Protein 2 sa nukleotid-vezujućim domenom oligomerizacije (NOD2), znan i kao protein 15 sa domenom regrotacije kaspaze (CARD15) ili protein 1 upalne bolesti crijeva (IBD1), jest protein koji je kod ljudi kodiran genom NOD2 sa p kraka hromosoma 16.[5][6] NOD2 ima važnu ulogu u imunskom sistemu. Prepoznaje bakterijske molekule (peptidoglikane) i stimulira imunsku reakciju.[7]

NOD2
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

5IRL, 5IRM, 5IRN

Identifikatori
AliasiNOD2
Vanjski ID-jeviOMIM: 605956 MGI: 2429397 HomoloGene: 11156 GeneCards: NOD2
Lokacija gena (čovjek)
Hromosom 16 (čovjek)
Hrom.Hromosom 16 (čovjek)[1]
Hromosom 16 (čovjek)
Genomska lokacija za NOD2
Genomska lokacija za NOD2
Bend16q12.1Početak50,693,588 bp[1]
Kraj50,734,041 bp[1]
Lokacija gena (miš)
Hromosom 8 (miš)
Hrom.Hromosom 8 (miš)[2]
Hromosom 8 (miš)
Genomska lokacija za NOD2
Genomska lokacija za NOD2
Bend8|8 C3Početak89,373,943 bp[2]
Kraj89,415,102 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija Hsp90 protein binding
nucleotide binding
Hsp70 protein binding
GO:0001948, GO:0016582 vezivanje za proteine
peptidoglycan binding
vezivanje enzima
actin binding
CARD domain binding
ATP binding
protein kinase binding
muramyl dipeptide binding
GO:0032403 protein-containing complex binding
Ćelijska komponenta citoplazma
citosol
Vezikula
membrana
ćelijska membrana
cell surface
basolateral plasma membrane
COP9 signalosome
citoskelet
Golđijev aparat
mitohondrija
GO:0009327 makromolekulani kompleks
Biološki proces positive regulation of prostaglandin-endoperoxide synthase activity
regulation of apoptotic process
defense response
detection of biotic stimulus
cytokine production involved in immune response
positive regulation of cytokine production involved in inflammatory response
GO:0007243 intracellular signal transduction
detection of muramyl dipeptide
positive regulation of interleukin-10 production
positive regulation of epithelial cell proliferation
immune system process
GO:1900490 positive regulation of oxidoreductase activity
response to muramyl dipeptide
positive regulation of prostaglandin-E synthase activity
positive regulation of JNK cascade
positive regulation of nitric-oxide synthase biosynthetic process
positive regulation of NIK/NF-kappaB signaling
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of gamma-delta T cell activation
cellular response to muramyl dipeptide
JNK cascade
negative regulation of macrophage apoptotic process
positive regulation of dendritic cell antigen processing and presentation
nucleotide-binding oligomerization domain containing 2 signaling pathway
maintenance of gastrointestinal epithelium
defense response to bacterium
positive regulation of NF-kappaB transcription factor activity
positive regulation of interleukin-8 production
detection of bacterium
positive regulation of interleukin-1 beta production
regulation of inflammatory response
positive regulation of interleukin-6 production
protein complex oligomerization
positive regulation of tumor necrosis factor production
positive regulation of ERK1 and ERK2 cascade
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of B cell activation
positive regulation of interleukin-17 production
positive regulation of type 2 immune response
nucleotide-binding oligomerization domain containing signaling pathway
positive regulation of stress-activated MAPK cascade
positive regulation of Notch signaling pathway
GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
GO:1904579 cellular response to organic cyclic compound
positive regulation of cell population proliferation
Urođeni imunski sistem
response to nutrient
positive regulation of dendritic cell cytokine production
positive regulation of protein K63-linked ubiquitination
cellular response to peptidoglycan
positive regulation of MAP kinase activity
interleukin-1-mediated signaling pathway
cellular response to lipopolysaccharide
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_001293557
NM_022162
NM_001370466

NM_145857

RefSeq (bjelančevina)

NP_001280486
NP_071445
NP_001357395

NP_665856

Lokacija (UCSC)Chr 16: 50.69 – 50.73 MbChr 8: 89.37 – 89.42 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

NOD2 je unutarćelijski receptor prepoznavanja uzorka, koji je po strukturi sličan rezistentnim proteinima biljaka i prepoznaje molekule koji sadrže specifičnu strukturu zvanu muramil-dipeptid (MDP) koja se nalazi u određenim bakterijama.[8]

Aminokiselinska sekvenca

uredi

Dužina polipeptidnog lanca je 1.040 aminokiselina, a molekulska težina 115.283 Da.[9]

1020304050
MGEEGGSASHDEEERASVLLGHSPGCEMCSQEAFQAQRSQLVELLVSGSL
EGFESVLDWLLSWEVLSWEDYEGFHLLGQPLSHLARRLLDTVWNKGTWAC
QKLIAAAQEAQADSQSPKLHGCWDPHSLHPARDLQSHRPAIVRRLHSHVE
NMLDLAWERGFVSQYECDEIRLPIFTPSQRARRLLDLATVKANGLAAFLL
QHVQELPVPLALPLEAATCKKYMAKLRTTVSAQSRFLSTYDGAETLCLED
IYTENVLEVWADVGMAGPPQKSPATLGLEELFSTPGHLNDDADTVLVVGE
AGSGKSTLLQRLHLLWAAGQDFQEFLFVFPFSCRQLQCMAKPLSVRTLLF
EHCCWPDVGQEDIFQLLLDHPDRVLLTFDGFDEFKFRFTDRERHCSPTDP
TSVQTLLFNLLQGNLLKNARKVVTSRPAAVSAFLRKYIRTEFNLKGFSEQ
GIELYLRKRHHEPGVADRLIRLLQETSALHGLCHLPVFSWMVSKCHQELL
LQEGGSPKTTTDMYLLILQHFLLHATPPDSASQGLGPSLLRGRLPTLLHL
GRLALWGLGMCCYVFSAQQLQAAQVSPDDISLGFLVRAKGVVPGSTAPLE
FLHITFQCFFAAFYLALSADVPPALLRHLFNCGRPGNSPMARLLPTMCIQ
ASEGKDSSVAALLQKAEPHNLQITAAFLAGLLSREHWGLLAECQTSEKAL
LRRQACARWCLARSLRKHFHSIPPAAPGEAKSVHAMPGFIWLIRSLYEMQ
EERLARKAARGLNVGHLKLTFCSVGPTECAALAFVLQHLRRPVALQLDYN
SVGDIGVEQLLPCLGVCKALYLRDNNISDRGICKLIECALHCEQLQKLAL
FNNKLTDGCAHSMAKLLACRQNFLALRLGNNYITAAGAQVLAEGLRGNTS
LQFLGFWGNRVGDEGAQALAEALGDHQSLRWLSLVGNNIGSVGAQALALM
LAKNVMLEELCLEENHLQDEGVCSLAEGLKKNSSLKILKLSNNCITYLGA
EALLQALERNDTILEVWLRGNTFSLEEVDKLGCRDTRLLL

Struktura

uredi
 
Proteinski model NOD2 koji se sastoji od dva N-terminalna CARD domena (crvena) povezana preko spiralnog linkera (plava) sa centralnim NOD domenom (zelena). Na C-terminalu nalazi se LRR domen (cijan).[10]

C-terminalni dio proteina sadrži ponavljanje bogato leucinom, domen za koji je poznato da ima ulogu u interakcijama protein-protein. Srednji dio proteina karakterizira NOD-ov domen uključen u samooligomerizaciju proteina. N-terminalni dio sadrži dva CARD domena za koje se zna da imaju ulogu u apoptozi i NF-κB putevima aktivacije.[11]

Funkcija

uredi

Ovaj gen je član porodice NOD1/Apaf-1 (također poznate kao porodica NOD-liki receptori) i kodira protein sa dva domena regrutacije kaspaze ( CARD-a) i jedanaest ponavljanja bogatih leucinom (LRR). Protein se prvenstveno eksprimira u leukocitima periferne krvi. Ima ulogu u imunskom odgovoru, tako što prepoznaje bakterijske molekule koje posjeduju muramil-dipeptidni (MDP) dio i aktivira NF-κB protein.[9]

Klinički značaj

uredi

Mutacije ovog gena su povezane sa Crohnovom bolešću,[10] Blauovim sindromom, teškom plućnom sarkoidozom[12] i bolešću transplanta protiv domaćina.[13]

NOD2 gen je povezan sa upalnim bolestima kao što su upalna bolest crijeva/Crohnova bolest i Blauov sindrom.[14][15]

Interakcije

uredi

Pokazalo se da NOD2 reaguje sa NLRC4.[16][17]

Također se pokazalo da se NOD2 vezuje za MAVS, kao odgovor na tretman ssRNK ili virusne RNK i aktivira IFN odgovor. Ovo je prvi izvještaj da NOD2 djeluje kao receptor za prepoznavanje uzoraka za viruse.[18]

Također pogledajte

uredi

Reference

uredi
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000167207 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000055994 - 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. ^ Gilberts EC, Greenstein AJ, Katsel P, Harpaz N, Greenstein RJ (Dec 1994). "Molecular evidence for two forms of Crohn disease". Proceedings of the National Academy of Sciences of the United States of America. 91 (26): 12721–4. Bibcode:1994PNAS...9112721G. doi:10.1073/pnas.91.26.12721. PMC 45511. PMID 7809109.
  6. ^ Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, Beaugerie L, Naom I, Dupas JL, Van Gossum A, Orholm M, Bonaiti-Pellie C, Weissenbach J, Mathew CG, Lennard-Jones JE, Cortot A, Colombel JF, Thomas G (Feb 1996). "Mapping of a susceptibility locus for Crohn's disease on chromosome 16". Nature. 379 (6568): 821–3. Bibcode:1996Natur.379..821H. doi:10.1038/379821a0. PMID 8587604. S2CID 4311407.
  7. ^ Mahla RS, Reddy MC, Prasad DV, Kumar H (septembar 2013). "Sweeten PAMPs: Role of Sugar Complexed PAMPs in Innate Immunity and Vaccine Biology". Frontiers in Immunology. 4: 248. doi:10.3389/fimmu.2013.00248. PMC 3759294. PMID 24032031.
  8. ^ Kufer TA, Banks DJ, Philpott DJ (Aug 2006). "Innate immune sensing of microbes by Nod proteins". Annals of the New York Academy of Sciences. 1072 (1): 19–27. Bibcode:2006NYASA1072...19K. doi:10.1196/annals.1326.020. PMID 17057187. S2CID 20217610.
  9. ^ a b "Entrez Gene: NOD2 nucleotide-binding oligomerization domain containing 2".
  10. ^ a b Nakagome S, Mano S, Kozlowski L, Bujnicki JM, Shibata H, Fukumaki Y, Kidd JR, Kidd KK, Kawamura S, Oota H (Jun 2012). "Crohn's disease risk alleles on the NOD2 locus have been maintained by natural selection on standing variation". Molecular Biology and Evolution. 29 (6): 1569–85. doi:10.1093/molbev/mss006. PMC 3697811. PMID 22319155.
  11. ^ Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G (Feb 2001). "Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB". The Journal of Biological Chemistry. 276 (7): 4812–8. doi:10.1074/jbc.M008072200. PMID 11087742.
  12. ^ Sato H, Williams HR, Spagnolo P, Abdallah A, Ahmad T, Orchard TR, Copley SJ, Desai SR, Wells AU, du Bois RM, Welsh KI (Feb 2010). "CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis". Eur Respir J. 35 (2): 324–30. doi:10.1183/09031936.00010209. PMID 19679608.
  13. ^ Zhao H, Jia M, Wang Z, Cheng Y, Luo Z, Chen Y, Xu X, Yang S, Tang Y (Jun 2015). "Association between NOD2 single nucleotide polymorphisms and Grade III-IV acute graft-versus-host disease: A meta-analysis". Hematology. 20 (5): 254–62. doi:10.1179/1607845414Y.0000000202. PMID 25248089. S2CID 206850232.
  14. ^ Radford-Smith G, Pandeya N (Nov 2006). "Associations between NOD2/CARD15 genotype and phenotype in Crohn's disease--Are we there yet?". World Journal of Gastroenterology. 12 (44): 7097–103. doi:10.3748/wjg.v12.i44.7097. PMC 4087769. PMID 17131470.
  15. ^ Kim TH, Payne U, Zhang X, Iwanaga Y, Davey MP, Rosenbaum JT, Inman RD (Jan 2007). "Altered host:pathogen interactions conferred by the Blau syndrome mutation of NOD2". Rheumatology International. 27 (3): 257–62. doi:10.1007/s00296-006-0250-0. PMID 17096091. S2CID 23739992.
  16. ^ Damiano JS, Oliveira V, Welsh K, Reed JC (Jul 2004). "Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses". The Biochemical Journal. 381 (Pt 1): 213–9. doi:10.1042/BJ20031506. PMC 1133779. PMID 15107016.
  17. ^ Damiano JS, Stehlik C, Pio F, Godzik A, Reed JC (Jul 2001). "CLAN, a novel human CED-4-like gene". Genomics. 75 (1–3): 77–83. doi:10.1006/geno.2001.6579. PMID 11472070.
  18. ^ Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, Bose S (Oct 2009). "Activation of innate immune antiviral responses by Nod2". Nature Immunology. 10 (10): 1073–80. doi:10.1038/ni.1782. PMC 2752345. PMID 19701189.

Dopunska literatura

uredi

Vanjski linkovi

uredi

Šablon:NOD-liki receptori