Reviewed,
UniProtKB/Swiss-Prot P35908 (K22E_HUMAN)
Last modified
July 22, 2008.
Version 74.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Keratin, type II cytoskeletal 2 epidermal Alternative name(s): Cytokeratin-2e Short name=CK 2e Short name=K2e Short name=keratin-2 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 645 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Probably contributes to terminal cornification. Associated with keratinocyte activation, proliferation and keratinization. |
| Subunit structure | Heterotetramer of two type I and two type II keratins. Associates with KRT10 By similarity. |
| Tissue specificity | Expressed in the upper spinous and granular suprabasal layers of normal adult epidermal tissues from most body sites including thigh, breast nipple, foot sole, penile shaft and axilla. Not present in foreskin, squamous metaplasias and carcinomas. Expression in hypertrophic and keloid scars begins in the deepest suprabasal layer. Weakly expressed in normal gingiva and tongue, however expression is induced in benign keratoses of lingual mucosa and in mild-to-moderate oral dysplasia with orthokeratinization. |
| Developmental stage | Synthesized during maturation of epidermal keratinocytes and localized in the upper intermediate cells of fetal skin. Earliest expression is at 10 weeks in the developing embryo in the presumptive nail bed of developing digits, shifting to the proximal nail fold by 13.5 weeks. At 12.5 weeks, detected in scattered cells of the intermediate layer of trunk skin. At 19.3 weeks, regional expression patterns were observed in upper intermediate keratinocytes of cheek, trunk, dorsal and ventral knee, elbow and dorsal hand. Distal areas around the periumbilical region showed increased number of positive cells and by 15 weeks is expressed in small groups of cells in the fetal hair follicles. |
| Involvement in disease | Defects in KRT2 are a cause of ichthyosis bullosa of Siemens (IBS) [MIM:146800]. IBS is a rare autosomal dominant skin disorder displaying a type of epidermolytic hyperkeratosis characterized by generalized erythema and extensive blistering from birth. Large, dark gray hyperkeratoses are observed in later weeks. The skin of IBS patients is unusually fragile and has a tendency to shed the outer layers of the epidermis, producing localized denuded areas (molting effect). IBS usually improves with age so that in most middle-aged patients the hyperkeratosis and keratotic lichenification is limited to the flexural folds of the major joints. |
| Miscellaneous | There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). |
| Sequence similarities | Belongs to the intermediate filament family. |
Ontologies
Keywords | |
|---|---|
| Cellular component | Intermediate filament Keratin |
| Disease | Disease mutation Ichthyosis |
| Domain | Coiled coil |
| PTM | Phosphoprotein |
Gene Ontology (GO) | |
| Biological process | keratinization Ref.5 Inferred from direct assay. Source: UniProtKB keratinocyte activation Ref.5Inferred from direct assay. Source: UniProtKB keratinocyte migrationInferred from direct assay. Source: UniProtKB keratinocyte proliferation Ref.5Inferred from direct assay. Source: UniProtKB |
| Cellular component | intermediate filament Ref.1 Traceable author statement. Source: ProtInc |
| Molecular function | protein binding Inferred from physical interaction. Source: IntAct structural constituent of cytoskeleton Ref.1Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | ||||
Molecule processing | ||||||||
|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 645 | 645 | Keratin, type II cytoskeletal 2 epidermal | |||||
Regions | ||||||||
| Region | 1 – 183 | 183 | Head | |||||
| Region | 184 – 493 | 310 | Rod | |||||
| Region | 184 – 219 | 36 | Coil 1A | |||||
| Region | 220 – 238 | 19 | Linker 1 | |||||
| Region | 239 – 330 | 92 | Coil 1B | |||||
| Region | 331 – 354 | 24 | Linker 12 | |||||
| Region | 355 – 493 | 139 | Coil 2 | |||||
| Region | 494 – 645 | 152 | Tail | |||||
Sites | ||||||||
| Site | 435 | 1 | Stutter | |||||
Amino acid modifications | ||||||||
| Modified residue | 62 | 1 | Phosphoserine By similarity | |||||
Natural variations | ||||||||
| Natural variant | 187 | 1 | Q → P in IBS. | |||||
| Natural variant | 188 | 1 | I → N in IBS. | |||||
| Natural variant | 192 | 1 | N → D in IBS. | |||||
| Natural variant | 192 | 1 | N → K in IBS. | |||||
| Natural variant | 192 | 1 | N → Y in IBS. | |||||
| Natural variant | 471 | 1 | E → D in IBS. | |||||
| Natural variant | 471 | 1 | E → K in IBS. | |||||
| Natural variant | 482 | 1 | E → K in IBS. | |||||
| Natural variant | 482 | 1 | E → V in IBS. | |||||
| Natural variant | 483 | 1 | I → N in IBS. | |||||
| Natural variant | 485 | 1 | T → P in IBS. | |||||
| Natural variant | 490 | 1 | L → P in IBS. | |||||
| Natural variant | 493 | 1 | E → D in IBS. | |||||
| Natural variant | 493 | 1 | E → K in IBS. | |||||
| Natural variant | 494 | 1 | E → K in IBS. | |||||
Experimental info | ||||||||
| Sequence conflict | 101 | 1 | G → S in AAH96294, AAH99643 and AAH99644. Ref.3 | |||||
| Sequence conflict | 105 – 110 | 6 | Missing in AAH96294, AAH99643 and AAH99644. Ref.3 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Characterization of human cytokeratin 2, an epidermal cytoskeletal protein synthesized late during differentiation." Collin C., Moll R., Kubicka S., Ouhayoun J.-P., Franke W.W. Exp. Cell Res. 202:132-141(1992) [PubMed: 1380918] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Thigh epidermis. |
| [2] | "Genomic organization and fine mapping of the keratin 2e gene (KRT2E): K2e V1 domain polymorphism and novel mutations in ichthyosis bullosa of Siemens." Smith F.J.D., Maingi C., Covello S.P., Higgins C., Schmidt M., Lane E.B., Uitto J., Leigh I.M., McLean W.H.I. J. Invest. Dermatol. 111:817-821(1998) [PubMed: 9804344] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS IBS TYR-192 AND LYS-482. |
| [3] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [4] | "Ontogeny and regional variability of keratin 2e (K2e) in developing human fetal skin: a unique spatial and temporal pattern of keratin expression in development." Smith L.T., Underwood R.A., McLean W.H.I. Br. J. Dermatol. 140:582-591(1999) [PubMed: 10233306] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. |
| [5] | "Expression of keratin K2e in cutaneous and oral lesions: association with keratinocyte activation, proliferation, and keratinization." Bloor B.K., Tidman N., Leigh I.M., Odell E., Dogan B., Wollina U., Ghali L., Waseem A. Am. J. Pathol. 162:963-975(2003) [PubMed: 12598329] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY. |
| [6] | "Ichthyosis bullosa of Siemens -- a disease involving keratin 2e." McLean W.H.I., Morley S.M., Lane E.B., Eady R.A.J., Griffiths W.A.D., Paige D.G., Harper J.I., Higgins C., Leigh I.M. J. Invest. Dermatol. 103:277-281(1994) [PubMed: 7521371] [Abstract] Cited for: VARIANT IBS LYS-493. |
| [7] | "Ichthyosis bullosa of Siemens is caused by mutations in the keratin 2e gene." Kremer H., Zeeuwen P., McLean W.H.I., Mariman E.C.M., Lane E.B., van de Kerkhof P.C.M., Ropers H.-H., Steijlen P.M. J. Invest. Dermatol. 103:286-289(1994) [PubMed: 8077693] [Abstract] Cited for: VARIANTS IBS PRO-187; PRO-490 AND LYS-493. |
| [8] | "Mutations in the rod domain of keratin 2e in patients with ichthyosis bullosa of Siemens." Rothnagel J.A., Traupe H., Wojcik S., Huber M., Hohl D., Pittelkow M.R., Saeki H., Ishibashi Y., Roop D.R. Nat. Genet. 7:485-490(1994) [PubMed: 7524919] [Abstract] Cited for: VARIANTS IBS ASP-493 AND LYS-493. |
| [9] | "A new keratin 2e mutation in ichthyosis bullosa of Siemens." Jones D.O., Watts C., Mills C., Sharpe G., Marks R., Bowden P.E. J. Invest. Dermatol. 108:354-356(1997) [PubMed: 9036938] [Abstract] Cited for: VARIANTS IBS LYS-493 AND LYS-494. |
| [10] | "A novel threonine-to-proline mutation at the end of 2B rod domain in the keratin 2e chain in ichthyosis bullosa of Siemens." Yang J.-M., Lee S., Bang H.-D., Kim W.-S., Lee E.-S., Steinert P.M. J. Invest. Dermatol. 109:116-118(1997) [PubMed: 9204966] [Abstract] Cited for: VARIANT IBS PRO-485. |
| [11] | "A glutamate to lysine mutation at the end of 2B rod domain of keratin 2e gene in ichthyosis bullosa of Siemens." Yang J.-M., Lee E.-S., Kang H.-J., Choi G.-S., Yoneda K., Jung S.-Y., Park K.-B., Steinert P.M., Lee E.-S. Acta Derm. Venereol. 78:417-419(1998) [PubMed: 9833038] [Abstract] Cited for: VARIANT IBS LYS-493. |
| [12] | "Ichthyosis bullosa of Siemens: report of a family with evidence of a keratin 2e mutation, and a review of the literature." Basarab T., Smith F.J., Jolliffe V.M., McLean W.H.I., Neill S., Rustin M.H., Eady R.A. Br. J. Dermatol. 140:689-695(1999) [PubMed: 10233323] [Abstract] Cited for: VARIANT IBS LYS-493. |
| [13] | "A novel mutation in the 1A domain of keratin 2e in ichthyosis bullosa of Siemens." Arin M.J., Longley M.A., Epstein E.H. Jr., Scott G., Goldsmith L.A., Rothnagel J.A., Roop D.R. J. Invest. Dermatol. 112:380-382(1999) [PubMed: 10084318] [Abstract] Cited for: VARIANT IBS ASN-188. |
| [14] | "Ichthyosis bullosa of Siemens resulting from a novel missense mutation near the helix termination motif of the keratin 2e gene." Moraru R., Cserhalmi-Friedman P.B., Grossman M.E., Schneiderman P., Christiano A.M. Clin. Exp. Dermatol. 24:412-415(1999) [PubMed: 10564334] [Abstract] Cited for: VARIANT IBS VAL-482. |
| [15] | "A novel mutation in the 2B domain of keratin 2e causing ichthyosis bullosa of Siemens." Irvine A.D., Smith F.J., Shum K.W., Williams H.C., McLean W.H.I. Clin. Exp. Dermatol. 25:648-651(2000) [PubMed: 11167982] [Abstract] Cited for: VARIANT IBS ASN-483. |
| [16] | "Hot spot mutations in keratin 2e suggest a correlation between genotype and phenotype in patients with ichthyosis bullosa of Siemens." Suga Y., Arin M.J., Scott G., Goldsmith L.A., Magro C.M., Baden L.A., Baden H.P., Roop D.R. Exp. Dermatol. 9:11-15(2000) [PubMed: 10688369] [Abstract] Cited for: VARIANTS IBS LYS-471 AND ASP-471. |
| [17] | "A novel asparagine-->aspartic acid mutation in the rod 1A domain in keratin 2e in a Japanese family with ichthyosis bullosa of Siemens." Takizawa Y., Akiyama M., Nagashima M., Shimizu H. J. Invest. Dermatol. 114:193-195(2000) [PubMed: 10620137] [Abstract] Cited for: VARIANT IBS ASP-192. |
| [18] | "New mutations in keratin 1 that cause bullous congenital ichthyosiform erythroderma and keratin 2e that cause ichthyosis bullosa of Siemens." Whittock N.V., Ashton G.H.S., Griffiths W.A.D., Eady R.A.J., McGrath J.A. Br. J. Dermatol. 145:330-335(2001) [PubMed: 11531804] [Abstract] Cited for: VARIANT IBS LYS-192. |
| [19] | "Ichthyosis bullosa of Siemens: its correct diagnosis facilitated by molecular genetic testing." Akiyama M., Tsuji-Abe Y., Yanagihara M., Nakajima K., Kodama H., Yaosaka M., Abe M., Sawamura D., Shimizu H. Br. J. Dermatol. 152:1353-1356(2005) [PubMed: 15949009] [Abstract] Cited for: VARIANTS IBS PRO-490 AND LYS-493. |
| + | Additional computationally mapped references. |
Web resources
| Human Intermediate Filament Mutation Database |
| GeneReviews |
| Wikipedia Keratin-2A entry |
Cross-references
Sequence databases | |
|---|---|
| M99061 mRNA. Translation: AAC83410.1. AF019084 Genomic DNA. Translation: AAB81946.1. BC096294 mRNA. Translation: AAH96294.1. BC099643 mRNA. Translation: AAH99643.1. BC099644 mRNA. Translation: AAH99644.1. | |
| PIR | A44861. |
| RefSeq | NP_000414.2. |
| UniGene | Hs.707 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1GK7 based on UniProtKB P08670. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P35908. |
PTM databases | |
| PhosphoSite | P35908. |
Proteomic databases | |
| PeptideAtlas | P35908. |
Genome annotation databases | |
| Ensembl | ENSG00000172867. Homo sapiens. [Contig view] |
| GeneID | 3849. |
| KEGG | hsa:3849. |
Organism-specific databases | |
| H-InvDB | HIX0036877. |
| HGNC | HGNC:6439. KRT2. |
| HPA | HPA006299. |
| MIM | 146800. phenotype. 600194. gene. |
| Orphanet | 455. Ichthyosis bullosa of Siemens. |
| GenAtlas | Search... |
| GeneCards | Search... |
Phylogenomic databases | |
| HOGENOM | P35908. |
| HOVERGEN | P35908. |
Gene expression databases | |
| ArrayExpress | P35908. |
| CleanEx | HS_KRT2. |
| GermOnline | ENSG00000172867. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR016044. F. IPR001664. IF. IPR002957. Keratin_I. IPR003054. Keratin_II. [Graphical view] |
| PANTHER | PTHR23239. IF. 1 hit. PTHR23239:SF18. Keratin_II. 1 hit. |
| Pfam | PF00038. Filament. 1 hit. [Graphical view] |
| PRINTS | PR01248. TYPE1KERATIN. PR01276. TYPE2KERATIN. |
| PROSITE | PS00226. IF. 1 hit. [Graphical view] |
| ProDom | P35908. [Graphical view] [Entries sharing at least one domain] |
| BLOCKS | Search... |
Other Resources | |
| SOURCE | Search... |
| ProtoNet | Search... |
Entry information
| Entry name | K22E_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P35908 Secondary accession number(s): Q4VAQ2 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 12 Human chromosome 12: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| UniProtKB secondary accession numbers Index of UniProtKB secondary accession numbers |
| SIMILARITY comments Index of protein domains and families |

Clusters with


