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0  structures 24  species 0  interactions 155  sequences 16  architectures

Family: Involucrin2 (PF06994)

Summary: Involucrin

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

Involucrin Edit Wikipedia article

Available structures
PDBHuman UniProt search: PDBe RCSB
AliasesIVL, involucrin
External IDsOMIM: 147360 HomoloGene: 136793 GeneCards: IVL
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for IVL
Genomic location for IVL
Band1q21.3Start152,908,546 bp[1]
End152,911,886 bp[1]
RNA expression pattern
PBB GE IVL 214599 at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 1: 152.91 – 152.91 Mbn/a
PubMed search[2]n/a
View/Edit Human
Involucrin of squamous epithelia N-terminus
Involucrin repeat
Involucrin repeat

Involucrin is a protein component of human skin and in humans is encoded by the IVL gene.[3][4] 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.[4]


Involucrin is a highly reactive, soluble, transglutaminase substrate protein present in keratinocytes of epidermis and other stratified squamous epithelia.[5][6] 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.[7]

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]

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.[8]

Clinical significance

As one of the precursor proteins of the cornified cell envelope, involucrin is markedly increased in inflammatory skin diseases such as psoriasis[9]

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.[10]


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 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]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000163207 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ Eckert RL, Green H (August 1986). "Structure and evolution of the human involucrin gene". Cell. 46 (4): 583–9. doi:10.1016/0092-8674(86)90884-6. PMID 2873896.
  4. ^ a b "Entrez Gene: IVL involucrin".
  5. ^ Green H, Djian P (November 1992). "Consecutive actions of different gene-altering mechanisms in the evolution of involucrin". Molecular Biology and Evolution. 9 (6): 977–1017. PMID 1359382.
  6. ^ 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". Molecular Biology and Evolution. 10 (6): 1136–49. PMID 8277848.
  7. ^ Eckert RL, Yaffe MB, Crish JF, Murthy S, Rorke EA, Welter JF (May 1993). "Involucrin--structure and role in envelope assembly". The Journal of Investigative Dermatology. 100 (5): 613–7. doi:10.1111/1523-1747.ep12472288. PMID 8098344.
  8. ^ 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". The Journal of Biological Chemistry. 281 (47): 36162–72. doi:10.1074/jbc.M605368200. PMID 16982614.
  9. ^ Takahashi H, Hashimoto Y, Ishida-Yamamoto A, Iizuka H (September 2005). "Roxithromycin suppresses involucrin expression by modulation of activator protein-1 and nuclear factor-kappaB activities of keratinocytes". Journal of Dermatological Science. 39 (3): 175–82. doi:10.1016/j.jdermsci.2005.03.006. PMID 16140218.
  10. ^ Peña-Penabad C, de Unamuno P, García Silva J, Ludeña MD, González Sarmiento R, Pérez-Arellano JL (1999). "Altered expression of immunoreactive involucrin in lamellar ichthyosis". European Journal of Dermatology. 9 (3): 197–201. PMID 10210784.

Further reading

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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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

This tab holds annotation information from the InterPro database.

InterPro entry IPR009733

This domain 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 ].

Gene Ontology

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Domain organisation

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Seed source: Pfam-B_8443 (release 10.0)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Vella Briffa B
Number in seed: 17
Number in full: 155
Average length of the domain: 37.90 aa
Average identity of full alignment: 49 %
Average coverage of the sequence by the domain: 49.78 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.9 20.9
Trusted cut-off 21.7 21.2
Noise cut-off 18.9 20.8
Model length: 41
Family (HMM) version: 13
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Species distribution

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Archea Archea Eukaryota Eukaryota
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trRosetta Structure

The structural model below was generated by the Baker group with the trRosetta software using the Pfam UniProt multiple sequence alignment.

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Improved protein structure prediction using predicted inter-residue orientations. Jianyi Yang, Ivan Anishchenko, Hahnbeom Park, Zhenling Peng, Sergey Ovchinnikov, David Baker Proceedings of the National Academy of Sciences Jan 2020, 117 (3) 1496-1503; DOI: 10.1073/pnas.1914677117;