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Protein

Keratin, type II cytoskeletal 4

Gene

KRT4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei402 – 4021Stutter

GO - Molecular functioni

GO - Biological processi

  • cytoskeleton organization Source: UniProtKB
  • epithelial cell differentiation Source: UniProtKB
  • negative regulation of epithelial cell proliferation Source: UniProtKB
Complete GO annotation...

Names & Taxonomyi

Protein namesi
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 namesi
Name:KRT4
Synonyms:CYK4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:6441. KRT4.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • intermediate filament Source: UniProtKB
  • intermediate filament cytoskeleton Source: UniProtKB
  • keratin filament Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Intermediate filament, Keratin

Pathology & Biotechi

Involvement in diseasei

White sponge nevus 1 (WSN1)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare disorder 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.
See also OMIM:193900
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti153 – 1531E → EQ in WSN1. 1 Publication
VAR_012845
Natural varianti449 – 4491E → K in WSN1. 1 Publication
VAR_016038

Keywords - Diseasei

Disease mutation

Organism-specific databases

MalaCardsiKRT4.
MIMi193900. phenotype.
Orphaneti171723. White sponge nevus.
PharmGKBiPA30229.

Polymorphism and mutation databases

DMDMi82654947.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 534534Keratin, type II cytoskeletal 4PRO_0000063722Add
BLAST

Proteomic databases

EPDiP19013.
MaxQBiP19013.
PaxDbiP19013.
PRIDEiP19013.

PTM databases

iPTMnetiP19013.
PhosphoSiteiP19013.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiP19013.
CleanExiHS_KRT4.
ExpressionAtlasiP19013. baseline and differential.
GenevisibleiP19013. HS.

Organism-specific databases

HPAiCAB002154.
HPA034881.

Interactioni

Subunit structurei

Heterotetramer of two type I and two type II keratins. Keratin-4 is generally associated with keratin-13.

Binary interactionsi

WithEntry#Exp.IntActNotes
KRT13A1A4E93EBI-2371606,EBI-10171552
KRT15P190123EBI-2371606,EBI-739566
KRT33BQ145253EBI-2371606,EBI-1049638
KRT38O760153EBI-2371606,EBI-1047263
KRT40Q6A1623EBI-2371606,EBI-10171697
taxP140793EBI-2371606,EBI-9675698From a different organism.

Protein-protein interaction databases

IntActiP19013. 20 interactions.
STRINGi9606.ENSP00000448220.

Structurei

3D structure databases

ProteinModelPortaliP19013.
SMRiP19013. Positions 148-289, 317-459.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 150150HeadAdd
BLAST
Regioni151 – 461311RodAdd
BLAST
Regioni151 – 18636Coil 1AAdd
BLAST
Regioni187 – 20519Linker 1Add
BLAST
Regioni206 – 29893Coil 1BAdd
BLAST
Regioni299 – 32123Linker 12Add
BLAST
Regioni322 – 461140Coil 2Add
BLAST
Regioni462 – 53473TailAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi10 – 122113Gly-richAdd
BLAST
Compositional biasi470 – 52657Ser-richAdd
BLAST

Sequence similaritiesi

Belongs to the intermediate filament family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IGG3. Eukaryota.
ENOG410ZE7B. LUCA.
HOGENOMiHOG000230976.
HOVERGENiHBG013015.
InParanoidiP19013.
OrthoDBiEOG7FV3Q8.
PhylomeDBiP19013.
TreeFamiTF317854.

Family and domain databases

InterProiIPR001664. IF.
IPR018039. Intermediate_filament_CS.
IPR032444. Keratin_2_head.
IPR003054. Keratin_II.
[Graphical view]
PANTHERiPTHR23239. PTHR23239. 1 hit.
PfamiPF00038. Filament. 1 hit.
PF16208. Keratin_2_head. 1 hit.
[Graphical view]
PRINTSiPR01276. TYPE2KERATIN.
SMARTiSM01391. Filament. 1 hit.
[Graphical view]
PROSITEiPS00226. IF. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P19013-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIARQQCVRG GPRGFSCGSA IVGGGKRGAF SSVSMSGGAG RCSSGGFGSR
60 70 80 90 100
SLYNLRGNKS ISMSVAGSRQ GACFGGAGGF GTGGFGAGGF GAGFGTGGFG
110 120 130 140 150
GGFGGSFSGK GGPGFPVCPA GGIQEVTINQ SLLTPLHVEI DPEIQKVRTE
160 170 180 190 200
EREQIKLLNN KFASFIDKVQ FLEQQNKVLE TKWNLLQQQT TTTSSKNLEP
210 220 230 240 250
LFETYLSVLR KQLDTLGNDK GRLQSELKTM QDSVEDFKTK YEEEINKRTA
260 270 280 290 300
AENDFVVLKK DVDAAYLNKV ELEAKVDSLN DEINFLKVLY DAELSQMQTH
310 320 330 340 350
VSDTSVVLSM DNNRNLDLDS IIAEVRAQYE EIAQRSKAEA EALYQTKVQQ
360 370 380 390 400
LQISVDQHGD NLKNTKSEIA ELNRMIQRLR AEIENIKKQC QTLQVSVADA
410 420 430 440 450
EQRGENALKD AHSKRVELEA ALQQAKEELA RMLREYQELM SVKLALDIEI
460 470 480 490 500
ATYRKLLEGE EYRMSGECQS AVSISVVSGS TSTGGISGGL GSGSGFGLSS
510 520 530
GFGSGSGSGF GFGGSVSGSS SSKIISTTTL NKRR
Length:534
Mass (Da):57,285
Last modified:November 22, 2005 - v4
Checksum:i3795B7C93092F97E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti118 – 1181C → L in CAA47914 (PubMed:7684424).Curated
Sequence conflicti127 – 1282TI → SL in CAA30534 (PubMed:2452170).Curated
Sequence conflicti236 – 2361D → Y in AAH03630 (PubMed:15489334).Curated

Polymorphismi

Three alleles of K4 are known: K4A2 (shown here), K4A1 and K4B.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti72 – 721A → V in allele K4A1. 1 Publication
VAR_003869
Natural varianti83 – 9614Missing in allele K4B. 2 Publications
VAR_003870Add
BLAST
Natural varianti153 – 1531E → EQ in WSN1. 1 Publication
VAR_012845
Natural varianti449 – 4491E → K in WSN1. 1 Publication
VAR_016038

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiI37942.
UniGeneiHs.654610.
Hs.731814.

Genome annotation databases

EnsembliENST00000293774; ENSP00000293774; ENSG00000170477.
ENST00000551956; ENSP00000448220; ENSG00000170477.
UCSCiuc031qhk.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Human Intermediate Filament Mutation Database

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiI37942.
UniGeneiHs.654610.
Hs.731814.

3D structure databases

ProteinModelPortaliP19013.
SMRiP19013. Positions 148-289, 317-459.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP19013. 20 interactions.
STRINGi9606.ENSP00000448220.

PTM databases

iPTMnetiP19013.
PhosphoSiteiP19013.

Polymorphism and mutation databases

DMDMi82654947.

Proteomic databases

EPDiP19013.
MaxQBiP19013.
PaxDbiP19013.
PRIDEiP19013.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000293774; ENSP00000293774; ENSG00000170477.
ENST00000551956; ENSP00000448220; ENSG00000170477.
UCSCiuc031qhk.2. human.

Organism-specific databases

GeneCardsiKRT4.
H-InvDBHIX0010659.
HGNCiHGNC:6441. KRT4.
HPAiCAB002154.
HPA034881.
MalaCardsiKRT4.
MIMi123940. gene.
193900. phenotype.
neXtProtiNX_P19013.
Orphaneti171723. White sponge nevus.
PharmGKBiPA30229.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGG3. Eukaryota.
ENOG410ZE7B. LUCA.
HOGENOMiHOG000230976.
HOVERGENiHBG013015.
InParanoidiP19013.
OrthoDBiEOG7FV3Q8.
PhylomeDBiP19013.
TreeFamiTF317854.

Miscellaneous databases

ChiTaRSiKRT4. human.
NextBioi13604950.
PROiP19013.
SOURCEiSearch...

Gene expression databases

BgeeiP19013.
CleanExiHS_KRT4.
ExpressionAtlasiP19013. baseline and differential.
GenevisibleiP19013. HS.

Family and domain databases

InterProiIPR001664. IF.
IPR018039. Intermediate_filament_CS.
IPR032444. Keratin_2_head.
IPR003054. Keratin_II.
[Graphical view]
PANTHERiPTHR23239. PTHR23239. 1 hit.
PfamiPF00038. Filament. 1 hit.
PF16208. Keratin_2_head. 1 hit.
[Graphical view]
PRINTSiPR01276. TYPE2KERATIN.
SMARTiSM01391. Filament. 1 hit.
[Graphical view]
PROSITEiPS00226. IF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. 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] [Europe PMC] [Abstract]
    Cited for: VARIANT WSN1 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] [Europe PMC] [Abstract]
    Cited for: VARIANT WSN1 LYS-449.

Entry informationi

Entry nameiK2C4_HUMAN
AccessioniPrimary (citable) accession number: P19013
Secondary accession number(s): F8VS64
, Q6GTR8, Q96LA7, Q9BTL1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 22, 2005
Last modified: May 11, 2016
This is version 158 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Miscellaneous

There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.