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CD81

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

975

12520

Ensembl

ENSG00000110651

ENSMUSG00000037706

UniProt

P60033

P35762

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

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

1020304050
MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTNLLYLELG
DKPAPNTFYVGIYILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVI
LFACEVAAGIWGFVNKDQIAKDVKQFYDQALQQAVVDDDANNAKAVVKTF
HETLDCCGSSTLTALTTSVLKNNLCPSGSNIISNLFKEDCHQKIDDLFSG
KLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY

Gen

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

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

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

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

Reference

  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

Vanjski linkovi

Šablon:Superporodica imunoglobulinskih receptora Šablon:Oataki ćelijski membranski proteini

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