Palladin

For other uses, see Paladin (disambiguation) and Palladin (surname).

PALLD
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2DM2, 2DM3
Identifiers
Aliases	PALLD , CGI-151, CGI151, MYN, PNCA1, SIH002, palladin, cytoskeletal associated protein
External IDs	OMIM: 608092 MGI: 1919583 HomoloGene: 75052 GeneCards: PALLD
Gene location (Human) Chr. Chromosome 4 (human) [1] Band 4q32.3 Start 168,497,052 bp [1] End 168,928,457 bp [1]
Gene location (Mouse) Chr. Chromosome 8 (mouse) [2] Band 8|8 B3.1 Start 61,964,467 bp [2] End 62,355,724 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in saphenous vein right ventricle hair follicle visceral pleura seminal vesicula myometrium right coronary artery popliteal artery gastric mucosa urethra Top expressed in belly cord atrium atrioventricular valve interventricular septum endocardial cushion left lung lobe ventricle uterus left ventricle myocardium of ventricle More reference expression data BioGPS n/a
Gene ontology Molecular function muscle alpha-actinin binding protein binding actin binding cell-cell adhesion mediator activity Cellular component cell projection focal adhesion growth cone ruffle plasma membrane axon cell junction Z disc actin filament actin cytoskeleton podosome cytoskeleton nucleus lamellipodium cytoplasm cytosol Biological process epithelial cell morphogenesis keratinocyte development cytoskeleton organization actin cytoskeleton organization cell migration homophilic cell adhesion via plasma membrane adhesion molecules axon guidance dendrite self-avoidance Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23022 72333 Ensembl ENSG00000129116 ENSMUSG00000058056 UniProt Q8WX93 Q9ET54 RefSeq (mRNA) NM_001166108 NM_001166109 NM_001166110 NM_016081 NM_001367567 NM_001367568 NM_001367569 NM_001367570 NM_001081390 NM_001293772 NM_001293773 NM_001293774 RefSeq (protein) NP_001159580 NP_001159581 NP_001159582 NP_057165 NP_001354496 NP_001354497 NP_001354498 NP_001354499 NP_001074859 NP_001280701 NP_001280702 NP_001280703 Location (UCSC) Chr 4: 168.5 – 168.93 Mb Chr 8: 61.96 – 62.36 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Palladin is a protein that in humans is encoded by the PALLD gene. ^{[5] [6] [7] [8]} Palladin is a component of actin-containing microfilaments that control cell shape, adhesion, and contraction. ^[8]

Discovery

Palladin was characterised independently by two research groups, first in the lab of Carol Otey (in 2000) ^[6] and then in the lab of Olli Carpén (in 2001). ^[9] It is a part of the myotilin-myopalladin-palladin family and may play an important role in modulating the actin cytoskeleton. ^[10] Palladin, in contrast to myotilin and myopalladin, which are expressed only in striated muscle, is expressed ubiquitously in cells of mesenchymal origin.

Palladin was named after the Italian Renaissance architect Andrea Palladio, reflecting its localization to architectural elements of the cell. ^[6]

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. ^[11] 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. ^[6]

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. ^[10]

Disease linkage

Recently, it has been demonstrated that palladin RNA is overexpressed in patients with pancreatic neoplasia, and that palladin is both overexpressed and mutated in an inherited form of pancreatic cancer. ^[12] 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. ^{[13] [14]}

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, ^[15] 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. Myotilin mutations cause a form of limb-girdle muscular dystrophy, and mutations in myopalladin cause an inherited form of heart disease (dilated cardiomyopathy).

Interactions

PALLD has been shown to interact with EZR. ^[9]

References

1. GRCh38: Ensembl release 89: ENSG00000129116 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000058056 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Jul 1999). "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". DNA Res. 6 (1): 63–70. doi: 10.1093/dnares/6.1.63 . PMID   10231032.
6. Parast MM, Otey CA (Sep 2000). "Characterization of Palladin, a Novel Protein Localized to Stress Fibers and Cell Adhesions". J Cell Biol. 150 (3): 643–56. doi:10.1083/jcb.150.3.643. PMC   2175193 . PMID   10931874.
7. 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 (2001). "Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC   311072 . PMID   11230166.
8. "Entrez Gene: PALLD palladin, cytoskeletal associated protein". nih.gov.
9. Mykkänen OM, Grönholm M, Rönty M, Lalowski M, Salmikangas P, Suila H, Carpén O (2001). "Characterization of Human Palladin, a Microfilament-associated Protein". Mol. Biol. Cell. 12 (10): 3060–73. doi:10.1091/mbc.12.10.3060. PMC   60155 . PMID   11598191.
10. Otey CA, Rachlin A, Moza M, Arneman D, Carpen O (2005). The palladin/myotilin/myopalladin family of actin-associated scaffolds. International Review of Cytology. Vol. 246. pp. 31–58. doi:10.1016/S0074-7696(05)46002-7. ISBN   9780123646507. PMID   16164966.{{cite book}}: |journal= ignored (help)
11. Rachlin AS, Otey CA (2006). "Identification of palladin isoforms and characterization of an isoform-specific interaction between Lasp-1 and palladin". J. Cell Sci. 119 (Pt 6): 995–1004. doi: 10.1242/jcs.02825 . PMID   16492705.
12. Pogue-Geile KL, Chen R, Bronner MP, Crnogorac-Jurcevic T, Moyes KW, Dowen S, Otey CA, Crispin DA, George RD, Whitcomb DC, Brentnall TA (2006). "Palladin Mutation Causes Familial Pancreatic Cancer and Suggests a New Cancer Mechanism". PLOS Med. 3 (12): e516. doi: 10.1371/journal.pmed.0030516 . PMC   1751121 . PMID   17194196.
13. Slater E, Amrillaeva V, Fendrich V, Bartsch D, Earl J, Vitone LJ, Neoptolemos JP, Greenhalf W (2007). "Palladin Mutation Causes Familial Pancreatic Cancer: Absence in European Families". PLOS Med. 4 (4): e164. doi: 10.1371/journal.pmed.0040164 . PMC   1855695 . PMID   17455999.
14. Zogopoulos G, Rothenmund H, Eppel A, Ash C, Akbari MR, Hedley D, Narod SA, Gallinger S (2007). "The P239S palladin variant does not account for a significant fraction of hereditary or early onset pancreas cancer". Hum. Genet. 121 (5): 635–7. doi:10.1007/s00439-007-0361-z. PMID   17415588. S2CID   2445261.
15. Salaria SN, Illei P, Sharma R, Walter KM, Klein AP, Eshleman JR, Maitra A, Schulick R, Winter J, Ouellette MM, Goggins M, Hruban R (2007). "Palladin is Overexpressed in the Non-Neoplastic Stroma of Infiltrating Ductal Adenocarcinomas of the Pancreas, but is only Rarely Overexpressed in Neoplastic Cells". Cancer Biol. Ther. 6 (3): 324–8. doi:10.4161/cbt.6.3.3904. PMC   3144721 . PMID   17404500.

Further reading

• King CM, Olive CW, Cardona RA (1975). "Activation of carcinogenic arylhydroxamic acids by human tissues". J. Natl. Cancer Inst. 55 (2): 285–7. doi:10.1093/jnci/55.2.285. PMID   1159819.
• Lai CH, Chou CY, Ch'ang LY, et al. (2000). "Identification of Novel Human Genes Evolutionarily Conserved in Caenorhabditis elegans by Comparative Proteomics". Genome Res. 10 (5): 703–13. doi:10.1101/gr.10.5.703. PMC   310876 . PMID   10810093.
• Bang ML, Mudry RE, McElhinny AS, et al. (2001). "Myopalladin, a Novel 145-Kilodalton Sarcomeric Protein with Multiple Roles in Z-Disc and I-Band Protein Assemblies". J. Cell Biol. 153 (2): 413–27. doi:10.1083/jcb.153.2.413. PMC   2169455 . PMID   11309420.
• Mykkänen OM, Grönholm M, Rönty M, et al. (2002). "Characterization of Human Palladin, a Microfilament-associated Protein". Mol. Biol. Cell. 12 (10): 3060–73. doi:10.1091/mbc.12.10.3060. PMC   60155 . PMID   11598191.
• Eberle MA, Pfützer R, Pogue-Geile KL, et al. (2002). "A New Susceptibility Locus for Autosomal Dominant Pancreatic Cancer Maps to Chromosome 4q32-34". Am. J. Hum. Genet. 70 (4): 1044–8. doi:10.1086/339692. PMC   379100 . PMID   11870593.
• Moriyama K, Bonifacino JS (2003). "Pallidin is a component of a multi-protein complex involved in the biogenesis of lysosome-related organelles". Traffic. 3 (9): 666–77. doi: 10.1034/j.1600-0854.2002.30908.x . PMID   12191018. S2CID   29888859.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Lee SY, Obata Y, Yoshida M, et al. (2003). "Immunomic analysis of human sarcoma". Proc. Natl. Acad. Sci. U.S.A. 100 (5): 2651–6. Bibcode:2003PNAS..100.2651L. doi: 10.1073/pnas.0437972100 . PMC   151395 . PMID   12601173.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID   14702039.
• Rönty M, Taivainen A, Moza M, et al. (2004). "Molecular analysis of the interaction between palladin and alpha-actinin". FEBS Lett. 566 (1–3): 30–4. doi:10.1016/j.febslet.2004.04.006. PMID   15147863. S2CID   86151740.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Hillier LW, Graves TA, Fulton RS, et al. (2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4". Nature. 434 (7034): 724–31. Bibcode:2005Natur.434..724H. doi: 10.1038/nature03466 . PMID   15815621.
• Rönty M, Taivainen A, Moza M, et al. (2005). "Involvement of palladin and alpha-actinin in targeting of the Abl/Arg kinase adaptor ArgBP2 to the actin cytoskeleton". Exp. Cell Res. 310 (1): 88–98. doi:10.1016/j.yexcr.2005.06.026. PMID   16125169.
• Shiffman D, Ellis SG, Rowland CM, et al. (2005). "Identification of Four Gene Variants Associated with Myocardial Infarction". Am. J. Hum. Genet. 77 (4): 596–605. doi:10.1086/491674. PMC   1275608 . PMID   16175505.
• Boukhelifa M, Moza M, Johansson T, et al. (2006). "The proline-rich protein palladin is a binding partner for profilin". FEBS J. 273 (1): 26–33. doi: 10.1111/j.1742-4658.2005.05036.x . PMID   16367745. S2CID   21207885.
• Rönty MJ, Leivonen SK, Hinz B, et al. (2007). "Isoform-specific regulation of the actin-organizing protein palladin during TGF-beta1-induced myofibroblast differentiation". J. Invest. Dermatol. 126 (11): 2387–96. doi: 10.1038/sj.jid.5700427 . PMID   16794588.
• Beausoleil SA, Villén J, Gerber SA, et al. (2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nat. Biotechnol. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID   16964243. S2CID   14294292.
• Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi: 10.1016/j.cell.2006.09.026 . PMID   17081983. S2CID   7827573.

External links

• palladin+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)