UniProtKB - P35908 (K22E_HUMAN)
Protein
Keratin, type II cytoskeletal 2 epidermal
Gene
KRT2
Organism
Homo sapiens (Human)
Status
Functioni
Probably contributes to terminal cornification (PubMed:1380918). Associated with keratinocyte activation, proliferation and keratinization (PubMed:12598329). Plays a role in the establishment of the epidermal barrier on plantar skin (By similarity).By similarity2 Publications
Miscellaneous
There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 429 | Stutter | 1 |
GO - Molecular functioni
- cytoskeletal protein binding Source: Ensembl
- structural constituent of cytoskeleton Source: ProtInc
- structural constituent of skin epidermis Source: CAFA
GO - Biological processi
- cornification Source: Reactome
- epidermis development Source: ProtInc
- intermediate filament organization Source: Ensembl
- keratinization Source: UniProtKB
- keratinocyte activation Source: UniProtKB
- keratinocyte development Source: Ensembl
- keratinocyte migration Source: UniProtKB
- keratinocyte proliferation Source: UniProtKB
- peptide cross-linking Source: CAFA
- positive regulation of epidermis development Source: UniProtKB
Enzyme and pathway databases
PathwayCommonsi | P35908 |
Reactomei | R-HSA-6805567, Keratinization R-HSA-6809371, Formation of the cornified envelope |
Names & Taxonomyi
Protein namesi | Recommended name: Keratin, type II cytoskeletal 2 epidermalAlternative name(s): Cytokeratin-2e Short name: CK-2e Epithelial keratin-2e Keratin-2 epidermis Keratin-2e Short name: K2e Type-II keratin Kb2 |
Gene namesi | Name:KRT2 Synonyms:KRT2A, KRT2E |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6439, KRT2 |
MIMi | 600194, gene |
neXtProti | NX_P35908 |
VEuPathDBi | HostDB:ENSG00000172867.3 |
Subcellular locationi
Cytoskeleton
- intermediate filament Source: ProtInc
- keratin filament Source: Ensembl
Cytosol
- cytosol Source: Reactome
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular space Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- cornified envelope Source: CAFA
Other locations
- membrane Source: UniProtKB
Keywords - Cellular componenti
Intermediate filament, KeratinPathology & Biotechi
Involvement in diseasei
Ichthyosis bullosa of Siemens (IBS)15 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA rare autosomal dominant skin disorder displaying a type of epidermolytic hyperkeratosis characterized by generalized erythema and extensive blistering from birth. Large, dark gray hyperkeratoses are observed in later weeks. The skin of IBS patients is unusually fragile and has a tendency to shed the outer layers of the epidermis, producing localized denuded areas (molting effect). IBS usually improves with age so that in most middle-aged patients the hyperkeratosis and keratotic lichenification is limited to the flexural folds of the major joints.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_003865 | 181 | Q → P in IBS. 1 PublicationCorresponds to variant dbSNP:rs57510142EnsemblClinVar. | 1 | |
Natural variantiVAR_010514 | 182 | I → N in IBS. 1 PublicationCorresponds to variant dbSNP:rs61622714EnsemblClinVar. | 1 | |
Natural variantiVAR_010515 | 186 | N → D in IBS. 1 PublicationCorresponds to variant dbSNP:rs137852631EnsemblClinVar. | 1 | |
Natural variantiVAR_017829 | 186 | N → K in IBS. 1 PublicationCorresponds to variant dbSNP:rs137852632EnsemblClinVar. | 1 | |
Natural variantiVAR_009185 | 186 | N → Y in IBS. 1 PublicationCorresponds to variant dbSNP:rs137852631EnsemblClinVar. | 1 | |
Natural variantiVAR_031082 | 465 | E → D in IBS. 1 Publication | 1 | |
Natural variantiVAR_031083 | 465 | E → K in IBS. 1 PublicationCorresponds to variant dbSNP:rs758760389Ensembl. | 1 | |
Natural variantiVAR_009186 | 476 | E → K in IBS. 1 PublicationCorresponds to variant dbSNP:rs56829062EnsemblClinVar. | 1 | |
Natural variantiVAR_031084 | 476 | E → V in IBS. 1 PublicationCorresponds to variant dbSNP:rs60537449EnsemblClinVar. | 1 | |
Natural variantiVAR_031085 | 477 | I → N in IBS. 1 Publication | 1 | |
Natural variantiVAR_009187 | 479 | T → P in IBS. 1 PublicationCorresponds to variant dbSNP:rs137852630EnsemblClinVar. | 1 | |
Natural variantiVAR_010516 | 484 | L → P in IBS. 2 PublicationsCorresponds to variant dbSNP:rs61726451EnsemblClinVar. | 1 | |
Natural variantiVAR_003866 | 487 | E → D in IBS. 1 PublicationCorresponds to variant dbSNP:rs137852628EnsemblClinVar. | 1 | |
Natural variantiVAR_003867 | 487 | E → K in IBS. 7 PublicationsCorresponds to variant dbSNP:rs137852629EnsemblClinVar. | 1 | |
Natural variantiVAR_031086 | 488 | E → K in IBS. 1 PublicationCorresponds to variant dbSNP:rs61726452EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variant, IchthyosisOrganism-specific databases
DisGeNETi | 3849 |
MalaCardsi | KRT2 |
MIMi | 146800, phenotype |
OpenTargetsi | ENSG00000172867 |
Orphaneti | 455, Superficial epidermolytic ichthyosis |
PharmGKBi | PA30227 |
Miscellaneous databases
Pharosi | P35908, Tbio |
Chemistry databases
DrugBanki | DB11157, Anthralin DB09130, Copper DB01593, Zinc DB14487, Zinc acetate |
Genetic variation databases
BioMutai | KRT2 |
DMDMi | 239938650 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000063715 | 1 – 639 | Keratin, type II cytoskeletal 2 epidermalAdd BLAST | 639 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 12 | Omega-N-methylarginineBy similarity | 1 | |
Modified residuei | 20 | Asymmetric dimethylarginineBy similarity | 1 | |
Modified residuei | 23 | PhosphoserineBy similarity | 1 | |
Modified residuei | 26 | PhosphoserineBy similarity | 1 | |
Modified residuei | 62 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Methylation, PhosphoproteinProteomic databases
CPTACi | non-CPTAC-1137 |
EPDi | P35908 |
jPOSTi | P35908 |
MassIVEi | P35908 |
PaxDbi | P35908 |
PeptideAtlasi | P35908 |
PRIDEi | P35908 |
ProteomicsDBi | 12657 55161 |
PTM databases
iPTMneti | P35908 |
PhosphoSitePlusi | P35908 |
SwissPalmi | P35908 |
Expressioni
Tissue specificityi
Expressed in the upper spinous and granular suprabasal layers of normal adult epidermal tissues from most body sites including thigh, breast nipple, foot sole, penile shaft and axilla. Not present in foreskin, squamous metaplasias and carcinomas. Expression in hypertrophic and keloid scars begins in the deepest suprabasal layer. Weakly expressed in normal gingiva and tongue, however expression is induced in benign keratoses of lingual mucosa and in mild-to-moderate oral dysplasia with orthokeratinization.3 Publications
Developmental stagei
Synthesized during maturation of epidermal keratinocytes and localized in the upper intermediate cells of fetal skin. Earliest expression is at 10 weeks in the developing embryo in the presumptive nail bed of developing digits, shifting to the proximal nail fold by 13.5 weeks. At 12.5 weeks, detected in scattered cells of the intermediate layer of trunk skin. At 19.3 weeks, regional expression patterns were observed in upper intermediate keratinocytes of cheek, trunk, dorsal and ventral knee, elbow and dorsal hand. Distal areas around the periumbilical region showed increased number of positive cells and by 15 weeks is expressed in small groups of cells in the fetal hair follicles.2 Publications
Gene expression databases
Bgeei | ENSG00000172867, Expressed in upper arm skin and 103 other tissues |
Genevisiblei | P35908, HS |
Organism-specific databases
HPAi | ENSG00000172867, Tissue enriched (skin) |
Interactioni
Subunit structurei
Heterotetramer of two type I and two type II keratins. Associates with KRT10 (By similarity).
By similarityBinary interactionsi
Hide detailsP35908
GO - Molecular functioni
- cytoskeletal protein binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 110047, 102 interactors |
IntActi | P35908, 41 interactors |
MINTi | P35908 |
STRINGi | 9606.ENSP00000310861 |
Miscellaneous databases
RNActi | P35908, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 178 – 491 | IF rodPROSITE-ProRule annotationAdd BLAST | 314 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 177 | HeadAdd BLAST | 177 | |
Regioni | 178 – 213 | Coil 1AAdd BLAST | 36 | |
Regioni | 214 – 232 | Linker 1Add BLAST | 19 | |
Regioni | 233 – 324 | Coil 1BAdd BLAST | 92 | |
Regioni | 325 – 348 | Linker 12Add BLAST | 24 | |
Regioni | 349 – 487 | Coil 2Add BLAST | 139 | |
Regioni | 488 – 639 | TailAdd BLAST | 152 |
Sequence similaritiesi
Belongs to the intermediate filament family.PROSITE-ProRule annotation
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | ENOG502QTM6, Eukaryota |
GeneTreei | ENSGT00940000162573 |
HOGENOMi | CLU_012560_6_1_1 |
InParanoidi | P35908 |
OMAi | RDYERHV |
OrthoDBi | 824246at2759 |
PhylomeDBi | P35908 |
TreeFami | TF317854 |
Family and domain databases
Gene3Di | 1.20.5.1160, 1 hit |
InterProi | View protein in InterPro IPR018039, IF_conserved IPR039008, IF_rod_dom IPR042180, IF_rod_dom_coil1B IPR032444, Keratin_2_head IPR003054, Keratin_II |
Pfami | View protein in Pfam PF00038, Filament, 1 hit PF16208, Keratin_2_head, 1 hit |
PRINTSi | PR01276, TYPE2KERATIN |
SMARTi | View protein in SMART SM01391, Filament, 1 hit |
PROSITEi | View protein in PROSITE PS00226, IF_ROD_1, 1 hit PS51842, IF_ROD_2, 1 hit |
i Sequence
Sequence statusi: Complete.
P35908-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSCQISCKSR GRGGGGGGFR GFSSGSAVVS GGSRRSTSSF SCLSRHGGGG
60 70 80 90 100
GGFGGGGFGS RSLVGLGGTK SISISVAGGG GGFGAAGGFG GRGGGFGGGS
110 120 130 140 150
SFGGGSGFSG GGFGGGGFGG GRFGGFGGPG GVGGLGGPGG FGPGGYPGGI
160 170 180 190 200
HEVSVNQSLL QPLNVKVDPE IQNVKAQERE QIKTLNNKFA SFIDKVRFLE
210 220 230 240 250
QQNQVLQTKW ELLQQMNVGT RPINLEPIFQ GYIDSLKRYL DGLTAERTSQ
260 270 280 290 300
NSELNNMQDL VEDYKKKYED EINKRTAAEN DFVTLKKDVD NAYMIKVELQ
310 320 330 340 350
SKVDLLNQEI EFLKVLYDAE ISQIHQSVTD TNVILSMDNS RNLDLDSIIA
360 370 380 390 400
EVKAQYEEIA QRSKEEAEAL YHSKYEELQV TVGRHGDSLK EIKIEISELN
410 420 430 440 450
RVIQRLQGEI AHVKKQCKNV QDAIADAEQR GEHALKDARN KLNDLEEALQ
460 470 480 490 500
QAKEDLARLL RDYQELMNVK LALDVEIATY RKLLEGEECR MSGDLSSNVT
510 520 530 540 550
VSVTSSTISS NVASKAAFGG SGGRGSSSGG GYSSGSSSYG SGGRQSGSRG
560 570 580 590 600
GSGGGGSISG GGYGSGGGSG GRYGSGGGSK GGSISGGGYG SGGGKHSSGG
610 620 630
GSRGGSSSGG GYGSGGGGSS SVKGSSGEAF GSSVTFSFR
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 108 | F → FGGGSGF in AAC83410 (PubMed:1380918).Curated | 1 | |
Sequence conflicti | 108 | F → FGGGSGF in AAB81946 (PubMed:9804344).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_058293 | 101 | S → G2 PublicationsCorresponds to variant dbSNP:rs2634041EnsemblClinVar. | 1 | |
Natural variantiVAR_003865 | 181 | Q → P in IBS. 1 PublicationCorresponds to variant dbSNP:rs57510142EnsemblClinVar. | 1 | |
Natural variantiVAR_010514 | 182 | I → N in IBS. 1 PublicationCorresponds to variant dbSNP:rs61622714EnsemblClinVar. | 1 | |
Natural variantiVAR_010515 | 186 | N → D in IBS. 1 PublicationCorresponds to variant dbSNP:rs137852631EnsemblClinVar. | 1 | |
Natural variantiVAR_017829 | 186 | N → K in IBS. 1 PublicationCorresponds to variant dbSNP:rs137852632EnsemblClinVar. | 1 | |
Natural variantiVAR_009185 | 186 | N → Y in IBS. 1 PublicationCorresponds to variant dbSNP:rs137852631EnsemblClinVar. | 1 | |
Natural variantiVAR_058294 | 219 | G → D. Corresponds to variant dbSNP:rs638043EnsemblClinVar. | 1 | |
Natural variantiVAR_031082 | 465 | E → D in IBS. 1 Publication | 1 | |
Natural variantiVAR_031083 | 465 | E → K in IBS. 1 PublicationCorresponds to variant dbSNP:rs758760389Ensembl. | 1 | |
Natural variantiVAR_009186 | 476 | E → K in IBS. 1 PublicationCorresponds to variant dbSNP:rs56829062EnsemblClinVar. | 1 | |
Natural variantiVAR_031084 | 476 | E → V in IBS. 1 PublicationCorresponds to variant dbSNP:rs60537449EnsemblClinVar. | 1 | |
Natural variantiVAR_031085 | 477 | I → N in IBS. 1 Publication | 1 | |
Natural variantiVAR_009187 | 479 | T → P in IBS. 1 PublicationCorresponds to variant dbSNP:rs137852630EnsemblClinVar. | 1 | |
Natural variantiVAR_010516 | 484 | L → P in IBS. 2 PublicationsCorresponds to variant dbSNP:rs61726451EnsemblClinVar. | 1 | |
Natural variantiVAR_003866 | 487 | E → D in IBS. 1 PublicationCorresponds to variant dbSNP:rs137852628EnsemblClinVar. | 1 | |
Natural variantiVAR_003867 | 487 | E → K in IBS. 7 PublicationsCorresponds to variant dbSNP:rs137852629EnsemblClinVar. | 1 | |
Natural variantiVAR_031086 | 488 | E → K in IBS. 1 PublicationCorresponds to variant dbSNP:rs61726452EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M99061 mRNA Translation: AAC83410.1 AF019084 Genomic DNA Translation: AAB81946.1 AC055715 Genomic DNA No translation available. AC055716 Genomic DNA No translation available. BC096294 mRNA Translation: AAH96294.1 BC099643 mRNA Translation: AAH99643.1 BC099644 mRNA Translation: AAH99644.1 |
CCDSi | CCDS8835.1 |
PIRi | A44861 |
RefSeqi | NP_000414.2, NM_000423.2 |
Genome annotation databases
Ensembli | ENST00000309680; ENSP00000310861; ENSG00000172867 |
GeneIDi | 3849 |
KEGGi | hsa:3849 |
UCSCi | uc001sat.4, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Human Intermediate Filament Mutation Database |
Wikipedia Keratin-2A entry |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M99061 mRNA Translation: AAC83410.1 AF019084 Genomic DNA Translation: AAB81946.1 AC055715 Genomic DNA No translation available. AC055716 Genomic DNA No translation available. BC096294 mRNA Translation: AAH96294.1 BC099643 mRNA Translation: AAH99643.1 BC099644 mRNA Translation: AAH99644.1 |
CCDSi | CCDS8835.1 |
PIRi | A44861 |
RefSeqi | NP_000414.2, NM_000423.2 |
3D structure databases
SMRi | P35908 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 110047, 102 interactors |
IntActi | P35908, 41 interactors |
MINTi | P35908 |
STRINGi | 9606.ENSP00000310861 |
Chemistry databases
DrugBanki | DB11157, Anthralin DB09130, Copper DB01593, Zinc DB14487, Zinc acetate |
PTM databases
iPTMneti | P35908 |
PhosphoSitePlusi | P35908 |
SwissPalmi | P35908 |
Genetic variation databases
BioMutai | KRT2 |
DMDMi | 239938650 |
Proteomic databases
CPTACi | non-CPTAC-1137 |
EPDi | P35908 |
jPOSTi | P35908 |
MassIVEi | P35908 |
PaxDbi | P35908 |
PeptideAtlasi | P35908 |
PRIDEi | P35908 |
ProteomicsDBi | 12657 55161 |
Protocols and materials databases
Antibodypediai | 1398, 275 antibodies |
Genome annotation databases
Ensembli | ENST00000309680; ENSP00000310861; ENSG00000172867 |
GeneIDi | 3849 |
KEGGi | hsa:3849 |
UCSCi | uc001sat.4, human |
Organism-specific databases
CTDi | 3849 |
DisGeNETi | 3849 |
GeneCardsi | KRT2 |
HGNCi | HGNC:6439, KRT2 |
HPAi | ENSG00000172867, Tissue enriched (skin) |
MalaCardsi | KRT2 |
MIMi | 146800, phenotype 600194, gene |
neXtProti | NX_P35908 |
OpenTargetsi | ENSG00000172867 |
Orphaneti | 455, Superficial epidermolytic ichthyosis |
PharmGKBi | PA30227 |
VEuPathDBi | HostDB:ENSG00000172867.3 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QTM6, Eukaryota |
GeneTreei | ENSGT00940000162573 |
HOGENOMi | CLU_012560_6_1_1 |
InParanoidi | P35908 |
OMAi | RDYERHV |
OrthoDBi | 824246at2759 |
PhylomeDBi | P35908 |
TreeFami | TF317854 |
Enzyme and pathway databases
PathwayCommonsi | P35908 |
Reactomei | R-HSA-6805567, Keratinization R-HSA-6809371, Formation of the cornified envelope |
Miscellaneous databases
BioGRID-ORCSi | 3849, 13 hits in 874 CRISPR screens |
GeneWikii | Keratin_2A |
GenomeRNAii | 3849 |
Pharosi | P35908, Tbio |
PROi | PR:P35908 |
RNActi | P35908, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000172867, Expressed in upper arm skin and 103 other tissues |
Genevisiblei | P35908, HS |
Family and domain databases
Gene3Di | 1.20.5.1160, 1 hit |
InterProi | View protein in InterPro IPR018039, IF_conserved IPR039008, IF_rod_dom IPR042180, IF_rod_dom_coil1B IPR032444, Keratin_2_head IPR003054, Keratin_II |
Pfami | View protein in Pfam PF00038, Filament, 1 hit PF16208, Keratin_2_head, 1 hit |
PRINTSi | PR01276, TYPE2KERATIN |
SMARTi | View protein in SMART SM01391, Filament, 1 hit |
PROSITEi | View protein in PROSITE PS00226, IF_ROD_1, 1 hit PS51842, IF_ROD_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | K22E_HUMAN | |
Accessioni | P35908Primary (citable) accession number: P35908 Secondary accession number(s): Q4VAQ2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 1, 1994 |
Last sequence update: | June 16, 2009 | |
Last modified: | February 10, 2021 | |
This is version 191 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families