请输入您要查询的百科知识：

　

词条 PDLIM3
释义

  1. Structure

  2. Function

  3. Clinical significance

  4. Interactions

  5. References

  6. Further reading

{{Infobox_gene}}

Actin-associated LIM protein (ALP), also known as PDZ and LIM domain protein 3 is a protein that in humans is encoded by the PDLIM3 gene.[1][2][3] ALP is highly expressed in cardiac and skeletal muscle, where it localizes to Z-discs and intercalated discs. ALP functions to enhance the crosslinking of actin by alpha actinin-2 and also appears to be essential for right ventricular chamber formation and contractile function.

Structure

ALP exists primarily as two alternatively spliced variants; a 39.2 kDa (364 amino acids) protein in skeletal muscle and a 34.3 kDa (316 amino acids) protein in cardiac muscle and smooth muscle.[4][5][6] ALP has a N-terminal PDZ domain and a C-terminal LIM domain. In addition, the ALP subfamily contains a specific 34 amino acid domain named the ALP-like motif, containing protein kinase C consensus sequences.[7] The PDZ domain of ALP binds to alpha actinin-2, specifically to its spectrin-like repeats.[8] The PDZ domain is a motif composed of 80-120 amino acids with conserved four residue GLGF sequences that typically interact with C-termini of cytoskeletal proteins.[9] The region of heterogeneity in the two isoforms is between the PDZ domain and LIM domain.[6] ALP is localized to chromosome 4q35.[8] It has been shown that deletion of muscleblind-like 1 in mice can alter the splicing pattern of PDLIM3.[10]

Function

Studies have shown that ALP is present at the first stage of myofibrilogenesis where it is bound to alpha actinin-2, and this association remains intact in mature myofibrils where ALP is localized to Z-discs and intercalated discs. Alpha actinin-2 is however not required for targeting ALP to Z-lines.[11] Studies in ALP knockout mice have shown that ALP facilitates the cross-linking of actin filaments by alpha actinin-2, and absence of ALP induces abnormal right ventricular chamber formation, dysplasia and cardiomyopathy.[12] Further studies using right ventricular epicardial systolic strain and geometric remodeling analysis in these animals unveiled that absence of ALP diminishes right ventricular contractile function and alters the pattern of cardiac hypertrophic remodeling.[13] Two studies using integrative genomic approaches to investigate genetic modifiers of collagen deposition[14] or intrinsic aerobic running capacity (ARC)[15] have mapped PDLIM3 to respective quantitative trait loci, suggesting that ALP may be involved in molecular networks related to these cardiac phenomena.

Clinical significance

Chromosome 4 pericentric inversion has been observed in 10 patients, with associated cardiac defects linked to terminal 4q35.1 deletions, which may affect PDLIM3.[16]

Interactions

ALP interacts with:

  • alpha actinin-2[8]
  • beta-catenin[12]
{{Clear}}

References

1. ^{{cite journal | vauthors = Bouju S, Piétu G, Le Cunff M, Cros N, Malzac P, Pellissier JF, Pons F, Léger JJ, Auffray C, Dechesne CA | title = Exclusion of muscle specific actinin-associated LIM protein (ALP) gene from 4q35 facioscapulohumeral muscular dystrophy (FSHD) candidate genes | journal = Neuromuscular Disorders | volume = 9 | issue = 1 | pages = 3–10 | date = Jan 1999 | pmid = 10063829 | pmc = | doi = 10.1016/S0960-8966(98)00087-X }}
2. ^{{cite journal | vauthors = Piétu G, Alibert O, Guichard V, Lamy B, Bois F, Leroy E, Mariage-Sampson R, Houlgatte R, Soularue P, Auffray C | title = Novel gene transcripts preferentially expressed in human muscles revealed by quantitative hybridization of a high density cDNA array | journal = Genome Research | volume = 6 | issue = 6 | pages = 492–503 | date = Jun 1996 | pmid = 8828038 | pmc = | doi = 10.1101/gr.6.6.492 }}
3. ^{{cite web | title = Entrez Gene: PDLIM3 PDZ and LIM domain 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27295| accessdate = }}
4. ^{{cite web|title=Protein sequence for human PDZ and LIM domain protein 3 (Uniprot: Q53GG5-2)|url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=Q53GG5-2|website=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)|accessdate=22 June 2015}}
5. ^{{cite web | title = Protein sequence for human PDZ and LIM domain protein 3 (Uniprot: Q53GG5) | url = http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=Q53GG5 | website = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | accessdate=22 June 2015}}
6. ^1 {{cite journal | vauthors = Pomiès P, Macalma T, Beckerle MC | title = Purification and characterization of an alpha-actinin-binding PDZ-LIM protein that is up-regulated during muscle differentiation | journal = The Journal of Biological Chemistry | volume = 274 | issue = 41 | pages = 29242–50 | date = Oct 1999 | pmid = 10506181 | doi=10.1074/jbc.274.41.29242}}
7. ^{{cite journal | vauthors = Te Velthuis AJ, Isogai T, Gerrits L, Bagowski CP | title = Insights into the molecular evolution of the PDZ/LIM family and identification of a novel conserved protein motif | journal = PLOS ONE | volume = 2 | issue = 2 | pages = e189 | date = 7 February 2007 | pmid = 17285143 | doi = 10.1371/journal.pone.0000189 | pmc=1781342}}
8. ^1 2 {{cite journal | vauthors = Xia H, Winokur ST, Kuo WL, Altherr MR, Bredt DS | title = Actinin-associated LIM protein: identification of a domain interaction between PDZ and spectrin-like repeat motifs | journal = The Journal of Cell Biology | volume = 139 | issue = 2 | pages = 507–15 | date = Oct 1997 | pmid = 9334352 | doi=10.1083/jcb.139.2.507 | pmc=2139795}}
9. ^{{cite journal | vauthors = Ponting CP, Phillips C | title = DHR domains in syntrophins, neuronal NO synthases and other intracellular proteins | journal = Trends in Biochemical Sciences | volume = 20 | issue = 3 | pages = 102–3 | date = Mar 1995 | pmid = 7535955 | doi=10.1016/s0968-0004(00)88973-2}}
10. ^{{cite journal | vauthors = Dixon DM, Choi J, El-Ghazali A, Park SY, Roos KP, Jordan MC, Fishbein MC, Comai L, Reddy S | title = Loss of muscleblind-like 1 results in cardiac pathology and persistence of embryonic splice isoforms | journal = Scientific Reports | volume = 5 | pages = 9042 | date = 12 March 2015 | pmid = 25761764 | doi = 10.1038/srep09042 | pmc=4356957}}
11. ^{{cite journal | vauthors = Henderson JR, Pomiès P, Auffray C, Beckerle MC | title = ALP and MLP distribution during myofibrillogenesis in cultured cardiomyocytes | journal = Cell Motility and the Cytoskeleton | volume = 54 | issue = 3 | pages = 254–65 | date = Mar 2003 | pmid = 12589684 | doi = 10.1002/cm.10102 }}
12. ^1 {{cite journal | vauthors = Pashmforoush M, Pomiès P, Peterson KL, Kubalak S, Ross J, Hefti A, Aebi U, Beckerle MC, Chien KR | title = Adult mice deficient in actinin-associated LIM-domain protein reveal a developmental pathway for right ventricular cardiomyopathy | journal = Nature Medicine | volume = 7 | issue = 5 | pages = 591–7 | date = May 2001 | pmid = 11329061 | doi = 10.1038/87920 }}
13. ^{{cite journal | vauthors = Lorenzen-Schmidt I, McCulloch AD, Omens JH | title = Deficiency of actinin-associated LIM protein alters regional right ventricular function and hypertrophic remodeling | journal = Annals of Biomedical Engineering | volume = 33 | issue = 7 | pages = 888–96 | date = Jul 2005 | pmid = 16060528 | doi=10.1007/s10439-005-3604-y | pmc=4482468}}
14. ^{{cite journal | vauthors = Lodder EM, Scicluna BP, Beekman L, Arends D, Moerland PD, Tanck MW, Adriaens ME, Bezzina CR | title = Integrative genomic approach identifies multiple genes involved in cardiac collagen deposition | journal = Circulation: Cardiovascular Genetics | volume = 7 | issue = 6 | pages = 790–8 | date = Dec 2014 | pmid = 25217174 | doi = 10.1161/CIRCGENETICS.114.000537 }}
15. ^{{cite journal | vauthors = Lee SJ, Ways JA, Barbato JC, Essig D, Pettee K, DeRaedt SJ, Yang S, Weaver DA, Koch LG, Cicila GT | title = Gene expression profiling of the left ventricles in a rat model of intrinsic aerobic running capacity | journal = Physiological Genomics | volume = 23 | issue = 1 | pages = 62–71 | date = Sep 2005 | pmid = 16033863 | doi = 10.1152/physiolgenomics.00251.2004 }}
16. ^{{cite journal | vauthors = Maurin ML, Labrune P, Brisset S, Le Lorc'h M, Pineau D, Castel C, Romana S, Tachdjian G | title = Molecular cytogenetic characterization of a 4p15.1-pter duplication and a 4q35.1-qter deletion in a recombinant of chromosome 4 pericentric inversion | journal = American Journal of Medical Genetics Part A | volume = 149A | issue = 2 | pages = 226–31 | date = Feb 2009 | pmid = 19161154 | doi = 10.1002/ajmg.a.32603 }}

Further reading

{{refbegin|33em}}
  • {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
  • {{cite journal | vauthors = Xia H, Winokur ST, Kuo WL, Altherr MR, Bredt DS | title = Actinin-associated LIM protein: identification of a domain interaction between PDZ and spectrin-like repeat motifs | journal = The Journal of Cell Biology | volume = 139 | issue = 2 | pages = 507–15 | date = Oct 1997 | pmid = 9334352 | pmc = 2139795 | doi = 10.1083/jcb.139.2.507 }}
  • {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
  • {{cite journal | vauthors = Klaavuniemi T, Kelloniemi A, Ylänne J | title = The ZASP-like motif in actinin-associated LIM protein is required for interaction with the alpha-actinin rod and for targeting to the muscle Z-line | journal = The Journal of Biological Chemistry | volume = 279 | issue = 25 | pages = 26402–10 | date = Jun 2004 | pmid = 15084604 | doi = 10.1074/jbc.M401871200 }}

´* {{cite journal | vauthors = Brown AK, O'Connor PJ, Roberts TE, Wakefield RJ, Karim Z, Emery P | title = Ultrasonography for rheumatologists: the development of specific competency based educational outcomes | journal = Annals of the Rheumatic Diseases | volume = 65 | issue = 5 | pages = 629–36 | date = May 2006 | pmid = 16192291 | pmc = 1798129 | doi = 10.1136/ard.2005.039974 }}

  • {{cite journal | vauthors = Arola AM, Sanchez X, Murphy RT, Hasle E, Li H, Elliott PM, McKenna WJ, Towbin JA, Bowles NE | title = Mutations in PDLIM3 and MYOZ1 encoding myocyte Z line proteins are infrequently found in idiopathic dilated cardiomyopathy | journal = Molecular Genetics and Metabolism | volume = 90 | issue = 4 | pages = 435–40 | date = Apr 2007 | pmid = 17254821 | doi = 10.1016/j.ymgme.2006.12.008 }}
{{refend}}{{PDB Gallery|geneid=27295}}
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/11/13 14:31:35