Q99456 (K1C12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Keratin, type I cytoskeletal 12

Alternative name(s):
Cytokeratin-12
Short name=CK-12
Keratin-12
Short name=K12

Gene names

Name:

KRT12

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	494 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a unique role in maintaining the normal corneal epithelial function. Together with KRT3, essential for the maintenance of corneal epithelium integrity By similarity.
Subunit structure	Heterotetramer of two type I and two type II keratins. Keratin-3 associates with keratin-12.
Tissue specificity	Cornea specific. Ref.1
Involvement in disease	Corneal dystrophy, Meesmann (MECD) [MIM:122100]: An autosomal dominant corneal disease characterized by fragility of the anterior corneal epithelium. Patients are usually asymptomatic until adulthood when rupture of the corneal microcysts may cause erosions, producing clinical symptoms such as photophobia, contact lens intolerance and intermittent diminution of visual acuity. Rarely, subepithelial scarring causes irregular corneal astigmatism and permanent visual impairment. Histological examination shows a disorganized and thickened epithelium with widespread cytoplasmic vacuolation and numerous small, round, debris-laden intraepithelial cysts. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.3 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
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
Coding sequence diversity	Polymorphism
Disease	Corneal dystrophy Disease mutation
Domain	Coiled coil
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cornea development in camera-type eye Inferred from electronic annotation. Source: Compara epithelium development Inferred from electronic annotation. Source: Compara visual perception Traceable author statement Ref.8. Source: ProtInc
Cellular_component	intermediate filament Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	structural molecule activity Non-traceable author statement Ref.8. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 494	494	Keratin, type I cytoskeletal 12		PRO_0000063644
Regions
	Region	1 – 124	124	Head
	Region	125 – 435	311	Rod
	Region	125 – 160	36	Coil 1A
	Region	164 – 182	19	Linker 1
	Region	183 – 274	92	Coil 1B
	Region	275 – 297	23	Linker 12
	Region	298 – 435	138	Coil 2
	Region	436 – 494	59	Tail
	Compositional bias	28 – 123	96	Gly-rich
Natural variations
	Natural variant	15	1	P → S. Corresponds to variant rs11650915 [ dbSNP | Ensembl ].		VAR_049783
	Natural variant	20	1	R → W. Ref.3 Corresponds to variant rs17566772 [ dbSNP | Ensembl ].		VAR_009547
	Natural variant	129	1	M → T in MECD. Ref.3 Ref.13 Corresponds to variant rs28936695 [ dbSNP | Ensembl ].		VAR_013126
	Natural variant	130	1	Q → P in MECD. Ref.9 Corresponds to variant rs58864803 [ dbSNP | Ensembl ].		VAR_013127
	Natural variant	135	1	R → G in MECD. Ref.2 Corresponds to variant rs58410481 [ dbSNP | Ensembl ].		VAR_008526
	Natural variant	135	1	R → I in MECD. Ref.2		VAR_008525
	Natural variant	135	1	R → S in MECD. Ref.11 Corresponds to variant rs61282718 [ dbSNP | Ensembl ].		VAR_031394
	Natural variant	135	1	R → T in MECD. Ref.3 Ref.8 Corresponds to variant rs57218384 [ dbSNP | Ensembl ].		VAR_003834
	Natural variant	137	1	A → P in MECD. Ref.10 Corresponds to variant rs58038639 [ dbSNP | Ensembl ].		VAR_031395
	Natural variant	140	1	L → R in MECD. Ref.2 Corresponds to variant rs58918655 [ dbSNP | Ensembl ].		VAR_008527
	Natural variant	143	1	V → L in MECD. Ref.8 Corresponds to variant rs58343600 [ dbSNP | Ensembl ].		VAR_003835
	Natural variant	399	1	L → LISNLEAQLL in MECD.		VAR_031396
	Natural variant	426	1	I → S in MECD. Ref.13 Corresponds to variant rs59350319 [ dbSNP | Ensembl ].		VAR_031397
	Natural variant	429	1	Y → C in MECD. Ref.12 Corresponds to variant rs59202432 [ dbSNP | Ensembl ].		VAR_031398
	Natural variant	429	1	Y → D in MECD. Ref.2 Corresponds to variant rs58162394 [ dbSNP | Ensembl ].		VAR_008528

Sequences

	Sequence		Length	Mass (Da)
	Q99456 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 75C981380532B682	FASTA	494	53,511
	10 20 30 40 50 60 MDLSNNTMSL SVRTPGLSRR LSSQSVIGRP RGMSASSVGS GYGGSAFGFG ASCGGGFSAA 70 80 90 100 110 120 SMFGSSSGFG GGSGSSMAGG LGAGYGRALG GGSFGGLGMG FGGSPGGGSL GILSGNDGGL 130 140 150 160 170 180 LSGSEKETMQ NLNDRLASYL DKVRALEEAN TELENKIREW YETRGTGTAD ASQSDYSKYY 190 200 210 220 230 240 PLIEDLRNKI ISASIGNAQL LLQIDNARLA AEDFRMKYEN ELALRQGVEA DINGLRRVLD 250 260 270 280 290 300 ELTLTRTDLE MQIESLNEEL AYMKKNHEDE LQSFRVGGPG EVSVEMDAAP GVDLTRLLND 310 320 330 340 350 360 MRAQYETIAE QNRKDAEAWF IEKSGELRKE ISTNTEQLQS SKSEVTDLRR AFQNLEIELQ 370 380 390 400 410 420 SQLAMKKSLE DSLAEAEGDY CAQLSQVQQL ISNLEAQLLQ VRADAERQNV DHQRLLNVKA 430 440 450 460 470 480 RLELEIETYR RLLDGEAQGD GLEESLFVTD SKSQAQSTDS SKDPTKTRKI KTVVQEMVNG 490 EVVSSQVQEI EELM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A gene expression profile of human corneal epithelium and the isolation of human keratin 12 cDNA." Nishida K., Adachi W., Shimizu-Matsumoto A., Kinoshita S., Mizuno K., Matsubara K., Okubo K. Invest. Ophthalmol. Vis. Sci. 37:1800-1809(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Cornea.
[2]	"Isolation and chromosomal localization of a cornea-specific human keratin 12 gene and detection of four mutations in Meesmann corneal epithelial dystrophy." Nishida K., Honma Y., Dota A., Kawasaki S., Adachi W., Nakamura T., Quantock A.J., Hosotani H., Yamamoto S., Okada M., Shimomura Y., Kinoshita S. Am. J. Hum. Genet. 61:1268-1275(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MECD GLY-135; ILE-135; ARG-140 AND ASP-429.
[3]	"Molecular genetics of Meesmann's corneal dystrophy: ancestral and novel mutations in keratin 12 (K12) and complete sequence of the human KRT12 gene." Corden L.D., Swensson O., Swensson B., Smith F.J.D., Rochels R., Uitto J., McLean W.H.I. Exp. Eye Res. 70:41-49(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS MECD THR-129 AND THR-135, VARIANT TRP-20.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-31. Tissue: Platelet.
[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]	"Mutations in cornea-specific keratin K3 or K12 genes cause Meesmann's corneal dystrophy." Irvine A.D., Corden L.D., Swensson O., Swensson B., Moore J.E., Frazer D.G., Smith F.J.D., Knowlton R.G., Christophers E., Rochels R., Uitto J., McLean W.H.I. Nat. Genet. 16:184-187(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MECD THR-135 AND LEU-143.
[9]	"A novel keratin 12 mutation in a German kindred with Meesmann's corneal dystrophy." Corden L.D., Swensson O., Swensson B., Rochels R., Wannke B., Thiel H.J., McLean W.H.I. Br. J. Ophthalmol. 84:527-530(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MECD PRO-130.
[10]	"Heterozygous Ala137Pro mutation in keratin 12 gene found in Japanese with Meesmann's corneal dystrophy." Takahashi K., Takahashi K., Murakami A., Okisaka S., Kimura T., Kanai A. Jpn. J. Ophthalmol. 46:673-674(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MECD PRO-137.
[11]	"A novel arginine substitution mutation in 1A domain and a novel 27 bp insertion mutation in 2B domain of keratin 12 gene associated with Meesmann's corneal dystrophy." Yoon M.K., Warren J.F., Holsclaw D.S., Gritz D.C., Margolis T.P. Br. J. Ophthalmol. 88:752-756(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MECD SER-135 AND ILE-SER-ASN-LEU-GLU-ALA-GLN-LEU-LEU-399 INS.
[12]	"Novel mutations in the helix termination motif of keratin 3 and keratin 12 in 2 Taiwanese families with Meesmann corneal dystrophy." Chen Y.T., Tseng S.H., Chao S.C. Cornea 24:928-932(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MECD CYS-429.
[13]	"Meesmann corneal dystrophy (MECD): report of 2 families and a novel mutation in the cornea specific keratin 12 (KRT12) gene." Nichini O., Manzi V., Munier F.L., Schorderet D.F. Ophthalmic Genet. 26:169-173(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MECD THR-129 AND SER-426.
+	Additional computationally mapped references.

Web resources

Human Intermediate Filament Mutation Database

Wikipedia

Keratin-12 entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	D78367 mRNA. Translation: BAA11376.1. AB007119 Genomic DNA. Translation: BAA25063.1. AF137286 Genomic DNA. Translation: AAF61432.1. AK313747 mRNA. Translation: BAG36487.1. CH471152 Genomic DNA. Translation: EAW60685.1.
IPI	IPI00015309.
RefSeq	NP_000214.1. NM_000223.3.
UniGene	Hs.66739.
3D structure databases
ProteinModelPortal	Q99456.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000251643.
PTM databases
PhosphoSite	Q99456.
Polymorphism databases
DMDM	2497269.
Proteomic databases
PaxDb	Q99456.
PeptideAtlas	Q99456.
PRIDE	Q99456.
Protocols and materials databases
DNASU	3859.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000251643; ENSP00000251643; ENSG00000187242. ENST00000572470; ENSP00000459559; ENSG00000263243.
GeneID	3859.
KEGG	hsa:3859.
UCSC	uc002hvk.2. human.
Organism-specific databases
CTD	3859.
GeneCards	GC17M039017.
HGNC	HGNC:6414. KRT12.
MIM	122100. phenotype. 601687. gene.
neXtProt	NX_Q99456.
Orphanet	98954. Meesmann corneal dystrophy.
PharmGKB	PA30201.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG148849.
HOGENOM	HOG000230975.
HOVERGEN	HBG013015.
InParanoid	Q99456.
KO	K07604.
OMA	QNDYSKY.
OrthoDB	EOG4P8FJH.
PhylomeDB	Q99456.
Gene expression databases
Bgee	Q99456.
CleanEx	HS_KRT12.
Genevestigator	Q99456.
GermOnline	ENSG00000187242. Homo sapiens.
Family and domain databases
InterPro	IPR016044. F. IPR001664. IF. IPR018039. Intermediate_filament_CS. IPR002957. Keratin_I. [Graphical view]
PANTHER	PTHR23239. PTHR23239. 1 hit.
Pfam	PF00038. Filament. 1 hit. [Graphical view]
PRINTS	PR01248. TYPE1KERATIN.
PROSITE	PS00226. IF. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	KRT12. human.
GenomeRNAi	3859.
NextBio	15185.
SOURCE	Search...

Entry information

Entry name

K1C12_HUMAN

Accession

Primary (citable) accession number: Q99456
Secondary accession number(s): B2R9E0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 115 of the entry and version 1 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.