[1]	NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. TISSUE=Thigh epidermis; DOI=10.1016/0014-4827(92)90412-2; PubMed=1380918 [NCBI, ExPASy, EBI, Israel, Japan] Collin C., Moll R., Kubicka S., Ouhayoun J.-P., Franke W.W.; "Characterization of human cytokeratin 2, an epidermal cytoskeletal protein synthesized late during differentiation."; Exp. Cell Res. 202:132-141(1992).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS IBS TYR-192 AND LYS-482. DOI=10.1046/j.1523-1747.1998.00371.x; PubMed=9804344 [NCBI, ExPASy, EBI, Israel, Japan] Smith F.J.D., Maingi C., Covello S.P., Higgins C., Schmidt M., Lane E.B., Uitto J., Leigh I.M., McLean W.H.I.; "Genomic organization and fine mapping of the keratin 2e gene (KRT2E): K2e V1 domain polymorphism and novel mutations in ichthyosis bullosa of Siemens."; J. Invest. Dermatol. 111:817-821(1998).
[3]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[4]	TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. DOI=10.1046/j.1365-2133.1999.02755.x; PubMed=10233306 [NCBI, ExPASy, EBI, Israel, Japan] Smith L.T., Underwood R.A., McLean W.H.I.; "Ontogeny and regional variability of keratin 2e (K2e) in developing human fetal skin: a unique spatial and temporal pattern of keratin expression in development."; Br. J. Dermatol. 140:582-591(1999).
[5]	FUNCTION, AND TISSUE SPECIFICITY. PubMed=12598329 [NCBI, ExPASy, EBI, Israel, Japan] Bloor B.K., Tidman N., Leigh I.M., Odell E., Dogan B., Wollina U., Ghali L., Waseem A.; "Expression of keratin K2e in cutaneous and oral lesions: association with keratinocyte activation, proliferation, and keratinization."; Am. J. Pathol. 162:963-975(2003).
[6]	VARIANT IBS LYS-493. DOI=10.1111/1523-1747.ep12394307; PubMed=7521371 [NCBI, ExPASy, EBI, Israel, Japan] McLean W.H.I., Morley S.M., Lane E.B., Eady R.A.J., Griffiths W.A.D., Paige D.G., Harper J.I., Higgins C., Leigh I.M.; "Ichthyosis bullosa of Siemens -- a disease involving keratin 2e."; J. Invest. Dermatol. 103:277-281(1994).
[7]	VARIANTS IBS PRO-187; PRO-490 AND LYS-493. DOI=10.1111/1523-1747.ep12394414; PubMed=8077693 [NCBI, ExPASy, EBI, Israel, Japan] Kremer H., Zeeuwen P., McLean W.H.I., Mariman E.C.M., Lane E.B., van de Kerkhof P.C.M., Ropers H.-H., Steijlen P.M.; "Ichthyosis bullosa of Siemens is caused by mutations in the keratin 2e gene."; J. Invest. Dermatol. 103:286-289(1994).
[8]	VARIANTS IBS ASP-493 AND LYS-493. DOI=10.1038/ng0894-485; PubMed=7524919 [NCBI, ExPASy, EBI, Israel, Japan] Rothnagel J.A., Traupe H., Wojcik S., Huber M., Hohl D., Pittelkow M.R., Saeki H., Ishibashi Y., Roop D.R.; "Mutations in the rod domain of keratin 2e in patients with ichthyosis bullosa of Siemens."; Nat. Genet. 7:485-490(1994).
[9]	VARIANTS IBS LYS-493 AND LYS-494. DOI=10.1111/1523-1747.ep12286487; PubMed=9036938 [NCBI, ExPASy, EBI, Israel, Japan] Jones D.O., Watts C., Mills C., Sharpe G., Marks R., Bowden P.E.; "A new keratin 2e mutation in ichthyosis bullosa of Siemens."; J. Invest. Dermatol. 108:354-356(1997).
[10]	VARIANT IBS PRO-485. DOI=10.1111/1523-1747.ep12276775; PubMed=9204966 [NCBI, ExPASy, EBI, Israel, Japan] Yang J.-M., Lee S., Bang H.-D., Kim W.-S., Lee E.-S., Steinert P.M.; "A novel threonine-to-proline mutation at the end of 2B rod domain in the keratin 2e chain in ichthyosis bullosa of Siemens."; J. Invest. Dermatol. 109:116-118(1997).
[11]	VARIANT IBS LYS-493. DOI=10.1080/000155598442683; PubMed=9833038 [NCBI, ExPASy, EBI, Israel, Japan] Yang J.-M., Lee E.-S., Kang H.-J., Choi G.-S., Yoneda K., Jung S.-Y., Park K.-B., Steinert P.M., Lee E.-S.; "A glutamate to lysine mutation at the end of 2B rod domain of keratin 2e gene in ichthyosis bullosa of Siemens."; Acta Derm. Venereol. 78:417-419(1998).
[12]	VARIANT IBS LYS-493. DOI=10.1046/j.1365-2133.1999.02772.x; PubMed=10233323 [NCBI, ExPASy, EBI, Israel, Japan] Basarab T., Smith F.J., Jolliffe V.M., McLean W.H.I., Neill S., Rustin M.H., Eady R.A.; "Ichthyosis bullosa of Siemens: report of a family with evidence of a keratin 2e mutation, and a review of the literature."; Br. J. Dermatol. 140:689-695(1999).
[13]	VARIANT IBS ASN-188. DOI=10.1046/j.1523-1747.1999.00529.x; PubMed=10084318 [NCBI, ExPASy, EBI, Israel, Japan] Arin M.J., Longley M.A., Epstein E.H. Jr., Scott G., Goldsmith L.A., Rothnagel J.A., Roop D.R.; "A novel mutation in the 1A domain of keratin 2e in ichthyosis bullosa of Siemens."; J. Invest. Dermatol. 112:380-382(1999).
[14]	VARIANT IBS VAL-482. DOI=10.1046/j.1365-2230.1999.00514.x; PubMed=10564334 [NCBI, ExPASy, EBI, Israel, Japan] Moraru R., Cserhalmi-Friedman P.B., Grossman M.E., Schneiderman P., Christiano A.M.; "Ichthyosis bullosa of Siemens resulting from a novel missense mutation near the helix termination motif of the keratin 2e gene."; Clin. Exp. Dermatol. 24:412-415(1999).
[15]	VARIANT IBS ASN-483. DOI=10.1046/j.1365-2230.2000.00728.x; PubMed=11167982 [NCBI, ExPASy, EBI, Israel, Japan] Irvine A.D., Smith F.J., Shum K.W., Williams H.C., McLean W.H.I.; "A novel mutation in the 2B domain of keratin 2e causing ichthyosis bullosa of Siemens."; Clin. Exp. Dermatol. 25:648-651(2000).
[16]	VARIANTS IBS LYS-471 AND ASP-471. DOI=10.1034/j.1600-0625.2000.009001011.x; PubMed=10688369 [NCBI, ExPASy, EBI, Israel, Japan] Suga Y., Arin M.J., Scott G., Goldsmith L.A., Magro C.M., Baden L.A., Baden H.P., Roop D.R.; "Hot spot mutations in keratin 2e suggest a correlation between genotype and phenotype in patients with ichthyosis bullosa of Siemens."; Exp. Dermatol. 9:11-15(2000).
[17]	VARIANT IBS ASP-192. DOI=10.1046/j.1523-1747.2000.00817.x; PubMed=10620137 [NCBI, ExPASy, EBI, Israel, Japan] Takizawa Y., Akiyama M., Nagashima M., Shimizu H.; "A novel asparagine-->aspartic acid mutation in the rod 1A domain in keratin 2e in a Japanese family with ichthyosis bullosa of Siemens."; J. Invest. Dermatol. 114:193-195(2000).
[18]	VARIANT IBS LYS-192. DOI=10.1046/j.1365-2133.2001.04327.x; PubMed=11531804 [NCBI, ExPASy, EBI, Israel, Japan] Whittock N.V., Ashton G.H.S., Griffiths W.A.D., Eady R.A.J., McGrath J.A.; "New mutations in keratin 1 that cause bullous congenital ichthyosiform erythroderma and keratin 2e that cause ichthyosis bullosa of Siemens."; Br. J. Dermatol. 145:330-335(2001).
[19]	VARIANTS IBS PRO-490 AND LYS-493. DOI=10.1111/j.1365-2133.2005.06598.x; PubMed=15949009 [NCBI, ExPASy, EBI, Israel, Japan] Akiyama M., Tsuji-Abe Y., Yanagihara M., Nakajima K., Kodama H., Yaosaka M., Abe M., Sawamura D., Shimizu H.; "Ichthyosis bullosa of Siemens: its correct diagnosis facilitated by molecular genetic testing."; Br. J. Dermatol. 152:1353-1356(2005).

Comments

FUNCTION: Probably contributes to terminal cornification. Associated with keratinocyte activation, proliferation and keratinization.
SUBUNIT: Heterotetramer of two type I and two type II keratins. Associates with KRT10 (By similarity).
INTERACTION:
Q00987:MDM2; NbExp=1; IntAct=EBI-1247312, EBI-389668;
TISSUE SPECIFICITY: 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.
DEVELOPMENTAL STAGE: 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.
DISEASE: Defects in KRT2 are a cause of ichthyosis bullosa of Siemens (IBS) [MIM:146800]. IBS is a 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.
MISCELLANEOUS: There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
SIMILARITY: Belongs to the intermediate filament family.
WEB RESOURCE: Name=Human Intermediate Filament Mutation Database; URL="http://www.interfil.org";.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=KRT2";.
WEB RESOURCE: Name=Wikipedia; Note=Keratin-2A entry; URL="http://en.wikipedia.org/wiki/Keratin_2A";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M99061; AAC83410.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF019084; AAB81946.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC096294; AAH96294.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC099643; AAH99643.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC099644; AAH99644.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

A44861; A44861.

NP_000414.2; -.

3D structure databases

HSSP

P08670; 1GK7. [HSSP ENTRY / PDB]

ModBase

P35908.

Protein-protein interaction databases

IntAct

P35908; -.

PTM databases

PhosphoSite

P35908; -.

Organism-specific databases

HIX0036877; -.

HGNC:6439; KRT2.

HPA006299; -.

146800; phenotype. [NCBI / EBI]
600194; gene. [NCBI / EBI]

Orphanet

455; Ichthyosis bullosa of Siemens.

GeneCards

P35908.

Gene expression databases

ArrayExpress

P35908; -.

CleanEx

HS_KRT2; -.

GermOnline

ENSG00000172867; Homo sapiens.

Ontologies

GO:0005813;	Cellular component: centrosome (inferred from direct assay from HPA).
GO:0005882;	Cellular component: intermediate filament (traceable author statement from ProtInc).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0005200;	Molecular function: structural constituent of cytoskeleton (traceable author statement from ProtInc).
GO:0031424;	Biological process: keratinization (inferred from direct assay from UniProtKB).
GO:0032980;	Biological process: keratinocyte activation (inferred from direct assay from UniProtKB).
GO:0051546;	Biological process: keratinocyte migration (inferred from direct assay from UniProtKB).
GO:0043616;	Biological process: keratinocyte proliferation (inferred from direct assay from UniProtKB).
QuickGo view.

Family and domain databases

InterPro

IPR016044; F.
IPR001664; IF.
IPR002957; Keratin_I.
IPR003054; Keratin_II.
Graphical view of domain structure.

PANTHER

PTHR23239; IF; 1.
PTHR23239:SF18; Keratin_II; 1.

Pfam

PF00038; Filament; 1.
Pfam graphical view of domain structure.

PRINTS

PR01248; TYPE1KERATIN.
PR01276; TYPE2KERATIN.

PS00226; IF; 1.

Proteomic databases

P35908; -.

Genome annotation databases

Ensembl

ENSG00000172867; Homo sapiens. [Contig view]

GeneID

3849; -.

KEGG

hsa:3849; -.

Phylogenomic databases

HOGENOM

P35908; -.

HOVERGEN

P35908; -.

Other

NextBio

15145; -.

SOURCE

KRT2; Homo sapiens.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Coiled coil; Disease mutation; Ichthyosis; Intermediate filament; Keratin; Phosphoprotein.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 645`	`645`	`Keratin, type II cytoskeletal 2 epidermal.`	`PRO_0000063715`
`REGION`	`1 183`	`183`	`Head.`
`REGION`	`184 493`	`310`	`Rod.`
`REGION`	`184 219`	`36`	`Coil 1A.`
`REGION`	`220 238`	`19`	`Linker 1.`
`REGION`	`239 330`	`92`	`Coil 1B.`
`REGION`	`331 354`	`24`	`Linker 12.`
`REGION`	`355 493`	`139`	`Coil 2.`
`REGION`	`494 645`	`152`	`Tail.`
`SITE`	`435 435`	`1`	`Stutter.`
`MOD_RES`	`62 62`		`Phosphoserine (By similarity).`
`VARIANT`	`187 187`	`1`	`Q -> P (in IBS).`	`VAR_003865`
`VARIANT`	`188 188`	`1`	`I -> N (in IBS).`	`VAR_010514`
`VARIANT`	`192 192`	`1`	`N -> D (in IBS).`	`VAR_010515`
`VARIANT`	`192 192`	`1`	`N -> K (in IBS).`	`VAR_017829`
`VARIANT`	`192 192`	`1`	`N -> Y (in IBS).`	`VAR_009185`
`VARIANT`	`471 471`	`1`	`E -> D (in IBS).`	`VAR_031082`
`VARIANT`	`471 471`	`1`	`E -> K (in IBS).`	`VAR_031083`
`VARIANT`	`482 482`	`1`	`E -> K (in IBS).`	`VAR_009186`
`VARIANT`	`482 482`	`1`	`E -> V (in IBS).`	`VAR_031084`
`VARIANT`	`483 483`	`1`	`I -> N (in IBS).`	`VAR_031085`
`VARIANT`	`485 485`	`1`	`T -> P (in IBS).`	`VAR_009187`
`VARIANT`	`490 490`	`1`	`L -> P (in IBS).`	`VAR_010516`
`VARIANT`	`493 493`	`1`	`E -> D (in IBS).`	`VAR_003866`
`VARIANT`	`493 493`	`1`	`E -> K (in IBS).`	`VAR_003867`
`VARIANT`	`494 494`	`1`	`E -> K (in IBS).`	`VAR_031086`
`CONFLICT`	`101 101`		`G -> S (in Ref. 3; AAH96294/AAH99643/AAH99644).`
`CONFLICT`	`105 110`		`Missing (in Ref. 3; AAH96294/AAH99643/AAH99644).`

Sequence information

Length: 645 AA [This is the length of the unprocessed precursor]

Molecular weight: 65865 Da [This is the MW of the unprocessed precursor]

CRC64: EE025A173E33409A [This is a checksum on the sequence]

        10         20         30         40         50         60 
MSCQISCKSR GRGGGGGGFR GFSSGSAVVS GGSRRSTSSF SCLSRHGGGG GGFGGGGFGS 

        70         80         90        100        110        120 
RSLVGLGGTK SISISVAGGG GGFGAAGGFG GRGGGFGGGS GFGGGSGFGG GSGFSGGGFG 

       130        140        150        160        170        180 
GGGFGGGRFG GFGGPGGVGG LGGPGGFGPG GYPGGIHEVS VNQSLLQPLN VKVDPEIQNV 

       190        200        210        220        230        240 
KAQEREQIKT LNNKFASFID KVRFLEQQNQ VLQTKWELLQ QMNVGTRPIN LEPIFQGYID 

       250        260        270        280        290        300 
SLKRYLDGLT AERTSQNSEL NNMQDLVEDY KKKYEDEINK RTAAENDFVT LKKDVDNAYM 

       310        320        330        340        350        360 
IKVELQSKVD LLNQEIEFLK VLYDAEISQI HQSVTDTNVI LSMDNSRNLD LDSIIAEVKA 

       370        380        390        400        410        420 
QYEEIAQRSK EEAEALYHSK YEELQVTVGR HGDSLKEIKI EISELNRVIQ RLQGEIAHVK 

       430        440        450        460        470        480 
KQCKNVQDAI ADAEQRGEHA LKDARNKLND LEEALQQAKE DLARLLRDYQ ELMNVKLALD 

       490        500        510        520        530        540 
VEIATYRKLL EGEECRMSGD LSSNVTVSVT SSTISSNVAS KAAFGGSGGR GSSSGGGYSS 

       550        560        570        580        590        600 
GSSSYGSGGR QSGSRGGSGG GGSISGGGYG SGGGSGGRYG SGGGSKGGSI SGGGYGSGGG 

       610        620        630        640 
KHSSGGGSRG GSSSGGGYGS GGGGSSSVKG SSGEAFGSSV TFSFR

P35908 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools