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0  structures 16  species 0  interactions 508  sequences 23  architectures

Family: Involucrin2 (PF06994)

Summary: Involucrin

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This is the Wikipedia entry entitled "Involucrin". More...

Involucrin Edit Wikipedia article

Available structures
PDB Ortholog search: PDBe, RCSB
Symbol IVL
External IDs OMIM147360 MGI96626 HomoloGene86915 GeneCards: IVL Gene
RNA expression pattern
PBB GE IVL 214599 at tn.png
More reference expression data
Species Human Mouse
Entrez 3713 16447
Ensembl ENSG00000163207 ENSMUSG00000049128
UniProt P07476 P48997
RefSeq (mRNA) NM_005547 NM_008412
RefSeq (protein) NP_005538 NP_032438
Location (UCSC) Chr 1:
152.88 – 152.88 Mb
Chr 3:
92.57 – 92.57 Mb
PubMed search [1] [2]
Involucrin of squamous epithelia N-terminus
Symbol Involucrin_N
Pfam PF10583
InterPro IPR019571
Involucrin repeat
Symbol Involucrin
Pfam PF00904
InterPro IPR000354
SCOP 1eu0
Involucrin repeat
Symbol Involucrin2
Pfam PF06994
InterPro IPR009733

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.


This gene is mapped to 1q21, among calpactin I light chain, trichohyalin, profillaggrin, loricrin, and calcyclin.[2]


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.

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]


Involucrin 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 tranglutaminase in the cross-linking reaction. The total size of the protein varies from 285 residues (in dog) to 835 residues (in orangutan).


  1. ^ Eckert RL, Green H (Sep 1986). "Structure and evolution of the human involucrin gene". Cell 46 (4): 583–9. doi:10.1016/0092-8674(86)90884-6. PMID 2873896. 
  2. ^ a b "Entrez Gene: IVL involucrin". 
  3. ^ Green H, Djian P (November 1992). "Consecutive actions of different gene-altering mechanisms in the evolution of involucrin". Mol. Biol. Evol. 9 (6): 977–1017. PMID 1359382. 
  4. ^ Djian P, Phillips M, Easley K, Huang E, Simon M, Rice RH, Green H (November 1993). "The involucrin genes of the mouse and the rat: study of their shared repeats". Mol. Biol. Evol. 10 (6): 1136–49. PMID 8277848. 
  5. ^ Eckert RL, Yaffe MB, Crish JF, Murthy S, Rorke EA, Welter JF (May 1993). "Involucrin--structure and role in envelope assembly". J. Invest. Dermatol. 100 (5): 613–7. doi:10.1111/1523-1747.ep12472288. PMID 8098344. 
  6. ^ Balasubramanian S, Zhu L, Eckert RL (November 2006). "Apigenin inhibition of involucrin gene expression is associated with a specific reduction in phosphorylation of protein kinase Cdelta Tyr311". J. Biol. Chem. 281 (47): 36162–72. doi:10.1074/jbc.M605368200. PMID 16982614. 

Further reading[edit]

  • Eckert RL, Crish JF, Efimova T, et al. (2004). "Regulation of involucrin gene expression.". J. Invest. Dermatol. 123 (1): 13–22. doi:10.1111/j.0022-202X.2004.22723.x. PMID 15191537. 
  • Rice RH, Green H (1980). "Presence in human epidermal cells of a soluble protein precursor of the cross-linked envelope: activation of the cross-linking by calcium ions.". Cell 18 (3): 681–94. doi:10.1016/0092-8674(79)90123-5. PMID 42494. 
  • Yaffe MB, Beegen H, Eckert RL (1992). "Biophysical characterization of involucrin reveals a molecule ideally suited to function as an intermolecular cross-bridge of the keratinocyte cornified envelope.". J. Biol. Chem. 267 (17): 12233–8. PMID 1601889. 
  • Simon M, Green H (1989). "The glutamine residues reactive in transglutaminase-catalyzed cross-linking of involucrin.". J. Biol. Chem. 263 (34): 18093–8. PMID 2461365. 
  • Heller M, Flemington E, Kieff E, Deininger P (1985). "Repeat arrays in cellular DNA related to the Epstein-Barr virus IR3 repeat.". Mol. Cell. Biol. 5 (3): 457–65. PMC 366737. PMID 2985954. 
  • Welter JF, Crish JF, Agarwal C, Eckert RL (1995). "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.". J. Biol. Chem. 270 (21): 12614–22. doi:10.1074/jbc.270.21.12614. PMID 7759510. 
  • Volz A, Korge BP, Compton JG, et al. (1994). "Physical mapping of a functional cluster of epidermal differentiation genes on chromosome 1q21.". Genomics 18 (1): 92–9. doi:10.1006/geno.1993.1430. PMID 8276421. 
  • Takahashi H, Iizuka H (1993). "Analysis of the 5'-upstream promoter region of human involucrin gene: activation by 12-O-tetradecanoylphorbol-13-acetate.". J. Invest. Dermatol. 100 (1): 10–5. doi:10.1111/1523-1747.ep12349867. PMID 8380829. 
  • Lopez-Bayghen E, Vega A, Cadena A, et al. (1996). "Transcriptional analysis of the 5'-noncoding region of the human involucrin gene.". J. Biol. Chem. 271 (1): 512–20. doi:10.1074/jbc.271.1.512. PMID 8550612. 
  • Takahashi H, Kobayashi H, Matsuo S, Iizuka H (1996). "Repression of involucrin gene expression by transcriptional enhancer factor 1 (TEF-1).". Arch. Dermatol. Res. 287 (8): 740–6. doi:10.1007/BF01105799. PMID 8554386. 
  • Steinert PM, Marekov LN (1997). "Direct evidence that involucrin is a major early isopeptide cross-linked component of the keratinocyte cornified cell envelope.". J. Biol. Chem. 272 (3): 2021–30. doi:10.1074/jbc.272.3.2021. PMID 8999895. 
  • Robinson NA, Lapic S, Welter JF, Eckert RL (1997). "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.". J. Biol. Chem. 272 (18): 12035–46. doi:10.1074/jbc.272.18.12035. PMID 9115270. 
  • Ng DC, Su MJ, Kim R, Bikle DD (2004). "Regulation of involucrin gene expression by calcium in normal human keratinocytes.". Front. Biosci. 1: a16–24. PMID 9159190. 
  • Banks EB, Crish JF, Welter JF, Eckert RL (1998). "Characterization of human involucrin promoter distal regulatory region transcriptional activator elements-a role for Sp1 and AP1 binding sites.". Biochem. J. 331 (1): 61–8. PMC 1219321. PMID 9512462. 
  • Marekov LN, Steinert PM (1998). "Ceramides are bound to structural proteins of the human foreskin epidermal cornified cell envelope.". J. Biol. Chem. 273 (28): 17763–70. doi:10.1074/jbc.273.28.17763. PMID 9651377. 
  • Crish JF, Zaim TM, Eckert RL (1998). "The distal regulatory region of the human involucrin promoter is required for expression in epidermis.". J. Biol. Chem. 273 (46): 30460–5. doi:10.1074/jbc.273.46.30460. PMID 9804813. 
  • Lee CH, Marekov LN, Kim S, et al. (2000). "Small proline-rich protein 1 is the major component of the cell envelope of normal human oral keratinocytes.". FEBS Lett. 477 (3): 268–72. doi:10.1016/S0014-5793(00)01806-8. PMID 10908733. 
  • Candi E, Oddi S, Terrinoni A, et al. (2001). "Transglutaminase 5 cross-links loricrin, involucrin, and small proline-rich proteins in vitro.". J. Biol. Chem. 276 (37): 35014–23. doi:10.1074/jbc.M010157200. PMID 11443109. 
  • Crish JF, Bone F, Banks EB, Eckert RL (2002). "The human involucrin gene contains spatially distinct regulatory elements that regulate expression during early versus late epidermal differentiation.". Oncogene 21 (5): 738–47. doi:10.1038/sj.onc.1205038. PMID 11850802. 

This article incorporates text from the public domain Pfam and InterPro IPR019571

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Involucrin Provide feedback

This family represents a conserved region approximately 60 residues long, multiple copies of which are found within eukaryotic involucrin, and which is rich in glutamine and glutamic acid residues. Involucrin forms part of the insoluble cornified cell envelope (a specialised protective barrier) of stratified squamous epithelia [1]. Members of this family seem to be restricted to mammals.

Literature references

  1. Kalinin AE, Kajava AV, Steinert PM; , Bioessays 2002;24:789-800.: Epithelial barrier function: assembly and structural features of the cornified cell envelope. PUBMED:12210515 EPMC:12210515

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR009733

This family represents a conserved region approximately 60 residues long, multiple copies of which are found within eukaryotic involucrin, and which is rich in glutamine and glutamic acid residues. Involucrin forms part of the insoluble cornified cell envelope (a specialised protective barrier) of stratified squamous epithelia [PUBMED:12210515]. Members of this family seem to be restricted to mammals.

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Seed source: Pfam-B_8443 (release 10.0)
Previous IDs: none
Type: Family
Author: Vella Briffa B
Number in seed: 38
Number in full: 508
Average length of the domain: 41.10 aa
Average identity of full alignment: 53 %
Average coverage of the sequence by the domain: 104.60 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.9 20.9
Trusted cut-off 25.3 20.9
Noise cut-off 19.0 20.1
Model length: 42
Family (HMM) version: 6
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