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Reviewed, UniProtKB/Swiss-Prot P04264 (K2C1_HUMAN)

Last modified September 2, 2008. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Keratin, type II cytoskeletal 1
Alternative name(s):
    Cytokeratin-1
      Short name=CK-1
      Short name=Keratin-1
      Short name=K1
    67 kDa cytokeratin
    Hair alpha protein
Gene names
Name: KRT1
Synonyms: KRTA
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length644 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Subunit structure

Heterotetramer of two type I and two type II keratins. keratin-1 is generally associated with keratin-10.

Tissue specificity

The source of this protein is neonatal foreskin. The 67-kDa type II keratins are expressed in terminally differentiating epidermis.

Post-translational modification

Undergoes deimination of some arginine residues (citrullination).

Polymorphism

There are two size variants of KRT1, termed allele 1A and allele 1B with allelic frequencies of 0.61 and 0.39. Allele 1B lacks 7 residues compared to allele 1A.

Involvement in disease

Defects in KRT1 are a cause of bullous congenital ichthyosiform erythroderma (BCIE) [MIM:113800]; also known as epidermolytic hyperkeratosis (EHK) or bullous erythroderma ichthyosiformis congenita of Brocq. BCIE is an autosomal dominant skin disorder characterized by widespread blistering and an ichthyotic erythroderma at birth that persist into adulthood. Histologically there is a diffuse epidermolytic degeneration in the lower spinous layer of the epidermis. Within a few weeks from birth, erythroderma and blister formation diminish and hyperkeratoses develop.

Defects in KRT1 are the cause of ichthyosis hystrix Curth-Macklin type (IHCM) [MIM:146590]. IHCM is a genodermatosis with severe verrucous hyperkeratosis. Affected individuals manifest congenital verrucous black scale on the scalp, neck, and limbs with truncal erythema, palmo-plantar keratoderma and keratoses on the lips, ears, nipples and buttocks.

Defects in KRT1 are a cause of palmoplantar keratoderma non-epidermolytic (NEPPK) [MIM:600962]. NEPKK is a dermatological disorder characterized by focal palmoplantar keratoderma with oral, genital, and follicular lesions.

Defects in KRT1 are a cause of ichthyosis annular epidermolytic (AEI) [MIM:607602]; also known as cyclic ichthyosis with epidermolytic hyperkeratosis. AEI is a skin disorder resembling bullous congenital ichthyosiform erythroderma. Affected individuals present with bullous ichthyosis in early childhood and hyperkeratotic lichenified plaques in the flexural areas and extensor surfaces at later ages. The feature that distinguishes AEI from BCIE is dramatic episodes of flares of annular polycyclic plaques with scale, which coalesce to involve most of the body surface and can persist for several weeks or even months.

Defects in KRT1 are the cause of palmoplantar keratoderma striate type 3 (SPPK3) [MIM:607654]; also known as keratosis palmoplantaris striata III. SPPK3 is a dermatological disorder affecting palm and sole skin where stratum corneum and epidermal layers are thickened. There is no involvement of non-palmoplantar skin, and both hair and nails are normal.

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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MDM2Q009871EBI-298429,EBI-389668

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Initiator methionine11Removed
Chain2 – 644643Keratin, type II cytoskeletal 1

Regions

Region2 – 179178Head
Region180 – 489310Rod
Region180 – 21536Coil 1A
Region216 – 23419Linker 1
Region235 – 32692Coil 1B
Region327 – 35024Linker 12
Region351 – 489139Coil 2
Region490 – 644155Tail
Compositional bias2 – 151150Gly/Phe/Ser-rich
Compositional bias502 – 641140Gly/Ser-rich

Sites

Site4331Stutter

Amino acid modifications

Modified residue211Phosphoserine
Modified residue661Phosphoserine By similarity
Modified residue2951Phosphotyrosine
Modified residue2971Phosphothreonine

Natural variations

Natural variant741K → I in NEPPK.
Natural variant1551V → D in BCIE.
Natural variant1551V → G in BCIE.
Natural variant1611L → P in BCIE.
Natural variant176 – 19722Missing in palmoplantar keratoderma; and mild ichthyosis largely limited to the flexural areas.
Natural variant1861S → P in BCIE.
Natural variant1881N → K in BCIE.
Natural variant1881N → S in BCIE.
Natural variant1881N → T in BCIE; severe.
Natural variant1931S → P in BCIE.
Natural variant2141L → P in BCIE.
Natural variant3121I → V
Natural variant3301I → T
Natural variant3401D → V in BCIE.
Natural variant3581N → Y: dbSNP rs1050872.
Natural variant4541A → S: dbSNP rs17678945.
Natural variant459 – 4668Missing in palmoplantar keratoderma; and mild ichthyosis largely limited to the flexural areas.
Natural variant4791I → F in AEI.
Natural variant4791I → T in AEI and BCIE.
Natural variant4821Y → C in BCIE.
Natural variant4861L → P in BCIE.
Natural variant4901E → Q in BCIE.
Natural variant5371G → C
Natural variant560 – 5667Missing in allele 1B.
Natural variant6331R → K: dbSNP rs14024.

Sequences

Sequence LengthMass (Da)Tools
P04264-1 [UniParc].

Last modified January 23, 2007. Version 5.
Checksum: 468F83CA61A455C4

FASTA64466,018
        10         20         30         40         50         60 
MSRQFSSRSG YRSGGGFSSG SAGIINYQRR TTSSSTRRSG GGGGRFSSCG GGGGSFGAGG 

        70         80         90        100        110        120 
GFGSRSLVNL GGSKSISISV ARGGGRGSGF GGGYGGGGFG GGGFGGGGFG GGGIGGGGFG 

       130        140        150        160        170        180 
GFGSGGGGFG GGGFGGGGYG GGYGPVCPPG GIQEVTINQS LLQPLNVEID PEIQKVKSRE 

       190        200        210        220        230        240 
REQIKSLNNQ FASFIDKVRF LEQQNQVLQT KWELLQQVDT STRTHNLEPY FESFINNLRR 

       250        260        270        280        290        300 
RVDQLKSDQS RLDSELKNMQ DMVEDYRNKY EDEINKRTNA ENEFVTIKKD VDGAYMTKVD 

       310        320        330        340        350        360 
LQAKLDNLQQ EIDFLTALYQ AELSQMQTQI SETNVILSMD NNRSLDLDSI IAEVKAQNED 

       370        380        390        400        410        420 
IAQKSKAEAE SLYQSKYEEL QITAGRHGDS VRNSKIEISE LNRVIQRLRS EIDNVKKQIS 

       430        440        450        460        470        480 
NLQQSISDAE QRGENALKDA KNKLNDLEDA LQQAKEDLAR LLRDYQELMN TKLALDLEIA 

       490        500        510        520        530        540 
TYRTLLEGEE SRMSGECAPN VSVSVSTSHT TISGGGSRGG GGGGYGSGGS SYGSGGGSYG 

       550        560        570        580        590        600 
SGGGGGGGRG SYGSGGSSYG SGGGSYGSGG GGGGHGSYGS GSSSGGYRGG SGGGGGGSSG 

       610        620        630        640 
GRGSGGGSSG GSIGGRGSSS GGVKSSGGSS SVRFVSTTYS GVTR 

« Hide

References

« Hide 'large scale' references
[1]"Structure of a gene for the human epidermal 67-kDa keratin."
Johnson L.D., Idler W.W., Zhou X.-M., Roop D.R., Steinert P.M.
Proc. Natl. Acad. Sci. U.S.A. 82:1896-1900(1985) [PubMed: 2580302] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Genomic organization and amplification of the human epidermal type II keratin genes K1 and K5."
Whittock N.V., Eady R.A.J., McGrath J.A.
Biochem. Biophys. Res. Commun. 274:149-152(2000) [PubMed: 10903910] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Novel splice site mutation in keratin 1 underlies mild epidermolytic palmoplantar keratoderma in three kindreds."
Hatsell S.J., Eady R.A.J., Wennerstrand L., Dopping-Hepenstal P.J., Leigh I.M., Munro C., Kelsell D.P.
J. Invest. Dermatol. 116:606-609(2001) [PubMed: 11286630] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], INVOLVEMENT IN NEPPK.
[4]"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], VARIANT TYR-358.
Tissue: Skin.
[5]"Amino acid sequences of mouse and human epidermal type II keratins of Mr 67,000 provide a systematic basis for the structural and functional diversity of the end domains of keratin intermediate filament subunits."
Steinert P.M., Parry D.A.D., Idler W.W., Johnson L.D., Steven A.C., Roop D.R.
J. Biol. Chem. 260:7142-7149(1985) [PubMed: 2581964] [Abstract]
Cited for: PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 152-644.
[6]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-8.
Tissue: Platelet.
[7]"Preferential deimination of keratin K1 and filaggrin during the terminal differentiation of human epidermis."
Senshu T., Kan S., Ogawa H., Manabe M., Asaga H.
Biochem. Biophys. Res. Commun. 225:712-719(1996) [PubMed: 8780679] [Abstract]
Cited for: CITRULLINATION.
[8]"Evidence for novel functions of the keratin tail emerging from a mutation causing ichthyosis hystrix."
Sprecher E., Ishida-Yamamoto A., Becker O.M., Marekov L.N., Miller C.J., Steinert P.M., Neldner K., Richard G.
J. Invest. Dermatol. 116:511-519(2001) [PubMed: 11286616] [Abstract]
Cited for: INVOLVEMENT IN IHCM.
[9]"Sequential reorganization of cornified cell keratin filaments involving filaggrin-mediated compaction and keratin 1 deimination."
Ishida-Yamamoto A., Senshu T., Eady R.A.J., Takahashi H., Shimizu H., Akiyama M., Iizuka H.
J. Invest. Dermatol. 118:282-287(2002) [PubMed: 11841545] [Abstract]
Cited for: CITRULLINATION.
[10]"Frameshift mutation in the V2 domain of human keratin 1 results in striate palmoplantar keratoderma."
Whittock N.V., Smith F.J., Wan H., Mallipeddi R., Griffiths W.A.D., Dopping-Hepenstal P.J., Ashton G.H.S., Eady R.A.J., McLean W.H.I., McGrath J.A.
J. Invest. Dermatol. 118:838-844(2002) [PubMed: 11982762] [Abstract]
Cited for: INVOLVEMENT IN SPPK3.
[11]"Phosphoproteome analysis of the human mitotic spindle."
Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R.
Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, MASS SPECTROMETRY.
Tissue: Epithelium.
[12]"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra."
Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.
J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-295 AND THR-297, MASS SPECTROMETRY.
Tissue: Epithelium.
[13]"A leucine-->proline mutation in the H1 subdomain of keratin 1 causes epidermolytic hyperkeratosis."
Chipev C.C., Korge B.P., Markova N., Bale S.J., Digiovanna J.J., Compton J.G., Steinert P.M.
Cell 70:821-828(1992) [PubMed: 1381288] [Abstract]
Cited for: VARIANT BCIE PRO-161.
[14]"The two size alleles of human keratin 1 are due to a deletion in the glycine-rich carboxyl-terminal V2 subdomain."
Korge B.P., Compton J.G., Steinert P.M., Mischke D.
J. Invest. Dermatol. 99:697-702(1992) [PubMed: 1281859] [Abstract]
Cited for: VARIANT ALLELE 1B 560-GLY--TYR-566 DEL.
[15]"Mutations in the rod domains of keratins 1 and 10 in epidermolytic hyperkeratosis."
Rothnagel J.A., Dominey A.M., Dempsey L.D., Longley M.A., Greenhalgh D.A., Gagne T.A., Huber M., Frenk E., Hohl D., Roop D.R.
Science 257:1128-1130(1992) [PubMed: 1380725] [Abstract]
Cited for: VARIANT BCIE GLN-490.
[16]"Genetic mutations in the K1 and K10 genes of patients with epidermolytic hyperkeratosis. Correlation between location and disease severity."
Syder A.J., Yu Q.-C., Paller A.S., Giudice G., Pearson R., Fuchs E.
J. Clin. Invest. 93:1533-1542(1994) [PubMed: 7512983] [Abstract]
Cited for: VARIANT BCIE CYS-482.
[17]"Mutations in the H1 and 1A domains in the keratin 1 gene in epidermolytic hyperkeratosis."
Yang J.-M., Chipev C.C., Digiovanna J.J., Bale S.J., Marekov L.N., Steinert P.M., Compton J.G.
J. Invest. Dermatol. 102:17-23(1994) [PubMed: 7507151] [Abstract]
Cited for: VARIANTS BCIE GLY-155; SER-188 AND PRO-193.
[18]"Mutations in the rod 1A domain of keratins 1 and 10 in bullous congenital ichthyosiform erythroderma (BCIE)."
McLean W.H.I., Eady R.A.J., Dopping-Hepenstal P.J.C., McMillan J.R., Leigh I.M., Navsaria H.A., Higgins C., Harper J.I., Paige D.G., Morley S.M.
J. Invest. Dermatol. 102:24-30(1994) [PubMed: 7507152] [Abstract]
Cited for: VARIANTS BCIE PRO-186 AND SER-188.
[19]"A mutation in the V1 end domain of keratin 1 in non-epidermolytic palmar-plantar keratoderma."
Kimonis V., DiGiovanna J.J., Yang J.-M., Doyle S.Z., Bale S.J., Compton J.G.
J. Invest. Dermatol. 103:764-769(1994) [PubMed: 7528239] [Abstract]
Cited for: VARIANT NEPPK ILE-74.
[20]"An atypical form of bullous congenital ichthyosiform erythroderma is caused by a mutation in the L12 linker region of keratin 1."
Kremer H., Lavrijsen A.P., McLean W.H.I., Lane E.B., Melchers D., Ruiter D.J., Mariman E.C., Steijlen P.M.
J. Invest. Dermatol. 111:1224-1226(1998) [PubMed: 9856846] [Abstract]
Cited for: VARIANT BCIE VAL-340.
[21]"Cyclic ichthyosis with epidermolytic hyperkeratosis: a phenotype conferred by mutations in the 2B domain of keratin K1."
Sybert V.P., Francis J.S., Corden L.D., Smith L.T., Weaver M., Stephens K., McLean W.H.I.
Am. J. Hum. Genet. 64:732-738(1999) [PubMed: 10053007] [Abstract]
Cited for: VARIANTS AEI PHE-479 AND THR-479.
[22]"An asparagine to threonine substitution in the 1A domain of keratin 1: a novel mutation that causes epidermolytic hyperkeratosis."
Arin M.J., Longley M.A., Kuster W., Huber M., Hohl D., Rothnagel J.A., Roop D.R.
Exp. Dermatol. 8:124-127(1999) [PubMed: 10232403] [Abstract]
Cited for: VARIANT BCIE THR-188.
[23]"Epidermolytic hyperkeratosis with polycyclic psoriasiform plaques resulting from a mutation in the keratin 1 gene."
Michael E.J., Schneiderman P., Grossman M.E., Christiano A.M.
Exp. Dermatol. 8:501-503(1999) [PubMed: 10597140] [Abstract]
Cited for: VARIANT AEI PHE-479.
[24]"Epidermolytic hyperkeratosis in a Hispanic family resulting from a mutation in the keratin 1 gene."
Cserhalmi-Friedman P.B., Squeo R., Gordon D., Garzon M., Schneiderman P., Grossman M.E., Christiano A.M.
Clin. Exp. Dermatol. 25:241-243(2000) [PubMed: 10844506] [Abstract]
Cited for: VARIANT BCIE PRO-214.
[25]"Identification of a novel mutation in keratin 1 in a family with epidermolytic hyperkeratosis."
Arin M.J., Longley M.A., Epstein E.H. Jr., Rothnagel J.A., Roop D.R.
Exp. Dermatol. 9:16-19(2000) [PubMed: 10688370] [Abstract]
Cited for: VARIANT BCIE THR-479.
[26]"New mutations in keratin 1 that cause bullous congenital ichthyosiform erythroderma and keratin 2e that cause ichthyosis bullosa of Siemens."
Whittock N.V., Ashton G.H.S., Griffiths W.A.D., Eady R.A.J., McGrath J.A.
Br. J. Dermatol. 145:330-335(2001) [PubMed: 11531804] [Abstract]
Cited for: VARIANT BCIE ASP-155.
[27]"Two cases of primarily palmoplantar keratoderma associated with novel mutations in keratin 1."
Terron-Kwiatkowski A., Paller A.S., Compton J., Atherton D.J., McLean W.H., Irvine A.D.
J. Invest. Dermatol. 119:966-971(2002) [PubMed: 12406346] [Abstract]
Cited for: VARIANTS PALMOPLANTAR KERATODERMA VAL-176--LYS-197 DEL AND ALA-459--466-GLN DEL.
[28]"Two novel mutations in the keratin 1 gene in epidermolytic hyperkeratosis."
Lee D.-Y., Ahn K.-S., Lee C.-H., Rho N.-K., Lee J.-H., Lee E.-S., Steinert P.M., Yang J.-M.
J. Invest. Dermatol. 119:976-977(2002) [PubMed: 12406348] [Abstract]
Cited for: VARIANTS BCIE LYS-188 AND PRO-486.
+Additional computationally mapped references.

Cross-references

Sequence databases

M98776 Genomic DNA. Translation: AAB47721.1.
AF237621 Genomic DNA. Translation: AAF60327.1.
AF304164 Genomic DNA. Translation: AAG41947.1.
BC063697 mRNA. Translation: AAH63697.1.
M10938 mRNA. Translation: AAA36153.1. Sequence problems.
PIRKRHU2. A22940.
RefSeqNP_006112.3.
UniGeneHs.80828

3D structure databases

HSSPHSSP built from PDB template 1GK7 based on UniProtKB P08670.
ModBaseSearch...

Protein-protein interaction databases

IntActP04264.

PTM databases

PhosphoSiteP04264.

2-D gel databases

SWISS-2DPAGEP04264.
Aarhus/Ghent-2DPAGE4606. NEPHGE.
REPRODUCTION-2DPAGEP04264.

Genome annotation databases

EnsemblENSG00000167768. Homo sapiens. [Contig view]
GeneID3848.
KEGGhsa:3848.

Organism-specific databases

HGNCHGNC:6412. KRT1.
HPACAB002153.
MIM