ID   K2C4_HUMAN              Reviewed;         534 AA.
AC   P19013; Q6GTR8; Q96LA7; Q9BTL1;
DT   01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT   22-NOV-2005, sequence version 4.
DT   24-NOV-2009, entry version 99.
DE   RecName: Full=Keratin, type II cytoskeletal 4;
DE   AltName: Full=Cytokeratin-4;
DE            Short=CK-4;
DE            Short=Keratin-4;
DE            Short=K4;
GN   Name=KRT4; Synonyms=CYK4;
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 [GENOMIC DNA].
RA   Cassidy A.J., Morley S.M., McLean W.H.I.;
RT   "A mutation detection strategy for oral mucosal keratins K4, K13, and
RT   K2p in white sponge nevus.";
RL   Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT
RP   83-GLY--THR-96 DEL.
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, and Ovary;
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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-144, AND VARIANTS VAL-72 AND
RP   83-GLY--THR-96 DEL.
RX   MEDLINE=93267125; PubMed=7684424; DOI=10.1111/1523-1747.ep12475671;
RA   Wanner R., Foerster H.-H., Tilmans I., Mischke D.;
RT   "Allelic variations of human keratins K4 and K5 provide polymorphic
RT   markers within the type II keratin gene cluster on chromosome 12.";
RL   J. Invest. Dermatol. 100:735-741(1993).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 127-534, AND TISSUE SPECIFICITY.
RX   MEDLINE=88198369; PubMed=2452170; DOI=10.1083/jcb.106.4.1249;
RA   Leube R.E., Bader B.L., Bosch F.X., Zimbelmann R., Achtstaetter T.,
RA   Franke W.W.;
RT   "Molecular characterization and expression of the stratification-
RT   related cytokeratins 4 and 15.";
RL   J. Cell Biol. 106:1249-1261(1988).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 411-534.
RA   Wanner R., Tilmans I., Mischke D.;
RL   Submitted (JUL-1991) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RA   Colinge J., Superti-Furga G., Bennett K.L.;
RL   Submitted (OCT-2008) to UniProtKB.
RN   [8]
RP   VARIANT WSN GLN-153 INS.
RX   MEDLINE=20117897; PubMed=10652003;
RX   DOI=10.1046/j.1523-1747.2000.00890.x;
RA   Terrinoni A., Candi E., Oddi S., Gobello T., Camaione D.B.,
RA   Mazzanti C., Zambruno G., Knight R., Melino G.;
RT   "A glutamine insertion in the 1A alpha helical domain of the keratin 4
RT   gene in a familial case of white sponge nevus.";
RL   J. Invest. Dermatol. 114:388-391(2000).
RN   [9]
RP   VARIANT WSN LYS-449.
RX   MEDLINE=22712780; PubMed=12828738;
RX   DOI=10.1046/j.1365-2133.2003.05337.x;
RA   Chao S.C., Tsai Y.M., Yang M.H., Lee Jy J.Y.;
RT   "A novel mutation in the keratin 4 gene causing white sponge naevus.";
RL   Br. J. Dermatol. 148:1125-1128(2003).
CC   -!- SUBUNIT: Heterotetramer of two type I and two type II keratins.
CC       Keratin-4 is generally associated with keratin-13.
CC   -!- TISSUE SPECIFICITY: Detected in the suprabasal layer of the
CC       stratified epithelium of the esophagus, exocervix, vagina, mouth
CC       and lingual mucosa, and in cells and cell clusters in the mucosa
CC       and serous gland ducts of the esophageal submucosa (at protein
CC       level). Expressed widely in the exocervix and esophageal
CC       epithelium, with lowest levels detected in the basal cell layer.
CC   -!- POLYMORPHISM: Three alleles of K4 are known: K4A2 (shown here),
CC       K4A1 and K4B.
CC   -!- DISEASE: Defects in KRT4 are a cause of white sponge nevus of
CC       cannon (WSN) [MIM:193900]. WSN is a rare autosomal dominant
CC       disorder which predominantly affects non-cornified stratified
CC       squamous epithelia. Clinically, it is characterized by the
CC       presence of soft, white, and spongy plaques in the oral mucosa.
CC       The characteristic histopathologic features are epithelial
CC       thickening, parakeratosis, and vacuolization of the suprabasal
CC       layer of oral epithelial keratinocytes. Less frequently the mucous
CC       membranes of the nose, esophagus, genitalia and rectum are
CC       involved.
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/KRT4";
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DR   EMBL; AY043326; AAL14196.1; -; Genomic_DNA.
DR   EMBL; AC107016; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC003630; AAH03630.2; -; mRNA.
DR   EMBL; BC042174; AAH42174.1; -; mRNA.
DR   EMBL; X67683; CAA47914.1; -; mRNA.
DR   EMBL; X07695; CAA30534.1; -; mRNA.
DR   EMBL; X61028; CAA43362.1; -; Genomic_DNA.
DR   IPI; IPI00290078; -.
DR   PIR; I37942; I37942.
DR   RefSeq; NP_002263.2; -.
DR   UniGene; Hs.654610; -.
DR   STRING; P19013; -.
DR   PhosphoSite; P19013; -.
DR   PRIDE; P19013; -.
DR   Ensembl; ENST00000293774; ENSP00000293774; ENSG00000170477; Homo sapiens.
DR   GeneID; 3851; -.
DR   KEGG; hsa:3851; -.
DR   UCSC; uc001saz.1; human.
DR   CTD; 3851; -.
DR   GeneCards; GC12M051486; -.
DR   H-InvDB; HIX0010659; -.
DR   HGNC; HGNC:6441; KRT4.
DR   MIM; 123940; gene.
DR   MIM; 193900; phenotype.
DR   Orphanet; 171723; White sponge nevus.
DR   PharmGKB; PA30229; -.
DR   HOGENOM; P19013; -.
DR   HOVERGEN; P19013; -.
DR   NextBio; 15153; -.
DR   ArrayExpress; P19013; -.
DR   Bgee; P19013; -.
DR   CleanEx; HS_KRT4; -.
DR   Genevestigator; P19013; -.
DR   GermOnline; ENSG00000170477; Homo sapiens.
DR   GO; GO:0045095; C:keratin filament; IEA:InterPro.
DR   GO; GO:0005198; F:structural molecule activity; NAS:UniProtKB.
DR   GO; GO:0007010; P:cytoskeleton organization; NAS:UniProtKB.
DR   GO; GO:0030855; P:epithelial cell differentiation; ISS:UniProtKB.
DR   GO; GO:0050680; P:negative regulation of epithelial cell prol...; ISS:UniProtKB.
DR   InterPro; IPR016044; F.
DR   InterPro; IPR001664; IF.
DR   InterPro; IPR018039; Intermediate_filament_CS.
DR   InterPro; IPR003054; Keratin_II.
DR   PANTHER; PTHR23239; IF; 1.
DR   PANTHER; PTHR23239:SF18; Keratin_II; 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;
KW   Intermediate filament; Keratin; Phosphoprotein; Polymorphism.
FT   CHAIN         1    534       Keratin, type II cytoskeletal 4.
FT                                /FTId=PRO_0000063722.
FT   REGION        1    150       Head.
FT   REGION      151    461       Rod.
FT   REGION      151    186       Coil 1A.
FT   REGION      187    205       Linker 1.
FT   REGION      206    298       Coil 1B.
FT   REGION      299    321       Linker 12.
FT   REGION      322    461       Coil 2.
FT   REGION      462    534       Tail.
FT   COMPBIAS     10    122       Gly-rich.
FT   COMPBIAS    470    526       Ser-rich.
FT   SITE        402    402       Stutter.
FT   MOD_RES      51     51       Phosphoserine (By similarity).
FT   VARIANT      72     72       A -> V (in allele K4A1).
FT                                /FTId=VAR_003869.
FT   VARIANT      83     96       Missing (in allele K4B).
FT                                /FTId=VAR_003870.
FT   VARIANT     153    153       E -> EQ (in WSN).
FT                                /FTId=VAR_012845.
FT   VARIANT     449    449       E -> K (in WSN).
FT                                /FTId=VAR_016038.
FT   CONFLICT    118    118       C -> L (in Ref. 4; CAA47914).
FT   CONFLICT    127    128       TI -> SL (in Ref. 5; CAA30534).
FT   CONFLICT    236    236       D -> Y (in Ref. 3; AAH03630).
SQ   SEQUENCE   534 AA;  57285 MW;  3795B7C93092F97E CRC64;
     MIARQQCVRG GPRGFSCGSA IVGGGKRGAF SSVSMSGGAG RCSSGGFGSR SLYNLRGNKS
     ISMSVAGSRQ GACFGGAGGF GTGGFGAGGF GAGFGTGGFG GGFGGSFSGK GGPGFPVCPA
     GGIQEVTINQ SLLTPLHVEI DPEIQKVRTE EREQIKLLNN KFASFIDKVQ FLEQQNKVLE
     TKWNLLQQQT TTTSSKNLEP LFETYLSVLR KQLDTLGNDK GRLQSELKTM QDSVEDFKTK
     YEEEINKRTA AENDFVVLKK DVDAAYLNKV ELEAKVDSLN DEINFLKVLY DAELSQMQTH
     VSDTSVVLSM DNNRNLDLDS IIAEVRAQYE EIAQRSKAEA EALYQTKVQQ LQISVDQHGD
     NLKNTKSEIA ELNRMIQRLR AEIENIKKQC QTLQVSVADA EQRGENALKD AHSKRVELEA
     ALQQAKEELA RMLREYQELM SVKLALDIEI ATYRKLLEGE EYRMSGECQS AVSISVVSGS
     TSTGGISGGL GSGSGFGLSS GFGSGSGSGF GFGGSVSGSS SSKIISTTTL NKRR
//