P02538 (K2C6A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Keratin, type II cytoskeletal 6A

Alternative name(s):
Cytokeratin-6A
Short name=CK-6A
Cytokeratin-6D
Short name=CK-6D
Keratin-6A
Short name=K6A
Type-II keratin Kb6
Allergen=Hom s 5

Gene names

Name:	KRT6A
Synonyms:	K6A, KRT6D

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	564 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Subunit structure	Heterodimer of a type I and a type II keratin. KRT6 isomers associate with KRT16 and/or KRT17. Interacts with TCHP. Ref.6
Tissue specificity	Constitutively expressed in distinct types of epithelia such as those in oral mucosa, esophagus, papillae of tongue and hair follicle outer root sheath.
Involvement in disease	Pachyonychia congenita 1 (PC1) [MIM:167200]: An autosomal dominant ectodermal dysplasia characterized by hypertrophic nail dystrophy resulting in onchyogryposis (thickening and increase in curvature of the nail), palmoplantar keratoderma, follicular hyperkeratosis, and oral leukokeratosis. Hyperhidrosis of the hands and feet is usually present. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9
Allergenic properties	Causes an allergic reaction in human. Binds to IgE from atopic dermatitis (AD) patients. Identified as an IgE autoantigen in atopic dermatitis (AD) patients with severe skin manifestations.
Miscellaneous	There are at least six isoforms of human type II keratin-6 (K6), K6A being the most abundant representing about 77% of all forms found in epithelia. There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively).
Sequence similarities	Belongs to the intermediate filament family.

Ontologies

Keywords
Cellular component	Intermediate filament Keratin
Coding sequence diversity	Polymorphism
Disease	Allergen Disease mutation Ectodermal dysplasia Palmoplantar keratoderma
Domain	Coiled coil
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Non-traceable author statement Ref.1. Source: UniProtKB ectoderm development Traceable author statement Ref.8. Source: ProtInc positive regulation of cell proliferation Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	intermediate filament Traceable author statement PubMed 2410904. Source: ProtInc keratin filament Inferred from electronic annotation. Source: InterPro
Molecular_function	structural constituent of cytoskeleton Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CCDC85B	Q15834	2	EBI-702198,EBI-739674

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.4
	Chain	2 – 564	563	Keratin, type II cytoskeletal 6A		PRO_0000063731
Regions
	Region	2 – 162	161	Head
	Region	163 – 472	310	Rod
	Region	163 – 198	36	Coil 1A
	Region	199 – 217	19	Linker 1
	Region	218 – 309	92	Coil 1B
	Region	310 – 333	24	Linker 12
	Region	334 – 472	139	Coil 2
	Region	473 – 564	92	Tail
Sites
	Site	414	1	Stutter
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.4
Natural variations
	Natural variant	21	1	N → S. Ref.3 Corresponds to variant rs17845411 [ dbSNP | Ensembl ].		VAR_021264
	Natural variant	111	1	G → D. Corresponds to variant rs681063 [ dbSNP | Ensembl ].		VAR_035030
	Natural variant	171	1	Missing in PC1. Ref.8		VAR_003878
	Natural variant	174	1	F → V in PC1. Ref.9 Corresponds to variant rs28933087 [ dbSNP | Ensembl ].		VAR_017075
	Natural variant	469	1	L → R in PC1. Ref.9 Corresponds to variant rs57052654 [ dbSNP | Ensembl ].		VAR_017076
	Natural variant	472	1	E → K in PC1. Ref.9 Corresponds to variant rs60554162 [ dbSNP | Ensembl ].		VAR_017077
Experimental info
	Sequence conflict	192	1	E → D in AAB60696. Ref.1
	Sequence conflict	241	1	G → N in AAB60696. Ref.1
	Sequence conflict	249	1	F → L in AAB60696. Ref.1
	Sequence conflict	395	1	I → S in CAA24760. Ref.5
	Sequence conflict	404	1	N → S in AAB60696. Ref.1
	Sequence conflict	443	1	R → W in AAH69269. Ref.3
	Sequence conflict	486	1	I → V in AAB60696. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P02538 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 26708916C7DC923A	FASTA	564	60,045
	10 20 30 40 50 60 MASTSTTIRS HSSSRRGFSA NSARLPGVSR SGFSSVSVSR SRGSGGLGGA CGGAGFGSRS 70 80 90 100 110 120 LYGLGGSKRI SIGGGSCAIS GGYGSRAGGS YGFGGAGSGF GFGGGAGIGF GLGGGAGLAG 130 140 150 160 170 180 GFGGPGFPVC PPGGIQEVTV NQSLLTPLNL QIDPTIQRVR AEEREQIKTL NNKFASFIDK 190 200 210 220 230 240 VRFLEQQNKV LETKWTLLQE QGTKTVRQNL EPLFEQYINN LRRQLDSIVG ERGRLDSELR 250 260 270 280 290 300 GMQDLVEDFK NKYEDEINKR TAAENEFVTL KKDVDAAYMN KVELQAKADT LTDEINFLRA 310 320 330 340 350 360 LYDAELSQMQ THISDTSVVL SMDNNRNLDL DSIIAEVKAQ YEEIAQRSRA EAESWYQTKY 370 380 390 400 410 420 EELQVTAGRH GDDLRNTKQE IAEINRMIQR LRSEIDHVKK QCANLQAAIA DAEQRGEMAL 430 440 450 460 470 480 KDAKNKLEGL EDALQKAKQD LARLLKEYQE LMNVKLALDV EIATYRKLLE GEECRLNGEG 490 500 510 520 530 540 VGQVNISVVQ STVSSGYGGA SGVGSGLGLG GGSSYSYGSG LGVGGGFSSS SGRAIGGGLS 550 560 SVGGGSSTIK YTTTSSSSRK SYKH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of multiple human genes and cDNAs encoding highly related type II keratin 6 isoforms." Takahashi K., Paladini R.D., Coulombe P.A. J. Biol. Chem. 270:18581-18592(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Skin.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-21. Tissue: Brain, Ovary and Pancreas.
[4]	Bienvenut W.V., Vousden K.H., Lukashchuk N., Lilla S., Lange E., Sumpton D.P. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-9; 31-40; 43-86; 169-204; 208-232; 241-347; 350-369; 379-386; 425-436; 447-475 AND 534-550, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[5]	"The cDNA sequence of a type II cytoskeletal keratin reveals constant and variable structural domains among keratins." Hanukoglu I., Fuchs E. Cell 33:915-924(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 208-564.
[6]	"Identification of trichoplein, a novel keratin filament-binding protein." Nishizawa M., Izawa I., Inoko A., Hayashi Y., Nagata K., Yokoyama T., Usukura J., Inagaki M. J. Cell Sci. 118:1081-1090(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TCHP.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"Mutation of a type II keratin gene (K6a) in pachyonychia congenita." Bowden P.E., Haley J.L., Kansky A., Rothnagel J.A., Jones D.O., Turner R.J. Nat. Genet. 10:363-365(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PC1 ASN-171 DEL.
[9]	"Novel and recurrent mutations in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia congenita." Terrinoni A., Smith F.J.D., Didona B., Canzona F., Paradisi M., Huber M., Hohl D., David A., Verloes A., Leigh I.M., Munro C.S., Melino G., McLean W.H.I. J. Invest. Dermatol. 117:1391-1396(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PC1 VAL-174; ARG-469 AND LYS-472.
+	Additional computationally mapped references.

Web resources

Human Intermediate Filament Mutation Database

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	L42583 , L42575, L42576, L42577, L42578, L42579, L42580, L42581 Genomic DNA. Translation: AAC41767.1. AH005420 Genomic DNA. Translation: AAB60696.1. BT006899 mRNA. Translation: AAP35545.1. BC008807 mRNA. Translation: AAH08807.1. BC014152 mRNA. Translation: AAH14152.1. BC069269 mRNA. Translation: AAH69269.1. BC125058 mRNA. Translation: AAI25059.1. BC139753 mRNA. Translation: AAI39754.1. V01516 Genomic DNA. Translation: CAA24760.1.
IPI	IPI00300725.
PIR	KRHUEA. A57398. I61769.
RefSeq	NP_005545.1. NM_005554.3.
UniGene	Hs.700779.
3D structure databases
ProteinModelPortal	P02538.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-533N.
IntAct	P02538. 11 interactions.
STRING	9606.ENSP00000369317.
Protein family/group databases
Allergome	3326. Hom s 5.0101. 415. Hom s 5.
PTM databases
PhosphoSite	P02538.
Polymorphism databases
DMDM	1346344.
Proteomic databases
PaxDb	P02538.
PeptideAtlas	P02538.
PRIDE	P02538.
Protocols and materials databases
DNASU	3853.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000330722; ENSP00000369317; ENSG00000205420.
GeneID	3853.
KEGG	hsa:3853.
UCSC	uc001sam.3. human.
Organism-specific databases
CTD	3853.
GeneCards	GC12M052880.
HGNC	HGNC:6443. KRT6A.
HPA	HPA045697.
MIM	148041. gene. 167200. phenotype.
neXtProt	NX_P02538.
Orphanet	2309. Pachyonychia congenita.
PharmGKB	PA30231.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG315845.
HOGENOM	HOG000230976.
HOVERGEN	HBG013015.
InParanoid	P02538.
KO	K07605.
OMA	MQDQVED.
Gene expression databases
Bgee	P02538.
CleanEx	HS_KRT6A.
Genevestigator	P02538.
GermOnline	ENSG00000205420. Homo sapiens.
Family and domain databases
InterPro	IPR016044. F. IPR001664. IF. IPR018039. Intermediate_filament_CS. IPR003054. Keratin_II. [Graphical view]
PANTHER	PTHR23239. PTHR23239. 1 hit. PTHR23239:SF18. PTHR23239:SF18. 1 hit.
Pfam	PF00038. Filament. 1 hit. [Graphical view]
PRINTS	PR01276. TYPE2KERATIN.
PROSITE	PS00226. IF. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	KRT6A. human.
GenomeRNAi	3853.
NextBio	15161.
SOURCE	Search...

Entry information

Entry name

K2C6A_HUMAN

Accession

Primary (citable) accession number: P02538
Secondary accession number(s): A4QPC1 , P48667, Q08AR4, Q6NT67, Q96CL4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 139 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.