View source for Palladin

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Other uses|Paladin (disambiguation)|Palladin (surname)}}
{{Infobox_gene}}
'''Palladin''' is a [[protein]] that in humans is encoded by the ''PALLD'' [[gene]].<ref name="pmid10231032">{{cite journal |vauthors=Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro | journal = DNA Res | volume = 6 | issue = 1 | pages = 63–70 |date=Jul 1999 | pmid = 10231032 | doi =10.1093/dnares/6.1.63  | doi-access = free }}</ref><ref name="pmid10931874">{{cite journal |vauthors=Parast MM, Otey CA | title = Characterization of Palladin, a Novel Protein Localized to Stress Fibers and Cell Adhesions | journal = J Cell Biol | volume = 150 | issue = 3 | pages = 643–56 |date=Sep 2000 | pmid = 10931874 | pmc = 2175193 | doi =10.1083/jcb.150.3.643  }}</ref><ref name="pmid11230166">{{cite journal |vauthors=Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A | title = Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs | journal = Genome Res. | volume = 11 | issue = 3 | pages = 422–35 | year = 2001 | pmid = 11230166 | doi = 10.1101/gr.GR1547R| pmc = 311072 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PALLD palladin, cytoskeletal associated protein| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23022| publisher = nih.gov}}</ref> Palladin is a component of [[actin]]-containing microfilaments that control cell shape, [[cell adhesion|adhesion]], and contraction.<ref name="entrez"/>
== Discovery ==
Palladin was characterised independently by two research groups, first in the lab of Carol Otey (in 2000)<ref name="pmid10931874"/> and then in the lab of Olli Carpén (in 2001).<ref name="pmid11598191">{{cite journal |vauthors=Mykkänen OM, Grönholm M, Rönty M, Lalowski M, Salmikangas P, Suila H, Carpén O | title = Characterization of Human Palladin, a Microfilament-associated Protein | journal = Mol. Biol. Cell | volume = 12 | issue = 10 | pages = 3060–73 | year = 2001 | pmid = 11598191 | doi = 10.1091/mbc.12.10.3060| url = http://www.molbiolcell.org/cgi/content/abstract/12/10/3060 | pmc = 60155 }}</ref> It is a part of the myotilin-myopalladin-palladin family and may play an important role in modulating the [[actin]] [[cytoskeleton]].<ref name="pmid16164966">{{cite book |vauthors=Otey CA, Rachlin A, Moza M, Arneman D, Carpen O | title = The palladin/myotilin/myopalladin family of actin-associated scaffolds | journal = Int. Rev. Cytol. | volume = 246 | pages = 31–58 | year = 2005 | pmid = 16164966 | doi = 10.1016/S0074-7696(05)46002-7 | series = International Review of Cytology | isbn = 9780123646507 }}</ref> Palladin, in contrast to [[MYOT|myotilin]] and [[MYPN|myopalladin]], which are expressed only in [[striated muscle]], is expressed ubiquitously in cells of [[mesenchymal stem cell|mesenchymal]] origin.
Palladin was named after the Italian Renaissance architect [[Andrea Palladio]], reflecting its localization to architectural elements of the cell.<ref name="pmid10931874"/>
{|
|[[File:FluorescentCells.jpg|thumb|The eukaryotic cytoskeleton. Palladin is one component of this complex cellular machinery.]]
|}
==Isoforms==
In humans, it appears that seven different isoforms exist, some of which arise through [[alternative splicing]].<ref name="pmid16492705">{{cite journal |vauthors=Rachlin AS, Otey CA | title = Identification of palladin isoforms and characterization of an isoform-specific interaction between Lasp-1 and palladin | journal = J. Cell Sci. | volume = 119 | issue = Pt 6 | pages = 995–1004 | year = 2006 | pmid = 16492705 | doi = 10.1242/jcs.02825 | doi-access = free | url = https://cdr.lib.unc.edu/downloads/p5548163z }}</ref>  In mice, three major isoforms of palladin arise from a single gene.  These isoforms contain between three and five copies (depending on the isoform) of an Ig-like domain and between one and two copies of a polyproline domain.<ref name="pmid10931874"/>
== Function ==
Palladin's precise biological role is poorly understood, but it has been shown to play a role in cytoskeletal organization, embryonic development, cell motility, scar formation in the skin, and nerve cell development.<ref name="pmid16164966"/>
== Disease linkage ==
Recently, it has been demonstrated that palladin [[RNA]] is overexpressed in patients with [[pancreas|pancreatic]] [[neoplasia]], and that palladin is both overexpressed and mutated in an inherited form of [[pancreatic cancer]].<ref name="pmid17194196">{{cite journal |vauthors=Pogue-Geile KL, Chen R, Bronner MP, Crnogorac-Jurcevic T, Moyes KW, Dowen S, Otey CA, Crispin DA, George RD, Whitcomb DC, Brentnall TA | title = Palladin Mutation Causes Familial Pancreatic Cancer and Suggests a New Cancer Mechanism | journal = PLOS Med. | volume = 3 | issue = 12 | pages = e516 | year = 2006 | pmid = 17194196 | doi = 10.1371/journal.pmed.0030516| pmc = 1751121 | doi-access = free }}</ref> The palladin mutation identified in familial pancreatic cancer may be unique to a single North American family, as this same mutation has not been found in any other European or North American populations, respectively, in two other genetic studies.<ref name="pmid17455999">{{cite journal |vauthors=Slater E, Amrillaeva V, Fendrich V, Bartsch D, Earl J, Vitone LJ, Neoptolemos JP, Greenhalf W | title = Palladin Mutation Causes Familial Pancreatic Cancer: Absence in European Families | journal = PLOS Med. | volume = 4 | issue = 4 | pages = e164 | year = 2007 | pmid = 17455999 | doi = 10.1371/journal.pmed.0040164| pmc = 1855695 | doi-access = free }}</ref><ref name="pmid17415588">{{cite journal |vauthors=Zogopoulos G, Rothenmund H, Eppel A, Ash C, Akbari MR, Hedley D, Narod SA, Gallinger S | title = The P239S palladin variant does not account for a significant fraction of hereditary or early onset pancreas cancer | journal = Hum. Genet. | volume = 121 | issue = 5 | pages = 635–7 | year = 2007 | pmid = 17415588 | doi = 10.1007/s00439-007-0361-z | s2cid = 2445261 }}</ref>
Further, Salaria et al. have shown that palladin is overexpressed in the non-neoplastic stroma of pancreatic cancer, but only rarely in the cancer cells per se,<ref name="pmid17404500">{{cite journal |vauthors=Salaria SN, Illei P, Sharma R, Walter KM, Klein AP, Eshleman JR, Maitra A, Schulick R, Winter J, Ouellette MM, Goggins M, Hruban R | title = Palladin is Overexpressed in the Non-Neoplastic Stroma of Infiltrating Ductal Adenocarcinomas of the Pancreas, but is only Rarely Overexpressed in Neoplastic Cells | journal = Cancer Biol. Ther. | volume = 6 | issue = 3 | pages = 324–8 | year = 2007 | pmid = 17404500 | doi = 10.4161/cbt.6.3.3904| url = http://www.landesbioscience.com/journals/cbt/abstract.php?id=3904 | pmc = 3144721 }}</ref> suggesting that palladin's role in this disease may involve changes in the tumor microenvironmment.  More research is clearly required before this protein and its role in neoplasia can be fully understood.
Disease-causing mutations have also been identified in the two other members of this gene family.  [[MYOT|Myotilin]] mutations cause a form of limb-girdle muscular dystrophy, and mutations in [[MYPN|myopalladin]] cause an inherited form of heart disease ([[dilated cardiomyopathy]]).
== Interactions ==
PALLD has been shown to [[Protein-protein interaction|interact]] with [[ezrin|EZR]].<ref name="pmid11598191"/>
==References==
{{Reflist|2}}
==Further reading==
{{refbegin | 2}}
*{{cite journal  |vauthors=King CM, Olive CW, Cardona RA |title=Activation of carcinogenic arylhydroxamic acids by human tissues |journal=J. Natl. Cancer Inst. |volume=55 |issue= 2 |pages= 285–7 |year= 1975 |pmid= 1159819 |doi= 10.1093/jnci/55.2.285 }}
*{{cite journal   |vauthors=Lai CH, Chou CY, Ch'ang LY, etal |title=Identification of Novel Human Genes Evolutionarily Conserved in Caenorhabditis elegans by Comparative Proteomics |journal=Genome Res. |volume=10 |issue= 5 |pages= 703–13 |year= 2000 |pmid= 10810093 |doi=10.1101/gr.10.5.703  | pmc=310876  }}
*{{cite journal   |vauthors=Bang ML, Mudry RE, McElhinny AS, etal |title=Myopalladin, a Novel 145-Kilodalton Sarcomeric Protein with Multiple Roles in Z-Disc and I-Band Protein Assemblies |journal=J. Cell Biol. |volume=153 |issue= 2 |pages= 413–27 |year= 2001 |pmid= 11309420 |doi=10.1083/jcb.153.2.413 | pmc=2169455  }}
*{{cite journal   |vauthors=Mykkänen OM, Grönholm M, Rönty M, etal |title=Characterization of Human Palladin, a Microfilament-associated Protein |journal=Mol. Biol. Cell |volume=12 |issue= 10 |pages= 3060–73 |year= 2002 |pmid= 11598191 |doi=  10.1091/mbc.12.10.3060| pmc=60155  }}
*{{cite journal   |vauthors=Eberle MA, Pfützer R, Pogue-Geile KL, etal |title=A New Susceptibility Locus for Autosomal Dominant Pancreatic Cancer Maps to Chromosome 4q32-34 |journal=Am. J. Hum. Genet. |volume=70 |issue= 4 |pages= 1044–8 |year= 2002 |pmid= 11870593 |doi=10.1086/339692 | pmc=379100  }}
*{{cite journal  |vauthors=Moriyama K, Bonifacino JS |title=Pallidin is a component of a multi-protein complex involved in the biogenesis of lysosome-related organelles |journal=Traffic |volume=3 |issue= 9 |pages= 666–77 |year= 2003 |pmid= 12191018 |doi=10.1034/j.1600-0854.2002.30908.x  |s2cid=29888859 |doi-access=free }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }}
*{{cite journal   |vauthors=Lee SY, Obata Y, Yoshida M, etal |title=Immunomic analysis of human sarcoma |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=100 |issue= 5 |pages= 2651–6 |year= 2003 |pmid= 12601173 |doi= 10.1073/pnas.0437972100 | pmc=151395 |bibcode=2003PNAS..100.2651L |doi-access=free }}
*{{cite journal   |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 |doi-access= free }}
*{{cite journal   |vauthors=Rönty M, Taivainen A, Moza M, etal |title=Molecular analysis of the interaction between palladin and alpha-actinin |journal=FEBS Lett. |volume=566 |issue= 1–3 |pages= 30–4 |year= 2004 |pmid= 15147863 |doi= 10.1016/j.febslet.2004.04.006 |s2cid=86151740 }}
*{{cite journal   |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928 }}
*{{cite journal   |vauthors=Hillier LW, Graves TA, Fulton RS, etal |title=Generation and annotation of the DNA sequences of human chromosomes 2 and 4 |journal=Nature |volume=434 |issue= 7034 |pages= 724–31 |year= 2005 |pmid= 15815621 |doi= 10.1038/nature03466 |bibcode=2005Natur.434..724H |doi-access= free }}
*{{cite journal   |vauthors=Rönty M, Taivainen A, Moza M, etal |title=Involvement of palladin and alpha-actinin in targeting of the Abl/Arg kinase adaptor ArgBP2 to the actin cytoskeleton |journal=Exp. Cell Res. |volume=310 |issue= 1 |pages= 88–98 |year= 2005 |pmid= 16125169 |doi= 10.1016/j.yexcr.2005.06.026 }}
*{{cite journal   |vauthors=Shiffman D, Ellis SG, Rowland CM, etal |title=Identification of Four Gene Variants Associated with Myocardial Infarction |journal=Am. J. Hum. Genet. |volume=77 |issue= 4 |pages= 596–605 |year= 2005 |pmid= 16175505 |doi= 10.1086/491674  | pmc=1275608 }}
*{{cite journal   |vauthors=Boukhelifa M, Moza M, Johansson T, etal |title=The proline-rich protein palladin is a binding partner for profilin |journal=FEBS J. |volume=273 |issue= 1 |pages= 26–33 |year= 2006 |pmid= 16367745 |doi= 10.1111/j.1742-4658.2005.05036.x |s2cid=21207885 |doi-access=free }}
*{{cite journal   |vauthors=Rönty MJ, Leivonen SK, Hinz B, etal |title=Isoform-specific regulation of the actin-organizing protein palladin during TGF-beta1-induced myofibroblast differentiation |journal=J. Invest. Dermatol. |volume=126 |issue= 11 |pages= 2387–96 |year= 2007 |pmid= 16794588 |doi= 10.1038/sj.jid.5700427 |doi-access= free |url= https://cdr.lib.unc.edu/downloads/wm117x803 }}
*{{cite journal   |vauthors=Beausoleil SA, Villén J, Gerber SA, etal |title=A probability-based approach for high-throughput protein phosphorylation analysis and site localization |journal=Nat. Biotechnol. |volume=24 |issue= 10 |pages= 1285–92 |year= 2006 |pmid= 16964243 |doi= 10.1038/nbt1240 |s2cid=14294292 }}
*{{cite journal   |vauthors=Olsen JV, Blagoev B, Gnad F, etal |title=Global, in vivo, and site-specific phosphorylation dynamics in signaling networks |journal=Cell |volume=127 |issue= 3 |pages= 635–48 |year= 2006 |pmid= 17081983 |doi= 10.1016/j.cell.2006.09.026 |s2cid=7827573 |doi-access=free }}
{{refend}}
==External links==
* {{MeshName|palladin+protein,+human}}
{{PDB Gallery|geneid=23022}}