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CD81

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CD81
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1G8Q, 1IV5, 3X0E, 5DFW, 5DFV

Identifikatori
AliasiCD81
Vanjski ID-jeviOMIM: 186845 MGI: 1096398 HomoloGene: 20915 GeneCards: CD81
Lokacija gena (čovjek)
Hromosom 11 (čovjek)
Hrom.Hromosom 11 (čovjek)[1]
Hromosom 11 (čovjek)
Genomska lokacija za CD81
Genomska lokacija za CD81
Bend11p15.5Početak2,376,177 bp[1]
Kraj2,397,397 bp[1]
Lokacija gena (miš)
Hromosom 7 (miš)
Hrom.Hromosom 7 (miš)[2]
Hromosom 7 (miš)
Genomska lokacija za CD81
Genomska lokacija za CD81
Bend7 F5|7 88.1 cMPočetak142,606,476 bp[2]
Kraj142,621,671 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija GO:0001948, GO:0016582 vezivanje za proteine
MHC class II protein complex binding
transferrin receptor binding
virus receptor activity
integrin binding
cholesterol binding
lipid binding
Ćelijska komponenta integral component of membrane
Vezikula
membrana
focal adhesion
integral component of plasma membrane
immunological synapse
Egzosom
ćelijska membrana
basolateral plasma membrane
Biološki proces positive regulation of 1-phosphatidylinositol 4-kinase activity
GO:0034613 protein localization
regulation of protein stability
receptor internalization
cellular response to low-density lipoprotein particle stimulus
regulation of cell motility
receptor-mediated virion attachment to host cell
protein localization to lysosome
cell surface receptor signaling pathway
positive regulation of B cell proliferation
positive regulation of cell population proliferation
regulation of immune response
positive regulation of peptidyl-tyrosine phosphorylation
viral entry into host cell
positive regulation of protein catabolic process in the vacuole
Ćelijska proliferacija
GO:0022415 viral process
GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
regulation of complement activation
humoral immune response mediated by circulating immunoglobulin
protein localization to plasma membrane
adaptive immune response
immune system process
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_001297649
NM_004356

NM_133655

RefSeq (bjelančevina)

NP_001284578
NP_004347

NP_598416

Lokacija (UCSC)Chr 11: 2.38 – 2.4 MbChr 7: 142.61 – 142.62 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Molekula CD81, znana i kao CD81 (eng. skr. Cluster of Differentiation 81), je protein koji je kod ljudi kodiran genom CD81.[5][6] Također je poznata i kao površinskoćelijski 26 kDa-ski protein TAPA-1 (Target of the Antiproliferative Antibody 1) i tetraspanin-28 (Tspan-28).

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je 236 aminokiselina, a molekulska težina 25.809 Da.[7].

1020304050
MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTNLLYLELG
DKPAPNTFYVGIYILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVI
LFACEVAAGIWGFVNKDQIAKDVKQFYDQALQQAVVDDDANNAKAVVKTF
HETLDCCGSSTLTALTTSVLKNNLCPSGSNIISNLFKEDCHQKIDDLFSG
KLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY

Gen se nalazi na plus lancu kratkog kraka hromosoma 11, sekvenvca 11p15.5.

. Dužina je 20.103 baza i kodira protein od 236 aminokiselina s (predviđena molekularna težina 25.809 kDa).[6]

Protein nije posttranslacijski modificiran i ima četiri transmembranska domena. I N– i C-terminali leže na unutarstaničnoj strani membrane.

Gen je eksprimiran u hemopoetskim, endotelnim i epitelnim ćelijama. Nema ga u eritrocitima, trombocitima i neutrofilima.

Funkcija

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Protein kodiran ovim genom član je transmembranske superporodice 4, poznate i kao tetraspanini porodica. Većina ovih članova su proteini na ćelijskoj površini koji se odlikuju prisustvom četiri hidrofobna domena. Proteini posreduju transdukcija signala koji igraju ulogu u regulaciji razvoja stanica, aktivaciji, rastu i pokretljivosti. Ovaj kodirani protein je glikoprotein ćelijske površine, za koju je poznato da se kompleksira s integrinom. Čini se da ovaj protein potiče fuziju mišićnih ćelija i podržava održavanje miotubula. Također može biti uključen u transdukciju signala. Ovaj gen je lokaliziran u području gena za suzbijanje tumora i stoga je gen kandidat za malignitete.[5]

Porodica tetraspanina uključujući CD9, CD37, CD53, CD63, CD81 (ovaj protein), CD82 i CD151.

CD81 direktno stupa u interakciju sa članom 8 superporodice imunoglobulina (IGSF8,[8] CD316) i CD36. Formira kompleks transdukcije signala sa CD19, CD21 i Leu-13 (CD225) na površini B-ćelija.[9] Na T-ćelijama CD81 se povezuje sa CD4 i CD8 i daje kostimulatorni signal sa CD3.[9]

Klinički značaj

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Ovaj protein ima ključnu ulogu u vezivanju hepatitisa C i/ili ulasku u ćeliju interakcijom s virusnim E1/E2 glikoproteinskim heterodimerom.[10] Velika vanćelijska petlja CD81 veže dimer glikoproteina hepatitisa E2. HCV-E2 i CD81 veza Kd iznosi 1,8 nM. CD81 zahvaćen HCV-E2 je samo 30% internaliziran nakon 12 sati, što sugerira da CD81 može biti primarno receptor za vezivanje za HCV.[11]

Također ima ulogu u jetrenoj invaziji vrsta roda Plasmodium.[12] CD81 je potreban za ulazak sporozoita Plasmodium vivax u ljudske hepatocite i za ulazak sporozoita Plasmodium yoelii u mišje hepatocite.[13]

HIV gag proteini koriste mikrodomene obogaćene tetraspaninom (koji sadrže minimalno CD81, CD82, CD63) kao platformu za sastavljanje i otpuštanje viriona. Pročišćeni HIV koji proizvode MOLT/HIV ćelije sadrži CD81. Antitijela na CD81 snižavaju proizvodnju HIV-a oko tri puta,ali virus bez proteina CD81 je zarazniji.[14] Angažovanje CD81 snižava signalni prag potreban za pokretanje provirusne DNK posredovane T-ćelijama/CD3 u CD4+ T-ćelijama.[15]

CD81 ima ulogu u patogenezi gripe.[16]

Interakcije

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Pokazano je da CD81 komunicira sa TSPAN4,[17] CD19,[18][19][20] CD9,[20][21] PTGFRN,[22][23] CD117[24] and CD29.[25][26]

Također pogledajte

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Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000110651 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037706 - 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 "Entrez Gene: CD81 CD81 molecule".
  6. ^ a b Andria ML, Hsieh CL, Oren R, Francke U, Levy S (august 1991). "Genomic organization and chromosomal localization of the TAPA-1 gene". Journal of Immunology. 147 (3): 1030–6. PMID 1650385.
  7. ^ "UniProt, P60033". Pristupljeno 19. 8. 2021.
  8. ^ Clark K.L.; Zeng Z.; Langford A.L.; Bowen S.M.; Todd S.C. (novembar 2001). "PGRL is a major CD81-associated protein on lymphocytes and distinguishes a new family of cell surface proteins". Journal of Immunology. 167 (9): 5115–5121. doi:10.4049/jimmunol.167.9.5115. PMID 11673522.
  9. ^ a b Levy S, Todd SC, Maecker HT (1998). "CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system". Annu Rev Immunol. 16: 89–109. doi:10.1146/annurev.immunol.16.1.89. PMID 9597125.
  10. ^ Bartosch B, Vitelli A, Granier C, Goujon C, Dubuisson J, Pascale S, Scarselli E, Cortese R, Nicosia A, Cosset FL (oktobar 2003). "Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor". The Journal of Biological Chemistry. 278 (43): 41624–30. doi:10.1074/jbc.M305289200. PMID 12913001.
  11. ^ Petracca R, Falugi F, Galli G, Norais N, Rosa D, Campagnoli S, Burgio V, Di Stasio E, Giardina B, Houghton M, Abrignani S, Grandi G (maj 2000). "Structure-function analysis of hepatitis C virus envelope-CD81 binding". J. Virol. 74 (10): 4824–30. doi:10.1128/jvi.74.10.4824-4830.2000. PMC 112005. PMID 10775621.
  12. ^ Yalaoui S, Zougbédé S, Charrin S, Silvie O, Arduise C, Farhati K, Boucheix C, Mazier D, Rubinstein E, Froissard P (februar 2008). "Hepatocyte Permissiveness to Plasmodium Infection Is Conveyed by a Short and Structurally Conserved Region of the CD81 Large Extracellular Domain". PLOS Pathogens. 4 (2): e1000010. doi:10.1371/journal.ppat.1000010. PMC 2279262. PMID 18389082.
  13. ^ Silvie O, Rubinstein E, Franetich JF, Prenant M, Belnoue E, Rénia L, Hannoun L, Eling W, Levy S, Boucheix C, Mazier D (januar 2003). "Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity". Nat. Med. 9 (1): 93–6. doi:10.1038/nm808. PMID 12483205. S2CID 6290736.
  14. ^ Grigorov B, Attuil-Audenis V, Perugi F, Nedelec M, Watson S, Pique C, Darlix JL, Conjeaud H, Muriaux D (2009). "A role for CD81 on the late steps of HIV-1 replication in a chronically infected T cell line". Retrovirology. 6: 28. doi:10.1186/1742-4690-6-28. PMC 2657109. PMID 19284574.
  15. ^ Tardif MR, Tremblay MJ (april 2005). "Tetraspanin CD81 provides a costimulatory signal resulting in increased human immunodeficiency virus type 1 gene expression in primary CD4+ T lymphocytes through NF-kappaB, NFAT, and AP-1 transduction pathways". J. Virol. 79 (7): 4316–28. doi:10.1128/JVI.79.7.4316-4328.2005. PMC 1061526. PMID 15767432.
  16. ^ He J, Sun E, Bujny MV, Kim D, Davidson MW, Zhuang X (oktobar 2013). "Dual Function of CD81 in Influenza Virus Uncoating and Budding". PLOS Pathog. 9 (10): e1003701. doi:10.1371/journal.ppat.1003701. PMC 3795033. PMID 24130495.
  17. ^ Tachibana I, Bodorova J, Berditchevski F, Zutter MM, Hemler ME (Nov 1997). "NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes with integrins and other TM4SF proteins". J. Biol. Chem. 272 (46): 29181–9. doi:10.1074/jbc.272.46.29181. PMID 9360996.
  18. ^ Bradbury LE, Kansas GS, Levy S, Evans RL, Tedder TF (Nov 1992). "The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules". J. Immunol. 149 (9): 2841–50. PMID 1383329.
  19. ^ Imai T, Kakizaki M, Nishimura M, Yoshie O (Aug 1995). "Molecular analyses of the association of CD4 with two members of the transmembrane 4 superfamily, CD81 and CD82". J. Immunol. 155 (3): 1229–39. PMID 7636191.
  20. ^ a b Horváth G, Serru V, Clay D, Billard M, Boucheix C, Rubinstein E (Nov 1998). "CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82". J. Biol. Chem. 273 (46): 30537–43. doi:10.1074/jbc.273.46.30537. PMID 9804823.
  21. ^ Radford KJ, Thorne RF, Hersey P (maj 1996). "CD63 associates with transmembrane 4 superfamily members, CD9 and CD81, and with beta 1 integrins in human melanoma". Biochem. Biophys. Res. Commun. 222 (1): 13–8. doi:10.1006/bbrc.1996.0690. PMID 8630057.
  22. ^ Charrin S, Le Naour F, Oualid M, Billard M, Faure G, Hanash SM, Boucheix C, Rubinstein E (Apr 2001). "The major CD9 and CD81 molecular partner. Identification and characterization of the complexes". J. Biol. Chem. 276 (17): 14329–37. doi:10.1074/jbc.M011297200. PMID 11278880.
  23. ^ Stipp CS, Orlicky D, Hemler ME (Feb 2001). "FPRP, a major, highly stoichiometric, highly specific CD81- and CD9-associated protein". J. Biol. Chem. 276 (7): 4853–62. doi:10.1074/jbc.M009859200. PMID 11087758.
  24. ^ Anzai N; Lee Younghee; Youn Byung-S; Fukuda Seiji; Kim Young-June; Mantel Charlie; Akashi Makoto; Broxmeyer Hal E (Jun 2002). "C-kit associated with the transmembrane 4 superfamily proteins constitutes a functionally distinct subunit in human hematopoietic progenitors". Blood. 99 (12): 4413–21. doi:10.1182/blood.V99.12.4413. PMID 12036870.
  25. ^ Serru V, Le Naour F, Billard M, Azorsa DO, Lanza F, Boucheix C, Rubinstein E (maj 1999). "Selective tetraspan-integrin complexes (CD81/alpha4beta1, CD151/alpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions". Biochem. J. 340 (Pt 1): 103–11. doi:10.1042/0264-6021:3400103. PMC 1220227. PMID 10229664.
  26. ^ Mazzocca A; Carloni Vinicio; Sciammetta Silvia; Cordella Claudia; Pantaleo Pietro; Caldini Anna; Gentilini Paolo; Pinzani Massimo (Sep 2002). "Expression of transmembrane 4 superfamily (TM4SF) proteins and their role in hepatic stellate cell motility and wound healing migration". J. Hepatol. 37 (3): 322–30. doi:10.1016/S0168-8278(02)00175-7. PMID 12175627.

Dopunska literatura

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Vanjski linkovi

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Šablon:Superporodica imunoglobulinskih receptora Šablon:Oataki ćelijski membranski proteini