PDCD10

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PDCD10
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

3AJM, 3L8I, 3L8J, 3RQE, 3RQF, 3RQG, 3W8H, 3W8I, 4GEH, 4TVQ

Identifikatori
AliasiPDCD10
Vanjski ID-jeviOMIM: 609118 MGI: 1928396 HomoloGene: 10505 GeneCards: PDCD10
Lokacija gena (čovjek)
Hromosom 3 (čovjek)
Hrom.Hromosom 3 (čovjek)[1]
Hromosom 3 (čovjek)
Genomska lokacija za PDCD10
Genomska lokacija za PDCD10
Bend3q26.1Početak167,683,298 bp[1]
Kraj167,734,939 bp[1]
Lokacija gena (miš)
Hromosom 3 (miš)
Hrom.Hromosom 3 (miš)[2]
Hromosom 3 (miš)
Genomska lokacija za PDCD10
Genomska lokacija za PDCD10
Bend3|3 E3Početak75,423,797 bp[2]
Kraj75,464,163 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija protein homodimerization activity
protein N-terminus binding
GO:0001948, GO:0016582 protein binding
protein kinase binding
Ćelijska komponenta citoplazma
citosol
Golđijev aparat
membrana
Golđijeva membrana
Ćelijska membrana
Egzosom
Biološki proces intrinsic apoptotic signaling pathway in response to hydrogen peroxide
positive regulation of MAP kinase activity
positive regulation of cell migration
protein stabilization
negative regulation of apoptotic process
negative regulation of gene expression
establishment of Golgi localization
stress fiber assembly
positive regulation of peptidyl-serine phosphorylation
positive regulation of protein serine/threonine kinase activity
Golgi reassembly
negative regulation of cell migration involved in sprouting angiogenesis
GO:1901313 positive regulation of gene expression
Angiogeneza
positive regulation of cell population proliferation
negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis
regulation of Rho protein signal transduction
response to hydrogen peroxide
wound healing, spreading of cells
positive regulation of Notch signaling pathway
positive regulation of stress-activated MAPK cascade
GO:0097285 Apoptoza
positive regulation of intracellular protein transport
cellular response to leukemia inhibitory factor
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_007217
NM_145859
NM_145860

NM_019745

RefSeq (bjelančevina)

NP_009148
NP_665858
NP_665859

NP_062719

Lokacija (UCSC)Chr 3: 167.68 – 167.73 MbChr 3: 75.42 – 75.46 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Protein 10 programirane ćelijske smrti jest protein koji je kod ljudi kodiran genom PDCD10 sa hromosoma 3.[5][6]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 212 aminokiselina, а molekulska težina 24.702 Da.[7].

1020304050
MRMTMEEMKNEAETTSMVSMPLYAVMYPVFNELERVNLSAAQTLRAAFIK
AEKENPGLTQDIIMKILEKKSVEVNFTESLLRMAADDVEEYMIERPEPEF
QDLNEKARALKQILSKIPDEINDRVRFLQTIKDIASAIKELLDTVNNVFK
KYQYQNRRALEHQKKEFVKYSKSFSDTLKTYFKDGKAINVFVSANRLIHQ
TNLILQTFKTVA

Funkcija[uredi | uredi izvor]

Ovaj gen kodira protein, prvobitno identifikovan u premijeloidnoj ćelijskoj liniji, sa sličnošću sa proteinima koji učestvuju u apoptozi. Za ovaj gen su identificirana tri alternativne varijante transkripta koji kodiraju isti protein, a razlikuju se samo po svojim 5' UTR-ima.[6]

Gen[uredi | uredi izvor]

Gubitak funkcijskih mutacija u PDCD10 dovodi do pojave bolesti cerebralnih kavernoznih malformacija (CCM).[5] Stoga se ovaj gen naziva i CCM3. Cerebralne kavernozne malformacije (CCM) su vaskularne malformacije u mozgu i kičkičmenoj moždini koje se sastoje od proširenih kapilarnih žila.

Interakcije[uredi | uredi izvor]

CCM3 kodira protein koji se zove proteonom programirane ćelijske smrti 10 (PDCD10). Funkcija ovog proteina je tek nedavno počela da se shvata. PDCD10 ima ulogu u vaskularnom razvoju i VEGF signalizaciji 1,[8] apoptosis[9] i funkcionira kao dio većeg signalnog kompleksa koji uključuje kinazu germinalnog centra III.[10][11] Konkretno, pokazalo se da PDCD10 međureagira sa
RP6-213H19.1,[12]
STK25,[12][13]
STRN,[12]
STRN3,[12]
MOBKL3,[12]
CTTNBP2NL,[12]
STK24[12][13][14] i
FAM40A.[12]

Modelni organizmi[uredi | uredi izvor]

Fenotip Pdcd10 nokaut-miševa
Svojstvo Fenotip
Vijabilnost homozigota Nenormalan
Studija recesivne letalnosti Nenormalan
Plodnost Normalan
Tjelesna težina Normalan
Anksioznost otvorenog polja Normalan
Neurološka procjena Normalan
Snaga stiska Normalan
Test vruće ploče Normalan
Dismorfologija Normalan
Indirektna kalorimetrija Normalan
Test tolerancije glukoze Normalan
Slušni odgovor moždanog stabla Normalan
DEXA Normalan
Radiografija Normalan
Tjelesna temperatura Normalan
Morfologija oka Normalan
Klinička hemija Normalan
Hematologija Normalan
Leukociti periferne krvis Normalan
Mikronukleus test Normalan
Težina srca Normalan
Histopatologija kože Normalan
Histopatologija oka Normalan
Salmonella infekcija Normalan[15]
Citrobacter infekcija Normalan[16]
Svi testovi i analze su prema[17][18]

U proučavanju funkcije PDCD10 korišteni su modelni organizmi. Uslovna linija nokaut-miševa, tzv. Pdcd10tm1a(KOMP)Wtsi[19][20] generirana je kao dio programa IKMC — projekta mutageneze visoke propusnosti za generiranje i distribuciju modela životinjskih bolesti zainteresiranim naučnicima.[21][22][23]

Mužjaci i ženke podvrgnute su standardiziranom fenotipskom pregledu, kako bi se utvrdili efekti delecija.[17][24] Izvršeno je 25 testova na mutant miševima i uočene su dvije značajne abnormalnosti.[17] Nijedan homozigotni mutantni embrion nije identifikovan tokom gestacije, pa stoga nijedan nije preživeo do odbijanja. Preostali testovi su izvedeni na heterozigotnim mutantnim odraslim miševima; nisu uočene dodatne značajne abnormalnosti kod ovih životinja.[17]

Reference[uredi | uredi izvor]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000114209 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027835 - Ensembl, maj 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. ^ a b Bergametti F, Denier C, Labauge P, Arnoult M, Boetto S, Clanet M, Coubes P, Echenne B, Ibrahim R, Irthum B, Jacquet G, Lonjon M, Moreau JJ, Neau JP, Parker F, Tremoulet M, Tournier-Lasserve E (Jan 2005). "Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations". American Journal of Human Genetics. 76 (1): 42–51. doi:10.1086/426952. PMC 1196432. PMID 15543491.
  6. ^ a b "Entrez Gene: PDCD10 programmed cell death 10".
  7. ^ "UniProt, Q9BUL8" (jezik: engleski). Pristupljeno 9. 11. 2021.
  8. ^ He Y, Zhang H, Yu L, Gunel M, Boggon TJ, Chen H, Min W (2010). "Stabilization of VEGFR2 signaling by cerebral cavernous malformation 3 is critical for vascular development". Science Signaling. 3 (116): ra26. doi:10.1126/scisignal.2000722. PMC 3052863. PMID 20371769.
  9. ^ Guclu B, Ozturk AK, Pricola KL, Bilguvar K, Shin D, O'Roak BJ, Gunel M (Nov 2005). "Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3". Neurosurgery. 57 (5): 1008–13. doi:10.1227/01.NEU.0000180811.56157.E1. PMID 16284570. S2CID 10303325.
  10. ^ Fidalgo M, Fraile M, Pires A, Force T, Pombo C, Zalvide J (Apr 2010). "CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation". Journal of Cell Science. 123 (Pt 8): 1274–84. doi:10.1242/jcs.061341. PMID 20332113.
  11. ^ Ceccarelli DF, Laister RC, Mulligan VK, Kean MJ, Goudreault M, Scott IC, Derry WB, Chakrabartty A, Gingras AC, Sicheri F (Jul 2011). "CCM3/PDCD10 heterodimerizes with germinal center kinase III (GCKIII) proteins using a mechanism analogous to CCM3 homodimerization". The Journal of Biological Chemistry. 286 (28): 25056–64. doi:10.1074/jbc.M110.213777. PMC 3137079. PMID 21561863.
  12. ^ a b c d e f g h Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, Sanchez A, Chaudhry S, Chen GI, Sicheri F, Nesvizhskii AI, Aebersold R, Raught B, Gingras AC (Jan 2009). "A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein". Molecular & Cellular Proteomics. 8 (1): 157–71. doi:10.1074/mcp.M800266-MCP200. PMC 2621004. PMID 18782753.
  13. ^ a b Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
  14. ^ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
  15. ^ "Salmonella infection data for Pdcd10". Wellcome Trust Sanger Institute.
  16. ^ "Citrobacter infection data for Pdcd10". Wellcome Trust Sanger Institute.
  17. ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  18. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  19. ^ "International Knockout Mouse Consortium". Arhivirano s originala, 3. 4. 2012. Pristupljeno 9. 11. 2021.
  20. ^ "Mouse Genome Informatics".
  21. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  22. ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  23. ^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  24. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Dopunska literatura[uredi | uredi izvor]

Vanjski linkovi[uredi | uredi izvor]