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PDB, Estrutura do dominio superenrolado da ocludina humana (aa. 416-522)
Ocludina
Identificadores
Símbolo	OCLN ; BLCPMG
Entrez	100506658
OMIM	602876
PDB	1XAW, 3G7C 1WPA, 1XAW, 3G7C
RefSeq	NP_001192183
UniProt	Q16625
Outros datos
Número EC	2.1.1.67
Locus	Cr. 5 68.79 – 68.85 Mb

A ocludina é unha proteína que nos humanos está codificada polo xene OCLN.^[1]^[2] É unha proteína integral de membrana de 65 kDa e 522 aminoácidos localizada nas unións herméticas que unen unhas células con outras. Foi descrita por primeira vez en 1993 por Shoichiro Tsukita.^[3] Xunto coas proteínas claudinas, as ocludinas son os principais compoñentes das unións herméticas.

Estrutura

Segundo a hidrofilidade global da molécula, esta atravesa a membrana catro veces, formando dous bucles extracelulares e expoñendo no citosol os seus extremos N-terminal e C-terminal. A interacción da ocludina con varias proteínas citoplasmáticas da placa de unión ocorre polo seu extremo C-terminal, mentres que os bucles extracelulares crese que están implicados na regulación da permeabilidade paracelular e a adhesión celular. A fosforilación/desfosforilación xoga un papel fundamental na regulación da ocludina e das unións herméticas. ^[4]

Asociación con enfermidades

Os trastornos na regulación da ocludina son un importante aspecto de diversas doenzas, xa que se distorsionan as barreiras celulares. As estratexias para previr ou reverter esta regulación á baixa poden ser un importante recurso terapéutico. Está implicada en diarreas, cancro, doenzas inflamatorias, alerxias, diabetes, esclerose múltiple, entre outras.^[4]

Interaccións

A ocludina interacciona coa proteína 2 das unións herméticas,^[5]^[6]^[7] YES1^[8] e coa proteína 1 das unións herméticas.^[9]^[10]

Notas

↑ Ando-Akatsuka Y, Saitou M, Hirase T, Kishi M, Sakakibara A, Itoh M, Yonemura S, Furuse M, Tsukita S (May 1996). "Interspecies diversity of the occludin sequence: cDNA cloning of human, mouse, dog, and rat-kangaroo homologues". J Cell Biol 133 (1): 43–47. PMC 2120780. PMID 8601611. doi:10.1083/jcb.133.1.43.
↑ "Entrez Gene: OCLN occludin".
↑ Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S (1993). "Occludin: a novel integral membrane protein localizing at tight junctions". J. Cell Biol. 123 (6 Pt 2): 1777–1788. PMC 2290891. PMID 8276896. doi:10.1083/jcb.123.6.1777.
↑ ^4,0 ^4,1 Feldman, Gemma J.; Mullin, James M; Ryan, Michael P (2005). "Occludin: Structure, function and regulation". Advanced Drug Delivery Reviews (en inglés) 57 (6): 883– 917. ISSN 0169-409X. PMID 15820558. doi:10.1016/j.addr.2005.01.009.
↑ Peng, Bi-Hung; Lee J Ching; Campbell Gerald A (Dec 2003). "In vitro protein complex formation with cytoskeleton-anchoring domain of occludin identified by limited proteolysis". J. Biol. Chem. 278 (49): 49644–49651 issn = 0021–9258. PMID 14512431. doi:10.1074/jbc.M302782200.
↑ Itoh, M; Morita K; Tsukita S (Feb 1999). "Characterization of ZO-2 as a MAGUK family member associated with tight as well as adherens junctions with a binding affinity to occludin and alpha catenin". J. Biol. Chem. 274 (9): 5981–5986. ISSN 0021-9258. PMID 10026224. doi:10.1074/jbc.274.9.5981.
↑ Wittchen, E S; Haskins J; Stevenson B R (Dec 1999). "Protein interactions at the tight junction. Actin has multiple binding partners, and ZO-1 forms independent complexes with ZO-2 and ZO-3". J. Biol. Chem. 274 (49): 35179–35185. ISSN 0021-9258. PMID 10575001. doi:10.1074/jbc.274.49.35179.
↑ Chen, Yan-Hua; Lu Qun; Goodenough Daniel A; Jeansonne Beverly (Apr 2002). "Nonreceptor tyrosine kinase c-Yes interacts with occludin during tight junction formation in canine kidney epithelial cells". Mol. Biol. Cell 13 (4): 1227–1237 issn = 1059–1524. PMC 102264. PMID 11950934. doi:10.1091/mbc.01-08-0423.
↑ Fanning, A S; Jameson B J; Jesaitis L A; Anderson J M (Nov 1998). "The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton". J. Biol. Chem. 273 (45): 29745–29753 issn = 0021–9258. PMID 9792688. doi:10.1074/jbc.273.45.29745.
↑ Rao, Radhakrishna K; Basuroy Shyamali, Rao Vijay U, Karnaky Jr Karl J, Gupta Akshay (Dec 2002). "Tyrosine phosphorylation and dissociation of occludin-ZO-1 and E-cadherin-beta-catenin complexes from the cytoskeleton by oxidative stress". Biochem. J. (England) 368 (Pt 2): 471–81. ISSN 0264-6021. PMC 1222996. PMID 12169098. doi:10.1042/BJ20011804.

Véxase tamén

Bibliografía

Furuse M; Itoh M; Hirase T; et al. (1994). "Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions". J. Cell Biol. 127 (6 Pt 1): 1617–1626. PMC 2120300. PMID 7798316. doi:10.1083/jcb.127.6.1617.
Van Itallie CM, Anderson JM (1997). "Occludin confers adhesiveness when expressed in fibroblasts". J. Cell. Sci. 110 (9): 1113–21. PMID 9175707.
Kimura Y; Shiozaki H; Hirao M; et al. (1997). "Expression of occludin, tight-junction-associated protein, in human digestive tract". Am. J. Pathol. 151 (1): 45–54. PMC 1857944. PMID 9212730.
Saitou M; Ando-Akatsuka Y; Itoh M; et al. (1997). "Mammalian occludin in epithelial cells: its expression and subcellular distribution". Eur. J. Cell Biol. 73 (3): 222–31. PMID 9243183.
Haskins J; Gu L; Wittchen ES; et al. (1998). "ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin". J. Cell Biol. 141 (1): 199–208. PMC 2132714. PMID 9531559. doi:10.1083/jcb.141.1.199.
Fanning AS, Jameson BJ, Jesaitis LA, Anderson JM (1998). "The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton". J. Biol. Chem. 273 (45): 29745–29753. PMID 9792688. doi:10.1074/jbc.273.45.29745.
Itoh M, Morita K, Tsukita S (1999). "Characterization of ZO-2 as a MAGUK family member associated with tight as well as adherens junctions with a binding affinity to occludin and alpha catenin". J. Biol. Chem. 274 (9): 5981–5986. PMID 10026224. doi:10.1074/jbc.274.9.5981.
Jiang WG; Martin TA; Matsumoto K; et al. (1999). "Hepatocyte growth factor/scatter factor decreases the expression of occludin and transendothelial resistance (TER) and increases paracellular permeability in human vascular endothelial cells". J. Cell. Physiol. 181 (2): 319–329. PMID 10497311. doi:10.1002/(SICI)1097-4652(199911)181:2<319::AID-JCP14>3.0.CO;2-S.
Wittchen ES, Haskins J, Stevenson BR (2000). "Protein interactions at the tight junction. Actin has multiple binding partners, and ZO-1 forms independent complexes with ZO-2 and ZO-3". J. Biol. Chem. 274 (49): 35179–35185. PMID 10575001. doi:10.1074/jbc.274.49.35179.
Kojima T; Sawada N; Chiba H; et al. (2000). "Induction of tight junctions in human connexin 32 (hCx32)-transfected mouse hepatocytes: connexin 32 interacts with occludin". Biochem. Biophys. Res. Commun. 266 (1): 222–229. PMID 10581193. doi:10.1006/bbrc.1999.1778.
Burns AR; Bowden RA; MacDonell SD; et al. (2000). "Analysis of tight junctions during neutrophil transendothelial migration". J. Cell. Sci. 113 (1): 45–57. PMID 10591624.
Itoh M; Furuse M; Morita K; et al. (2000). "Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins". J. Cell Biol. 147 (6): 1351–1363. PMC 2168087. PMID 10601346. doi:10.1083/jcb.147.6.1351.
Singh U; Van Itallie CM; Mitic LL; et al. (2000). "CaCo-2 cells treated with Clostridium perfringens enterotoxin form multiple large complex species, one of which contains the tight junction protein occludin". J. Biol. Chem. 275 (24): 18407–18417. PMID 10749869. doi:10.1074/jbc.M001530200.
Marzioni D; Banita M; Felici A; et al. (2001). "Expression of ZO-1 and occludin in normal human placenta and in hydatidiform moles". Mol. Hum. Reprod. 7 (3): 279–285. PMID 11228248. doi:10.1093/molehr/7.3.279.
Andreeva AY; Krause E; Müller EC; et al. (2001). "Protein kinase C regulates the phosphorylation and cellular localization of occludin". J. Biol. Chem. 276 (42): 38480–38486. PMID 11502742. doi:10.1074/jbc.M104923200.
Papadopoulos MC; Saadoun S; Woodrow CJ; et al. (2001). "Occludin expression in microvessels of neoplastic and non-neoplastic human brain". Neuropathol. Appl. Neurobiol. 27 (5): 384–395. PMID 11679090. doi:10.1046/j.0305-1846.2001.00341.x.
Schmidt A, Utepbergenov DI, Krause G, Blasig IE (2001). "Use of surface plasmon resonance for real-time analysis of the interaction of ZO-1 and occludin". Biochem. Biophys. Res. Commun. 288 (5): 1194–1199. PMID 11700038. doi:10.1006/bbrc.2001.5914.
Pummi K; Malminen M; Aho H; et al. (2001). "Epidermal tight junctions: ZO-1 and occludin are expressed in mature, developing, and affected skin and in vitro differentiating keratinocytes". J. Invest. Dermatol. 117 (5): 1050–1058. PMID 11710912. doi:10.1046/j.0022-202x.2001.01493.x.
Traweger A; Fang D; Liu YC; et al. (2002). "The tight junction-specific protein occludin is a functional target of the E3 ubiquitin-protein ligase itch". J. Biol. Chem. 277 (12): 10201–10208. PMID 11782481. doi:10.1074/jbc.M111384200.