Reviewed, UniProtKB/Swiss-Prot P35527 (K1C9_HUMAN)

Names and origin

Protein names

Recommended name:
    Keratin, type I cytoskeletal 9
Alternative name(s):
    Cytokeratin-9
      Short name=CK-9
      Short name=Keratin-9
      Short name=K9

Gene names

Name:

KRT9

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

General annotation (Comments)

Function	May serve an important special function either in the mature palmar and plantar skin tissue or in the morphogenetic program of the formation of these tissues. Plays a role in keratin filament assembly.
Subunit structure	Heterotetramer of two type I and two type II keratins.
Tissue specificity	Expressed in the terminally differentiated epidermis of palms and soles.
Induction	Induced by intrinsic regulatory mechanisms and by extrinsic signals from a subset of dermal palmoplantar fibroblasts.
Involvement in disease	Defects in KRT9 are a cause of palmoplantar keratoderma epidermolytic (EPPK) [MIM:144200]; also abbreviated EHPPK. EPPK is a dermatological disorder characterized by diffuse thickening of the epidermis on the entire surface of palms and soles sharply bordered with erythematous margins. Knuckle pads are sometimes associated with EPPK [MIM:149100]. Knuckle pads consist of an autosomal dominant trait, in which thick pads of skin appear over the proximal phalangeal joints.
Miscellaneous	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.
Caution	Was originally (Ref.6) thought to be a 60 kDa chain of placental scatter protein.

Ontologies

Keywords
Cellular component	Intermediate filament Keratin
Disease	Disease mutation
Domain	Coiled coil
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	intermediate filament organization Ref.7 Inferred from mutant phenotype. Source: UniProtKB skin development Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: IntAct structural constituent of cytoskeleton Ref.4 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDM2	Q00987	1	EBI-356382,EBI-389668

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 623	623	Keratin, type I cytoskeletal 9
Regions
	Region	1 – 152	152	Head
	Region	153 – 461	309	Rod
	Region	153 – 188	36	Coil 1A
	Region	189 – 207	19	Linker 1
	Region	208 – 299	92	Coil 1B
	Region	300 – 322	23	Linker 12
	Region	323 – 461	139	Coil 2
	Region	462 – 623	162	Tail
	Compositional bias	15 – 26	12	Poly-Gly
Natural variations
	Natural variant	157	1	M → R in EPPK.
	Natural variant	157	1	M → T in EPPK.
	Natural variant	157	1	M → V in EPPK.
	Natural variant	160	1	L → F in EPPK; with knuckle pads.
	Natural variant	160	1	L → V in EPPK.
	Natural variant	161	1	N → H in EPPK.
	Natural variant	161	1	N → I in EPPK.
	Natural variant	161	1	N → K in EPPK.
	Natural variant	161	1	N → S in EPPK.
	Natural variant	161	1	N → Y in EPPK.
	Natural variant	163	1	R → P in EPPK.
	Natural variant	163	1	R → Q in EPPK.
	Natural variant	163	1	R → W in EPPK.
	Natural variant	167	1	Y → WL in EPPK.
	Natural variant	168	1	L → S in EPPK.
	Natural variant	171	1	V → M in EPPK.
	Natural variant	172	1	Q → P in EPPK.
	Natural variant	458	1	L → F in EPPK.
Experimental info
	Mutagenesis	163	1	R → QHA: Leads to aggregate formation
	Sequence conflict	12 – 13	2	SR → T in AAC60619. Ref.1
	Sequence conflict	12 – 13	2	SR → T in CAA52924. Ref.2
	Sequence conflict	157 – 170	14	MQELN…SYLDK → HLGAGSTPITASQP in AAI21171. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P35527-1 [UniParc]. Last modified November 8, 2005. Version 2. Checksum: DE1D5A462FF96D10	FASTA	623	62,129
	10 20 30 40 50 60 MSCRQFSSSY LSRSGGGGGG GLGSGGSIRS SYSRFSSSGG RGGGGRFSSS SGYGGGSSRV 70 80 90 100 110 120 CGRGGGGSFG YSYGGGSGGG FSASSLGGGF GGGSRGFGGA SGGGYSSSGG FGGGFGGGSG 130 140 150 160 170 180 GGFGGGYGSG FGGLGGFGGG AGGGDGGILT ANEKSTMQEL NSRLASYLDK VQALEEANND 190 200 210 220 230 240 LENKIQDWYD KKGPAAIQKN YSPYYNTIDD LKDQIVDLTV GNNKTLLDID NTRMTLDDFR 250 260 270 280 290 300 IKFEMEQNLR QGVDADINGL RQVLDNLTME KSDLEMQYET LQEELMALKK NHKEEMSQLT 310 320 330 340 350 360 GQNSGDVNVE INVAPGKDLT KTLNDMRQEY EQLIAKNRKD IENQYETQIT QIEHEVSSSG 370 380 390 400 410 420 QEVQSSAKEV TQLRHGVQEL EIELQSQLSK KAALEKSLED TKNRYCGQLQ MIQEQISNLE 430 440 450 460 470 480 AQITDVRQEI ECQNQEYSLL LSIKMRLEKE IETYHNLLEG GQEDFESSGA GKIGLGGRGG 490 500 510 520 530 540 SGGSYGRGSR GGSGGSYGGG GSGGGYGGGS GSRGGSGGSY GGGSGSGGGS GGGYGGGSGG 550 560 570 580 590 600 GHSGGSGGGH SGGSGGNYGG GSGSGGGSGG GYGGGSGSRG GSGGSHGGGS GFGGESGGSY 610 620 GGGEEASGSG GGYGGGSGKS SHS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular characterization of the body site-specific human epidermal cytokeratin 9: cDNA cloning, amino acid sequence, and tissue specificity of gene expression." Langbein L., Heid H.W., Moll I., Franke W.W. Differentiation 55:57-72(1993) [PubMed: 7507869] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, TISSUE SPECIFICITY. Tissue: Foot sole tissue.
[2]	"Keratin 9 gene mutations in epidermolytic palmoplantar keratoderma (EPPK)." Reis A., Hennies H.-C., Langbein L., Digweed M., Mischke D., Dreschler M., Schroek E., Royer-Pokora B., Franke W.W., Sperling K., Kuester W. Nat. Genet. 6:174-179(1994) [PubMed: 7512862] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS EPPK LYS-161; GLN-163 AND TRP-163.
[3]	Bienvenut W.V. Submitted (AUG-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 14-29, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[4]	"Keratin 9 point mutation in the pedigree of epidermolytic hereditary palmoplantar keratoderma perturbs keratin intermediate filament network formation." Kobayashi S., Tanaka T., Matsuyoshi N., Imamura S. FEBS Lett. 386:149-155(1996) [PubMed: 8647270] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 147-372, VARIANT EPPK GLN-163.
[5]	"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] OF 157-623.
[6]	"Human placenta contains an epithelial scatter protein." Rosen E.M., Meromsky L., Romero R., Setter E., Goldberg I. Biochem. Biophys. Res. Commun. 168:1082-1088(1990) [PubMed: 2140676] [Abstract] Cited for: PROTEIN SEQUENCE OF 450-466.
[7]	"Demonstration of the pathogenic effect of point mutated keratin 9 in vivo." Kobayashi S., Kore-eda S., Tanaka T. FEBS Lett. 447:39-43(1999) [PubMed: 10218578] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ARG-163.
[8]	"Regulation of keratin 9 in nonpalmoplantar keratinocytes by palmoplantar fibroblasts through epithelial-mesenchymal interactions." Yamaguchi Y., Itami S., Tarutani M., Hosokawa K., Miura H., Yoshikawa K. J. Invest. Dermatol. 112:483-488(1999) [PubMed: 10201533] [Abstract] Cited for: INDUCTION.
[9]	"Keratin 9 gene mutational heterogeneity in patients with epidermolytic palmoplantar keratoderma." Hennies H.-C., Zehender D., Kunze J., Kuester W., Reis A. Hum. Genet. 93:649-654(1994) [PubMed: 7516304] [Abstract] Cited for: VARIANTS EPPK VAL-157 AND PRO-172.
[10]	"Mutations of keratin 9 in two families with palmoplantar epidermolytic hyperkeratosis." Bonifas J.M., Matsumura K., Chen M.A., Berth-Jones J., Hutchinson P.E., Zloczower M., Fritsch P.O., Epstein E.H. Jr. J. Invest. Dermatol. 103:474-477(1994) [PubMed: 7523529] [Abstract] Cited for: VARIANT EPPK SER-161.
[11]	"Epidermolytic palmoplantar keratoderma cosegregates with a keratin 9 mutation in a pedigree with breast and ovarian cancer." Torchard D., Blanchet-Bardon C., Serova O., Langbein L., Narod S., Janin N., Goguel A.F., Bernheim A., Franke W.W., Lenoir G.M., Feunteun J. Nat. Genet. 6:106-110(1994) [PubMed: 7511021] [Abstract] Cited for: VARIANT EPPK TYR-161.
[12]	"Mutations in the 1A domain of keratin 9 in patients with epidermolytic palmoplantar keratoderma." Rothnagel J.A., Wojcik S., Liefer K.M., Dominey A.M., Huber M., Hohl D., Roop D.R. J. Invest. Dermatol. 104:430-433(1995) [PubMed: 7532199] [Abstract] Cited for: VARIANTS EPPK TRP-163 AND SER-168.
[13]	"A novel mutation of a leucine residue in coil 1A of keratin 9 in epidermolytic palmoplantar keratoderma." Endo H., Hatamochi A., Shinkai H. J. Invest. Dermatol. 109:113-115(1997) [PubMed: 9204965] [Abstract] Cited for: VARIANT EPPK VAL-160.
[14]	"Mutations in keratin K9 in kindreds with epidermolytic palmoplantar keratoderma and epidemiology in Northern Ireland." Covello S.P., Irvine A.D., McKenna K.E., Munro C.S., Nevin N.C., Smith F.J.D., Uitto J., McLean W.H.I. J. Invest. Dermatol. 111:1207-1209(1998) [PubMed: 9856842] [Abstract] Cited for: VARIANTS EPPK THR-157; VAL-157 AND GLN-163.
[15]	"Keratin 9 mutations in the coil 1A region in epidermolytic palmoplantar keratoderma." Szalai S., Szalai C., Becker K., Torok E. Pediatr. Dermatol. 16:430-435(1999) [PubMed: 10632938] [Abstract] Cited for: VARIANTS EPPK GLN-163 AND STOP-170.
[16]	"Epidermolytic palmoplantar keratoderma in a Hispanic kindred resulting from a mutation in the keratin 9 gene." Warmuth I., Cserhalmi-Friedman P.B., Schneiderman P., Grossman M.E., Christiano A.M. Clin. Exp. Dermatol. 25:244-246(2000) [PubMed: 10844507] [Abstract] Cited for: VARIANT EPPK TRP-163.
[17]	"Epidermolytic palmoplantar keratoderma of Vorner: re-evaluation of Vorner's original family and identification of a novel keratin 9 mutation." Kuster W., Reis A., Hennies H.C. Arch. Dermatol. Res. 294:268-272(2002) [PubMed: 12192490] [Abstract] Cited for: VARIANT EPPK ILE-161.
[18]	"Diagnosis and confirmation of epidermolytic palmoplantar keratoderma by the identification of mutations in keratin 9 using denaturing high-performance liquid chromatography." Rugg E.L., Common J.E., Wilgoss A., Stevens H.P., Buchan J., Leigh I.M., Kelsell D.P. Br. J. Dermatol. 146:952-957(2002) [PubMed: 12072061] [Abstract] Cited for: VARIANTS EPPK VAL-157; TRP-163; GLN-163 AND MET-171.
[19]	"Novel N160I mutation of keratin 9 in a large pedigree from Hungary with epidermolytic palmoplantar keratoderma." Csikos M., Hollo P., Becker K., Racz E., Horvath A., Karpati S. Acta Derm. Venereol. 83:303-305(2003) [PubMed: 12926810] [Abstract] Cited for: VARIANT EPPK ILE-161.
[20]	"A novel mutation of keratin 9 in epidermolytic palmoplantar keratoderma combined with knuckle pads." Lu Y., Guo C., Liu Q., Zhang X., Cheng L., Li J., Chen B., Gao G., Zhou H., Guo Y., Li Y., Gong Y. Am. J. Med. Genet. A 120:345-349(2003) [PubMed: 12838553] [Abstract] Cited for: VARIANT EPPK PHE-160.
[21]	"Keratin 9 gene mutations in five Korean families with epidermolytic palmoplantar keratoderma." Lee J.-H., Ahn K.-S., Lee C.-H., Youn S.-J., Kim J.-W., Lee D.-Y., Lee E.-S., Steinert P.M., Yang J.-M. Exp. Dermatol. 12:876-881(2003) [PubMed: 14675368] [Abstract] Cited for: VARIANTS EPPK HIS-161; SER-161 AND TRP-163.
[22]	"A novel mutation of keratin 9 in a large Chinese family with epidermolytic palmoplantar keratoderma." He X.-H., Zhang X.-N., Mao W., Chen H.-P., Xu L.-R., Chen H., He X.-L., Le Y.-P. Br. J. Dermatol. 150:647-651(2004) [PubMed: 15099359] [Abstract] Cited for: VARIANT EPPK TYR-167 DEL TRP-LEU INS.
[23]	"A novel keratin 9 gene mutation (Asn160His) in a Taiwanese family with epidermolytic palmoplantar keratoderma." Lin J.-H., Lin M.-H., Yang M.-H., Chao S.-C. Clin. Exp. Dermatol. 29:308-310(2004) [PubMed: 15115518] [Abstract] Cited for: VARIANT EPPK HIS-161.
[24]	"A novel mutation of keratin 9 gene (R162P) in a Japanese family with epidermolytic palmoplantar keratoderma." Kon A., Itagaki K., Yoneda K., Takagaki K. Arch. Dermatol. Res. 296:375-378(2005) [PubMed: 15605275] [Abstract] Cited for: VARIANT EPPK PRO-163.
[25]	"L457F missense mutation within the 2B rod domain of keratin 9 in a Japanese family with epidermolytic palmoplantar keratoderma." Kon A., Ito N., Kudo Y., Nomura K., Yoneda K., Hanada K., Hashimoto I., Takagaki K. Br. J. Dermatol. 155:624-626(2006) [PubMed: 16911293] [Abstract] Cited for: VARIANT EPPK PHE-458.
[26]	"A novel keratin 9 gene mutation (Met156Arg) in a Japanese patient with epidermolytic palmoplantar keratoderma." Shimazu K., Tsunemi Y., Hattori N., Saeki H., Komine M., Adachi M., Tamaki K. Int. J. Dermatol. 45:1128-1130(2006) [PubMed: 16961539] [Abstract] Cited for: VARIANT EPPK ARG-157.
+	Additional computationally mapped references.

Web resources

Human Intermediate Filament Mutation Database

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	Z29074 mRNA. Translation: CAA82315.1. S69510 mRNA. Translation: AAC60619.1. X75015 Genomic DNA. Translation: CAA52924.1. AB001594 mRNA. Translation: BAA19418.1. BC121170 mRNA. Translation: AAI21171.1.
PIR	I37984.
UniGene	Hs.654569
3D structure databases
HSSP	HSSP built from PDB template 1GK7 based on UniProtKB P08670.
ModBase	Search...
Protein-protein interaction databases
IntAct	P35527.
PTM databases
PhosphoSite	P35527.
2-D gel databases
DOSAC-COBS-2DPAGE	P35527.
Proteomic databases
PeptideAtlas	P35527.
Genome annotation databases
Ensembl	ENSG00000171403. Homo sapiens. [Contig view]
Organism-specific databases
H-InvDB	HIX0039018.
HGNC	HGNC:6447. KRT9.
HPA	HPA007261. HPA009673.
MIM	144200. phenotype. 149100. phenotype. 607606. gene.
Orphanet	2199. Hyperkeratosis palmoplantar, localized, epidermolytic.
PharmGKB	PA30235.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P35527.
HOVERGEN	P35527.
Gene expression databases
ArrayExpress	P35527.
CleanEx	HS_KRT9.
GermOnline	ENSG00000171403. Homo sapiens.
Family and domain databases
InterPro	IPR016044. F. IPR001664. IF. IPR002957. Keratin_I. [Graphical view]
PANTHER	PTHR23239. IF. 1 hit.
Pfam	PF00038. Filament. 1 hit. [Graphical view]
PRINTS	PR01248. TYPE1KERATIN.
PROSITE	PS00226. IF. 1 hit. [Graphical view]
ProDom	P35527. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

K1C9_HUMAN

Accession

Primary (citable) accession number: P35527
Secondary accession number(s): O00109, Q0IJ47, Q14665

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	November 8, 2005
Last modified:	September 2, 2008
This is version 82 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)