Keratin, type II cytoskeletal 1 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P04264 (K2C1_HUMAN)

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

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	644 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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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.

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Ontologies

Keywords
Cellular component	Intermediate filament Keratin
Coding sequence diversity	Polymorphism
Disease	Disease mutation Ichthyosis
Domain	Coiled coil
PTM	Citrullination Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	complement activation, lectin pathway Inferred from physical interaction. Source: UniProtKB epidermis development Ref.15 Traceable author statement. Source: ProtInc fibrinolysis Non-traceable author statement. Source: UniProtKB regulation of angiogenesis Non-traceable author statement. Source: UniProtKB response to oxidative stress Non-traceable author statement. Source: UniProtKB
Cellular component	intermediate filament Ref.15 Traceable author statement. Source: ProtInc membrane Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Inferred from mutant phenotype. Source: UniProtKB receptor activity Non-traceable author statement. Source: UniProtKB structural constituent of cytoskeleton Ref.15 Traceable author statement. Source: ProtInc sugar binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDM2	Q00987	1	EBI-298429,EBI-389668

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Initiator methionine

Removed

Chain

2 – 644

643

Keratin, type II cytoskeletal 1

Regions

Region

2 – 179

178

Head

Region

180 – 489

310

Rod

Region

180 – 215

Coil 1A

Region

216 – 234

Linker 1

Region

235 – 326

Coil 1B

Region

327 – 350

Linker 12

Region

351 – 489

139

Coil 2

Region

490 – 644

155

Tail

Compositional bias

2 – 151

150

Gly/Phe/Ser-rich

Compositional bias

502 – 641

140

Gly/Ser-rich

Sites

Site

433

Stutter

Amino acid modifications

Modified residue

Phosphoserine

Modified residue

Phosphoserine By similarity

Modified residue

295

Phosphotyrosine

Modified residue

297

Phosphothreonine

Natural variations

Natural variant

K → I in NEPPK.

Natural variant

155

V → D in BCIE.

Natural variant

155

V → G in BCIE.

Natural variant

161

L → P in BCIE.

Natural variant

176 – 197

Missing in palmoplantar keratoderma; and mild ichthyosis largely limited to the flexural areas.

Natural variant

186

S → P in BCIE.

Natural variant

188

N → K in BCIE.

Natural variant

188

N → S in BCIE.

Natural variant

188

N → T in BCIE; severe.

Natural variant

193

S → P in BCIE.

Natural variant

214

L → P in BCIE.

Natural variant

Natural variant

Natural variant

D → V in BCIE.

Natural variant

358

N → Y: dbSNP rs1050872.

Natural variant

454

A → S: dbSNP rs17678945.

Natural variant

459 – 466

Missing in palmoplantar keratoderma; and mild ichthyosis largely limited to the flexural areas.

Natural variant

479

I → F in AEI.

Natural variant

479

I → T in AEI and BCIE.

Natural variant

482

Y → C in BCIE.

Natural variant

486

L → P in BCIE.

Natural variant

490

E → Q in BCIE.

Natural variant

537

G → C

Natural variant

560 – 566

Missing in allele 1B.

Natural variant

633

R → K: dbSNP rs14024.

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Sequences

Sequence

Length

Mass (Da)

Tools

P04264-1 [UniParc].

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

644

66,018

        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

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References

	« Hide 'large scale' referencesShow '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.

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Web resources

Human Intermediate Filament Mutation Database

GeneReviews

Wikipedia

Keratin-1 entry

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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.
PIR	KRHU2. A22940.
RefSeq	NP_006112.3.
UniGene	Hs.80828
3D structure databases
HSSP	HSSP built from PDB template 1GK7 based on UniProtKB P08670.
ModBase	Search...
Protein-protein interaction databases
IntAct	P04264.
PTM databases
PhosphoSite	P04264.
2-D gel databases
SWISS-2DPAGE	P04264.
Aarhus/Ghent-2DPAGE	4606. NEPHGE.
REPRODUCTION-2DPAGE	P04264.
Genome annotation databases
Ensembl	ENSG00000167768. Homo sapiens. [Contig view]
GeneID	3848.
KEGG	hsa:3848.
Organism-specific databases
HGNC	HGNC:6412. KRT1.
HPA	CAB002153.
MIM

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

2-D gel databases

Genome annotation databases

Organism-specific databases