Reviewed, UniProtKB/Swiss-Prot P35908 (K22E_HUMAN)

Names and origin

Protein names

Recommended name:
    Keratin, type II cytoskeletal 2 epidermal
Alternative name(s):
    Cytokeratin-2e
      Short name=CK 2e
      Short name=K2e
      Short name=keratin-2

Gene names

Name:	KRT2
Synonyms:	KRT2A, KRT2E

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	645 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Probably contributes to terminal cornification. Associated with keratinocyte activation, proliferation and keratinization.
Subunit structure	Heterotetramer of two type I and two type II keratins. Associates with KRT10 By similarity.
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.
Involvement in 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).
Sequence similarities	Belongs to the intermediate filament family.

Ontologies

Keywords
Cellular component	Intermediate filament Keratin
Disease	Disease mutation Ichthyosis
Domain	Coiled coil
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	keratinization Ref.5 Inferred from direct assay. Source: UniProtKB keratinocyte activation Ref.5 Inferred from direct assay. Source: UniProtKB keratinocyte migration Inferred from direct assay. Source: UniProtKB keratinocyte proliferation Ref.5 Inferred from direct assay. Source: UniProtKB
Cellular component	intermediate filament Ref.1 Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from physical interaction. Source: IntAct structural constituent of cytoskeleton Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDM2	Q00987	1	EBI-1247312,EBI-389668

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 645	645	Keratin, type II cytoskeletal 2 epidermal
Regions
	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
Sites
	Site	435	1	Stutter
Amino acid modifications
	Modified residue	62	1	Phosphoserine By similarity
Natural variations
	Natural variant	187	1	Q → P in IBS.
	Natural variant	188	1	I → N in IBS.
	Natural variant	192	1	N → D in IBS.
	Natural variant	192	1	N → K in IBS.
	Natural variant	192	1	N → Y in IBS.
	Natural variant	471	1	E → D in IBS.
	Natural variant	471	1	E → K in IBS.
	Natural variant	482	1	E → K in IBS.
	Natural variant	482	1	E → V in IBS.
	Natural variant	483	1	I → N in IBS.
	Natural variant	485	1	T → P in IBS.
	Natural variant	490	1	L → P in IBS.
	Natural variant	493	1	E → D in IBS.
	Natural variant	493	1	E → K in IBS.
	Natural variant	494	1	E → K in IBS.
Experimental info
	Sequence conflict	101	1	G → S in AAH96294, AAH99643 and AAH99644. Ref.3
	Sequence conflict	105 – 110	6	Missing in AAH96294, AAH99643 and AAH99644. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P35908-1 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: EE025A173E33409A	FASTA	645	65,865
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of human cytokeratin 2, an epidermal cytoskeletal protein synthesized late during differentiation." Collin C., Moll R., Kubicka S., Ouhayoun J.-P., Franke W.W. Exp. Cell Res. 202:132-141(1992) [PubMed: 1380918] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Thigh epidermis.
[2]	"Genomic organization and fine mapping of the keratin 2e gene (KRT2E): K2e V1 domain polymorphism and novel mutations in ichthyosis bullosa of Siemens." 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. J. Invest. Dermatol. 111:817-821(1998) [PubMed: 9804344] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS IBS TYR-192 AND LYS-482.
[3]	"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].
[4]	"Ontogeny and regional variability of keratin 2e (K2e) in developing human fetal skin: a unique spatial and temporal pattern of keratin expression in development." Smith L.T., Underwood R.A., McLean W.H.I. Br. J. Dermatol. 140:582-591(1999) [PubMed: 10233306] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[5]	"Expression of keratin K2e in cutaneous and oral lesions: association with keratinocyte activation, proliferation, and keratinization." Bloor B.K., Tidman N., Leigh I.M., Odell E., Dogan B., Wollina U., Ghali L., Waseem A. Am. J. Pathol. 162:963-975(2003) [PubMed: 12598329] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[6]	"Ichthyosis bullosa of Siemens -- a disease involving keratin 2e." 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. J. Invest. Dermatol. 103:277-281(1994) [PubMed: 7521371] [Abstract] Cited for: VARIANT IBS LYS-493.
[7]	"Ichthyosis bullosa of Siemens is caused by mutations in the keratin 2e gene." 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. J. Invest. Dermatol. 103:286-289(1994) [PubMed: 8077693] [Abstract] Cited for: VARIANTS IBS PRO-187; PRO-490 AND LYS-493.
[8]	"Mutations in the rod domain of keratin 2e in patients with ichthyosis bullosa of Siemens." Rothnagel J.A., Traupe H., Wojcik S., Huber M., Hohl D., Pittelkow M.R., Saeki H., Ishibashi Y., Roop D.R. Nat. Genet. 7:485-490(1994) [PubMed: 7524919] [Abstract] Cited for: VARIANTS IBS ASP-493 AND LYS-493.
[9]	"A new keratin 2e mutation in ichthyosis bullosa of Siemens." Jones D.O., Watts C., Mills C., Sharpe G., Marks R., Bowden P.E. J. Invest. Dermatol. 108:354-356(1997) [PubMed: 9036938] [Abstract] Cited for: VARIANTS IBS LYS-493 AND LYS-494.
[10]	"A novel threonine-to-proline mutation at the end of 2B rod domain in the keratin 2e chain in ichthyosis bullosa of Siemens." Yang J.-M., Lee S., Bang H.-D., Kim W.-S., Lee E.-S., Steinert P.M. J. Invest. Dermatol. 109:116-118(1997) [PubMed: 9204966] [Abstract] Cited for: VARIANT IBS PRO-485.
[11]	"A glutamate to lysine mutation at the end of 2B rod domain of keratin 2e gene in ichthyosis bullosa of Siemens." 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. Acta Derm. Venereol. 78:417-419(1998) [PubMed: 9833038] [Abstract] Cited for: VARIANT IBS LYS-493.
[12]	"Ichthyosis bullosa of Siemens: report of a family with evidence of a keratin 2e mutation, and a review of the literature." Basarab T., Smith F.J., Jolliffe V.M., McLean W.H.I., Neill S., Rustin M.H., Eady R.A. Br. J. Dermatol. 140:689-695(1999) [PubMed: 10233323] [Abstract] Cited for: VARIANT IBS LYS-493.
[13]	"A novel mutation in the 1A domain of keratin 2e in ichthyosis bullosa of Siemens." Arin M.J., Longley M.A., Epstein E.H. Jr., Scott G., Goldsmith L.A., Rothnagel J.A., Roop D.R. J. Invest. Dermatol. 112:380-382(1999) [PubMed: 10084318] [Abstract] Cited for: VARIANT IBS ASN-188.
[14]	"Ichthyosis bullosa of Siemens resulting from a novel missense mutation near the helix termination motif of the keratin 2e gene." Moraru R., Cserhalmi-Friedman P.B., Grossman M.E., Schneiderman P., Christiano A.M. Clin. Exp. Dermatol. 24:412-415(1999) [PubMed: 10564334] [Abstract] Cited for: VARIANT IBS VAL-482.
[15]	"A novel mutation in the 2B domain of keratin 2e causing ichthyosis bullosa of Siemens." Irvine A.D., Smith F.J., Shum K.W., Williams H.C., McLean W.H.I. Clin. Exp. Dermatol. 25:648-651(2000) [PubMed: 11167982] [Abstract] Cited for: VARIANT IBS ASN-483.
[16]	"Hot spot mutations in keratin 2e suggest a correlation between genotype and phenotype in patients with ichthyosis bullosa of Siemens." Suga Y., Arin M.J., Scott G., Goldsmith L.A., Magro C.M., Baden L.A., Baden H.P., Roop D.R. Exp. Dermatol. 9:11-15(2000) [PubMed: 10688369] [Abstract] Cited for: VARIANTS IBS LYS-471 AND ASP-471.
[17]	"A novel asparagine-->aspartic acid mutation in the rod 1A domain in keratin 2e in a Japanese family with ichthyosis bullosa of Siemens." Takizawa Y., Akiyama M., Nagashima M., Shimizu H. J. Invest. Dermatol. 114:193-195(2000) [PubMed: 10620137] [Abstract] Cited for: VARIANT IBS ASP-192.
[18]	"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 IBS LYS-192.
[19]	"Ichthyosis bullosa of Siemens: its correct diagnosis facilitated by molecular genetic testing." Akiyama M., Tsuji-Abe Y., Yanagihara M., Nakajima K., Kodama H., Yaosaka M., Abe M., Sawamura D., Shimizu H. Br. J. Dermatol. 152:1353-1356(2005) [PubMed: 15949009] [Abstract] Cited for: VARIANTS IBS PRO-490 AND LYS-493.
+	Additional computationally mapped references.

Web resources

Human Intermediate Filament Mutation Database

GeneReviews

Wikipedia

Keratin-2A entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	M99061 mRNA. Translation: AAC83410.1. AF019084 Genomic DNA. Translation: AAB81946.1. BC096294 mRNA. Translation: AAH96294.1. BC099643 mRNA. Translation: AAH99643.1. BC099644 mRNA. Translation: AAH99644.1.
PIR	A44861.
RefSeq	NP_000414.2.
UniGene	Hs.707
3D structure databases
HSSP	HSSP built from PDB template 1GK7 based on UniProtKB P08670.
ModBase	Search...
Protein-protein interaction databases
IntAct	P35908.
PTM databases
PhosphoSite	P35908.
Proteomic databases
PeptideAtlas	P35908.
Genome annotation databases
Ensembl	ENSG00000172867. Homo sapiens. [Contig view]
GeneID	3849.
KEGG	hsa:3849.
Organism-specific databases
H-InvDB	HIX0036877.
HGNC	HGNC:6439. KRT2.
HPA	HPA006299.
MIM	146800. phenotype. 600194. gene.
Orphanet	455. Ichthyosis bullosa of Siemens.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P35908.
HOVERGEN	P35908.
Gene expression databases
ArrayExpress	P35908.
CleanEx	HS_KRT2.
GermOnline	ENSG00000172867. Homo sapiens.
Family and domain databases
InterPro	IPR016044. F. IPR001664. IF. IPR002957. Keratin_I. IPR003054. Keratin_II. [Graphical view]
PANTHER	PTHR23239. IF. 1 hit. PTHR23239:SF18. Keratin_II. 1 hit.
Pfam	PF00038. Filament. 1 hit. [Graphical view]
PRINTS	PR01248. TYPE1KERATIN. PR01276. TYPE2KERATIN.
PROSITE	PS00226. IF. 1 hit. [Graphical view]
ProDom	P35908. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

K22E_HUMAN

Accession

Primary (citable) accession number: P35908
Secondary accession number(s): Q4VAQ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	July 22, 2008
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)