Full text data of KRT2
KRT2
(KRT2A, KRT2E)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Keratin, type II cytoskeletal 2 epidermal (Cytokeratin-2e; CK-2e; Epithelial keratin-2e; Keratin-2 epidermis; Keratin-2e; K2e; Type-II keratin Kb2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Keratin, type II cytoskeletal 2 epidermal (Cytokeratin-2e; CK-2e; Epithelial keratin-2e; Keratin-2 epidermis; Keratin-2e; K2e; Type-II keratin Kb2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P35908
ID K22E_HUMAN Reviewed; 639 AA.
AC P35908; Q4VAQ2;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-JUN-2009, sequence version 2.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Keratin, type II cytoskeletal 2 epidermal;
DE AltName: Full=Cytokeratin-2e;
DE Short=CK-2e;
DE AltName: Full=Epithelial keratin-2e;
DE AltName: Full=Keratin-2 epidermis;
DE AltName: Full=Keratin-2e;
DE Short=K2e;
DE AltName: Full=Type-II keratin Kb2;
GN Name=KRT2; Synonyms=KRT2A, KRT2E;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND VARIANT GLY-101.
RC TISSUE=Thigh epidermis;
RX PubMed=1380918; DOI=10.1016/0014-4827(92)90412-2;
RA Collin C., Moll R., Kubicka S., Ouhayoun J.-P., Franke W.W.;
RT "Characterization of human cytokeratin 2, an epidermal cytoskeletal
RT protein synthesized late during differentiation.";
RL Exp. Cell Res. 202:132-141(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS IBS TYR-186 AND LYS-476,
RP AND VARIANT GLY-101.
RX PubMed=9804344; DOI=10.1046/j.1523-1747.1998.00371.x;
RA Smith F.J.D., Maingi C., Covello S.P., Higgins C., Schmidt M.,
RA Lane E.B., Uitto J., Leigh I.M., McLean W.H.I.;
RT "Genomic organization and fine mapping of the keratin 2e gene (KRT2E):
RT K2e V1 domain polymorphism and novel mutations in ichthyosis bullosa
RT of Siemens.";
RL J. Invest. Dermatol. 111:817-821(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10233306; DOI=10.1046/j.1365-2133.1999.02755.x;
RA Smith L.T., Underwood R.A., McLean W.H.I.;
RT "Ontogeny and regional variability of keratin 2e (K2e) in developing
RT human fetal skin: a unique spatial and temporal pattern of keratin
RT expression in development.";
RL Br. J. Dermatol. 140:582-591(1999).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12598329; DOI=10.1016/S0002-9440(10)63891-6;
RA Bloor B.K., Tidman N., Leigh I.M., Odell E., Dogan B., Wollina U.,
RA Ghali L., Waseem A.;
RT "Expression of keratin K2e in cutaneous and oral lesions: association
RT with keratinocyte activation, proliferation, and keratinization.";
RL Am. J. Pathol. 162:963-975(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP VARIANT IBS LYS-487.
RX PubMed=7521371; DOI=10.1111/1523-1747.ep12394307;
RA McLean W.H.I., Morley S.M., Lane E.B., Eady R.A.J., Griffiths W.A.D.,
RA Paige D.G., Harper J.I., Higgins C., Leigh I.M.;
RT "Ichthyosis bullosa of Siemens -- a disease involving keratin 2e.";
RL J. Invest. Dermatol. 103:277-281(1994).
RN [10]
RP VARIANTS IBS PRO-181; PRO-484 AND LYS-487.
RX PubMed=8077693; DOI=10.1111/1523-1747.ep12394414;
RA Kremer H., Zeeuwen P., McLean W.H.I., Mariman E.C.M., Lane E.B.,
RA van de Kerkhof P.C.M., Ropers H.-H., Steijlen P.M.;
RT "Ichthyosis bullosa of Siemens is caused by mutations in the keratin
RT 2e gene.";
RL J. Invest. Dermatol. 103:286-289(1994).
RN [11]
RP VARIANTS IBS ASP-487 AND LYS-487.
RX PubMed=7524919; DOI=10.1038/ng0894-485;
RA Rothnagel J.A., Traupe H., Wojcik S., Huber M., Hohl D.,
RA Pittelkow M.R., Saeki H., Ishibashi Y., Roop D.R.;
RT "Mutations in the rod domain of keratin 2e in patients with ichthyosis
RT bullosa of Siemens.";
RL Nat. Genet. 7:485-490(1994).
RN [12]
RP VARIANTS IBS LYS-487 AND LYS-488.
RX PubMed=9036938; DOI=10.1111/1523-1747.ep12286487;
RA Jones D.O., Watts C., Mills C., Sharpe G., Marks R., Bowden P.E.;
RT "A new keratin 2e mutation in ichthyosis bullosa of Siemens.";
RL J. Invest. Dermatol. 108:354-356(1997).
RN [13]
RP VARIANT IBS PRO-479.
RX PubMed=9204966; DOI=10.1111/1523-1747.ep12276775;
RA Yang J.-M., Lee S., Bang H.-D., Kim W.-S., Lee E.-S., Steinert P.M.;
RT "A novel threonine-to-proline mutation at the end of 2B rod domain in
RT the keratin 2e chain in ichthyosis bullosa of Siemens.";
RL J. Invest. Dermatol. 109:116-118(1997).
RN [14]
RP VARIANT IBS LYS-487.
RX PubMed=9833038; DOI=10.1080/000155598442683;
RA Yang J.-M., Lee E.-S., Kang H.-J., Choi G.-S., Yoneda K., Jung S.-Y.,
RA Park K.-B., Steinert P.M., Lee E.-S.;
RT "A glutamate to lysine mutation at the end of 2B rod domain of keratin
RT 2e gene in ichthyosis bullosa of Siemens.";
RL Acta Derm. Venereol. 78:417-419(1998).
RN [15]
RP VARIANT IBS LYS-487.
RX PubMed=10233323; DOI=10.1046/j.1365-2133.1999.02772.x;
RA Basarab T., Smith F.J., Jolliffe V.M., McLean W.H.I., Neill S.,
RA Rustin M.H., Eady R.A.;
RT "Ichthyosis bullosa of Siemens: report of a family with evidence of a
RT keratin 2e mutation, and a review of the literature.";
RL Br. J. Dermatol. 140:689-695(1999).
RN [16]
RP VARIANT IBS ASN-182.
RX PubMed=10084318; DOI=10.1046/j.1523-1747.1999.00529.x;
RA Arin M.J., Longley M.A., Epstein E.H. Jr., Scott G., Goldsmith L.A.,
RA Rothnagel J.A., Roop D.R.;
RT "A novel mutation in the 1A domain of keratin 2e in ichthyosis bullosa
RT of Siemens.";
RL J. Invest. Dermatol. 112:380-382(1999).
RN [17]
RP VARIANT IBS VAL-476.
RX PubMed=10564334; DOI=10.1046/j.1365-2230.1999.00514.x;
RA Moraru R., Cserhalmi-Friedman P.B., Grossman M.E., Schneiderman P.,
RA Christiano A.M.;
RT "Ichthyosis bullosa of Siemens resulting from a novel missense
RT mutation near the helix termination motif of the keratin 2e gene.";
RL Clin. Exp. Dermatol. 24:412-415(1999).
RN [18]
RP VARIANT IBS ASN-477.
RX PubMed=11167982; DOI=10.1046/j.1365-2230.2000.00728.x;
RA Irvine A.D., Smith F.J., Shum K.W., Williams H.C., McLean W.H.I.;
RT "A novel mutation in the 2B domain of keratin 2e causing ichthyosis
RT bullosa of Siemens.";
RL Clin. Exp. Dermatol. 25:648-651(2000).
RN [19]
RP VARIANTS IBS LYS-465 AND ASP-465.
RX PubMed=10688369; DOI=10.1034/j.1600-0625.2000.009001011.x;
RA Suga Y., Arin M.J., Scott G., Goldsmith L.A., Magro C.M., Baden L.A.,
RA Baden H.P., Roop D.R.;
RT "Hot spot mutations in keratin 2e suggest a correlation between
RT genotype and phenotype in patients with ichthyosis bullosa of
RT Siemens.";
RL Exp. Dermatol. 9:11-15(2000).
RN [20]
RP VARIANT IBS ASP-186.
RX PubMed=10620137; DOI=10.1046/j.1523-1747.2000.00817.x;
RA Takizawa Y., Akiyama M., Nagashima M., Shimizu H.;
RT "A novel asparagine-->aspartic acid mutation in the rod 1A domain in
RT keratin 2e in a Japanese family with ichthyosis bullosa of Siemens.";
RL J. Invest. Dermatol. 114:193-195(2000).
RN [21]
RP VARIANT IBS LYS-186.
RX PubMed=11531804; DOI=10.1046/j.1365-2133.2001.04327.x;
RA Whittock N.V., Ashton G.H.S., Griffiths W.A.D., Eady R.A.J.,
RA McGrath J.A.;
RT "New mutations in keratin 1 that cause bullous congenital
RT ichthyosiform erythroderma and keratin 2e that cause ichthyosis
RT bullosa of Siemens.";
RL Br. J. Dermatol. 145:330-335(2001).
RN [22]
RP VARIANTS IBS PRO-484 AND LYS-487.
RX PubMed=15949009; DOI=10.1111/j.1365-2133.2005.06598.x;
RA Akiyama M., Tsuji-Abe Y., Yanagihara M., Nakajima K., Kodama H.,
RA Yaosaka M., Abe M., Sawamura D., Shimizu H.;
RT "Ichthyosis bullosa of Siemens: its correct diagnosis facilitated by
RT molecular genetic testing.";
RL Br. J. Dermatol. 152:1353-1356(2005).
CC -!- FUNCTION: Probably contributes to terminal cornification.
CC Associated with keratinocyte activation, proliferation and
CC keratinization.
CC -!- SUBUNIT: Heterotetramer of two type I and two type II keratins.
CC Associates with KRT10 (By similarity).
CC -!- TISSUE SPECIFICITY: Expressed in the upper spinous and granular
CC suprabasal layers of normal adult epidermal tissues from most body
CC sites including thigh, breast nipple, foot sole, penile shaft and
CC axilla. Not present in foreskin, squamous metaplasias and
CC carcinomas. Expression in hypertrophic and keloid scars begins in
CC the deepest suprabasal layer. Weakly expressed in normal gingiva
CC and tongue, however expression is induced in benign keratoses of
CC lingual mucosa and in mild-to-moderate oral dysplasia with
CC orthokeratinization.
CC -!- DEVELOPMENTAL STAGE: Synthesized during maturation of epidermal
CC keratinocytes and localized in the upper intermediate cells of
CC fetal skin. Earliest expression is at 10 weeks in the developing
CC embryo in the presumptive nail bed of developing digits, shifting
CC to the proximal nail fold by 13.5 weeks. At 12.5 weeks, detected
CC in scattered cells of the intermediate layer of trunk skin. At
CC 19.3 weeks, regional expression patterns were observed in upper
CC intermediate keratinocytes of cheek, trunk, dorsal and ventral
CC knee, elbow and dorsal hand. Distal areas around the periumbilical
CC region showed increased number of positive cells and by 15 weeks
CC is expressed in small groups of cells in the fetal hair follicles.
CC -!- DISEASE: Ichthyosis bullosa of Siemens (IBS) [MIM:146800]: A rare
CC autosomal dominant skin disorder displaying a type of
CC epidermolytic hyperkeratosis characterized by generalized erythema
CC and extensive blistering from birth. Large, dark gray
CC hyperkeratoses are observed in later weeks. The skin of IBS
CC patients is unusually fragile and has a tendency to shed the outer
CC layers of the epidermis, producing localized denuded areas
CC (molting effect). IBS usually improves with age so that in most
CC middle-aged patients the hyperkeratosis and keratotic
CC lichenification is limited to the flexural folds of the major
CC joints. Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- MISCELLANEOUS: There are two types of cytoskeletal and
CC microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to
CC basic; 56-70 kDa).
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC -!- WEB RESOURCE: Name=Human Intermediate Filament Mutation Database;
CC URL="http://www.interfil.org";
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/KRT2";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Keratin-2A entry;
CC URL="http://en.wikipedia.org/wiki/Keratin_2A";
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DR EMBL; M99061; AAC83410.1; -; mRNA.
DR EMBL; AF019084; AAB81946.1; -; Genomic_DNA.
DR EMBL; AC055715; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC055716; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096294; AAH96294.1; -; mRNA.
DR EMBL; BC099643; AAH99643.1; -; mRNA.
DR EMBL; BC099644; AAH99644.1; -; mRNA.
DR PIR; A44861; A44861.
DR RefSeq; NP_000414.2; NM_000423.2.
DR UniGene; Hs.707; -.
DR ProteinModelPortal; P35908; -.
DR SMR; P35908; 178-317, 344-486.
DR IntAct; P35908; 8.
DR MINT; MINT-1208580; -.
DR STRING; 9606.ENSP00000310861; -.
DR PhosphoSite; P35908; -.
DR DMDM; 239938650; -.
DR PaxDb; P35908; -.
DR PeptideAtlas; P35908; -.
DR PRIDE; P35908; -.
DR ProMEX; P35908; -.
DR Ensembl; ENST00000309680; ENSP00000310861; ENSG00000172867.
DR GeneID; 3849; -.
DR KEGG; hsa:3849; -.
DR UCSC; uc001sat.3; human.
DR CTD; 3849; -.
DR GeneCards; GC12M053038; -.
DR H-InvDB; HIX0036877; -.
DR HGNC; HGNC:6439; KRT2.
DR HPA; HPA006299; -.
DR MIM; 146800; phenotype.
DR MIM; 600194; gene.
DR neXtProt; NX_P35908; -.
DR Orphanet; 455; Superficial epidermolytic ichthyosis.
DR PharmGKB; PA30227; -.
DR eggNOG; NOG146769; -.
DR HOGENOM; HOG000230976; -.
DR HOVERGEN; HBG013015; -.
DR InParanoid; P35908; -.
DR KO; K07605; -.
DR OMA; TNLDPIF; -.
DR OrthoDB; EOG7FV3Q8; -.
DR PhylomeDB; P35908; -.
DR GeneWiki; Keratin_2A; -.
DR GenomeRNAi; 3849; -.
DR NextBio; 15145; -.
DR PRO; PR:P35908; -.
DR Bgee; P35908; -.
DR CleanEx; HS_KRT2; -.
DR Genevestigator; P35908; -.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005882; C:intermediate filament; TAS:ProtInc.
DR GO; GO:0045095; C:keratin filament; IEA:InterPro.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0031424; P:keratinization; IDA:UniProtKB.
DR GO; GO:0032980; P:keratinocyte activation; IDA:UniProtKB.
DR GO; GO:0051546; P:keratinocyte migration; IDA:UniProtKB.
DR GO; GO:0043616; P:keratinocyte proliferation; IDA:UniProtKB.
DR InterPro; IPR001664; IF.
DR InterPro; IPR018039; Intermediate_filament_CS.
DR InterPro; IPR003054; Keratin_II.
DR PANTHER; PTHR23239; PTHR23239; 1.
DR Pfam; PF00038; Filament; 1.
DR PRINTS; PR01276; TYPE2KERATIN.
DR PROSITE; PS00226; IF; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Complete proteome; Disease mutation; Ichthyosis;
KW Intermediate filament; Keratin; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT CHAIN 1 639 Keratin, type II cytoskeletal 2
FT epidermal.
FT /FTId=PRO_0000063715.
FT REGION 1 177 Head.
FT REGION 178 487 Rod.
FT REGION 178 213 Coil 1A.
FT REGION 214 232 Linker 1.
FT REGION 233 324 Coil 1B.
FT REGION 325 348 Linker 12.
FT REGION 349 487 Coil 2.
FT REGION 488 639 Tail.
FT SITE 429 429 Stutter.
FT MOD_RES 62 62 Phosphoserine.
FT VARIANT 101 101 S -> G (in dbSNP:rs2634041).
FT /FTId=VAR_058293.
FT VARIANT 181 181 Q -> P (in IBS).
FT /FTId=VAR_003865.
FT VARIANT 182 182 I -> N (in IBS; dbSNP:rs61622714).
FT /FTId=VAR_010514.
FT VARIANT 186 186 N -> D (in IBS).
FT /FTId=VAR_010515.
FT VARIANT 186 186 N -> K (in IBS; dbSNP:rs61726457).
FT /FTId=VAR_017829.
FT VARIANT 186 186 N -> Y (in IBS; dbSNP:rs61726454).
FT /FTId=VAR_009185.
FT VARIANT 219 219 G -> D (in dbSNP:rs638043).
FT /FTId=VAR_058294.
FT VARIANT 465 465 E -> D (in IBS).
FT /FTId=VAR_031082.
FT VARIANT 465 465 E -> K (in IBS).
FT /FTId=VAR_031083.
FT VARIANT 476 476 E -> K (in IBS; dbSNP:rs56829062).
FT /FTId=VAR_009186.
FT VARIANT 476 476 E -> V (in IBS; dbSNP:rs60537449).
FT /FTId=VAR_031084.
FT VARIANT 477 477 I -> N (in IBS).
FT /FTId=VAR_031085.
FT VARIANT 479 479 T -> P (in IBS; dbSNP:rs61726453).
FT /FTId=VAR_009187.
FT VARIANT 484 484 L -> P (in IBS; dbSNP:rs61726451).
FT /FTId=VAR_010516.
FT VARIANT 487 487 E -> D (in IBS; dbSNP:rs61726450).
FT /FTId=VAR_003866.
FT VARIANT 487 487 E -> K (in IBS; dbSNP:rs61726449).
FT /FTId=VAR_003867.
FT VARIANT 488 488 E -> K (in IBS; dbSNP:rs61726452).
FT /FTId=VAR_031086.
FT CONFLICT 108 108 F -> FGGGSGF (in Ref. 1; AAC83410 and 2;
FT AAB81946).
SQ SEQUENCE 639 AA; 65433 MW; B80526BAF70078A7 CRC64;
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
//
ID K22E_HUMAN Reviewed; 639 AA.
AC P35908; Q4VAQ2;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-JUN-2009, sequence version 2.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Keratin, type II cytoskeletal 2 epidermal;
DE AltName: Full=Cytokeratin-2e;
DE Short=CK-2e;
DE AltName: Full=Epithelial keratin-2e;
DE AltName: Full=Keratin-2 epidermis;
DE AltName: Full=Keratin-2e;
DE Short=K2e;
DE AltName: Full=Type-II keratin Kb2;
GN Name=KRT2; Synonyms=KRT2A, KRT2E;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND VARIANT GLY-101.
RC TISSUE=Thigh epidermis;
RX PubMed=1380918; DOI=10.1016/0014-4827(92)90412-2;
RA Collin C., Moll R., Kubicka S., Ouhayoun J.-P., Franke W.W.;
RT "Characterization of human cytokeratin 2, an epidermal cytoskeletal
RT protein synthesized late during differentiation.";
RL Exp. Cell Res. 202:132-141(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS IBS TYR-186 AND LYS-476,
RP AND VARIANT GLY-101.
RX PubMed=9804344; DOI=10.1046/j.1523-1747.1998.00371.x;
RA Smith F.J.D., Maingi C., Covello S.P., Higgins C., Schmidt M.,
RA Lane E.B., Uitto J., Leigh I.M., McLean W.H.I.;
RT "Genomic organization and fine mapping of the keratin 2e gene (KRT2E):
RT K2e V1 domain polymorphism and novel mutations in ichthyosis bullosa
RT of Siemens.";
RL J. Invest. Dermatol. 111:817-821(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10233306; DOI=10.1046/j.1365-2133.1999.02755.x;
RA Smith L.T., Underwood R.A., McLean W.H.I.;
RT "Ontogeny and regional variability of keratin 2e (K2e) in developing
RT human fetal skin: a unique spatial and temporal pattern of keratin
RT expression in development.";
RL Br. J. Dermatol. 140:582-591(1999).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12598329; DOI=10.1016/S0002-9440(10)63891-6;
RA Bloor B.K., Tidman N., Leigh I.M., Odell E., Dogan B., Wollina U.,
RA Ghali L., Waseem A.;
RT "Expression of keratin K2e in cutaneous and oral lesions: association
RT with keratinocyte activation, proliferation, and keratinization.";
RL Am. J. Pathol. 162:963-975(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP VARIANT IBS LYS-487.
RX PubMed=7521371; DOI=10.1111/1523-1747.ep12394307;
RA McLean W.H.I., Morley S.M., Lane E.B., Eady R.A.J., Griffiths W.A.D.,
RA Paige D.G., Harper J.I., Higgins C., Leigh I.M.;
RT "Ichthyosis bullosa of Siemens -- a disease involving keratin 2e.";
RL J. Invest. Dermatol. 103:277-281(1994).
RN [10]
RP VARIANTS IBS PRO-181; PRO-484 AND LYS-487.
RX PubMed=8077693; DOI=10.1111/1523-1747.ep12394414;
RA Kremer H., Zeeuwen P., McLean W.H.I., Mariman E.C.M., Lane E.B.,
RA van de Kerkhof P.C.M., Ropers H.-H., Steijlen P.M.;
RT "Ichthyosis bullosa of Siemens is caused by mutations in the keratin
RT 2e gene.";
RL J. Invest. Dermatol. 103:286-289(1994).
RN [11]
RP VARIANTS IBS ASP-487 AND LYS-487.
RX PubMed=7524919; DOI=10.1038/ng0894-485;
RA Rothnagel J.A., Traupe H., Wojcik S., Huber M., Hohl D.,
RA Pittelkow M.R., Saeki H., Ishibashi Y., Roop D.R.;
RT "Mutations in the rod domain of keratin 2e in patients with ichthyosis
RT bullosa of Siemens.";
RL Nat. Genet. 7:485-490(1994).
RN [12]
RP VARIANTS IBS LYS-487 AND LYS-488.
RX PubMed=9036938; DOI=10.1111/1523-1747.ep12286487;
RA Jones D.O., Watts C., Mills C., Sharpe G., Marks R., Bowden P.E.;
RT "A new keratin 2e mutation in ichthyosis bullosa of Siemens.";
RL J. Invest. Dermatol. 108:354-356(1997).
RN [13]
RP VARIANT IBS PRO-479.
RX PubMed=9204966; DOI=10.1111/1523-1747.ep12276775;
RA Yang J.-M., Lee S., Bang H.-D., Kim W.-S., Lee E.-S., Steinert P.M.;
RT "A novel threonine-to-proline mutation at the end of 2B rod domain in
RT the keratin 2e chain in ichthyosis bullosa of Siemens.";
RL J. Invest. Dermatol. 109:116-118(1997).
RN [14]
RP VARIANT IBS LYS-487.
RX PubMed=9833038; DOI=10.1080/000155598442683;
RA Yang J.-M., Lee E.-S., Kang H.-J., Choi G.-S., Yoneda K., Jung S.-Y.,
RA Park K.-B., Steinert P.M., Lee E.-S.;
RT "A glutamate to lysine mutation at the end of 2B rod domain of keratin
RT 2e gene in ichthyosis bullosa of Siemens.";
RL Acta Derm. Venereol. 78:417-419(1998).
RN [15]
RP VARIANT IBS LYS-487.
RX PubMed=10233323; DOI=10.1046/j.1365-2133.1999.02772.x;
RA Basarab T., Smith F.J., Jolliffe V.M., McLean W.H.I., Neill S.,
RA Rustin M.H., Eady R.A.;
RT "Ichthyosis bullosa of Siemens: report of a family with evidence of a
RT keratin 2e mutation, and a review of the literature.";
RL Br. J. Dermatol. 140:689-695(1999).
RN [16]
RP VARIANT IBS ASN-182.
RX PubMed=10084318; DOI=10.1046/j.1523-1747.1999.00529.x;
RA Arin M.J., Longley M.A., Epstein E.H. Jr., Scott G., Goldsmith L.A.,
RA Rothnagel J.A., Roop D.R.;
RT "A novel mutation in the 1A domain of keratin 2e in ichthyosis bullosa
RT of Siemens.";
RL J. Invest. Dermatol. 112:380-382(1999).
RN [17]
RP VARIANT IBS VAL-476.
RX PubMed=10564334; DOI=10.1046/j.1365-2230.1999.00514.x;
RA Moraru R., Cserhalmi-Friedman P.B., Grossman M.E., Schneiderman P.,
RA Christiano A.M.;
RT "Ichthyosis bullosa of Siemens resulting from a novel missense
RT mutation near the helix termination motif of the keratin 2e gene.";
RL Clin. Exp. Dermatol. 24:412-415(1999).
RN [18]
RP VARIANT IBS ASN-477.
RX PubMed=11167982; DOI=10.1046/j.1365-2230.2000.00728.x;
RA Irvine A.D., Smith F.J., Shum K.W., Williams H.C., McLean W.H.I.;
RT "A novel mutation in the 2B domain of keratin 2e causing ichthyosis
RT bullosa of Siemens.";
RL Clin. Exp. Dermatol. 25:648-651(2000).
RN [19]
RP VARIANTS IBS LYS-465 AND ASP-465.
RX PubMed=10688369; DOI=10.1034/j.1600-0625.2000.009001011.x;
RA Suga Y., Arin M.J., Scott G., Goldsmith L.A., Magro C.M., Baden L.A.,
RA Baden H.P., Roop D.R.;
RT "Hot spot mutations in keratin 2e suggest a correlation between
RT genotype and phenotype in patients with ichthyosis bullosa of
RT Siemens.";
RL Exp. Dermatol. 9:11-15(2000).
RN [20]
RP VARIANT IBS ASP-186.
RX PubMed=10620137; DOI=10.1046/j.1523-1747.2000.00817.x;
RA Takizawa Y., Akiyama M., Nagashima M., Shimizu H.;
RT "A novel asparagine-->aspartic acid mutation in the rod 1A domain in
RT keratin 2e in a Japanese family with ichthyosis bullosa of Siemens.";
RL J. Invest. Dermatol. 114:193-195(2000).
RN [21]
RP VARIANT IBS LYS-186.
RX PubMed=11531804; DOI=10.1046/j.1365-2133.2001.04327.x;
RA Whittock N.V., Ashton G.H.S., Griffiths W.A.D., Eady R.A.J.,
RA McGrath J.A.;
RT "New mutations in keratin 1 that cause bullous congenital
RT ichthyosiform erythroderma and keratin 2e that cause ichthyosis
RT bullosa of Siemens.";
RL Br. J. Dermatol. 145:330-335(2001).
RN [22]
RP VARIANTS IBS PRO-484 AND LYS-487.
RX PubMed=15949009; DOI=10.1111/j.1365-2133.2005.06598.x;
RA Akiyama M., Tsuji-Abe Y., Yanagihara M., Nakajima K., Kodama H.,
RA Yaosaka M., Abe M., Sawamura D., Shimizu H.;
RT "Ichthyosis bullosa of Siemens: its correct diagnosis facilitated by
RT molecular genetic testing.";
RL Br. J. Dermatol. 152:1353-1356(2005).
CC -!- FUNCTION: Probably contributes to terminal cornification.
CC Associated with keratinocyte activation, proliferation and
CC keratinization.
CC -!- SUBUNIT: Heterotetramer of two type I and two type II keratins.
CC Associates with KRT10 (By similarity).
CC -!- TISSUE SPECIFICITY: Expressed in the upper spinous and granular
CC suprabasal layers of normal adult epidermal tissues from most body
CC sites including thigh, breast nipple, foot sole, penile shaft and
CC axilla. Not present in foreskin, squamous metaplasias and
CC carcinomas. Expression in hypertrophic and keloid scars begins in
CC the deepest suprabasal layer. Weakly expressed in normal gingiva
CC and tongue, however expression is induced in benign keratoses of
CC lingual mucosa and in mild-to-moderate oral dysplasia with
CC orthokeratinization.
CC -!- DEVELOPMENTAL STAGE: Synthesized during maturation of epidermal
CC keratinocytes and localized in the upper intermediate cells of
CC fetal skin. Earliest expression is at 10 weeks in the developing
CC embryo in the presumptive nail bed of developing digits, shifting
CC to the proximal nail fold by 13.5 weeks. At 12.5 weeks, detected
CC in scattered cells of the intermediate layer of trunk skin. At
CC 19.3 weeks, regional expression patterns were observed in upper
CC intermediate keratinocytes of cheek, trunk, dorsal and ventral
CC knee, elbow and dorsal hand. Distal areas around the periumbilical
CC region showed increased number of positive cells and by 15 weeks
CC is expressed in small groups of cells in the fetal hair follicles.
CC -!- DISEASE: Ichthyosis bullosa of Siemens (IBS) [MIM:146800]: A rare
CC autosomal dominant skin disorder displaying a type of
CC epidermolytic hyperkeratosis characterized by generalized erythema
CC and extensive blistering from birth. Large, dark gray
CC hyperkeratoses are observed in later weeks. The skin of IBS
CC patients is unusually fragile and has a tendency to shed the outer
CC layers of the epidermis, producing localized denuded areas
CC (molting effect). IBS usually improves with age so that in most
CC middle-aged patients the hyperkeratosis and keratotic
CC lichenification is limited to the flexural folds of the major
CC joints. Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- MISCELLANEOUS: There are two types of cytoskeletal and
CC microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to
CC basic; 56-70 kDa).
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC -!- WEB RESOURCE: Name=Human Intermediate Filament Mutation Database;
CC URL="http://www.interfil.org";
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/KRT2";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Keratin-2A entry;
CC URL="http://en.wikipedia.org/wiki/Keratin_2A";
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DR EMBL; M99061; AAC83410.1; -; mRNA.
DR EMBL; AF019084; AAB81946.1; -; Genomic_DNA.
DR EMBL; AC055715; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC055716; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096294; AAH96294.1; -; mRNA.
DR EMBL; BC099643; AAH99643.1; -; mRNA.
DR EMBL; BC099644; AAH99644.1; -; mRNA.
DR PIR; A44861; A44861.
DR RefSeq; NP_000414.2; NM_000423.2.
DR UniGene; Hs.707; -.
DR ProteinModelPortal; P35908; -.
DR SMR; P35908; 178-317, 344-486.
DR IntAct; P35908; 8.
DR MINT; MINT-1208580; -.
DR STRING; 9606.ENSP00000310861; -.
DR PhosphoSite; P35908; -.
DR DMDM; 239938650; -.
DR PaxDb; P35908; -.
DR PeptideAtlas; P35908; -.
DR PRIDE; P35908; -.
DR ProMEX; P35908; -.
DR Ensembl; ENST00000309680; ENSP00000310861; ENSG00000172867.
DR GeneID; 3849; -.
DR KEGG; hsa:3849; -.
DR UCSC; uc001sat.3; human.
DR CTD; 3849; -.
DR GeneCards; GC12M053038; -.
DR H-InvDB; HIX0036877; -.
DR HGNC; HGNC:6439; KRT2.
DR HPA; HPA006299; -.
DR MIM; 146800; phenotype.
DR MIM; 600194; gene.
DR neXtProt; NX_P35908; -.
DR Orphanet; 455; Superficial epidermolytic ichthyosis.
DR PharmGKB; PA30227; -.
DR eggNOG; NOG146769; -.
DR HOGENOM; HOG000230976; -.
DR HOVERGEN; HBG013015; -.
DR InParanoid; P35908; -.
DR KO; K07605; -.
DR OMA; TNLDPIF; -.
DR OrthoDB; EOG7FV3Q8; -.
DR PhylomeDB; P35908; -.
DR GeneWiki; Keratin_2A; -.
DR GenomeRNAi; 3849; -.
DR NextBio; 15145; -.
DR PRO; PR:P35908; -.
DR Bgee; P35908; -.
DR CleanEx; HS_KRT2; -.
DR Genevestigator; P35908; -.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005882; C:intermediate filament; TAS:ProtInc.
DR GO; GO:0045095; C:keratin filament; IEA:InterPro.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0031424; P:keratinization; IDA:UniProtKB.
DR GO; GO:0032980; P:keratinocyte activation; IDA:UniProtKB.
DR GO; GO:0051546; P:keratinocyte migration; IDA:UniProtKB.
DR GO; GO:0043616; P:keratinocyte proliferation; IDA:UniProtKB.
DR InterPro; IPR001664; IF.
DR InterPro; IPR018039; Intermediate_filament_CS.
DR InterPro; IPR003054; Keratin_II.
DR PANTHER; PTHR23239; PTHR23239; 1.
DR Pfam; PF00038; Filament; 1.
DR PRINTS; PR01276; TYPE2KERATIN.
DR PROSITE; PS00226; IF; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Complete proteome; Disease mutation; Ichthyosis;
KW Intermediate filament; Keratin; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT CHAIN 1 639 Keratin, type II cytoskeletal 2
FT epidermal.
FT /FTId=PRO_0000063715.
FT REGION 1 177 Head.
FT REGION 178 487 Rod.
FT REGION 178 213 Coil 1A.
FT REGION 214 232 Linker 1.
FT REGION 233 324 Coil 1B.
FT REGION 325 348 Linker 12.
FT REGION 349 487 Coil 2.
FT REGION 488 639 Tail.
FT SITE 429 429 Stutter.
FT MOD_RES 62 62 Phosphoserine.
FT VARIANT 101 101 S -> G (in dbSNP:rs2634041).
FT /FTId=VAR_058293.
FT VARIANT 181 181 Q -> P (in IBS).
FT /FTId=VAR_003865.
FT VARIANT 182 182 I -> N (in IBS; dbSNP:rs61622714).
FT /FTId=VAR_010514.
FT VARIANT 186 186 N -> D (in IBS).
FT /FTId=VAR_010515.
FT VARIANT 186 186 N -> K (in IBS; dbSNP:rs61726457).
FT /FTId=VAR_017829.
FT VARIANT 186 186 N -> Y (in IBS; dbSNP:rs61726454).
FT /FTId=VAR_009185.
FT VARIANT 219 219 G -> D (in dbSNP:rs638043).
FT /FTId=VAR_058294.
FT VARIANT 465 465 E -> D (in IBS).
FT /FTId=VAR_031082.
FT VARIANT 465 465 E -> K (in IBS).
FT /FTId=VAR_031083.
FT VARIANT 476 476 E -> K (in IBS; dbSNP:rs56829062).
FT /FTId=VAR_009186.
FT VARIANT 476 476 E -> V (in IBS; dbSNP:rs60537449).
FT /FTId=VAR_031084.
FT VARIANT 477 477 I -> N (in IBS).
FT /FTId=VAR_031085.
FT VARIANT 479 479 T -> P (in IBS; dbSNP:rs61726453).
FT /FTId=VAR_009187.
FT VARIANT 484 484 L -> P (in IBS; dbSNP:rs61726451).
FT /FTId=VAR_010516.
FT VARIANT 487 487 E -> D (in IBS; dbSNP:rs61726450).
FT /FTId=VAR_003866.
FT VARIANT 487 487 E -> K (in IBS; dbSNP:rs61726449).
FT /FTId=VAR_003867.
FT VARIANT 488 488 E -> K (in IBS; dbSNP:rs61726452).
FT /FTId=VAR_031086.
FT CONFLICT 108 108 F -> FGGGSGF (in Ref. 1; AAC83410 and 2;
FT AAB81946).
SQ SEQUENCE 639 AA; 65433 MW; B80526BAF70078A7 CRC64;
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
//
MIM
146800
*RECORD*
*FIELD* NO
146800
*FIELD* TI
#146800 ICHTHYOSIS, BULLOUS TYPE
;;ICHTHYOSIS BULLOSA OF SIEMENS;;
IBS
ICHTHYOSIS EXFOLIATIVA, INCLUDED
read more*FIELD* TX
A number sign (#) is used with this entry because of the demonstration
that the disorder is caused by mutation in the keratin 2e gene (KRT2E;
600194).
Schnyder (1970) concluded that the bullous type of ichthyosis, called
ichthyosis bullosa of Siemens (Siemens, 1937), represents a distinct
entity. IBS is a rare autosomal dominant disorder that is highly
penetrant and clinically evident from birth. In affected individuals,
the clinical findings are similar to those of epidermolytic
hyperkeratosis (EHK; 113800). IBS patients are born with a generalized
reddening of the skin (erythema) and widespread blistering. In later
weeks, they develop large, dark gray hyperkeratoses predominantly on
their arms and legs and particularly on the flexural areas where the
hyperkeratoses have a lichenified appearance (Traupe et al., 1986;
Steijlen et al., 1990). The skin on the limbs of these patients bruises
easily and blisters are readily induced by mild physical trauma. The
condition 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. As for EHK and most autosomal
dominant disorders, IBS patients exhibit a wide variability in the
severity of their symptoms. Siemens (1937), who first made the
distinction between EHK and IBS, noted that the skin of IBS patients was
unusually fragile and had a tendency to shed the outer layers of the
epidermis, producing localized denuded areas. He applied the term
'Mauserung' (molting) to this distinctive clinical finding. Siemens'
work was largely overlooked until Traupe et al. (1986) reported
histologic and ultrastructural findings on a second family with IBS. In
the family reported by Steijlen et al. (1990), affected individuals had
brownish rippled hyperkeratosis and superficial blistering from early
childhood. Blistering was more pronounced during hot and humid weather
and could be provoked by mild trauma. Erythroderma had never been
present in any of the affected persons. Skin lesions were localized,
especially on the extensor surfaces of the arms and legs and around the
umbilicus, knees, and ankles. In the hyperkeratotic regions,
superficially denuded areas were present. Occasionally, fresh blisters
ranging in size from 0.5 to 2 cm appeared. On ultrastructural
examination of the skin, keratinocytes in the upper spinous layer
displayed aggregates of tonofilaments forming V shapes or shells around
the nuclei.
In the family with IBS reported by Steijlen et al. (1990), Steijlen et
al. (1994) demonstrated linkage of IBS to the region of chromosome 12 in
which the keratin type II gene cluster is located. The keratin type I
gene cluster on chromosome 17 was excluded. In 2 families originally
diagnosed as having EHK and in 4 families diagnosed with IBS, Rothnagel
et al. (1994) identified mutations at the same codon in the highly
conserved carboxy-terminus of the rod domain of keratin 2e, thus
revealing a mutation hotspot. These results allow a differential
diagnosis to be made between IBS and EHK at the DNA level. Rothnagel et
al. (1994) suggested that patients thought to have EHK who lack keratin
1 (KRT1; 139350) or keratin 10 (KRT10; 148080) mutations should be
reexamined for mutations in the KRT2E gene. McLean et al. (1994) also
found mutations in the KRT2E gene in 2 unrelated British families.
Ichthyosis exfoliativa is an autosomal dominant skin disorder described
by Vakilzadeh and Kolde (1991) in a single family. The clinical
manifestations were very similar to those of IBS, but the histologic
features of epidermolytic hyperkeratosis were absent. The patients
showed dark gray hyperkeratotic lesions with denuded areas. Superficial
blistering occurred spontaneously, especially during the summer, but
occurred also after trivial trauma. There was no history of
erythroderma. On electron microscopic examination, it was said that 'the
number of tonofilaments and keratohyaline granules were markedly reduced
with no grouping of the tonofilaments.' Steijlen et al. (1994)
demonstrated that, like IBS, ichthyosis exfoliativa in this family was
linked to the region of chromosome 12 carrying the type II keratin gene
cluster; furthermore, Kremer et al. (1994) detected a mutation in the
KRT2E gene identical to that identified in one of the families with IBS.
Thus, these are the same disease.
Nomenclature: Epidermolytic hyperkeratosis is a histopathologic
characteristic of a variety of monogenic keratinization disorders
comprising bullous congenital ichthyosiform erythroderma of Brocq,
epidermolytic palmoplantar keratoderma of Vorner (EPPK; 144200),
ichthyosis hystrix of Curth-Macklin (IHCM; 146590), and ichthyosis
bullosa of Siemens. The term epidermolytic hyperkeratosis is also used
to refer to the diseases themselves.
*FIELD* RF
1. 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.:
Ichthyosis bullosa of Siemens is caused by mutations in the keratin
2e gene. J. Invest. Derm. 103: 286-289, 1994.
2. 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.:
Ichthyosis bullosa of Siemens--a disease involving keratin 2e. J.
Invest. Derm. 103: 277-281, 1994.
3. Rothnagel, J. A.; Traupe, H.; Wojcik, S.; Huber, M.; Hohl, D.;
Pittelkow, M. R.; Saeki, H.; Ishibashi, Y.; Roop, D. R.: Mutations
in the rod domain of keratin 2e in patients with ichthyosis bullosa
of Siemens. Nature Genet. 7: 485-490, 1994.
4. Schnyder, U. W.: Inherited ichthyoses. Arch. Derm. 102: 240-252,
1970.
5. Siemens, H. W.: Dichtung und Wahrheit ueber die Ichthyosis bullosa,
mit Bemerkungen zur Systematik der Epidermolysen. Arch. Derm. Syph. 175:
590-608, 1937.
6. Steijlen, P. M.; Kremer, H.; Vakilzadeh, F.; Happle, R.; Lavrijsen,
A. P. M.; Ropers, H.-H.; Mariman, E. C. M.: Genetic linkage of the
keratin type II gene cluster with ichthyosis bullosa of Siemens and
with autosomal dominant ichthyosis exfoliativa. J. Invest. Derm. 103:
282-285, 1994.
7. Steijlen, P. M.; Perret, C. M.; Schuurmans-Stekhoven, J. H.; Ruiter,
D. J.; Happle, R.: Ichthyosis bullosa of Siemens: further delineation
of the phenotype. Arch. Derm. Res. 282: 1-5, 1990.
8. Traupe, H.; Kolde, G.; Hamm, H.; Happle, R.: Ichthyosis bullosa
of Siemens: a unique type of epidermolytic hyperkeratosis. J. Am.
Acad. Derm. 14: 1000-1005, 1986.
9. Vakilzadeh, F.; Kolde, G.: Autosomal dominant ichthyosis exfoliativa. Brit.
J. Derm. 124: 191-194, 1991.
*FIELD* CS
Skin:
Bullous ichthyosis
Inheritance:
Autosomal dominant;
? same as erythroderma ichthyosiformis congenita of Brocq (113800)
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
terry: 08/03/2005
alopez: 5/14/1998
mimadm: 1/14/1995
terry: 11/29/1994
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
*RECORD*
*FIELD* NO
146800
*FIELD* TI
#146800 ICHTHYOSIS, BULLOUS TYPE
;;ICHTHYOSIS BULLOSA OF SIEMENS;;
IBS
ICHTHYOSIS EXFOLIATIVA, INCLUDED
read more*FIELD* TX
A number sign (#) is used with this entry because of the demonstration
that the disorder is caused by mutation in the keratin 2e gene (KRT2E;
600194).
Schnyder (1970) concluded that the bullous type of ichthyosis, called
ichthyosis bullosa of Siemens (Siemens, 1937), represents a distinct
entity. IBS is a rare autosomal dominant disorder that is highly
penetrant and clinically evident from birth. In affected individuals,
the clinical findings are similar to those of epidermolytic
hyperkeratosis (EHK; 113800). IBS patients are born with a generalized
reddening of the skin (erythema) and widespread blistering. In later
weeks, they develop large, dark gray hyperkeratoses predominantly on
their arms and legs and particularly on the flexural areas where the
hyperkeratoses have a lichenified appearance (Traupe et al., 1986;
Steijlen et al., 1990). The skin on the limbs of these patients bruises
easily and blisters are readily induced by mild physical trauma. The
condition 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. As for EHK and most autosomal
dominant disorders, IBS patients exhibit a wide variability in the
severity of their symptoms. Siemens (1937), who first made the
distinction between EHK and IBS, noted that the skin of IBS patients was
unusually fragile and had a tendency to shed the outer layers of the
epidermis, producing localized denuded areas. He applied the term
'Mauserung' (molting) to this distinctive clinical finding. Siemens'
work was largely overlooked until Traupe et al. (1986) reported
histologic and ultrastructural findings on a second family with IBS. In
the family reported by Steijlen et al. (1990), affected individuals had
brownish rippled hyperkeratosis and superficial blistering from early
childhood. Blistering was more pronounced during hot and humid weather
and could be provoked by mild trauma. Erythroderma had never been
present in any of the affected persons. Skin lesions were localized,
especially on the extensor surfaces of the arms and legs and around the
umbilicus, knees, and ankles. In the hyperkeratotic regions,
superficially denuded areas were present. Occasionally, fresh blisters
ranging in size from 0.5 to 2 cm appeared. On ultrastructural
examination of the skin, keratinocytes in the upper spinous layer
displayed aggregates of tonofilaments forming V shapes or shells around
the nuclei.
In the family with IBS reported by Steijlen et al. (1990), Steijlen et
al. (1994) demonstrated linkage of IBS to the region of chromosome 12 in
which the keratin type II gene cluster is located. The keratin type I
gene cluster on chromosome 17 was excluded. In 2 families originally
diagnosed as having EHK and in 4 families diagnosed with IBS, Rothnagel
et al. (1994) identified mutations at the same codon in the highly
conserved carboxy-terminus of the rod domain of keratin 2e, thus
revealing a mutation hotspot. These results allow a differential
diagnosis to be made between IBS and EHK at the DNA level. Rothnagel et
al. (1994) suggested that patients thought to have EHK who lack keratin
1 (KRT1; 139350) or keratin 10 (KRT10; 148080) mutations should be
reexamined for mutations in the KRT2E gene. McLean et al. (1994) also
found mutations in the KRT2E gene in 2 unrelated British families.
Ichthyosis exfoliativa is an autosomal dominant skin disorder described
by Vakilzadeh and Kolde (1991) in a single family. The clinical
manifestations were very similar to those of IBS, but the histologic
features of epidermolytic hyperkeratosis were absent. The patients
showed dark gray hyperkeratotic lesions with denuded areas. Superficial
blistering occurred spontaneously, especially during the summer, but
occurred also after trivial trauma. There was no history of
erythroderma. On electron microscopic examination, it was said that 'the
number of tonofilaments and keratohyaline granules were markedly reduced
with no grouping of the tonofilaments.' Steijlen et al. (1994)
demonstrated that, like IBS, ichthyosis exfoliativa in this family was
linked to the region of chromosome 12 carrying the type II keratin gene
cluster; furthermore, Kremer et al. (1994) detected a mutation in the
KRT2E gene identical to that identified in one of the families with IBS.
Thus, these are the same disease.
Nomenclature: Epidermolytic hyperkeratosis is a histopathologic
characteristic of a variety of monogenic keratinization disorders
comprising bullous congenital ichthyosiform erythroderma of Brocq,
epidermolytic palmoplantar keratoderma of Vorner (EPPK; 144200),
ichthyosis hystrix of Curth-Macklin (IHCM; 146590), and ichthyosis
bullosa of Siemens. The term epidermolytic hyperkeratosis is also used
to refer to the diseases themselves.
*FIELD* RF
1. 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.:
Ichthyosis bullosa of Siemens is caused by mutations in the keratin
2e gene. J. Invest. Derm. 103: 286-289, 1994.
2. 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.:
Ichthyosis bullosa of Siemens--a disease involving keratin 2e. J.
Invest. Derm. 103: 277-281, 1994.
3. Rothnagel, J. A.; Traupe, H.; Wojcik, S.; Huber, M.; Hohl, D.;
Pittelkow, M. R.; Saeki, H.; Ishibashi, Y.; Roop, D. R.: Mutations
in the rod domain of keratin 2e in patients with ichthyosis bullosa
of Siemens. Nature Genet. 7: 485-490, 1994.
4. Schnyder, U. W.: Inherited ichthyoses. Arch. Derm. 102: 240-252,
1970.
5. Siemens, H. W.: Dichtung und Wahrheit ueber die Ichthyosis bullosa,
mit Bemerkungen zur Systematik der Epidermolysen. Arch. Derm. Syph. 175:
590-608, 1937.
6. Steijlen, P. M.; Kremer, H.; Vakilzadeh, F.; Happle, R.; Lavrijsen,
A. P. M.; Ropers, H.-H.; Mariman, E. C. M.: Genetic linkage of the
keratin type II gene cluster with ichthyosis bullosa of Siemens and
with autosomal dominant ichthyosis exfoliativa. J. Invest. Derm. 103:
282-285, 1994.
7. Steijlen, P. M.; Perret, C. M.; Schuurmans-Stekhoven, J. H.; Ruiter,
D. J.; Happle, R.: Ichthyosis bullosa of Siemens: further delineation
of the phenotype. Arch. Derm. Res. 282: 1-5, 1990.
8. Traupe, H.; Kolde, G.; Hamm, H.; Happle, R.: Ichthyosis bullosa
of Siemens: a unique type of epidermolytic hyperkeratosis. J. Am.
Acad. Derm. 14: 1000-1005, 1986.
9. Vakilzadeh, F.; Kolde, G.: Autosomal dominant ichthyosis exfoliativa. Brit.
J. Derm. 124: 191-194, 1991.
*FIELD* CS
Skin:
Bullous ichthyosis
Inheritance:
Autosomal dominant;
? same as erythroderma ichthyosiformis congenita of Brocq (113800)
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
terry: 08/03/2005
alopez: 5/14/1998
mimadm: 1/14/1995
terry: 11/29/1994
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
MIM
600194
*RECORD*
*FIELD* NO
600194
*FIELD* TI
*600194 KERATIN 2; KRT2
;;KERATIN 2A; KRT2A;;
KERATIN 2e; KRT2E
*FIELD* TX
GENE FAMILY
read more
Keratins are the major gene product of keratinocytes and form the
intermediate filament cytoskeletal network in these cells. Intermediate
filament proteins consist of a central alpha-helical rod domain flanked
by nonhelical sequences of varying size and composition. Keratin
proteins fall into 2 classes on the basis of their electrophoretic
properties and sequence similarities. One member of each class is
required to form the heterodimeric coiled-coil precursor which through
both lateral and longitudinal associations form the mature keratin
intermediate filament. The major epidermal keratins of the type I class
are KRT9 (607606), KRT10 (148080), KRT14 (148066), and KRT16 (148067);
the major epidermal keratins of the type II class are KRT1 (139350),
KRT2, KRT5 (148040), KRT6A (148041), and KRT6B (148042). The expression
of individual keratins is specific both for body site and for stage of
differentiation of the epidermal keratinocyte. Keratinocytes in the
basal layer express KRT5 and KRT14. Upon differentiation and migration
to the spinous layer, these genes are downregulated and the expression
of KRT1 and KRT10 is induced. In cells of the upper spinous layer, KRT2
and KRT9 are expressed. Although the expression of KRT9 is limited to
palmoplantar epidermis, KRT2 is expressed not only in this tissue but
also in other regions, notably the epidermis covering the knee, thigh,
and groin. It is not known whether these keratins simply replace their
respective type I or type II counterpart in the preexisting KRT1/KRT10
network or dimerize with another, as yet undiscovered keratin partner.
The other major epidermal keratins, KRT6 and KRT16, are normally
expressed in the outer root sheath of the hair follicle and in
palmoplantar epidermis.
CLONING
Keratin 2e is a protein of molecular weight 65.8 kD encoded by a 2.6-kb
mRNA species. Collin et al. (1992) determined the sequence of the KRT2e
cDNA.
GENE STRUCTURE
Smith et al. (1998) determined the genomic organization and complete
sequence of the KRT2 gene, which consists of 9 exons spanning 7,634 bp
of DNA.
MAPPING
Presumably the KRT2 gene maps to 12q11-q13, the site of the other class
II genes, such as KRT1 and KRT5. By high-resolution radiation hybrid
mapping, Smith et al. (1998) localized the gene to the interval between
microsatellite markers D12S368 and a specific CHLC marker.
MOLECULAR GENETICS
Mutations in the basal cell-specific keratins KRT5 and KRT14 are found
in patients with epidermolysis bullosa simplex (e.g., 131900); mutations
in the differentiation-specific keratins KRT1 and KRT10 have been found
in patients with epidermolytic hyperkeratosis (113800); and mutations in
the palmoplantar-specific keratin KRT9 have been found in patients with
epidermolytic palmoplantar keratoderma (144200). Rothnagel et al. (1994)
and McLean et al. (1994) demonstrated mutations in the KRT2 gene in
patients with ichthyosis bullosa of Siemens (IBS; 146800). Kremer et al.
(1994) also found mutations in the KRT2 gene in patients with IBS and in
patients with a phenotypically related, if not identical, disorder,
ichthyosis exfoliativa.
Smith et al. (1998) detected several intragenic polymorphisms in the
KRT2 gene, including an 18-bp duplication in exon 1, corresponding to
the V1 domain of the K2e polypeptide. Two novel mutations, N192Y in the
1A domain and E482K in the 2B domain of K2e, were found in families with
IBS.
*FIELD* AV
.0001
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, GLU493ASP
In an Asian family with ichthyosis bullosa of Siemens (146800;
originally diagnosed as epidermolytic hyperkeratosis), Rothnagel et al.
(1994) identified a G-to-T transversion at basepair 1512 of the
published sequence (Collin et al., 1992) of the KRT2 gene, resulting in
a glutamic acid to aspartic acid substitution at residue 117 in the
highly conserved C terminal of the rod domain. (According to Rothnagel
et al. (1994), the residue designated 117 corresponds to codon 493 of
the published sequence.)
.0002
ICHTHYOSIS BULLOSA OF SIEMENS
ICHTHYOSIS EXFOLIATIVA, INCLUDED
KRT2, GLU493LYS
In 4 families with autosomal dominant inheritance of ichthyosis bullosa
of Siemens (146800) and in 1 sporadic case of this disorder, Rothnagel
et al. (1994) found a G-to-A transition at nucleotide 1510 resulting in
a lysine for glutamic acid substitution at residue 117 of the KRT2
protein. Thus in a total of 6 instances, the mutation occurred in the
same codon, GAG (glu); the mutation was to GAT in 1 family and to AAG in
the 5 others. (According to Rothnagel et al. (1994), the residue
designated 117 corresponds to codon 493 of the published sequence.)
In 2 unrelated British families with ichthyosis bullosa of Siemens,
McLean et al. (1994) found a glu493-to-lys mutation in the highly
conserved LLEGEE helix termination motif, producing a change to LLEGKE.
The mutation was predicted to be highly detrimental to keratin filament
assembly and/or functional integrity. A G-to-A transition at nucleotide
1510 of the cDNA sequence occurred in a CpG dinucleotide.
Kremer et al. (1994) identified the same mutation in a family described
as having ichthyosis exfoliativa and in yet another Dutch family with
ichthyosis bullosa of Siemens.
In a large family with ichthyosis bullosa of Siemens in 8 members
spanning 3 generations, Basarab et al. (1999) identified the E493K
mutation in the KRT2 gene. The patients showed blistering, superficial
peeling of the skin, and localized lichenified hyperkeratosis, mainly
confined to the limbs. Phenotypic variation with some individuals
exhibiting unusual clinical features was also observed. The index
patient was erythrodermic at birth and subsequently developed a
widespread pustular eruption. She also had hypertrichosis of the limbs,
as did an affected female first cousin. Basarab et al. (1999) found that
E493K is by far the most frequent mutation in this disorder.
.0003
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, GLN187PRO
In a Dutch family with ichthyosis bullosa of Siemens (146800), Kremer et
al. (1994) found a heterozygous transversion of adenosine to cytosine at
nucleotide 593. This transversion led to the substitution of a proline
for a glutamine at codon 187 (numbering according to Collin et al.
(1992)) of the predicted protein sequence.
.0004
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, THR485PRO
In a 4-year-old Korean boy, Yang et al. (1997) observed a sporadic case
of ichthyosis bullosa of Siemens (146800) and demonstrated a
thr485-to-pro amino acid substitution in the highly conserved consensus
motif at the end of the 2-B rod domain segment of the keratin 2 chain.
The disease phenotype was consistent with the inappropriate substitution
of proline near the end of the rod domain, because it was situated near
the predicted molecular overlap region of coiled-coil molecules, which
is critical for the maintenance of the structural integrity of keratin
intermediate filaments. The patient had brownish, wrinkled, and
encrusted hyperkeratosis and blistering over the entirety of his trunk
and limbs, especially on flexural areas, beginning at the age of 100
days. Blistering was more pronounced during summer and could be provoked
by mild trauma. Erythroderma had never been present. Light microscopic
examination showed epidermolytic hyperkeratosis limited to the upper
part of the epidermis.
.0005
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, ASN192TYR
In a family with ichthyosis bullosa of Siemens (146800), Smith et al.
(1998) identified an asn192-to-tyr substitution in the KRT2 gene.
.0006
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, GLU482LYS
In a family with ichthyosis bullosa of Siemens (146800), Smith et al.
(1998) identified a glu482-to-lys substitution in the KRT2 gene.
.0007
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, ASN192ASP
In a family with ichthyosis bullosa of Siemens (146800), Takizawa et al.
(2000) identified an A-to-G transition at nucleotide position 607 of the
KRT2 gene, resulting in an asn192-to-asp substitution.
.0008
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, ASN192LYS
In a patient with ichthyosis bullosa of Siemens (146800), Whittock et
al. (2001) reported a heterozygous C-to-A transversion at nucleotide 576
of the KRT2 gene that resulted in an asn192-to-lys (N192K) amino acid
substitution in the conserved 1A helix initiation peptide.
*FIELD* RF
1. Basarab, T.; Smith, F. J. D.; Jolliffe, V. M. L.; McLean, W. H.
I.; Neill, S.; Rustin, M. H. A.; Eady, R. A. J.: Ichthyosis bullosa
of Siemens: report of a family with evidence of a keratin 2e mutation,
and a review of the literature. Brit. J. Derm. 140: 689-695, 1999.
2. Collin, C.; Moll, R.; Kubicka, S.; Ouhayoun, J.-P.; Franke, W.
W.: Characterization of human cytokeratin 2, an epidermal cytoskeletal
protein synthesized late during differentiation. Exp. Cell Res. 202:
132-141, 1992.
3. 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.:
Ichthyosis bullosa of Siemens is caused by mutations in the keratin
2e gene. J. Invest. Derm. 103: 286-289, 1994.
4. 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.:
Ichthyosis bullosa of Siemens--a disease involving keratin 2e. J.
Invest. Derm. 103: 277-281, 1994.
5. Rothnagel, J. A.; Traupe, H.; Wojcik, S.; Huber, M.; Hohl, D.;
Pittelkow, M. R.; Saeki, H.; Ishibashi, Y.; Roop, D. R.: Mutations
in the rod domain of keratin 2e in patients with ichthyosis bullosa
of Siemens. Nature Genet. 7: 485-490, 1994.
6. 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.: Genomic
organization and fine mapping of the keratin 2e gene (KRT2E): K2e
V1 domain polymorphism and novel mutations in ichthyosis bullosa of
Siemens. J. Invest. Derm. 111: 817-821, 1998.
7. Takizawa, Y.; Akiyama, M.; Nagashima, M.; Shimizu, H.: A novel
asparagine-aspartic acid mutation in the rod 1A domain in keratin
2e in a Japanese family with ichthyosis bullosa of Siemens J. Invest.
Derm. 114: 193-195, 2000.
8. Whittock, N. V.; Ashton, G. H. S.; Griffiths, W. A. D.; Eady, R.
A. J.; McGrath, J. A.: New mutations in keratin 1 that cause bullous
congenital ichthyosiform erythroderma and keratin 2e that cause ichthyosis
bullosa of Siemens. Brit. J. Derm. 145: 330-335, 2001.
9. Yang, J.-M.; Lee, S.; Bang, H.-D.; Kim, W.-S.; Lee, E.-S.; Steinert,
P. M.: A novel threonine-to-proline mutation at the end of 2B rod
domain in the keratin 2e chain in ichthyosis bullosa of Siemens. J.
Invest. Derm. 109: 116-118, 1997.
*FIELD* CN
Gary A. Bellus - updated: 3/7/2003
Gary A. Bellus - updated: 6/13/2000
Victor A. McKusick - updated: 6/11/1999
Victor A. McKusick - updated: 1/27/1999
Victor A. McKusick - updated: 9/8/1997
*FIELD* CD
Victor A. McKusick: 11/14/1994
*FIELD* ED
carol: 03/26/2008
alopez: 3/12/2003
alopez: 3/7/2003
alopez: 6/13/2000
jlewis: 6/21/1999
jlewis: 6/17/1999
terry: 6/11/1999
carol: 2/12/1999
terry: 1/27/1999
terry: 9/8/1997
terry: 8/5/1997
mark: 6/19/1997
alopez: 6/10/1997
jamie: 1/17/1997
mark: 4/1/1996
mimadm: 9/23/1995
terry: 6/24/1995
terry: 11/29/1994
carol: 11/16/1994
carol: 11/15/1994
*RECORD*
*FIELD* NO
600194
*FIELD* TI
*600194 KERATIN 2; KRT2
;;KERATIN 2A; KRT2A;;
KERATIN 2e; KRT2E
*FIELD* TX
GENE FAMILY
read more
Keratins are the major gene product of keratinocytes and form the
intermediate filament cytoskeletal network in these cells. Intermediate
filament proteins consist of a central alpha-helical rod domain flanked
by nonhelical sequences of varying size and composition. Keratin
proteins fall into 2 classes on the basis of their electrophoretic
properties and sequence similarities. One member of each class is
required to form the heterodimeric coiled-coil precursor which through
both lateral and longitudinal associations form the mature keratin
intermediate filament. The major epidermal keratins of the type I class
are KRT9 (607606), KRT10 (148080), KRT14 (148066), and KRT16 (148067);
the major epidermal keratins of the type II class are KRT1 (139350),
KRT2, KRT5 (148040), KRT6A (148041), and KRT6B (148042). The expression
of individual keratins is specific both for body site and for stage of
differentiation of the epidermal keratinocyte. Keratinocytes in the
basal layer express KRT5 and KRT14. Upon differentiation and migration
to the spinous layer, these genes are downregulated and the expression
of KRT1 and KRT10 is induced. In cells of the upper spinous layer, KRT2
and KRT9 are expressed. Although the expression of KRT9 is limited to
palmoplantar epidermis, KRT2 is expressed not only in this tissue but
also in other regions, notably the epidermis covering the knee, thigh,
and groin. It is not known whether these keratins simply replace their
respective type I or type II counterpart in the preexisting KRT1/KRT10
network or dimerize with another, as yet undiscovered keratin partner.
The other major epidermal keratins, KRT6 and KRT16, are normally
expressed in the outer root sheath of the hair follicle and in
palmoplantar epidermis.
CLONING
Keratin 2e is a protein of molecular weight 65.8 kD encoded by a 2.6-kb
mRNA species. Collin et al. (1992) determined the sequence of the KRT2e
cDNA.
GENE STRUCTURE
Smith et al. (1998) determined the genomic organization and complete
sequence of the KRT2 gene, which consists of 9 exons spanning 7,634 bp
of DNA.
MAPPING
Presumably the KRT2 gene maps to 12q11-q13, the site of the other class
II genes, such as KRT1 and KRT5. By high-resolution radiation hybrid
mapping, Smith et al. (1998) localized the gene to the interval between
microsatellite markers D12S368 and a specific CHLC marker.
MOLECULAR GENETICS
Mutations in the basal cell-specific keratins KRT5 and KRT14 are found
in patients with epidermolysis bullosa simplex (e.g., 131900); mutations
in the differentiation-specific keratins KRT1 and KRT10 have been found
in patients with epidermolytic hyperkeratosis (113800); and mutations in
the palmoplantar-specific keratin KRT9 have been found in patients with
epidermolytic palmoplantar keratoderma (144200). Rothnagel et al. (1994)
and McLean et al. (1994) demonstrated mutations in the KRT2 gene in
patients with ichthyosis bullosa of Siemens (IBS; 146800). Kremer et al.
(1994) also found mutations in the KRT2 gene in patients with IBS and in
patients with a phenotypically related, if not identical, disorder,
ichthyosis exfoliativa.
Smith et al. (1998) detected several intragenic polymorphisms in the
KRT2 gene, including an 18-bp duplication in exon 1, corresponding to
the V1 domain of the K2e polypeptide. Two novel mutations, N192Y in the
1A domain and E482K in the 2B domain of K2e, were found in families with
IBS.
*FIELD* AV
.0001
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, GLU493ASP
In an Asian family with ichthyosis bullosa of Siemens (146800;
originally diagnosed as epidermolytic hyperkeratosis), Rothnagel et al.
(1994) identified a G-to-T transversion at basepair 1512 of the
published sequence (Collin et al., 1992) of the KRT2 gene, resulting in
a glutamic acid to aspartic acid substitution at residue 117 in the
highly conserved C terminal of the rod domain. (According to Rothnagel
et al. (1994), the residue designated 117 corresponds to codon 493 of
the published sequence.)
.0002
ICHTHYOSIS BULLOSA OF SIEMENS
ICHTHYOSIS EXFOLIATIVA, INCLUDED
KRT2, GLU493LYS
In 4 families with autosomal dominant inheritance of ichthyosis bullosa
of Siemens (146800) and in 1 sporadic case of this disorder, Rothnagel
et al. (1994) found a G-to-A transition at nucleotide 1510 resulting in
a lysine for glutamic acid substitution at residue 117 of the KRT2
protein. Thus in a total of 6 instances, the mutation occurred in the
same codon, GAG (glu); the mutation was to GAT in 1 family and to AAG in
the 5 others. (According to Rothnagel et al. (1994), the residue
designated 117 corresponds to codon 493 of the published sequence.)
In 2 unrelated British families with ichthyosis bullosa of Siemens,
McLean et al. (1994) found a glu493-to-lys mutation in the highly
conserved LLEGEE helix termination motif, producing a change to LLEGKE.
The mutation was predicted to be highly detrimental to keratin filament
assembly and/or functional integrity. A G-to-A transition at nucleotide
1510 of the cDNA sequence occurred in a CpG dinucleotide.
Kremer et al. (1994) identified the same mutation in a family described
as having ichthyosis exfoliativa and in yet another Dutch family with
ichthyosis bullosa of Siemens.
In a large family with ichthyosis bullosa of Siemens in 8 members
spanning 3 generations, Basarab et al. (1999) identified the E493K
mutation in the KRT2 gene. The patients showed blistering, superficial
peeling of the skin, and localized lichenified hyperkeratosis, mainly
confined to the limbs. Phenotypic variation with some individuals
exhibiting unusual clinical features was also observed. The index
patient was erythrodermic at birth and subsequently developed a
widespread pustular eruption. She also had hypertrichosis of the limbs,
as did an affected female first cousin. Basarab et al. (1999) found that
E493K is by far the most frequent mutation in this disorder.
.0003
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, GLN187PRO
In a Dutch family with ichthyosis bullosa of Siemens (146800), Kremer et
al. (1994) found a heterozygous transversion of adenosine to cytosine at
nucleotide 593. This transversion led to the substitution of a proline
for a glutamine at codon 187 (numbering according to Collin et al.
(1992)) of the predicted protein sequence.
.0004
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, THR485PRO
In a 4-year-old Korean boy, Yang et al. (1997) observed a sporadic case
of ichthyosis bullosa of Siemens (146800) and demonstrated a
thr485-to-pro amino acid substitution in the highly conserved consensus
motif at the end of the 2-B rod domain segment of the keratin 2 chain.
The disease phenotype was consistent with the inappropriate substitution
of proline near the end of the rod domain, because it was situated near
the predicted molecular overlap region of coiled-coil molecules, which
is critical for the maintenance of the structural integrity of keratin
intermediate filaments. The patient had brownish, wrinkled, and
encrusted hyperkeratosis and blistering over the entirety of his trunk
and limbs, especially on flexural areas, beginning at the age of 100
days. Blistering was more pronounced during summer and could be provoked
by mild trauma. Erythroderma had never been present. Light microscopic
examination showed epidermolytic hyperkeratosis limited to the upper
part of the epidermis.
.0005
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, ASN192TYR
In a family with ichthyosis bullosa of Siemens (146800), Smith et al.
(1998) identified an asn192-to-tyr substitution in the KRT2 gene.
.0006
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, GLU482LYS
In a family with ichthyosis bullosa of Siemens (146800), Smith et al.
(1998) identified a glu482-to-lys substitution in the KRT2 gene.
.0007
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, ASN192ASP
In a family with ichthyosis bullosa of Siemens (146800), Takizawa et al.
(2000) identified an A-to-G transition at nucleotide position 607 of the
KRT2 gene, resulting in an asn192-to-asp substitution.
.0008
ICHTHYOSIS BULLOSA OF SIEMENS
KRT2, ASN192LYS
In a patient with ichthyosis bullosa of Siemens (146800), Whittock et
al. (2001) reported a heterozygous C-to-A transversion at nucleotide 576
of the KRT2 gene that resulted in an asn192-to-lys (N192K) amino acid
substitution in the conserved 1A helix initiation peptide.
*FIELD* RF
1. Basarab, T.; Smith, F. J. D.; Jolliffe, V. M. L.; McLean, W. H.
I.; Neill, S.; Rustin, M. H. A.; Eady, R. A. J.: Ichthyosis bullosa
of Siemens: report of a family with evidence of a keratin 2e mutation,
and a review of the literature. Brit. J. Derm. 140: 689-695, 1999.
2. Collin, C.; Moll, R.; Kubicka, S.; Ouhayoun, J.-P.; Franke, W.
W.: Characterization of human cytokeratin 2, an epidermal cytoskeletal
protein synthesized late during differentiation. Exp. Cell Res. 202:
132-141, 1992.
3. 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.:
Ichthyosis bullosa of Siemens is caused by mutations in the keratin
2e gene. J. Invest. Derm. 103: 286-289, 1994.
4. 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.:
Ichthyosis bullosa of Siemens--a disease involving keratin 2e. J.
Invest. Derm. 103: 277-281, 1994.
5. Rothnagel, J. A.; Traupe, H.; Wojcik, S.; Huber, M.; Hohl, D.;
Pittelkow, M. R.; Saeki, H.; Ishibashi, Y.; Roop, D. R.: Mutations
in the rod domain of keratin 2e in patients with ichthyosis bullosa
of Siemens. Nature Genet. 7: 485-490, 1994.
6. 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.: Genomic
organization and fine mapping of the keratin 2e gene (KRT2E): K2e
V1 domain polymorphism and novel mutations in ichthyosis bullosa of
Siemens. J. Invest. Derm. 111: 817-821, 1998.
7. Takizawa, Y.; Akiyama, M.; Nagashima, M.; Shimizu, H.: A novel
asparagine-aspartic acid mutation in the rod 1A domain in keratin
2e in a Japanese family with ichthyosis bullosa of Siemens J. Invest.
Derm. 114: 193-195, 2000.
8. Whittock, N. V.; Ashton, G. H. S.; Griffiths, W. A. D.; Eady, R.
A. J.; McGrath, J. A.: New mutations in keratin 1 that cause bullous
congenital ichthyosiform erythroderma and keratin 2e that cause ichthyosis
bullosa of Siemens. Brit. J. Derm. 145: 330-335, 2001.
9. Yang, J.-M.; Lee, S.; Bang, H.-D.; Kim, W.-S.; Lee, E.-S.; Steinert,
P. M.: A novel threonine-to-proline mutation at the end of 2B rod
domain in the keratin 2e chain in ichthyosis bullosa of Siemens. J.
Invest. Derm. 109: 116-118, 1997.
*FIELD* CN
Gary A. Bellus - updated: 3/7/2003
Gary A. Bellus - updated: 6/13/2000
Victor A. McKusick - updated: 6/11/1999
Victor A. McKusick - updated: 1/27/1999
Victor A. McKusick - updated: 9/8/1997
*FIELD* CD
Victor A. McKusick: 11/14/1994
*FIELD* ED
carol: 03/26/2008
alopez: 3/12/2003
alopez: 3/7/2003
alopez: 6/13/2000
jlewis: 6/21/1999
jlewis: 6/17/1999
terry: 6/11/1999
carol: 2/12/1999
terry: 1/27/1999
terry: 9/8/1997
terry: 8/5/1997
mark: 6/19/1997
alopez: 6/10/1997
jamie: 1/17/1997
mark: 4/1/1996
mimadm: 9/23/1995
terry: 6/24/1995
terry: 11/29/1994
carol: 11/16/1994
carol: 11/15/1994