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Q99456 (K1C12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Keratin, type I cytoskeletal 12
Alternative name(s):
Cytokeratin-12
Short name=CK-12
Keratin-12
Short name=K12
Gene names
Name:KRT12
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length494 AA.
Sequence statusComplete.
Protein existenceEvidence 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 componentIntermediate filament
Keratin
   Coding sequence diversityPolymorphism
   DiseaseCorneal dystrophy
Disease mutation
   DomainCoiled coil
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processvisual perception

Traceable author statement Ref.8. Source: ProtInc

   Cellular_componentextracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

intermediate filament

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionstructural molecule activity

Non-traceable author statement Ref.8. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 494494Keratin, type I cytoskeletal 12
PRO_0000063644

Regions

Region1 – 124124Head
Region125 – 435311Rod
Region125 – 16036Coil 1A
Region164 – 18219Linker 1
Region183 – 27492Coil 1B
Region275 – 29723Linker 12
Region298 – 435138Coil 2
Region436 – 49459Tail
Compositional bias28 – 12396Gly-rich

Natural variations

Natural variant151P → S.
Corresponds to variant rs11650915 [ dbSNP | Ensembl ].
VAR_049783
Natural variant201R → W. Ref.3
Corresponds to variant rs17566772 [ dbSNP | Ensembl ].
VAR_009547
Natural variant1291M → T in MECD. Ref.3 Ref.13
Corresponds to variant rs28936695 [ dbSNP | Ensembl ].
VAR_013126
Natural variant1301Q → P in MECD. Ref.9
Corresponds to variant rs58864803 [ dbSNP | Ensembl ].
VAR_013127
Natural variant1351R → G in MECD. Ref.2
Corresponds to variant rs58410481 [ dbSNP | Ensembl ].
VAR_008526
Natural variant1351R → I in MECD. Ref.2
VAR_008525
Natural variant1351R → S in MECD. Ref.11
Corresponds to variant rs61282718 [ dbSNP | Ensembl ].
VAR_031394
Natural variant1351R → T in MECD. Ref.3 Ref.8
Corresponds to variant rs57218384 [ dbSNP | Ensembl ].
VAR_003834
Natural variant1371A → P in MECD. Ref.10
Corresponds to variant rs58038639 [ dbSNP | Ensembl ].
VAR_031395
Natural variant1401L → R in MECD. Ref.2
Corresponds to variant rs58918655 [ dbSNP | Ensembl ].
VAR_008527
Natural variant1431V → L in MECD. Ref.8
Corresponds to variant rs58343600 [ dbSNP | Ensembl ].
VAR_003835
Natural variant3991L → LISNLEAQLL in MECD.
VAR_031396
Natural variant4261I → S in MECD. Ref.13
Corresponds to variant rs59350319 [ dbSNP | Ensembl ].
VAR_031397
Natural variant4291Y → C in MECD. Ref.12
Corresponds to variant rs59202432 [ dbSNP | Ensembl ].
VAR_031398
Natural variant4291Y → D in MECD. Ref.2
Corresponds to variant rs58162394 [ dbSNP | Ensembl ].
VAR_008528

Sequences

Sequence LengthMass (Da)Tools
Q99456 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 75C981380532B682

FASTA49453,511
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.

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.
CCDSCCDS11378.1.
RefSeqNP_000214.1. NM_000223.3.
UniGeneHs.66739.

3D structure databases

ProteinModelPortalQ99456.
SMRQ99456. Positions 179-275, 293-435.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110057. 3 interactions.
STRING9606.ENSP00000251643.

PTM databases

PhosphoSiteQ99456.

Polymorphism databases

DMDM2497269.

Proteomic databases

PaxDbQ99456.
PeptideAtlasQ99456.
PRIDEQ99456.

Protocols and materials databases

DNASU3859.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000251643; ENSP00000251643; ENSG00000187242.
ENST00000572470; ENSP00000459559; ENSG00000263243.
GeneID3859.
KEGGhsa:3859.
UCSCuc002hvk.2. human.

Organism-specific databases

CTD3859.
GeneCardsGC17M039017.
HGNCHGNC:6414. KRT12.
MIM122100. phenotype.
601687. gene.
neXtProtNX_Q99456.
Orphanet98954. Meesmann corneal dystrophy.
PharmGKBPA30201.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG148849.
HOGENOMHOG000230975.
HOVERGENHBG013015.
InParanoidQ99456.
KOK07604.
OMAYETIAEQ.
OrthoDBEOG7FV3Q8.
PhylomeDBQ99456.
TreeFamTF332742.

Gene expression databases

BgeeQ99456.
CleanExHS_KRT12.
GenevestigatorQ99456.

Family and domain databases

InterProIPR001664. IF.
IPR018039. Intermediate_filament_CS.
IPR002957. Keratin_I.
[Graphical view]
PANTHERPTHR23239. PTHR23239. 1 hit.
PfamPF00038. Filament. 1 hit.
[Graphical view]
PRINTSPR01248. TYPE1KERATIN.
PROSITEPS00226. IF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSKRT12. human.
GeneWikiKeratin_12.
GenomeRNAi3859.
NextBio15185.
PROQ99456.
SOURCESearch...

Entry information

Entry nameK1C12_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM