofibroblast differentiation. Together, these data obtained from in vitro, in vivo, and ex vivo models of lung fibrogenesis show that DXM has the potential to limit fibrosis through inhibition of COL1 membrane trafficking in the ER. - Source: PubMed
Publication date: 2024/12/18
Khan Muzamil MGalea GeorgeJung JuanZukowska JoannaLauer DavidTuechler NadineHalavatyi AliaksandrTischer ChristianHaberkant PerStein FrankJung FerrisLandry Jonathan J MKhan Arif MOorschot ViolaBecher IsabelleNeumann BeateMuley ThomasWinter HaukeDuerr JuliaMall Marcus AGrassi Alessandrode la Cueva ErnestoBenes VladimirGote-Schniering JanineSavitski MikhailPepperkok Rainer - Zinc-finger proteins are involved in many biological processes. However, the role of Zinc-finger protein 334 (ZNF334) in cervical cancer remains unidentified. This study showed that promoter methylation of ZNF334 was responsible for its reduced expression. ZNF334 suppressed malignant biological behaviors in cervical cancer. Notably, ZNF334 reversed the EMT process both in vitro and in vivo. RNA-seq coupled with bioinformatics analysis caught P3H3 which is upregulated by ZNF334. Dual-luciferase reporter and Chromatin immunoprecipitation assays illustrated that ZNF334 directly regulate P3H3. Knockdown of P3H3 attenuated the reversal of EMT induced by ZNF334. Additionally, ZNF334 overexpression sensitized cervical cancer cells to the cytotoxic effects of paclitaxel, cyclosporine and sunitinib. In conclusions, this study illustrated that DNA methylation-based silencing ZNF334 played a vital role in cervical cancer, by regulating P3H3 in turn affects EMT. ZNF334 has the potential to become a novel diagnostic biomarker and a potential treatment target for cervical cancer. - Source: PubMed
Publication date: 2024/07/02
Li QianZhou XiangyiXiao JiayiGong YijiaGong XueShao BianfeiWang JianhuaZhao LijuanXiong QiWu YueTang JunYang QiyuTang JunyingXiang Tingxiu - Prolyl 3-hydroxylases (P3H) are crucial enzymes in collagen biosynthesis and are known to be involved in a variety of physiological processes. However, their specific roles in cancer progression, modulation of the tumor microenvironment (TME), and impact on patient prognosis remain areas that require further investigation. - Source: PubMed
Publication date: 2024/04/19
Wang ZiyunWang Hua