释义 |
- Gene
- Function
- Clinical significance
- Structure
- References
- Further reading
{{Infobox_gene}}{{Infobox protein family | Symbol = Involucrin_N | Name = Involucrin of squamous epithelia N-terminus | image = | width = | caption = | Pfam = PF10583 | Pfam_clan = | InterPro = IPR019571 | SMART = | PROSITE = | MEROPS = | SCOP = | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }}{{Infobox protein family | Symbol = Involucrin | Name = Involucrin repeat | image = | width = | caption = | Pfam = PF00904 | Pfam_clan = | InterPro = IPR000354 | SMART = | PROSITE = | MEROPS = | SCOP = 1eu0 | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }}{{Infobox protein family | Symbol = Involucrin2 | Name = Involucrin repeat | image = | width = | caption = | Pfam = PF06994 | Pfam_clan = | InterPro = IPR009733 | SMART = | PROSITE = | MEROPS = | SCOP = | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }}Involucrin is a protein component of human skin and in humans is encoded by the IVL gene.[1][2] In binding the protein loricrin, involucrin contributes to the formation of a cell envelope that protects corneocytes in the skin. Gene This gene is mapped to 1q21, among calpactin I light chain, trichohyalin, profillaggrin, loricrin, and calcyclin.[2] Function Involucrin is a highly reactive, soluble, transglutaminase substrate protein present in keratinocytes of epidermis and other stratified squamous epithelia.[3][4] It first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase thus helping in the formation of an insoluble envelope beneath the plasma membrane functioning as a glutamyl donor during assembly of the cornified envelope.[5] Involucrin is synthesised in the stratum spinosum and cross linked in the stratum granulosum by the transglutaminase enzyme that makes it highly stable. Thus it provides structural support to the cell, thereby allowing the cell to resist invasion by micro-organisms.{{citation needed|date=January 2017}} Apigenin, a plant-derived flavanoid that has significant promise as a skin cancer chemopreventive agent, has been found to regulate normal human keratinocyte differentiation by suppressing involucrin, and this is associated with reduced cell proliferation without apoptosis.[6] Clinical significance As one of the precursor proteins of the cornified cell envelope, involucrin is markedly increased in inflammatory skin diseases such as psoriasis[7] Lamellar ichthyosis involves a decrease in expression of involucrin. This decrease could contribute to the altered desquamation process seen in the disease, since the clinical improvement associated with retinoid treatment is accompanied by increased expression of involucrin.[8]StructureInvolucrin consists of a conserved N-terminal region of about 75 amino acid residues followed by two extremely variable length segments that contain glutamine-rich tandem repeats. The glutamine residues in the tandem repeats are the substrate for the transglutaminase in the cross-linking reaction. The total size of the protein varies from 285 residues (in dog) to 835 residues (in orangutan).{{citation needed|date=January 2017}} References 1. ^{{cite journal | vauthors = Eckert RL, Green H | title = Structure and evolution of the human involucrin gene | journal = Cell | volume = 46 | issue = 4 | pages = 583–9 | date = August 1986 | pmid = 2873896 | doi = 10.1016/0092-8674(86)90884-6 }} 2. ^1 {{cite web | title = Entrez Gene: IVL involucrin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3713| accessdate = }} 3. ^{{cite journal | vauthors = Green H, Djian P | title = Consecutive actions of different gene-altering mechanisms in the evolution of involucrin | journal = Molecular Biology and Evolution | volume = 9 | issue = 6 | pages = 977–1017 | date = November 1992 | pmid = 1359382 | url = http://mbe.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=1359382 }} 4. ^{{cite journal | vauthors = Djian P, Phillips M, Easley K, Huang E, Simon M, Rice RH, Green H | title = The involucrin genes of the mouse and the rat: study of their shared repeats | journal = Molecular Biology and Evolution | volume = 10 | issue = 6 | pages = 1136–49 | date = November 1993 | pmid = 8277848 | url = http://mbe.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=8277848 }} 5. ^{{cite journal | vauthors = Eckert RL, Yaffe MB, Crish JF, Murthy S, Rorke EA, Welter JF | title = Involucrin--structure and role in envelope assembly | journal = The Journal of Investigative Dermatology | volume = 100 | issue = 5 | pages = 613–7 | date = May 1993 | pmid = 8098344 | doi = 10.1111/1523-1747.ep12472288 }} 6. ^{{cite journal | vauthors = Balasubramanian S, Zhu L, Eckert RL | title = Apigenin inhibition of involucrin gene expression is associated with a specific reduction in phosphorylation of protein kinase Cdelta Tyr311 | journal = The Journal of Biological Chemistry | volume = 281 | issue = 47 | pages = 36162–72 | date = November 2006 | pmid = 16982614 | doi = 10.1074/jbc.M605368200 }} 7. ^{{cite journal | vauthors = Takahashi H, Hashimoto Y, Ishida-Yamamoto A, Iizuka H | title = Roxithromycin suppresses involucrin expression by modulation of activator protein-1 and nuclear factor-kappaB activities of keratinocytes | journal = Journal of Dermatological Science | volume = 39 | issue = 3 | pages = 175–82 | date = September 2005 | pmid = 16140218 | doi = 10.1016/j.jdermsci.2005.03.006 }} 8. ^{{cite journal | vauthors = Peña-Penabad C, de Unamuno P, García Silva J, Ludeña MD, González Sarmiento R, Pérez-Arellano JL | title = Altered expression of immunoreactive involucrin in lamellar ichthyosis | journal = European Journal of Dermatology | volume = 9 | issue = 3 | pages = 197–201 | year = 1999 | pmid = 10210784 | url = http://www.john-libbey-eurotext.fr/medline.md?issn=1167-1122&vol=9&iss=3&page=197 }}
Further reading {{refbegin | 2}}- {{cite journal | vauthors = Eckert RL, Crish JF, Efimova T, Dashti SR, Deucher A, Bone F, Adhikary G, Huang G, Gopalakrishnan R, Balasubramanian S | title = Regulation of involucrin gene expression | journal = The Journal of Investigative Dermatology | volume = 123 | issue = 1 | pages = 13–22 | date = July 2004 | pmid = 15191537 | doi = 10.1111/j.0022-202X.2004.22723.x }}
- {{cite journal | vauthors = Rice RH, Green H | title = Presence in human epidermal cells of a soluble protein precursor of the cross-linked envelope: activation of the cross-linking by calcium ions | journal = Cell | volume = 18 | issue = 3 | pages = 681–94 | date = November 1979 | pmid = 42494 | doi = 10.1016/0092-8674(79)90123-5 }}
- {{cite journal | vauthors = Yaffe MB, Beegen H, Eckert RL | title = Biophysical characterization of involucrin reveals a molecule ideally suited to function as an intermolecular cross-bridge of the keratinocyte cornified envelope | journal = The Journal of Biological Chemistry | volume = 267 | issue = 17 | pages = 12233–8 | date = June 1992 | pmid = 1601889 | url = http://www.jbc.org/cgi/pmidlookup?view=long&pmid=1601889 }}
- {{cite journal | vauthors = Simon M, Green H | title = The glutamine residues reactive in transglutaminase-catalyzed cross-linking of involucrin | journal = The Journal of Biological Chemistry | volume = 263 | issue = 34 | pages = 18093–8 | date = December 1988 | pmid = 2461365 | url = http://www.jbc.org/cgi/pmidlookup?view=long&pmid=2461365 }}
- {{cite journal | vauthors = Heller M, Flemington E, Kieff E, Deininger P | title = Repeat arrays in cellular DNA related to the Epstein-Barr virus IR3 repeat | journal = Molecular and Cellular Biology | volume = 5 | issue = 3 | pages = 457–65 | date = March 1985 | pmid = 2985954 | pmc = 366737 | url = http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=2985954 | doi=10.1128/mcb.5.3.457}}
- {{cite journal | vauthors = Welter JF, Crish JF, Agarwal C, Eckert RL | title = Fos-related antigen (Fra-1), junB, and junD activate human involucrin promoter transcription by binding to proximal and distal AP1 sites to mediate phorbol ester effects on promoter activity | journal = The Journal of Biological Chemistry | volume = 270 | issue = 21 | pages = 12614–22 | date = May 1995 | pmid = 7759510 | doi = 10.1074/jbc.270.21.12614 }}
- {{cite journal | vauthors = Volz A, Korge BP, Compton JG, Ziegler A, Steinert PM, Mischke D | title = Physical mapping of a functional cluster of epidermal differentiation genes on chromosome 1q21 | journal = Genomics | volume = 18 | issue = 1 | pages = 92–9 | date = October 1993 | pmid = 8276421 | doi = 10.1006/geno.1993.1430 }}
- {{cite journal | vauthors = Takahashi H, Iizuka H | title = Analysis of the 5'-upstream promoter region of human involucrin gene: activation by 12-O-tetradecanoylphorbol-13-acetate | journal = The Journal of Investigative Dermatology | volume = 100 | issue = 1 | pages = 10–5 | date = January 1993 | pmid = 8380829 | doi = 10.1111/1523-1747.ep12349867 }}
- {{cite journal | vauthors = Lopez-Bayghen E, Vega A, Cadena A, Granados SE, Jave LF, Gariglio P, Alvarez-Salas LM | title = Transcriptional analysis of the 5'-noncoding region of the human involucrin gene | journal = The Journal of Biological Chemistry | volume = 271 | issue = 1 | pages = 512–20 | date = January 1996 | pmid = 8550612 | doi = 10.1074/jbc.271.1.512 }}
- {{cite journal | vauthors = Takahashi H, Kobayashi H, Matsuo S, Iizuka H | title = Repression of involucrin gene expression by transcriptional enhancer factor 1 (TEF-1) | journal = Archives of Dermatological Research | volume = 287 | issue = 8 | pages = 740–6 | year = 1995 | pmid = 8554386 | doi = 10.1007/BF01105799 }}
- {{cite journal | vauthors = Steinert PM, Marekov LN | title = Direct evidence that involucrin is a major early isopeptide cross-linked component of the keratinocyte cornified cell envelope | journal = The Journal of Biological Chemistry | volume = 272 | issue = 3 | pages = 2021–30 | date = January 1997 | pmid = 8999895 | doi = 10.1074/jbc.272.3.2021 }}
- {{cite journal | vauthors = Robinson NA, Lapic S, Welter JF, Eckert RL | title = S100A11, S100A10, annexin I, desmosomal proteins, small proline-rich proteins, plasminogen activator inhibitor-2, and involucrin are components of the cornified envelope of cultured human epidermal keratinocytes | journal = The Journal of Biological Chemistry | volume = 272 | issue = 18 | pages = 12035–46 | date = May 1997 | pmid = 9115270 | doi = 10.1074/jbc.272.18.12035 }}
- {{cite journal | vauthors = Ng DC, Su MJ, Kim R, Bikle DD | title = Regulation of involucrin gene expression by calcium in normal human keratinocytes | journal = Frontiers in Bioscience | volume = 1 | pages = a16-24 | date = January 1996 | pmid = 9159190 | doi = 10.2741/A101 }}
- {{cite journal | vauthors = Banks EB, Crish JF, Welter JF, Eckert RL | title = Characterization of human involucrin promoter distal regulatory region transcriptional activator elements-a role for Sp1 and AP1 binding sites | journal = The Biochemical Journal | volume = 331 | issue = 1 | pages = 61–8 | date = April 1998 | pmid = 9512462 | pmc = 1219321 | url = http://www.biochemj.org/cgi/pmidlookup?view=long&pmid=9512462 | doi=10.1042/bj3310061}}
- {{cite journal | vauthors = Marekov LN, Steinert PM | title = Ceramides are bound to structural proteins of the human foreskin epidermal cornified cell envelope | journal = The Journal of Biological Chemistry | volume = 273 | issue = 28 | pages = 17763–70 | date = July 1998 | pmid = 9651377 | doi = 10.1074/jbc.273.28.17763 }}
- {{cite journal | vauthors = Crish JF, Zaim TM, Eckert RL | title = The distal regulatory region of the human involucrin promoter is required for expression in epidermis | journal = The Journal of Biological Chemistry | volume = 273 | issue = 46 | pages = 30460–5 | date = November 1998 | pmid = 9804813 | doi = 10.1074/jbc.273.46.30460 }}
- {{cite journal | vauthors = Lee CH, Marekov LN, Kim S, Brahim JS, Park MH, Steinert PM | title = Small proline-rich protein 1 is the major component of the cell envelope of normal human oral keratinocytes | journal = FEBS Letters | volume = 477 | issue = 3 | pages = 268–72 | date = July 2000 | pmid = 10908733 | doi = 10.1016/S0014-5793(00)01806-8 }}
- {{cite journal | vauthors = Candi E, Oddi S, Terrinoni A, Paradisi A, Ranalli M, Finazzi-Agró A, Melino G | title = Transglutaminase 5 cross-links loricrin, involucrin, and small proline-rich proteins in vitro | journal = The Journal of Biological Chemistry | volume = 276 | issue = 37 | pages = 35014–23 | date = September 2001 | pmid = 11443109 | doi = 10.1074/jbc.M010157200 }}
- {{cite journal | vauthors = Crish JF, Bone F, Banks EB, Eckert RL | title = The human involucrin gene contains spatially distinct regulatory elements that regulate expression during early versus late epidermal differentiation | journal = Oncogene | volume = 21 | issue = 5 | pages = 738–47 | date = January 2002 | pmid = 11850802 | doi = 10.1038/sj.onc.1205038 }}
{{refend}}{{InterPro content|IPR019571}} 1 : Protein domains |