K2C5_MOUSE
ID K2C5_MOUSE Reviewed; 580 AA.
AC Q922U2; Q920F2;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Keratin, type II cytoskeletal 5;
DE AltName: Full=Cytokeratin-5;
DE Short=CK-5;
DE AltName: Full=Keratin-5;
DE Short=K5;
DE AltName: Full=Type-II keratin Kb5;
GN Name=Krt5 {ECO:0000250|UniProtKB:P13647};
GN Synonyms=Krt2-5 {ECO:0000312|EMBL:AAH06780.1};
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] {ECO:0000305, ECO:0000312|EMBL:AAL16774.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, TISSUE SPECIFICITY, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=129/Ola {ECO:0000312|EMBL:AAL16774.1};
RX PubMed=11408584; DOI=10.1091/mbc.12.6.1775;
RA Peters B., Kirfel J., Bussow H., Vidal M., Magin T.M.;
RT "Complete cytolysis and neonatal lethality in keratin 5 knockout mice
RT reveal its fundamental role in skin integrity and in epidermolysis bullosa
RT simplex.";
RL Mol. Biol. Cell 12:1775-1789(2001).
RN [2] {ECO:0000312|EMBL:AAH06780.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II {ECO:0000312|EMBL:AAH06780.1};
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAH06780.1};
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 [3]
RP PROTEIN SEQUENCE OF 326-337 AND 455-465, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP INTERACTION WITH AMELX, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND
RP ACETYLATION.
RX PubMed=12657653; DOI=10.1074/jbc.m211184200;
RA Ravindranath R.M., Basilrose R.M. Sr., Ravindranath N.H., Vaitheesvaran B.;
RT "Amelogenin interacts with cytokeratin-5 in ameloblasts during enamel
RT growth.";
RL J. Biol. Chem. 278:20293-20302(2003).
RN [5]
RP INTERACTION WITH EPPK1.
RX PubMed=18285451; DOI=10.1242/jcs.013755;
RA Spazierer D., Raberger J., Gross K., Fuchs P., Wiche G.;
RT "Stress-induced recruitment of epiplakin to keratin networks increases
RT their resistance to hyperphosphorylation-induced disruption.";
RL J. Cell Sci. 121:825-833(2008).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19267394; DOI=10.1002/humu.20981;
RA Roth W., Reuter U., Wohlenberg C., Bruckner-Tuderman L., Magin T.M.;
RT "Cytokines as genetic modifiers in K5-/- mice and in human epidermolysis
RT bullosa simplex.";
RL Hum. Mutat. 30:832-841(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; SER-21; SER-26; SER-47
RP AND SER-61, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, 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 [8]
RP TISSUE SPECIFICITY.
RX PubMed=24751727; DOI=10.1038/jid.2014.197;
RA Fischer H., Langbein L., Reichelt J., Praetzel-Wunder S., Buchberger M.,
RA Ghannadan M., Tschachler E., Eckhart L.;
RT "Loss of keratin K2 expression causes aberrant aggregation of K10,
RT hyperkeratosis, and inflammation.";
RL J. Invest. Dermatol. 134:2579-2588(2014).
RN [9]
RP IDENTIFICATION IN A COMPLEX WITH KRT14, AND INTERACTION WITH KRT14 AND
RP PLEC.
RX PubMed=24940650; DOI=10.1038/jid.2014.255;
RA Bouameur J.E., Favre B., Fontao L., Lingasamy P., Begre N., Borradori L.;
RT "Interaction of plectin with keratins 5 and 14: dependence on several
RT plectin domains and keratin quaternary structure.";
RL J. Invest. Dermatol. 134:2776-2783(2014).
RN [10]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-526, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=26758872; DOI=10.1093/hmg/ddw001;
RA Allen E.H., Courtney D.G., Atkinson S.D., Moore J.E., Mairs L.,
RA Poulsen E.T., Schiroli D., Maurizi E., Cole C., Hickerson R.P., James J.,
RA Murgatroyd H., Smith F.J., MacEwen C., Enghild J.J., Nesbit M.A.,
RA Leslie Pedrioli D.M., McLean W.H., Moore C.B.;
RT "Keratin 12 missense mutation induces the unfolded protein response and
RT apoptosis in Meesmann epithelial corneal dystrophy.";
RL Hum. Mol. Genet. 25:1176-1191(2016).
RN [12]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, PHOSPHORYLATION AT THR-24;
RP THR-145 AND THR-160, AND MUTAGENESIS OF THR-24; SER-31; THR-145 AND
RP THR-160.
RX PubMed=29518391; DOI=10.1016/j.bbrc.2018.03.016;
RA Inaba H., Yamakawa D., Tomono Y., Enomoto A., Mii S., Kasahara K., Goto H.,
RA Inagaki M.;
RT "Regulation of keratin 5/14 intermediate filaments by CDK1, Aurora-B, and
RT Rho-kinase.";
RL Biochem. Biophys. Res. Commun. 498:544-550(2018).
RN [13]
RP DEVELOPMENTAL STAGE.
RX PubMed=32758484; DOI=10.1016/j.ydbio.2020.07.016;
RA Simonson L., Vold S., Mowers C., Massey R.J., Ong I.M., Longley B.J.,
RA Chang H.;
RT "Keratin 13 deficiency causes white sponge nevus in mice.";
RL Dev. Biol. 468:146-153(2020).
CC -!- FUNCTION: Required for the formation of keratin intermediate filaments
CC in the basal epidermis and maintenance of the skin barrier in response
CC to mechanical stress (PubMed:11408584). Regulates the recruitment of
CC Langerhans cells to the epidermis, potentially by modulation of the
CC abundance of macrophage chemotactic cytokines, macrophage inflammatory
CC cytokines and CTNND1 localization in keratinocytes (PubMed:19267394).
CC {ECO:0000269|PubMed:11408584, ECO:0000269|PubMed:19267394}.
CC -!- SUBUNIT: Heterodimer of a type I and a type II keratin. Heterodimer
CC with type I keratin KRT25 leading to the formation of keratin
CC intermediate filament (KIF) network (By similarity). Forms a
CC heterodimer (via 2B domains) with KRT14 (via 2B domains)
CC (PubMed:24940650). Interacts with PLEC isoform 1C, when in a
CC heterodimer with KRT14 (PubMed:24940650). Interacts with TCHP (By
CC similarity). Interacts with EPPK1 (PubMed:18285451). Interacts with
CC AMELX (PubMed:12657653). {ECO:0000250|UniProtKB:P13647,
CC ECO:0000269|PubMed:12657653, ECO:0000269|PubMed:18285451,
CC ECO:0000269|PubMed:24940650}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12657653,
CC ECO:0000269|PubMed:29518391}.
CC -!- TISSUE SPECIFICITY: Expressed in the corneal epithelium (at protein
CC level) (PubMed:26758872, PubMed:11408584). Expressed in the epidermis
CC of the ear (at protein level) (PubMed:24751727). Expressed in the basal
CC and spinous layers of the skin at birth (at protein level)
CC (PubMed:11408584). {ECO:0000269|PubMed:11408584,
CC ECO:0000269|PubMed:24751727}.
CC -!- DEVELOPMENTAL STAGE: Expressed in basal layer cells of the stratified
CC squamous epithelia at 15.5 dpc (PubMed:29518391). Expressed in the skin
CC after birth (PubMed:29518391). Expressed in ameloblasts at the cervical
CC and apical mid-regions of mandibular molars at birth, abundance at the
CC apical mid-region significantly increases at P1, and is maintained
CC throughout enamel development until P9 when ameloblasts start losing
CC their integrity (PubMed:12657653). Expressed in ameloblasts at the
CC incisal region of mandibular molars at P3 (PubMed:12657653). Expressed
CC at the Tomes' processes of ameloblasts at the incisal region at P5
CC (PubMed:12657653). Expression at the incisal region decreased at P7 and
CC P9 (PubMed:12657653). Weakly expressed in the spinous and granular
CC layers of the tongue at P20 (PubMed:32758484).
CC {ECO:0000269|PubMed:12657653, ECO:0000269|PubMed:29518391,
CC ECO:0000269|PubMed:32758484}.
CC -!- PTM: Phosphorylated by CDK1, AURKB and Rho-kinase, phosphorylation is
CC regulated by the cell cycle (PubMed:29518391). Thr-24 phosphorylation,
CC mediated by CDK1, peaks during prometaphase or metaphase cells with
CC phosphorylated filamentous structures evident throughout the cytoplasm
CC during early mitosis (PubMed:29518391). CDK1 phosphorylates Thr-24 in
CC mitotic cells at the site of injury (PubMed:29518391).
CC {ECO:0000269|PubMed:29518391}.
CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:12657653}.
CC -!- DISRUPTION PHENOTYPE: Paws are frequently denuded and epidermis loses
CC contact with the dermis following the mechanical stress of birth, mice
CC die within 1 hour of birth (PubMed:11408584). Tongue cytolysis is
CC evident following birth even before the first milk uptake
CC (PubMed:11408584). Complete loss of keratin filaments in the basal
CC layer, leading to cleavage of the epidermis in the subnuclear cytoplasm
CC just superficial to the hemidesmosomes (PubMed:11408584). Increase in
CC Krt6 expression in the spinous and lower granular layers as well as
CC weakly in basal layer of the blistering roof of cytolyzing cells at
CC birth (PubMed:11408584). Decrease in Krt14 expression in the skin
CC following birth (PubMed:11408584). Increase in Langerhans cells in the
CC epidermis (PubMed:19267394). Decrease in Ctnnd1/p120 localization to
CC the plasma membrane and adherens junctions of basal keratinocytes
CC (PubMed:19267394). Increase in the cytokines Cxcl16, Ccl2, Ccl19 and
CC Ccl20 in the epidermis at birth (PubMed:19267394).
CC {ECO:0000269|PubMed:11408584, ECO:0000269|PubMed:19267394}.
CC -!- MISCELLANEOUS: There are two types of cytoskeletal and microfibrillar
CC keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC {ECO:0000255|PROSITE-ProRule:PRU01188}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF306785; AAL16774.1; -; Genomic_DNA.
DR EMBL; BC006780; AAH06780.1; -; mRNA.
DR CCDS; CCDS27861.1; -.
DR RefSeq; NP_081287.1; NM_027011.2.
DR AlphaFoldDB; Q922U2; -.
DR SMR; Q922U2; -.
DR BioGRID; 225482; 19.
DR ComplexPortal; CPX-5867; Keratin-5 - Keratin-14 dimer complex.
DR STRING; 10090.ENSMUSP00000023709; -.
DR iPTMnet; Q922U2; -.
DR PhosphoSitePlus; Q922U2; -.
DR CPTAC; non-CPTAC-3797; -.
DR jPOST; Q922U2; -.
DR PaxDb; Q922U2; -.
DR PRIDE; Q922U2; -.
DR ProteomicsDB; 269168; -.
DR DNASU; 110308; -.
DR Ensembl; ENSMUST00000023709; ENSMUSP00000023709; ENSMUSG00000061527.
DR GeneID; 110308; -.
DR KEGG; mmu:110308; -.
DR UCSC; uc007xtw.1; mouse.
DR CTD; 3852; -.
DR MGI; MGI:96702; Krt5.
DR VEuPathDB; HostDB:ENSMUSG00000061527; -.
DR eggNOG; ENOG502QURK; Eukaryota.
DR GeneTree; ENSGT00940000160458; -.
DR HOGENOM; CLU_012560_6_1_1; -.
DR InParanoid; Q922U2; -.
DR OMA; MHTHISD; -.
DR OrthoDB; 824246at2759; -.
DR PhylomeDB; Q922U2; -.
DR TreeFam; TF317854; -.
DR Reactome; R-MMU-446107; Type I hemidesmosome assembly.
DR Reactome; R-MMU-6805567; Keratinization.
DR Reactome; R-MMU-6809371; Formation of the cornified envelope.
DR BioGRID-ORCS; 110308; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Krt5; mouse.
DR PRO; PR:Q922U2; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q922U2; protein.
DR Bgee; ENSMUSG00000061527; Expressed in lip and 135 other tissues.
DR ExpressionAtlas; Q922U2; baseline and differential.
DR Genevisible; Q922U2; MM.
DR GO; GO:0001533; C:cornified envelope; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005882; C:intermediate filament; ISO:MGI.
DR GO; GO:0045095; C:keratin filament; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
DR GO; GO:0030280; F:structural constituent of skin epidermis; IBA:GO_Central.
DR GO; GO:0045109; P:intermediate filament organization; IBA:GO_Central.
DR GO; GO:0045107; P:intermediate filament polymerization; IMP:UniProtKB.
DR GO; GO:0031424; P:keratinization; IBA:GO_Central.
DR GO; GO:0030334; P:regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IMP:UniProtKB.
DR GO; GO:0009612; P:response to mechanical stimulus; IMP:UniProtKB.
DR InterPro; IPR018039; IF_conserved.
DR InterPro; IPR039008; IF_rod_dom.
DR InterPro; IPR032444; Keratin_2_head.
DR InterPro; IPR003054; Keratin_II.
DR Pfam; PF00038; Filament; 1.
DR Pfam; PF16208; Keratin_2_head; 1.
DR PRINTS; PR01276; TYPE2KERATIN.
DR SMART; SM01391; Filament; 1.
DR PROSITE; PS00226; IF_ROD_1; 1.
DR PROSITE; PS51842; IF_ROD_2; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; Direct protein sequencing; Intermediate filament;
KW Keratin; Methylation; Phosphoprotein; Reference proteome.
FT CHAIN 1..580
FT /note="Keratin, type II cytoskeletal 5"
FT /id="PRO_0000063728"
FT DOMAIN 162..475
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT REGION 1..161
FT /note="Head"
FT /evidence="ECO:0000255"
FT REGION 162..197
FT /note="Coil 1A"
FT /evidence="ECO:0000255"
FT REGION 198..216
FT /note="Linker 1"
FT /evidence="ECO:0000255"
FT REGION 217..309
FT /note="Coil 1B"
FT /evidence="ECO:0000255"
FT REGION 310..332
FT /note="Linker 12"
FT /evidence="ECO:0000255"
FT REGION 333..471
FT /note="Coil 2"
FT /evidence="ECO:0000255"
FT REGION 472..580
FT /note="Tail"
FT /evidence="ECO:0000255"
FT REGION 555..580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 413
FT /note="Stutter"
FT /evidence="ECO:0000255"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6Q2"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6Q2"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 24
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000269|PubMed:29518391"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 36
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6Q2"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6Q2"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6Q2"
FT MOD_RES 75
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6Q2"
FT MOD_RES 79
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6Q2"
FT MOD_RES 145
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000269|PubMed:29518391"
FT MOD_RES 160
FT /note="Phosphothreonine; by AURKB"
FT /evidence="ECO:0000269|PubMed:29518391"
FT MOD_RES 526
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MUTAGEN 24
FT /note="T->A: Decreases phosphorylation by CDK1."
FT /evidence="ECO:0000269|PubMed:29518391"
FT MUTAGEN 31
FT /note="S->A: Decreases phosphorylation by AURKB."
FT /evidence="ECO:0000269|PubMed:29518391"
FT MUTAGEN 145
FT /note="T->A: Decreases phosphorylation by CDK1."
FT /evidence="ECO:0000269|PubMed:29518391"
FT MUTAGEN 160
FT /note="T->A: Decreases phosphorylation by AURKB."
FT /evidence="ECO:0000269|PubMed:29518391"
FT CONFLICT 139
FT /note="V -> I (in Ref. 1; AAL16774)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 580 AA; 61767 MW; 304B341FD4224B41 CRC64;
MSRQSSVSFR SGGSRSFSAA SAITPSVSRT SFSSVSRSGG GGGGRISLGG ACGAGGYGSR
SLYNVGGSKR ISYSSGGGSF RNQFGAGGFG FGGGAGSGFG FGGGAGSGFG FGGGAGFGGG
YGGAGFPVCP PGGIQEVTVN QNLLTPLNLQ IDPTIQRVRT EEREQIKTLN NKFASFIDKV
RFLEQQNKVL DTKWALLQEQ GTKTIKQNLD PLFEQYINNL RRQLDGVLGE RGRLDSELRN
MQDLVEDYKN KYEDEINKRT TAENEFVMLK KDVDAAYMNK VELEARVDAL MDEINFMKMF
FDAELSQMQT HVSDTSVVLS MDNNRSLDLD SIIAEVKAQY EDIANRSRTE AESWYQTKYE
ELQQTAGRHG DDLRNTKHEI SEMNRMIQRL RSEIDNVKKQ CANLQNAIAE AEQRGELALK
DARNKLTELE EALQKAKQDM ARLLREYQEL MNTKLALDVE IATYRKLLEG EECRLSGEGV
GPVNISVVTN SVSSGYGGGS SIGVGSGFGG GLGSGFAGGL GPRFTRGGGG LGLGSGLSVG
GSGFSAGSSQ GGMSFGSGGG SGSSVKFVST TSSSRRSFKS
