ID K2C6A_MOUSE Reviewed; 553 AA.
AC P50446; Q9Z332;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 173.
DE RecName: Full=Keratin, type II cytoskeletal 6A;
DE AltName: Full=Cytokeratin-6A;
DE Short=CK-6A;
DE AltName: Full=Keratin-6-alpha;
DE Short=mK6-alpha;
DE AltName: Full=Keratin-6A;
DE Short=K6A;
GN Name=Krt6a; Synonyms=Ker2, Krt2-6, Krt2-6a, Krt6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Epidermis;
RX PubMed=6207530; DOI=10.1073/pnas.81.18.5709;
RA Steinert P.M., Parry D.A.D., Racoosin E.L., Idler W.W., Steven A.C.,
RA Trus B.L., Roop D.R.;
RT "The complete cDNA and deduced amino acid sequence of a type II mouse
RT epidermal keratin of 60,000 Da: analysis of sequence differences between
RT type I and type II keratins.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:5709-5713(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=129/Sv; TISSUE=Skin;
RX PubMed=9790766; DOI=10.1006/geno.1998.5476;
RA Takahashi K., Yan B., Yamanishi K., Imamura S., Coulombe P.A.;
RT "The two functional keratin 6 genes of mouse are differentially regulated
RT and evolved independently from their human orthologs.";
RL Genomics 53:170-183(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Jaw, and Limb;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE OF 528-553.
RX PubMed=1713533; DOI=10.1093/carcin/12.8.1519;
RA Finch J., Andrews K., Krieg P., Furstenberger G., Slaga T., Ootsuyama A.,
RA Tanooka H., Bowden G.T.;
RT "Identification of a cloned sequence activated during multi-stage
RT carcinogenesis in mouse skin.";
RL Carcinogenesis 12:1519-1522(1991).
RN [5]
RP SUBUNIT, AND INDUCTION.
RX PubMed=8636216; DOI=10.1083/jcb.132.3.381;
RA Paladini R.D., Takahashi K., Bravo N.S., Coulombe P.A.;
RT "Onset of re-epithelialization after skin injury correlates with a
RT reorganization of keratin filaments in wound edge keratinocytes: defining a
RT potential role for keratin 16.";
RL J. Cell Biol. 132:381-397(1996).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=11069616; DOI=10.1046/j.1523-1747.2000.00132.x;
RA Mahony D., Karunaratne S., Cam G., Rothnagel J.A.;
RT "Analysis of mouse keratin 6a regulatory sequences in transgenic mice
RT reveals constitutive, tissue-specific expression by a keratin 6a
RT minigene.";
RL J. Invest. Dermatol. 115:795-804(2000).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=10866680; DOI=10.1128/mcb.20.14.5248-5255.2000;
RA Wojcik S.M., Bundman D.S., Roop D.R.;
RT "Delayed wound healing in keratin 6a knockout mice.";
RL Mol. Cell. Biol. 20:5248-5255(2000).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Liver, Lung, Pancreas, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION.
RX PubMed=22529101; DOI=10.1083/jcb.201107078;
RA Rotty J.D., Coulombe P.A.;
RT "A wound-induced keratin inhibits Src activity during keratinocyte
RT migration and tissue repair.";
RL J. Cell Biol. 197:381-389(2012).
CC -!- FUNCTION: Epidermis-specific type I keratin involved in wound healing
CC (PubMed:10866680). Involved in the activation of follicular
CC keratinocytes after wounding, while it does not play a major role in
CC keratinocyte proliferation or migration (PubMed:10866680). Participates
CC in the regulation of epithelial migration by inhibiting the activity of
CC SRC during wound repair (PubMed:22529101).
CC {ECO:0000269|PubMed:10866680, ECO:0000269|PubMed:22529101}.
CC -!- SUBUNIT: Heterodimer of a type I and a type II keratin. KRT6 isomers
CC associate with KRT16 and/or KRT17 (PubMed:8636216). Interacts with TCHP
CC (By similarity). {ECO:0000250, ECO:0000269|PubMed:8636216}.
CC -!- TISSUE SPECIFICITY: Predominates in the adult trunk skin, tongue,
CC trachea/esophagus and eye. In adult skin, localization is restricted to
CC hair follicles, where it is localized predominantly in the outer root
CC sheath. {ECO:0000269|PubMed:11069616, ECO:0000269|PubMed:9790766}.
CC -!- INDUCTION: With the exception of specific body sites, expression is
CC induced under conditions of epithelial hyperproliferation such as wound
CC healing, certain skin diseases, cancer, and by treatment of the skin
CC with the phorbol ester PMA. Upon wounding, induced in the outer root
CC sheath and the interfollicular epidermis including the basal cell layer
CC (PubMed:10866680). {ECO:0000269|PubMed:10866680,
CC ECO:0000269|PubMed:8636216, ECO:0000269|PubMed:9790766}.
CC -!- DISRUPTION PHENOTYPE: Wound healing defects. Delay in
CC reepithelialization from the hair follicle while the healing of full-
CC thickness skin wounds is not impaired. {ECO:0000269|PubMed:10866680}.
CC -!- MISCELLANEOUS: There are two types of cytoskeletal and microfibrillar
CC keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa,
CC respectively).
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC {ECO:0000255|PROSITE-ProRule:PRU01188}.
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DR EMBL; K02108; AAA39395.1; -; mRNA.
DR EMBL; AB012033; BAA34178.1; -; Genomic_DNA.
DR EMBL; BC080820; AAH80820.1; -; mRNA.
DR CCDS; CCDS27860.1; -.
DR PIR; I59009; I59009.
DR RefSeq; NP_032502.3; NM_008476.3.
DR AlphaFoldDB; P50446; -.
DR SMR; P50446; -.
DR BioGRID; 201035; 16.
DR IntAct; P50446; 1.
DR MINT; P50446; -.
DR STRING; 10090.ENSMUSP00000023788; -.
DR GlyGen; P50446; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P50446; -.
DR PhosphoSitePlus; P50446; -.
DR SwissPalm; P50446; -.
DR CPTAC; non-CPTAC-4031; -.
DR jPOST; P50446; -.
DR PaxDb; 10090-ENSMUSP00000023788; -.
DR PeptideAtlas; P50446; -.
DR ProteomicsDB; 268943; -.
DR DNASU; 16687; -.
DR Ensembl; ENSMUST00000023788.8; ENSMUSP00000023788.7; ENSMUSG00000058354.8.
DR GeneID; 16687; -.
DR KEGG; mmu:16687; -.
DR UCSC; uc007xtv.1; mouse.
DR AGR; MGI:1100845; -.
DR CTD; 3853; -.
DR MGI; MGI:1100845; Krt6a.
DR VEuPathDB; HostDB:ENSMUSG00000058354; -.
DR eggNOG; ENOG502QURK; Eukaryota.
DR GeneTree; ENSGT00940000154600; -.
DR HOGENOM; CLU_012560_6_1_1; -.
DR InParanoid; P50446; -.
DR OMA; YGAPSHF; -.
DR OrthoDB; 4640531at2759; -.
DR PhylomeDB; P50446; -.
DR TreeFam; TF317854; -.
DR Reactome; R-MMU-6805567; Keratinization.
DR Reactome; R-MMU-6809371; Formation of the cornified envelope.
DR BioGRID-ORCS; 16687; 2 hits in 60 CRISPR screens.
DR ChiTaRS; Krt6a; mouse.
DR PRO; PR:P50446; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; P50446; Protein.
DR Bgee; ENSMUSG00000058354; Expressed in substantia propria of cornea and 87 other cell types or tissues.
DR Genevisible; P50446; MM.
DR GO; GO:0045095; C:keratin filament; IBA:GO_Central.
DR GO; GO:0030280; F:structural constituent of skin epidermis; IBA:GO_Central.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IMP:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
DR GO; GO:0045109; P:intermediate filament organization; IGI:MGI.
DR GO; GO:0031424; P:keratinization; IGI:MGI.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IMP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IDA:MGI.
DR GO; GO:0042060; P:wound healing; IMP:UniProtKB.
DR Gene3D; 1.20.5.170; -; 1.
DR Gene3D; 1.20.5.500; Single helix bin; 1.
DR Gene3D; 1.20.5.1160; Vasodilator-stimulated phosphoprotein; 1.
DR InterPro; IPR018039; IF_conserved.
DR InterPro; IPR039008; IF_rod_dom.
DR InterPro; IPR032444; Keratin_2_head.
DR InterPro; IPR003054; Keratin_II.
DR PANTHER; PTHR45616; GATA-TYPE DOMAIN-CONTAINING PROTEIN; 1.
DR PANTHER; PTHR45616:SF39; KERATIN, TYPE II CYTOSKELETAL 6A; 1.
DR Pfam; PF00038; Filament; 1.
DR Pfam; PF16208; Keratin_2_head; 1.
DR PRINTS; PR01276; TYPE2KERATIN.
DR SMART; SM01391; Filament; 1.
DR SUPFAM; SSF64593; Intermediate filament protein, coiled coil region; 3.
DR PROSITE; PS00226; IF_ROD_1; 1.
DR PROSITE; PS51842; IF_ROD_2; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Intermediate filament; Keratin; Reference proteome.
FT CHAIN 1..553
FT /note="Keratin, type II cytoskeletal 6A"
FT /id="PRO_0000063736"
FT DOMAIN 152..465
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT REGION 1..151
FT /note="Head"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 152..187
FT /note="Coil 1A"
FT REGION 188..206
FT /note="Linker 1"
FT REGION 207..298
FT /note="Coil 1B"
FT REGION 299..322
FT /note="Linker 12"
FT REGION 323..461
FT /note="Coil 2"
FT REGION 462..553
FT /note="Tail"
FT REGION 528..553
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 529..553
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 403
FT /note="Stutter"
FT CONFLICT 24
FT /note="P -> L (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="P -> L (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="L -> M (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="L -> M (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 191
FT /note="G -> D (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="L -> M (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 224..225
FT /note="LD -> MN (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 233..240
FT /note="DTVEDYKS -> ELVEELRN (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 251
FT /note="A -> D (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="D -> V (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 318
FT /note="D -> V (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 330..332
FT /note="YED -> FEV (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 344
FT /note="W -> L (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 432
FT /note="R -> M (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 438
FT /note="Q -> H (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
FT CONFLICT 498
FT /note="L -> M (in Ref. 1; AAA39395)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 553 AA; 59335 MW; C4DF69569E738DAF CRC64;
MSTKTTIKSQ TSHRGYSASS ARVPGLNRSG FSSVSVCRSR GSGGSSAMCG GAGFGSRSLY
GVGSSKRISI GGGSCGIGGG YGSRFGGSFG IGGGAGSGFG FGGGAGFGGG YGGAGFPVCP
PGGIQEVTIN QSLLTPLNLQ IDPTIQRVRT EEREQIKTLN NKFASFIDKV RFLEQQNKVL
DTKWALLQEQ GTKTVRQNLE PMFEQYISNL RRQLDSIIGE RGRLDSELRN MQDTVEDYKS
KYEDEINKRT AAENEFVTLK KDVDAAYMNK VELQAKADSL TDDINFLRAL YEAELSQMQT
HISDTSVVLS MDNNRSLDLD SIIAEVKAQY EDIAQRSRAE AESWYQTKYE ELQVTAGRHG
DDLRNTKQEI AEINRMIQRL RSEIDHVKKQ CANLQAAIAD AEQRGEMALK DARGKLEGLE
DALQKAKQDM ARLLKEYQEL MNVKLALDVE IATYRKLLEG EECRLNGEGV GPVNISVVQS
TVSSGYGSAG GASSSLGLGG GSSYSYSSSH GLGGGFSAGS GRAIGGGLSS SGGLSSSTIK
YTTTSSSKKS YRQ
//
