ZC3HC1
| ZC3HC1 | |||
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Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 7: 130.02 – 130.05 Mb | Chr 6: 30.37 – 30.39 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Nuclear-interacting partner of ALK (NIPA), also known as zinc finger C3HC-type protein 1 (ZC3HC1), is a
Structure
Gene
The ZC3HC1 gene resides on chromosome 7 at the band 7q32.2 and includes 14 exons.[6]
Protein
NIPA is a 60-kDa E3 ligase that contains one C3HC-type
Function
NIPA is broadly expressed in the human tissues, with the highest expression in heart, skeletal muscle, and testis.
Clinical relevance
In humans, NIPA has been implicated in cardiovascular diseases by genome-wide association (GWAS) studies. Specifically, a single-nucleotide polymorphism (SNP) situated in ZC3HC1 has been shown to predict coronary artery disease.[15][16] This prediction appears to be independent of traditional risk factors for cardiovascular disease such as high cholesterol levels, high blood pressure, obesity, smoking and diabetes mellitus, which are primary targets of current treatments for coronary artery disease. Therefore, studying the function of this gene may identify novel pathways contributing to coronary artery disease that result in the development of novel therapeutics.
Clinical marker
At the coronary artery disease-associated locus 7q32.2, only a single SNP (rs11556924) is associated with coronary artery disease risk, with no other variants in strong linkage disequilibrium. The rs11556924 SNP in the ZC3HC1 gene results in an arginine-histidine polymorphism at amino acid residue 363 in NIPA.[17] Furthermore, rs11556924 has also been associated with altered carotid intima-media thickness in patients with rheumatoid arthritis[18] and with altered risk of atrial fibrillation.[19]
Additionally, a multi-locus genetic risk score study based on a combination of 27 loci, including the ZC3HC1 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).[10]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000091732 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039130 – Ensembl, May 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.
- PMID 11042152.
- ^ a b "Entrez Gene: ZC3HC1 zinc finger, C3HC-type containing 1".
- ^ "BioGPS - your Gene Portal System". biogps.org. Retrieved 2016-10-11.
- ^ S2CID 16122567.
- ^ PMID 17389604.
- ^ PMID 25748612.
- ^ PMID 12748172.
- PMID 26266351.
- ^ "ZC3HC1 - Nuclear-interacting partner of ALK - Homo sapiens (Human) - ZC3HC1 gene & protein". www.uniprot.org. Retrieved 2016-10-11.
- PMID 16258267.
- PMID 27226629.
- PMID 27226629.
- S2CID 16122567.
- PMID 24286297.
- PMID 26893834.
Further reading
- Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ (March 2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3491–6. PMID 10737800.
- Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. PMID 11076863.
- Ouyang T, Bai RY, Bassermann F, von Klitzing C, Klumpen S, Miething C, Morris SW, Peschel C, Duyster J (August 2003). "Identification and characterization of a nuclear interacting partner of anaplastic lymphoma kinase (NIPA)". The Journal of Biological Chemistry. 278 (32): 30028–36. PMID 12748172.
- Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. PMID 15489336.
- Bassermann F, von Klitzing C, Münch S, Bai RY, Kawaguchi H, Morris SW, Peschel C, Duyster J (July 2005). "NIPA defines an SCF-type mammalian E3 ligase that regulates mitotic entry". Cell. 122 (1): 45–57. S2CID 16122567.
- Ambrogio C, Voena C, Manazza AD, Piva R, Riera L, Barberis L, Costa C, Tarone G, Defilippi P, Hirsch E, Boeri Erba E, Mohammed S, Jensen ON, Palestro G, Inghirami G, Chiarle R (December 2005). "p130Cas mediates the transforming properties of the anaplastic lymphoma kinase". Blood. 106 (12): 3907–16. PMID 16105984.
- Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–8. PMID 16381901.
- Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (October 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–92. S2CID 14294292.
- Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. S2CID 7827573.