K22E_HUMAN
ID K22E_HUMAN Reviewed; 639 AA.
AC P35908; Q4VAQ2;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 2.
DT 03-AUG-2022, entry version 197.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP 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 protein
RT 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, AND
RP 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., Lane E.B.,
RA Uitto J., Leigh I.M., McLean W.H.I.;
RT "Genomic organization and fine mapping of the keratin 2e gene (KRT2E): K2e
RT V1 domain polymorphism and novel mutations in ichthyosis bullosa of
RT 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., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., 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., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., 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., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA 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 project:
RT 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 human
RT fetal skin: a unique spatial and temporal pattern of keratin expression in
RT 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 with
RT keratinocyte activation, proliferation, and keratinization.";
RL Am. J. Pathol. 162:963-975(2003).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
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., Buerckstuemmer T.,
RA 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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP SUBCELLULAR LOCATION, AND INDUCTION BY ATRA.
RX PubMed=32179842; DOI=10.1038/s41598-020-61640-9;
RA Aldehlawi H., Usman S., Lalli A., Ahmad F., Williams G., Teh M.T.,
RA Waseem A.;
RT "Serum lipids, retinoic acid and phenol red differentially regulate
RT expression of keratins K1, K10 and K2 in cultured keratinocytes.";
RL Sci. Rep. 10:4829-4829(2020).
RN [13]
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 [14]
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 2e
RT gene.";
RL J. Invest. Dermatol. 103:286-289(1994).
RN [15]
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., Pittelkow M.R.,
RA 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 [16]
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 [17]
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 the
RT keratin 2e chain in ichthyosis bullosa of Siemens.";
RL J. Invest. Dermatol. 109:116-118(1997).
RN [18]
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 2e
RT gene in ichthyosis bullosa of Siemens.";
RL Acta Derm. Venereol. 78:417-419(1998).
RN [19]
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 [20]
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 of
RT Siemens.";
RL J. Invest. Dermatol. 112:380-382(1999).
RN [21]
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 mutation
RT near the helix termination motif of the keratin 2e gene.";
RL Clin. Exp. Dermatol. 24:412-415(1999).
RN [22]
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 bullosa
RT of Siemens.";
RL Clin. Exp. Dermatol. 25:648-651(2000).
RN [23]
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 genotype
RT and phenotype in patients with ichthyosis bullosa of Siemens.";
RL Exp. Dermatol. 9:11-15(2000).
RN [24]
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 [25]
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., McGrath J.A.;
RT "New mutations in keratin 1 that cause bullous congenital ichthyosiform
RT erythroderma and keratin 2e that cause ichthyosis bullosa of Siemens.";
RL Br. J. Dermatol. 145:330-335(2001).
RN [26]
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).
RN [27]
RP VARIANT IBS LYS-178.
RX PubMed=17408392; DOI=10.1111/j.1365-2133.2007.07832.x;
RA Nishizawa A., Toyomaki Y., Nakano A., Takeuchi S., Matsuzaki Y., Takeda H.,
RA Kaneko T., Mitsuhashi Y., Nakano H.;
RT "A novel H1 domain mutation in the keratin 2 gene in a Japanese family with
RT ichthyosis bullosa of Siemens.";
RL Br. J. Dermatol. 156:1042-1044(2007).
CC -!- FUNCTION: Probably contributes to terminal cornification
CC (PubMed:1380918). Associated with keratinocyte activation,
CC proliferation and keratinization (PubMed:12598329). Required for
CC maintenance of corneocytes and keratin filaments in suprabasal
CC keratinocytes in the epidermis of the ear, potentially via moderation
CC of expression and localization of keratins and their partner proteins
CC (By similarity). Plays a role in the establishment of the epidermal
CC barrier on plantar skin (By similarity). {ECO:0000250|UniProtKB:Q3TTY5,
CC ECO:0000269|PubMed:12598329, ECO:0000269|PubMed:1380918}.
CC -!- SUBUNIT: Heterotetramer of two type I and two type II keratins.
CC Associates with KRT10. {ECO:0000250|UniProtKB:Q3TTY5}.
CC -!- INTERACTION:
CC P35908; A1A4E9: KRT13; NbExp=3; IntAct=EBI-1247312, EBI-10171552;
CC P35908; P13646: KRT13; NbExp=5; IntAct=EBI-1247312, EBI-1223876;
CC P35908; P19012: KRT15; NbExp=7; IntAct=EBI-1247312, EBI-739566;
CC P35908; P08779: KRT16; NbExp=3; IntAct=EBI-1247312, EBI-356410;
CC P35908; P08727: KRT19; NbExp=10; IntAct=EBI-1247312, EBI-742756;
CC P35908; Q7Z3Z0: KRT25; NbExp=5; IntAct=EBI-1247312, EBI-11980019;
CC P35908; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-1247312, EBI-3044087;
CC P35908; Q15323: KRT31; NbExp=10; IntAct=EBI-1247312, EBI-948001;
CC P35908; Q14525: KRT33B; NbExp=3; IntAct=EBI-1247312, EBI-1049638;
CC P35908; Q92764: KRT35; NbExp=3; IntAct=EBI-1247312, EBI-1058674;
CC P35908; O76013-2: KRT36; NbExp=3; IntAct=EBI-1247312, EBI-11958506;
CC P35908; O76015: KRT38; NbExp=11; IntAct=EBI-1247312, EBI-1047263;
CC P35908; Q6A162: KRT40; NbExp=11; IntAct=EBI-1247312, EBI-10171697;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:32179842}.
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 carcinomas.
CC Expression in hypertrophic and keloid scars begins in the deepest
CC suprabasal layer. Weakly expressed in normal gingiva and tongue,
CC however expression is induced in benign keratoses of lingual mucosa and
CC in mild-to-moderate oral dysplasia with orthokeratinization.
CC {ECO:0000269|PubMed:10233306, ECO:0000269|PubMed:12598329,
CC ECO:0000269|PubMed:1380918}.
CC -!- DEVELOPMENTAL STAGE: Synthesized during maturation of epidermal
CC keratinocytes and localized in the upper intermediate cells of fetal
CC skin. Earliest expression is at 10 weeks in the developing embryo in
CC the presumptive nail bed of developing digits, shifting to the proximal
CC nail fold by 13.5 weeks. At 12.5 weeks, detected in scattered cells of
CC the intermediate layer of trunk skin. At 19.3 weeks, regional
CC expression patterns were observed in upper intermediate keratinocytes
CC of cheek, trunk, dorsal and ventral knee, elbow and dorsal hand. Distal
CC areas around the periumbilical region showed increased number of
CC positive cells and by 15 weeks is expressed in small groups of cells in
CC the fetal hair follicles. {ECO:0000269|PubMed:10233306,
CC ECO:0000269|PubMed:1380918}.
CC -!- INDUCTION: Induced in keratinocytes by all-trans retinoic acid (ATRA),
CC via increase in mRNA stability. {ECO:0000269|PubMed:32179842}.
CC -!- DISEASE: Ichthyosis bullosa of Siemens (IBS) [MIM:146800]: A rare
CC autosomal dominant skin disorder displaying a type of epidermolytic
CC hyperkeratosis characterized by generalized erythema and extensive
CC blistering from birth. Large, dark gray hyperkeratoses are observed in
CC later weeks. The skin of IBS patients is unusually fragile and has a
CC tendency to shed the outer layers of the epidermis, producing localized
CC denuded areas (molting effect). IBS usually improves with age so that
CC in most middle-aged patients the hyperkeratosis and keratotic
CC lichenification is limited to the flexural folds of the major joints.
CC {ECO:0000269|PubMed:10084318, ECO:0000269|PubMed:10233323,
CC ECO:0000269|PubMed:10564334, ECO:0000269|PubMed:10620137,
CC ECO:0000269|PubMed:10688369, ECO:0000269|PubMed:11167982,
CC ECO:0000269|PubMed:11531804, ECO:0000269|PubMed:15949009,
CC ECO:0000269|PubMed:17408392, ECO:0000269|PubMed:7521371,
CC ECO:0000269|PubMed:7524919, ECO:0000269|PubMed:8077693,
CC ECO:0000269|PubMed:9036938, ECO:0000269|PubMed:9204966,
CC ECO:0000269|PubMed:9804344, ECO:0000269|PubMed:9833038}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: There are two types of cytoskeletal and microfibrillar
CC keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC {ECO:0000255|PROSITE-ProRule:PRU01188}.
CC -!- WEB RESOURCE: Name=Human Intermediate Filament Mutation Database;
CC URL="http://www.interfil.org";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Keratin-2A entry;
CC URL="https://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 CCDS; CCDS8835.1; -.
DR PIR; A44861; A44861.
DR RefSeq; NP_000414.2; NM_000423.2.
DR AlphaFoldDB; P35908; -.
DR SMR; P35908; -.
DR BioGRID; 110047; 179.
DR IntAct; P35908; 47.
DR MINT; P35908; -.
DR STRING; 9606.ENSP00000310861; -.
DR DrugBank; DB11157; Anthralin.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR GlyGen; P35908; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; P35908; -.
DR PhosphoSitePlus; P35908; -.
DR SwissPalm; P35908; -.
DR BioMuta; KRT2; -.
DR DMDM; 239938650; -.
DR CPTAC; non-CPTAC-1137; -.
DR EPD; P35908; -.
DR jPOST; P35908; -.
DR MassIVE; P35908; -.
DR PaxDb; P35908; -.
DR PeptideAtlas; P35908; -.
DR PRIDE; P35908; -.
DR ProteomicsDB; 55161; -.
DR Antibodypedia; 1398; 291 antibodies from 30 providers.
DR DNASU; 3849; -.
DR Ensembl; ENST00000309680.4; ENSP00000310861.3; ENSG00000172867.4.
DR GeneID; 3849; -.
DR KEGG; hsa:3849; -.
DR MANE-Select; ENST00000309680.4; ENSP00000310861.3; NM_000423.3; NP_000414.2.
DR UCSC; uc001sat.4; human.
DR CTD; 3849; -.
DR DisGeNET; 3849; -.
DR GeneCards; KRT2; -.
DR HGNC; HGNC:6439; KRT2.
DR HPA; ENSG00000172867; Tissue enriched (skin).
DR MalaCards; KRT2; -.
DR MIM; 146800; phenotype.
DR MIM; 600194; gene.
DR neXtProt; NX_P35908; -.
DR OpenTargets; ENSG00000172867; -.
DR Orphanet; 455; Superficial epidermolytic ichthyosis.
DR PharmGKB; PA30227; -.
DR VEuPathDB; HostDB:ENSG00000172867; -.
DR eggNOG; ENOG502QTM6; Eukaryota.
DR GeneTree; ENSGT00940000162573; -.
DR HOGENOM; CLU_012560_6_1_1; -.
DR InParanoid; P35908; -.
DR OMA; YERHVWE; -.
DR OrthoDB; 824246at2759; -.
DR PhylomeDB; P35908; -.
DR TreeFam; TF317854; -.
DR PathwayCommons; P35908; -.
DR Reactome; R-HSA-6805567; Keratinization.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; P35908; -.
DR BioGRID-ORCS; 3849; 19 hits in 1071 CRISPR screens.
DR GeneWiki; Keratin_2A; -.
DR GenomeRNAi; 3849; -.
DR Pharos; P35908; Tbio.
DR PRO; PR:P35908; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P35908; protein.
DR Bgee; ENSG00000172867; Expressed in upper arm skin and 93 other tissues.
DR Genevisible; P35908; HS.
DR GO; GO:0001533; C:cornified envelope; IDA:CAFA.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005882; C:intermediate filament; TAS:ProtInc.
DR GO; GO:0045095; C:keratin filament; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0008092; F:cytoskeletal protein binding; IEA:Ensembl.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0030280; F:structural constituent of skin epidermis; IDA:CAFA.
DR GO; GO:0008544; P:epidermis development; TAS:ProtInc.
DR GO; GO:0045109; P:intermediate filament organization; IBA:GO_Central.
DR GO; GO:0031424; P:keratinization; IDA:UniProtKB.
DR GO; GO:0032980; P:keratinocyte activation; IDA:UniProtKB.
DR GO; GO:0003334; P:keratinocyte development; IEA:Ensembl.
DR GO; GO:0051546; P:keratinocyte migration; IDA:UniProtKB.
DR GO; GO:0043616; P:keratinocyte proliferation; IDA:UniProtKB.
DR GO; GO:0018149; P:peptide cross-linking; IDA:CAFA.
DR GO; GO:0045684; P:positive regulation of epidermis development; ISS:UniProtKB.
DR InterPro; IPR018039; IF_conserved.
DR InterPro; IPR039008; IF_rod_dom.
DR InterPro; IPR032444; Keratin_2_head.
DR InterPro; IPR003054; Keratin_II.
DR Pfam; PF00038; Filament; 1.
DR Pfam; PF16208; Keratin_2_head; 1.
DR PRINTS; PR01276; TYPE2KERATIN.
DR SMART; SM01391; Filament; 1.
DR PROSITE; PS00226; IF_ROD_1; 1.
DR PROSITE; PS51842; IF_ROD_2; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; Disease variant; Ichthyosis; Intermediate filament;
KW Keratin; Methylation; Phosphoprotein; Reference proteome.
FT CHAIN 1..639
FT /note="Keratin, type II cytoskeletal 2 epidermal"
FT /id="PRO_0000063715"
FT DOMAIN 178..491
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT REGION 1..177
FT /note="Head"
FT REGION 178..213
FT /note="Coil 1A"
FT REGION 214..232
FT /note="Linker 1"
FT REGION 233..324
FT /note="Coil 1B"
FT REGION 325..348
FT /note="Linker 12"
FT REGION 349..487
FT /note="Coil 2"
FT REGION 488..639
FT /note="Tail"
FT REGION 514..559
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 574..639
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 526..553
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 600..639
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 429
FT /note="Stutter"
FT MOD_RES 12
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P04104"
FT MOD_RES 20
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q3TTY5"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04104"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04104"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT VARIANT 101
FT /note="S -> G (in dbSNP:rs2634041)"
FT /evidence="ECO:0000269|PubMed:1380918,
FT ECO:0000269|PubMed:9804344"
FT /id="VAR_058293"
FT VARIANT 178
FT /note="E -> K (in IBS; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:17408392"
FT /id="VAR_086330"
FT VARIANT 181
FT /note="Q -> P (in IBS; dbSNP:rs57510142)"
FT /evidence="ECO:0000269|PubMed:8077693"
FT /id="VAR_003865"
FT VARIANT 182
FT /note="I -> N (in IBS; dbSNP:rs61622714)"
FT /evidence="ECO:0000269|PubMed:10084318"
FT /id="VAR_010514"
FT VARIANT 186
FT /note="N -> D (in IBS; dbSNP:rs137852631)"
FT /evidence="ECO:0000269|PubMed:10620137"
FT /id="VAR_010515"
FT VARIANT 186
FT /note="N -> K (in IBS; dbSNP:rs137852632)"
FT /evidence="ECO:0000269|PubMed:11531804"
FT /id="VAR_017829"
FT VARIANT 186
FT /note="N -> Y (in IBS; dbSNP:rs137852631)"
FT /evidence="ECO:0000269|PubMed:9804344"
FT /id="VAR_009185"
FT VARIANT 219
FT /note="G -> D (in dbSNP:rs638043)"
FT /id="VAR_058294"
FT VARIANT 465
FT /note="E -> D (in IBS)"
FT /evidence="ECO:0000269|PubMed:10688369"
FT /id="VAR_031082"
FT VARIANT 465
FT /note="E -> K (in IBS; dbSNP:rs758760389)"
FT /evidence="ECO:0000269|PubMed:10688369"
FT /id="VAR_031083"
FT VARIANT 476
FT /note="E -> K (in IBS; dbSNP:rs56829062)"
FT /evidence="ECO:0000269|PubMed:9804344"
FT /id="VAR_009186"
FT VARIANT 476
FT /note="E -> V (in IBS; dbSNP:rs60537449)"
FT /evidence="ECO:0000269|PubMed:10564334"
FT /id="VAR_031084"
FT VARIANT 477
FT /note="I -> N (in IBS)"
FT /evidence="ECO:0000269|PubMed:11167982"
FT /id="VAR_031085"
FT VARIANT 479
FT /note="T -> P (in IBS; dbSNP:rs137852630)"
FT /evidence="ECO:0000269|PubMed:9204966"
FT /id="VAR_009187"
FT VARIANT 484
FT /note="L -> P (in IBS; dbSNP:rs61726451)"
FT /evidence="ECO:0000269|PubMed:15949009,
FT ECO:0000269|PubMed:8077693"
FT /id="VAR_010516"
FT VARIANT 487
FT /note="E -> D (in IBS; dbSNP:rs137852628)"
FT /evidence="ECO:0000269|PubMed:7524919"
FT /id="VAR_003866"
FT VARIANT 487
FT /note="E -> K (in IBS; dbSNP:rs137852629)"
FT /evidence="ECO:0000269|PubMed:10233323,
FT ECO:0000269|PubMed:15949009, ECO:0000269|PubMed:7521371,
FT ECO:0000269|PubMed:7524919, ECO:0000269|PubMed:8077693,
FT ECO:0000269|PubMed:9036938, ECO:0000269|PubMed:9833038"
FT /id="VAR_003867"
FT VARIANT 488
FT /note="E -> K (in IBS; dbSNP:rs61726452)"
FT /evidence="ECO:0000269|PubMed:9036938"
FT /id="VAR_031086"
FT CONFLICT 108
FT /note="F -> FGGGSGF (in Ref. 1; AAC83410 and 2; AAB81946)"
FT /evidence="ECO:0000305"
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
