KRT1

Protein identityUniProt · HPA

UniProt accession

P04264

Gene

KRT1

Ensembl

ENSG00000167768

Chromosome

12

Canonical length

644 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

OverviewNCBI Gene

The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the spinous and granular layers of the epidermis with family member KRT10 and mutations in these genes have been associated with bullous congenital ichthyosiform erythroderma. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

644 residues, UniProt reviewed canonical sequence.

>P04264|KRT1
     1  MSRQFSSRSG YRSGGGFSSG SAGIINYQRR TTSSSTRRSG GGGGRFSSCG GGGGSFGAGG
    61  GFGSRSLVNL GGSKSISISV ARGGGRGSGF GGGYGGGGFG GGGFGGGGFG GGGIGGGGFG
   121  GFGSGGGGFG GGGFGGGGYG GGYGPVCPPG GIQEVTINQS LLQPLNVEID PEIQKVKSRE
   181  REQIKSLNNQ FASFIDKVRF LEQQNQVLQT KWELLQQVDT STRTHNLEPY FESFINNLRR
   241  RVDQLKSDQS RLDSELKNMQ DMVEDYRNKY EDEINKRTNA ENEFVTIKKD VDGAYMTKVD
   301  LQAKLDNLQQ EIDFLTALYQ AELSQMQTQI SETNVILSMD NNRSLDLDSI IAEVKAQYED
   361  IAQKSKAEAE SLYQSKYEEL QITAGRHGDS VRNSKIEISE LNRVIQRLRS EIDNVKKQIS
   421  NLQQSISDAE QRGENALKDA KNKLNDLEDA LQQAKEDLAR LLRDYQELMN TKLALDLEIA
   481  TYRTLLEGEE SRMSGECAPN VSVSVSTSHT TISGGGSRGG GGGGYGSGGS SYGSGGGSYG
   541  SGGGGGGGRG SYGSGGSSYG SGGGSYGSGG GGGGHGSYGS GSSSGGYRGG SGGGGGGSSG
   601  GRGSGGGSSG GSIGGRGSSS GGVKSSGGSS SVKFVSTTYS GVTR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KRT1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.62

Highest tissue expression

12,288 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about KRT1.

Disease | AllUniProt

Conditions KRT1 is implicated in, by any mechanism.

• Epidermolytic hyperkeratosis 1 (EHK1) MIM:113800
• Ichthyosis hystrix, Curth-Macklin type (IHCM) MIM:146590
• Keratoderma, palmoplantar, non-epidermolytic (NEPPK) MIM:600962
• Ichthyosis, annular epidermolytic, 2 (AEI2) MIM:620148
• Keratoderma, palmoplantar, striate 3 (SPPK3) MIM:607654
• Palmoplantar keratoderma, epidermolytic, 2 (EPPK2) MIM:620411

Disease | GeneticClinVar

48 pathogenic / likely-pathogenic of 281 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Epidermolytic ichthyosis
• Epidermolytic hyperkeratosis 1
• Diffuse nonepidermolytic palmoplantar keratoderma
• Ichthyosis hystrix of Curth-Macklin
• Annular epidermolytic ichthyosis

Disease | ImmuneIEDB

Conditions an epitope on KRT1 was assayed in.

• multiple sclerosis B cell
• amyotrophic lateral sclerosis B cell
• neuromyelitis optica B cell

ReferencesPubMed · IEDB

Publications for KRT1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.4

gnomAD pLI

0.74

gnomAD missense Z

0.25

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• complement activation, lectin pathway
• cornification
• establishment of skin barrier
• fibrinolysis
• intermediate filament organization
• keratinization
• negative regulation of inflammatory response
• protein heterotetramerization
• regulation of angiogenesis
• response to oxidative stress

Molecular functions

• carbohydrate binding
• protein heterodimerization activity
• signaling receptor activity
• structural constituent of skin epidermis

Cellular components

• blood microparticle
• cornified envelope
• cytoplasm
• cytoskeleton
• cytosol
• extracellular exosome
• extracellular region
• extracellular space
• ficolin-1-rich granule lumen
• keratin filament
• membrane
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Keratin, type II
• Intermediate filament protein, conserved site
• Keratin type II head
• Intermediate filament, rod domain
• Intermediate filament protein
• Keratin type II head
• Keratin type II cytoskeletal 1, tail
• Keratin type II cytoskeletal 1 tail

KeywordsUniProt

• Cell membrane
• Citrullination
• Coiled coil
• Cytoplasm
• Ichthyosis
• Intermediate filament
• Keratin
• Membrane
• Methylation
• Palmoplantar keratoderma
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of KRT1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• C1QBP
• EPPK1
• ITGB1
• RACK1
• KRT10
• KRT19