Details for: KRT2

Gene ID: 3849

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: KRT2

Ensembl ID: ENSG00000172867

Description: keratin 2

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • keratinocyte CL0000312
    CSI 5.73
    rCSI 4.8%
    PRS 99.98

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [KRT2](/details-gene/3849), or Keratin 2, is a type II intermediate filament protein encoded on chromosome 12. As a fundamental component of the cytoskeleton, its primary role is to provide structural integrity to epithelial cells. Gene expression data indicates that [KRT2](/details-gene/3849) is a highly specific marker for terminally differentiating [keratinocytes](/details-cell/CL0000312) in the suprabasal layers of the epidermis ([Link](https://doi.org/10.1016/0014-4827(92)90412-2)). Functionally, it is integral to the process of '[Keratinization](/details-go/GO:0031424)' and the formation of the cornified envelope, which are essential for skin barrier function. Mutations in the [KRT2](/details-gene/3849) gene are causally linked to Ichthyosis bullosa of Siemens ([146800](https://omim.org/entry/146800)), a genetic skin disorder characterized by blistering and hyperkeratosis, highlighting its critical role in epidermal stability ([Link](https://doi.org/10.1111/1523-1747.ep12394414)). ## Cellular Roles and Expression Landscape The expression profile of [KRT2](/details-gene/3849) demonstrates remarkable cell-type specificity. **Overall**, the gene shows exceptionally high and significant expression exclusively in the [keratinocyte](/details-cell/CL0000312) (CSI: 5.73), positioning it as a definitive molecular marker for this lineage, particularly during the later stages of epidermal differentiation. Its function as a '[structural constituent of skin epidermis](/details-go/GO:0030280)' is consistent with this highly restricted expression pattern. Studies have shown that [KRT2](/details-gene/3849) is synthesized late in the differentiation program of epidermal [keratinocytes](/details-cell/CL0000312), contributing to the mechanical resilience of the uppermost skin layers ([Link](https://doi.org/10.1016/0014-4827(92)90412-2)). Furthermore, its expression is not only a feature of normal epidermal turnover but is also associated with cellular states of activation. For instance, [KRT2](/details-gene/3849) expression is upregulated in cutaneous lesions characterized by [keratinocyte](/details-cell/CL0000312) activation, proliferation, and keratinization, suggesting a role in pathological and regenerative skin processes ([Link](https://doi.org/10.1016/s0002-9440(10)63891-6)). ## Pathways and Molecular Function [KRT2](/details-gene/3849) is a canonical intermediate filament protein, and its molecular functions are centered on maintaining cytoskeletal structure and cellular integrity. Its primary GO annotation is as a '[structural constituent of cytoskeleton](/details-go/GO:0005200)', where it polymerizes with type I keratins to form the robust keratin filament network ([GO:0045095](https://www.ebi.ac.uk/QuickGO/term/GO:0045095)) within the cytoplasm of [keratinocytes](/details-cell/CL0000312). The biological processes involving [KRT2](/details-gene/3849) are intimately tied to skin biology. It plays a central role in '[Epidermis development](/details-go/GO:0008544)' and is a key molecule in the Reactome pathway '[Keratinization](/details-reactome/R-HSA-6805567)'. This process culminates in the '[Formation of the cornified envelope](/details-reactome/R-HSA-6809371)', a highly cross-linked protein structure that provides the primary barrier function of the skin. [KRT2](/details-gene/3849) also participates in dynamic cellular events such as '[Keratinocyte proliferation](/details-go/GO:0043616)' and '[Keratinocyte migration](/details-go/GO:0051546)', indicating that beyond a static structural role, it is involved in the epidermis's response to stimuli and injury. ## Research Directions The well-defined role of [KRT2](/details-gene/3849) in both normal epidermal homeostasis and genetic skin disease provides a strong foundation for further investigation. The causal link between dominant-negative mutations in [KRT2](/details-gene/3849) and Ichthyosis bullosa of Siemens ([146800](https://omim.org/entry/146800)) confirms its non-redundant structural function. Future research could focus on the regulatory networks governing its expression and its potential involvement in other skin pathologies. Based on the available data, several testable hypotheses can be proposed: 1. Given that its expression is regulated by retinoic acid ([Link](https://doi.org/10.1038/s41598-020-61640-9)), the transcriptional control of [KRT2](/details-gene/3849) by retinoid signaling pathways may serve as a master switch for the terminal differentiation of [keratinocytes](/details-cell/CL0000312). Dysregulation of this signaling axis could be a contributing factor to acquired disorders of keratinization beyond inherited ichthyoses. 2. Considering its upregulation during '[Keratinocyte activation](/details-go/GO:0032980)' ([Link](https://doi.org/10.1016/s0002-9440(10)63891-6)), [KRT2](/details-gene/3849) may function as a crucial mechanotransducer in the wound healing process. Its induction following injury could be necessary to reinforce the cytoskeletal architecture of migrating and proliferating [keratinocytes](/details-cell/CL0000312), thereby facilitating efficient re-epithelialization. To test the first hypothesis regarding retinoid regulation, a key experiment would involve using an *in vitro* 3D human skin equivalent model. Primary human [keratinocytes](/details-cell/CL0000312) would be cultured to form a stratified epidermis and then treated with specific retinoic acid receptor (RAR) agonists and antagonists. The impact on epidermal architecture would be assessed histologically, while changes in [KRT2](/details-gene/3849) expression and other terminal differentiation markers (e.g., Loricrin, Filaggrin) would be quantified by RT-qPCR, Western blotting, and immunofluorescence. This would directly test whether retinoid signaling is a necessary and sufficient upstream regulator of the [KRT2](/details-gene/3849)-driven differentiation program. Therapeutically, [KRT2](/details-gene/3849) presents a challenging target. For the monogenic disorder Ichthyosis bullosa of Siemens, which arises from dominant-negative mutations, the most promising long-term strategy would be gene therapy or allele-specific silencing using RNA interference or antisense oligonucleotides to eliminate the toxic mutant protein. Direct inhibition of a structural protein is generally not a viable strategy. However, modulating the upstream signaling pathways that regulate its expression, such as retinoid pathways, could offer a pharmacological approach to managing hyperkeratotic conditions where [KRT2](/details-gene/3849) expression is pathologically elevated.

Genular Protein ID: 592569752

Symbol: K22E_HUMAN

Name: Keratin, type II cytoskeletal 2 epidermal

UniProtKB Accession Codes:

P35908 Q4VAQ2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CPTAC 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 4 EMBL 7 Ensembl 1 GO 21 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PIR 1 PRIDE 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1380918

Title: Characterization of human cytokeratin 2, an epidermal cytoskeletal protein synthesized late during differentiation.

PubMed ID: 1380918

DOI: 10.1016/0014-4827(92)90412-2

PubMed ID: 9804344

Title: Genomic organization and fine mapping of the keratin 2e gene (KRT2E): K2e V1 domain polymorphism and novel mutations in ichthyosis bullosa of Siemens.

PubMed ID: 9804344

DOI: 10.1046/j.1523-1747.1998.00371.x

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 10233306

Title: Ontogeny and regional variability of keratin 2e (K2e) in developing human fetal skin: a unique spatial and temporal pattern of keratin expression in development.

PubMed ID: 10233306

DOI: 10.1046/j.1365-2133.1999.02755.x

PubMed ID: 12598329

Title: Expression of keratin K2e in cutaneous and oral lesions: association with keratinocyte activation, proliferation, and keratinization.

PubMed ID: 12598329

DOI: 10.1016/s0002-9440(10)63891-6

PubMed ID: 14654843

Title: Proteomic characterization of the human centrosome by protein correlation profiling.

PubMed ID: 14654843

DOI: 10.1038/nature02166

PubMed ID: 18691976

Title: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

PubMed ID: 18691976

DOI: 10.1016/j.molcel.2008.07.007

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 32179842

Title: Serum lipids, retinoic acid and phenol red differentially regulate expression of keratins K1, K10 and K2 in cultured keratinocytes.

PubMed ID: 32179842

DOI: 10.1038/s41598-020-61640-9

PubMed ID: 7521371

Title: Ichthyosis bullosa of Siemens -- a disease involving keratin 2e.

PubMed ID: 7521371

DOI: 10.1111/1523-1747.ep12394307

PubMed ID: 8077693

Title: Ichthyosis bullosa of Siemens is caused by mutations in the keratin 2e gene.

PubMed ID: 8077693

DOI: 10.1111/1523-1747.ep12394414

PubMed ID: 7524919

Title: Mutations in the rod domain of keratin 2e in patients with ichthyosis bullosa of Siemens.

PubMed ID: 7524919

DOI: 10.1038/ng0894-485

PubMed ID: 9036938

Title: A new keratin 2e mutation in ichthyosis bullosa of Siemens.

PubMed ID: 9036938

DOI: 10.1111/1523-1747.ep12286487

PubMed ID: 9204966

Title: A novel threonine-to-proline mutation at the end of 2B rod domain in the keratin 2e chain in ichthyosis bullosa of Siemens.

PubMed ID: 9204966

DOI: 10.1111/1523-1747.ep12276775

PubMed ID: 9833038

Title: A glutamate to lysine mutation at the end of 2B rod domain of keratin 2e gene in ichthyosis bullosa of Siemens.

PubMed ID: 9833038

DOI: 10.1080/000155598442683

PubMed ID: 10233323

Title: Ichthyosis bullosa of Siemens: report of a family with evidence of a keratin 2e mutation, and a review of the literature.

PubMed ID: 10233323

DOI: 10.1046/j.1365-2133.1999.02772.x

PubMed ID: 10084318

Title: A novel mutation in the 1A domain of keratin 2e in ichthyosis bullosa of Siemens.

PubMed ID: 10084318

DOI: 10.1046/j.1523-1747.1999.00529.x

PubMed ID: 10564334

Title: Ichthyosis bullosa of Siemens resulting from a novel missense mutation near the helix termination motif of the keratin 2e gene.

PubMed ID: 10564334

DOI: 10.1046/j.1365-2230.1999.00514.x

PubMed ID: 11167982

Title: A novel mutation in the 2B domain of keratin 2e causing ichthyosis bullosa of Siemens.

PubMed ID: 11167982

DOI: 10.1046/j.1365-2230.2000.00728.x

PubMed ID: 10688369

Title: Hot spot mutations in keratin 2e suggest a correlation between genotype and phenotype in patients with ichthyosis bullosa of Siemens.

PubMed ID: 10688369

DOI: 10.1034/j.1600-0625.2000.009001011.x

PubMed ID: 10620137

Title: A novel asparagine-->aspartic acid mutation in the rod 1A domain in keratin 2e in a Japanese family with ichthyosis bullosa of Siemens.

PubMed ID: 10620137

DOI: 10.1046/j.1523-1747.2000.00817.x

PubMed ID: 11531804

Title: New mutations in keratin 1 that cause bullous congenital ichthyosiform erythroderma and keratin 2e that cause ichthyosis bullosa of Siemens.

PubMed ID: 11531804

DOI: 10.1046/j.1365-2133.2001.04327.x

PubMed ID: 15949009

Title: Ichthyosis bullosa of Siemens: its correct diagnosis facilitated by molecular genetic testing.

PubMed ID: 15949009

DOI: 10.1111/j.1365-2133.2005.06598.x

PubMed ID: 17408392

Title: A novel H1 domain mutation in the keratin 2 gene in a Japanese family with ichthyosis bullosa of Siemens.

PubMed ID: 17408392

DOI: 10.1111/j.1365-2133.2007.07832.x

Sequence Information:

  • Length: 639
  • Mass: 65433
  • Checksum: B80526BAF70078A7
  • Sequence:
    • MSCQISCKSR GRGGGGGGFR GFSSGSAVVS GGSRRSTSSF SCLSRHGGGG GGFGGGGFGS 
RSLVGLGGTK SISISVAGGG GGFGAAGGFG GRGGGFGGGS SFGGGSGFSG GGFGGGGFGG 
GRFGGFGGPG GVGGLGGPGG FGPGGYPGGI HEVSVNQSLL QPLNVKVDPE IQNVKAQERE 
QIKTLNNKFA SFIDKVRFLE QQNQVLQTKW ELLQQMNVGT RPINLEPIFQ GYIDSLKRYL 
DGLTAERTSQ NSELNNMQDL VEDYKKKYED EINKRTAAEN DFVTLKKDVD NAYMIKVELQ 
SKVDLLNQEI EFLKVLYDAE ISQIHQSVTD TNVILSMDNS RNLDLDSIIA EVKAQYEEIA 
QRSKEEAEAL YHSKYEELQV TVGRHGDSLK EIKIEISELN RVIQRLQGEI AHVKKQCKNV 
QDAIADAEQR GEHALKDARN KLNDLEEALQ QAKEDLARLL RDYQELMNVK LALDVEIATY 
RKLLEGEECR MSGDLSSNVT VSVTSSTISS NVASKAAFGG SGGRGSSSGG GYSSGSSSYG 
SGGRQSGSRG GSGGGGSISG GGYGSGGGSG GRYGSGGGSK GGSISGGGYG SGGGKHSSGG 
GSRGGSSSGG GYGSGGGGSS SVKGSSGEAF GSSVTFSFR