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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)DescriptionActionsGraphical viewLength
Sitei402Stutter1

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...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000110815-MONOMER.
ReactomeiR-HSA-6805567. Keratinization.
R-HSA-6809371. Formation of the cornified envelope.

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_012845153E → EQ in WSN1. 1 Publication1
Natural variantiVAR_016038449E → K in WSN1. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3851.
MalaCardsiKRT4.
MIMi193900. phenotype.
Orphaneti171723. White sponge nevus.
PharmGKBiPA30229.

Polymorphism and mutation databases

DMDMi82654947.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000637221 – 534Keratin, type II cytoskeletal 4Add BLAST534

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei13Omega-N-methylarginineBy similarity1

Keywords - PTMi

Methylation

Proteomic databases

PaxDbiP19013.
PeptideAtlasiP19013.
PRIDEiP19013.

PTM databases

iPTMnetiP19013.
PhosphoSitePlusiP19013.
SwissPalmiP19013.

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

BgeeiENSG00000170477.
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
KRT15P190125EBI-2371606,EBI-739566
KRT33BQ145255EBI-2371606,EBI-1049638
KRT38O760155EBI-2371606,EBI-1047263
KRT40Q6A1625EBI-2371606,EBI-10171697
taxP140793EBI-2371606,EBI-9675698From a different organism.

Protein-protein interaction databases

IntActiP19013. 32 interactors.
STRINGi9606.ENSP00000448220.

Structurei

3D structure databases

ProteinModelPortaliP19013.
SMRiP19013.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 150HeadAdd BLAST150
Regioni151 – 461RodAdd BLAST311
Regioni151 – 186Coil 1AAdd BLAST36
Regioni187 – 205Linker 1Add BLAST19
Regioni206 – 298Coil 1BAdd BLAST93
Regioni299 – 321Linker 12Add BLAST23
Regioni322 – 461Coil 2Add BLAST140
Regioni462 – 534TailAdd BLAST73

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi10 – 122Gly-richAdd BLAST113
Compositional biasi470 – 526Ser-richAdd BLAST57

Sequence similaritiesi

Belongs to the intermediate filament family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IGG3. Eukaryota.
ENOG410ZE7B. LUCA.
HOGENOMiHOG000230976.
HOVERGENiHBG013015.
InParanoidiP19013.
OrthoDBiEOG091G09KR.
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)DescriptionActionsGraphical viewLength
Sequence conflicti118C → L in CAA47914 (PubMed:7684424).Curated1
Sequence conflicti127 – 128TI → SL in CAA30534 (PubMed:2452170).Curated2
Sequence conflicti236D → Y in AAH03630 (PubMed:15489334).Curated1

Polymorphismi

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00386972A → V in allele K4A1. 1 Publication1
Natural variantiVAR_00387083 – 96Missing in allele K4B. 2 PublicationsAdd BLAST14
Natural variantiVAR_012845153E → EQ in WSN1. 1 Publication1
Natural variantiVAR_016038449E → K in WSN1. 1 Publication1

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP19013. 32 interactors.
STRINGi9606.ENSP00000448220.

PTM databases

iPTMnetiP19013.
PhosphoSitePlusiP19013.
SwissPalmiP19013.

Polymorphism and mutation databases

DMDMi82654947.

Proteomic databases

PaxDbiP19013.
PeptideAtlasiP19013.
PRIDEiP19013.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

DisGeNETi3851.
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.
OrthoDBiEOG091G09KR.
PhylomeDBiP19013.
TreeFamiTF317854.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000110815-MONOMER.
ReactomeiR-HSA-6805567. Keratinization.
R-HSA-6809371. Formation of the cornified envelope.

Miscellaneous databases

ChiTaRSiKRT4. human.
PROiP19013.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170477.
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...

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: November 30, 2016
This is version 164 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.