P19013 (K2C4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Keratin, type II cytoskeletal 4

Alternative name(s):
Cytokeratin-4
Short name=CK-4
Keratin-4
Short name=K4
Type-II keratin Kb4

Gene names

Name:	KRT4
Synonyms:	CYK4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	534 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Subunit structure	Heterotetramer of two type I and two type II keratins. Keratin-4 is generally associated with keratin-13.
Tissue specificity	Detected in the suprabasal layer of the stratified epithelium of the esophagus, exocervix, vagina, mouth and lingual mucosa, and in cells and cell clusters in the mucosa and serous gland ducts of the esophageal submucosa (at protein level). Expressed widely in the exocervix and esophageal epithelium, with lowest levels detected in the basal cell layer. Ref.5
Polymorphism	Three alleles of K4 are known: K4A2 (shown here), K4A1 and K4B.
Involvement in disease	Defects in KRT4 are a cause of white sponge nevus of cannon (WSN) [MIM:193900]. WSN is a rare autosomal dominant disorder which predominantly affects non-cornified stratified squamous epithelia. Clinically, it is characterized by the presence of soft, white, and spongy plaques in the oral mucosa. The characteristic histopathologic features are epithelial thickening, parakeratosis, and vacuolization of the suprabasal layer of oral epithelial keratinocytes. Less frequently the mucous membranes of the nose, esophagus, genitalia and rectum are involved. Ref.8 Ref.9
Miscellaneous	There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
Sequence similarities	Belongs to the intermediate filament family.

Ontologies

Keywords
Cellular component	Intermediate filament Keratin
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cytoskeleton organization Non-traceable author statement Ref.5. Source: UniProtKB epithelial cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of epithelial cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	keratin filament Inferred from electronic annotation. Source: InterPro
Molecular function	structural molecule activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 534	534	Keratin, type II cytoskeletal 4		PRO_0000063722
Regions
	Region	1 – 150	150	Head
	Region	151 – 461	311	Rod
	Region	151 – 186	36	Coil 1A
	Region	187 – 205	19	Linker 1
	Region	206 – 298	93	Coil 1B
	Region	299 – 321	23	Linker 12
	Region	322 – 461	140	Coil 2
	Region	462 – 534	73	Tail
	Compositional bias	10 – 122	113	Gly-rich
	Compositional bias	470 – 526	57	Ser-rich
Sites
	Site	402	1	Stutter
Amino acid modifications
	Modified residue	51	1	Phosphoserine By similarity
Natural variations
	Natural variant	72	1	A → V in allele K4A1. Ref.4		VAR_003869
	Natural variant	83 – 96	14	Missing in allele K4B.		VAR_003870
	Natural variant	153	1	E → EQ in WSN. Ref.8		VAR_012845
	Natural variant	449	1	E → K in WSN. Ref.9		VAR_016038
Experimental info
	Sequence conflict	118	1	C → L in CAA47914. Ref.4
	Sequence conflict	127 – 128	2	TI → SL in CAA30534. Ref.5
	Sequence conflict	236	1	D → Y in AAH03630. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P19013 [UniParc]. Last modified November 22, 2005. Version 4. Checksum: 3795B7C93092F97E	FASTA	534	57,285
	10 20 30 40 50 60 MIARQQCVRG GPRGFSCGSA IVGGGKRGAF SSVSMSGGAG RCSSGGFGSR SLYNLRGNKS 70 80 90 100 110 120 ISMSVAGSRQ GACFGGAGGF GTGGFGAGGF GAGFGTGGFG GGFGGSFSGK GGPGFPVCPA 130 140 150 160 170 180 GGIQEVTINQ SLLTPLHVEI DPEIQKVRTE EREQIKLLNN KFASFIDKVQ FLEQQNKVLE 190 200 210 220 230 240 TKWNLLQQQT TTTSSKNLEP LFETYLSVLR KQLDTLGNDK GRLQSELKTM QDSVEDFKTK 250 260 270 280 290 300 YEEEINKRTA AENDFVVLKK DVDAAYLNKV ELEAKVDSLN DEINFLKVLY DAELSQMQTH 310 320 330 340 350 360 VSDTSVVLSM DNNRNLDLDS IIAEVRAQYE EIAQRSKAEA EALYQTKVQQ LQISVDQHGD 370 380 390 400 410 420 NLKNTKSEIA ELNRMIQRLR AEIENIKKQC QTLQVSVADA EQRGENALKD AHSKRVELEA 430 440 450 460 470 480 ALQQAKEELA RMLREYQELM SVKLALDIEI ATYRKLLEGE EYRMSGECQS AVSISVVSGS 490 500 510 520 530 TSTGGISGGL GSGSGFGLSS GFGSGSGSGF GFGGSVSGSS SSKIISTTTL NKRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A mutation detection strategy for oral mucosal keratins K4, K13, and K2p in white sponge nevus." Cassidy A.J., Morley S.M., McLean W.H.I. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT 83-GLY--THR-96 DEL.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Ovary.
[4]	"Allelic variations of human keratins K4 and K5 provide polymorphic markers within the type II keratin gene cluster on chromosome 12." Wanner R., Foerster H.-H., Tilmans I., Mischke D. J. Invest. Dermatol. 100:735-741(1993) [PubMed: 7684424] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-144, VARIANTS VAL-72 AND 83-GLY--THR-96 DEL.
[5]	"Molecular characterization and expression of the stratification-related cytokeratins 4 and 15." Leube R.E., Bader B.L., Bosch F.X., Zimbelmann R., Achtstaetter T., Franke W.W. J. Cell Biol. 106:1249-1261(1988) [PubMed: 2452170] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 127-534, TISSUE SPECIFICITY.
[6]	Wanner R., Tilmans I., Mischke D. Submitted (JUL-1991) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 411-534.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"A glutamine insertion in the 1A alpha helical domain of the keratin 4 gene in a familial case of white sponge nevus." Terrinoni A., Candi E., Oddi S., Gobello T., Camaione D.B., Mazzanti C., Zambruno G., Knight R., Melino G. J. Invest. Dermatol. 114:388-391(2000) [PubMed: 10652003] [Abstract] Cited for: VARIANT WSN GLN-153 INS.
[9]	"A novel mutation in the keratin 4 gene causing white sponge naevus." Chao S.C., Tsai Y.M., Yang M.H., Lee Jy J.Y. Br. J. Dermatol. 148:1125-1128(2003) [PubMed: 12828738] [Abstract] Cited for: VARIANT WSN LYS-449.
+	Additional computationally mapped references.

Web resources

Human Intermediate Filament Mutation Database

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY043326 Genomic DNA. Translation: AAL14196.1. AC107016 Genomic DNA. No translation available. BC003630 mRNA. Translation: AAH03630.2. BC042174 mRNA. Translation: AAH42174.1. X67683 mRNA. Translation: CAA47914.1. X07695 mRNA. Translation: CAA30534.1. X61028 Genomic DNA. Translation: CAA43362.1.
IPI	IPI00797452.
PIR	I37942.
UniGene	Hs.654610.
3D structure databases
ProteinModelPortal	P19013.
SMR	P19013. Positions 149-186, 195-300, 317-460.
ModBase	Search...
Protein-protein interaction databases
IntAct	P19013. 11 interactions.
STRING	P19013.
PTM databases
PhosphoSite	P19013.
Polymorphism databases
DMDM	82654947.
Proteomic databases
PRIDE	P19013.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000293774; ENSP00000293774; ENSG00000170477.
UCSC	uc001saz.1. human.
Organism-specific databases
GeneCards	GC12M053200.
H-InvDB	HIX0010659.
HGNC	HGNC:6441. KRT4.
HPA	CAB002154.
MIM	123940. gene. 193900. phenotype.
neXtProt	NX_P19013.
Orphanet	171723. White sponge nevus.
PharmGKB	PA30229.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11319.
HOGENOM	HBG715391.
HOVERGEN	HBG013015.
InParanoid	P19013.
OrthoDB	EOG46HG9P.
Gene expression databases
ArrayExpress	P19013.
Bgee	P19013.
CleanEx	HS_KRT4.
Genevestigator	P19013.
GermOnline	ENSG00000170477. Homo sapiens.
Family and domain databases
InterPro	IPR016044. F. IPR001664. IF. IPR018039. Intermediate_filament_CS. IPR003054. Keratin_II. [Graphical view]
PANTHER	PTHR23239. IF. 1 hit. PTHR23239:SF18. Keratin_II. 1 hit.
Pfam	PF00038. Filament. 1 hit. [Graphical view]
PRINTS	PR01276. TYPE2KERATIN.
PROSITE	PS00226. IF. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	15153.
SOURCE	Search...

Entry information

Entry name

K2C4_HUMAN

Accession

Primary (citable) accession number: P19013
Secondary accession number(s): Q6GTR8, Q96LA7, Q9BTL1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 22, 2005
Last modified:	January 25, 2012
This is version 120 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.