K1C25_HUMAN
ID K1C25_HUMAN Reviewed; 450 AA.
AC Q7Z3Z0;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Keratin, type I cytoskeletal 25;
DE AltName: Full=Cytokeratin-25;
DE Short=CK-25;
DE AltName: Full=Keratin-25;
DE Short=K25;
DE AltName: Full=Keratin-25A;
DE Short=K25A;
DE AltName: Full=Type I inner root sheath-specific keratin-K25irs1;
GN Name=KRT25 {ECO:0000312|HGNC:HGNC:30839};
GN Synonyms=KRT25A {ECO:0000312|EMBL:CAD91904.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAD91904.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Scalp {ECO:0000312|EMBL:CAD91904.1};
RX PubMed=15617563; DOI=10.1111/j.1432-0436.2004.07209006.x;
RA Rogers M.A., Winter H., Langbein L., Bleiler R., Schweizer J.;
RT "The human type I keratin gene family: characterization of new hair
RT follicle specific members and evaluation of the chromosome 17q21.2 gene
RT domain.";
RL Differentiation 72:527-540(2004).
RN [2] {ECO:0000312|EMBL:EAW60676.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=16874310; DOI=10.1038/sj.jid.5700494;
RA Langbein L., Rogers M.A., Praetzel-Wunder S., Helmke B., Schirmacher P.,
RA Schweizer J.;
RT "K25 (K25irs1), K26 (K25irs2), K27 (K25irs3), and K28 (K25irs4) represent
RT the type I inner root sheath keratins of the human hair follicle.";
RL J. Invest. Dermatol. 126:2377-2386(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-442, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP VARIANT ARWH3 PRO-317.
RX PubMed=26160856; DOI=10.1136/jmedgenet-2015-103255;
RA Ansar M., Raza S.I., Lee K., Irfanullah X., Shahi S., Acharya A., Dai H.,
RA Smith J.D., Shendure J., Bamshad M.J., Nickerson D.A., Santos-Cortez R.L.,
RA Ahmad W., Leal S.M.;
RT "A homozygous missense variant in type I keratin KRT25 causes autosomal
RT recessive woolly hair.";
RL J. Med. Genet. 52:676-680(2015).
RN [6]
RP VARIANT ARWH3 LEU-238, CHARACTERIZATION OF VARIANT ARWH3 LEU-238, FUNCTION,
RP AND SUBUNIT.
RX PubMed=26902920; DOI=10.1016/j.jid.2016.01.037;
RA Zernov N.V., Skoblov M.Y., Marakhonov A.V., Shimomura Y., Vasilyeva T.A.,
RA Konovalov F.A., Abrukova A.V., Zinchenko R.A.;
RT "Autosomal recessive hypotrichosis with woolly hair caused by a mutation in
RT the keratin 25 gene expressed in hair follicles.";
RL J. Invest. Dermatol. 136:1097-1105(2016).
RN [7]
RP VARIANT ARWH3 ARG-376, CHARACTERIZATION OF VARIANT ARWH3 ARG-376, AND
RP SUBUNIT.
RX PubMed=28899683; DOI=10.1016/j.jid.2017.08.035;
RA Yu X., Chen F., Ni C., Zhang G., Zheng L., Zhang J., Li C., Sandilands A.,
RA Yao Z., Li M.;
RT "A missense mutation within the helix termination motif of KRT25 causes
RT autosomal dominant woolly hair/hypotrichosis.";
RL J. Invest. Dermatol. 138:230-233(2018).
CC -!- FUNCTION: Essential for the proper assembly of type I and type II
CC keratin protein complexes and formation of keratin intermediate
CC filaments in the inner root sheath (irs) (By similarity). Plays a role
CC in the cytoskeleton organization (PubMed:26902920).
CC {ECO:0000250|UniProtKB:Q8VCW2, ECO:0000269|PubMed:26902920}.
CC -!- SUBUNIT: Heterodimer of a type I and a type II keratin
CC (PubMed:26902920). Heterodimer with type II keratin KRT5 leading to the
CC formation of keratin intermediate filament (KIF) network
CC (PubMed:28899683). Interacts with KRT6A to form filaments (By
CC similarity). {ECO:0000250|UniProtKB:Q8VCW2,
CC ECO:0000269|PubMed:26902920, ECO:0000269|PubMed:28899683, ECO:0000305}.
CC -!- INTERACTION:
CC Q7Z3Z0; O14964: HGS; NbExp=3; IntAct=EBI-11980019, EBI-740220;
CC Q7Z3Z0; P04264: KRT1; NbExp=3; IntAct=EBI-11980019, EBI-298429;
CC Q7Z3Z0; P35908: KRT2; NbExp=5; IntAct=EBI-11980019, EBI-1247312;
CC Q7Z3Z0; P12035: KRT3; NbExp=3; IntAct=EBI-11980019, EBI-2430095;
CC Q7Z3Z0; P19013: KRT4; NbExp=3; IntAct=EBI-11980019, EBI-2371606;
CC Q7Z3Z0; P13647: KRT5; NbExp=3; IntAct=EBI-11980019, EBI-702187;
CC Q7Z3Z0; P02538: KRT6A; NbExp=3; IntAct=EBI-11980019, EBI-702198;
CC Q7Z3Z0; P04259: KRT6B; NbExp=3; IntAct=EBI-11980019, EBI-740907;
CC Q7Z3Z0; P48668: KRT6C; NbExp=3; IntAct=EBI-11980019, EBI-2564105;
CC Q7Z3Z0; Q3SY84: KRT71; NbExp=5; IntAct=EBI-11980019, EBI-2952676;
CC Q7Z3Z0; Q14CN4: KRT72; NbExp=3; IntAct=EBI-11980019, EBI-1221280;
CC Q7Z3Z0; Q7RTS7: KRT74; NbExp=5; IntAct=EBI-11980019, EBI-968660;
CC Q7Z3Z0; O95678: KRT75; NbExp=3; IntAct=EBI-11980019, EBI-2949715;
CC Q7Z3Z0; Q01546: KRT76; NbExp=3; IntAct=EBI-11980019, EBI-2952745;
CC Q7Z3Z0; Q8N1N4: KRT78; NbExp=3; IntAct=EBI-11980019, EBI-1056564;
CC Q7Z3Z0; Q5XKE5: KRT79; NbExp=3; IntAct=EBI-11980019, EBI-2514135;
CC Q7Z3Z0; P05787: KRT8; NbExp=3; IntAct=EBI-11980019, EBI-297852;
CC Q7Z3Z0; P78385: KRT83; NbExp=3; IntAct=EBI-11980019, EBI-10221390;
CC Q7Z3Z0; P78386: KRT85; NbExp=5; IntAct=EBI-11980019, EBI-1049371;
CC Q7Z3Z0; O43790: KRT86; NbExp=3; IntAct=EBI-11980019, EBI-9996498;
CC Q7Z3Z0; Q8NDC4: MORN4; NbExp=3; IntAct=EBI-11980019, EBI-10269566;
CC Q7Z3Z0; O60437: PPL; NbExp=3; IntAct=EBI-11980019, EBI-368321;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8VCW2}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in skin and scalp, and weak
CC expression observed in thymus and tongue. In the hair follicle,
CC expressed in Henle layer, Huxley layer and in the inner root sheath
CC cuticle of the hair follicle. Expression extends from the bulb region
CC up to the point of differentiation into the three layers. Also present
CC in the medulla of beard hair (at protein level).
CC {ECO:0000269|PubMed:15617563, ECO:0000269|PubMed:16874310}.
CC -!- DISEASE: Woolly hair autosomal recessive 3 (ARWH3) [MIM:616760]: A hair
CC shaft disorder characterized by fine and tightly curled hair. Compared
CC to normal curly hair that is observed in some populations, woolly hair
CC grows slowly and stops growing after a few inches. Under light
CC microscopy, woolly hair shows some structural anomalies, including
CC trichorrhexis nodosa and tapered ends. Some individuals may present
CC with hypotrichosis. {ECO:0000269|PubMed:26160856,
CC ECO:0000269|PubMed:26902920, ECO:0000269|PubMed:28899683}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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 {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC {ECO:0000255|PROSITE-ProRule:PRU01188}.
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DR EMBL; AJ564204; CAD91904.1; -; mRNA.
DR EMBL; CH471152; EAW60676.1; -; Genomic_DNA.
DR CCDS; CCDS11373.1; -.
DR RefSeq; NP_853512.1; NM_181534.3.
DR AlphaFoldDB; Q7Z3Z0; -.
DR SMR; Q7Z3Z0; -.
DR BioGRID; 127044; 28.
DR ComplexPortal; CPX-5665; Keratin-25 - Keratin-71 dimer complex.
DR IntAct; Q7Z3Z0; 22.
DR STRING; 9606.ENSP00000310573; -.
DR iPTMnet; Q7Z3Z0; -.
DR PhosphoSitePlus; Q7Z3Z0; -.
DR SwissPalm; Q7Z3Z0; -.
DR BioMuta; KRT25; -.
DR DMDM; 74723316; -.
DR jPOST; Q7Z3Z0; -.
DR MassIVE; Q7Z3Z0; -.
DR PaxDb; Q7Z3Z0; -.
DR PeptideAtlas; Q7Z3Z0; -.
DR PRIDE; Q7Z3Z0; -.
DR ProteomicsDB; 69098; -.
DR Antibodypedia; 57604; 105 antibodies from 19 providers.
DR DNASU; 147183; -.
DR Ensembl; ENST00000312150.5; ENSP00000310573.4; ENSG00000204897.7.
DR GeneID; 147183; -.
DR KEGG; hsa:147183; -.
DR MANE-Select; ENST00000312150.5; ENSP00000310573.4; NM_181534.4; NP_853512.1.
DR UCSC; uc002hve.3; human.
DR CTD; 147183; -.
DR DisGeNET; 147183; -.
DR GeneCards; KRT25; -.
DR HGNC; HGNC:30839; KRT25.
DR HPA; ENSG00000204897; Tissue enriched (skin).
DR MalaCards; KRT25; -.
DR MIM; 616646; gene.
DR MIM; 616760; phenotype.
DR neXtProt; NX_Q7Z3Z0; -.
DR OpenTargets; ENSG00000204897; -.
DR Orphanet; 170; Woolly hair.
DR PharmGKB; PA134977088; -.
DR VEuPathDB; HostDB:ENSG00000204897; -.
DR eggNOG; ENOG502SKJN; Eukaryota.
DR GeneTree; ENSGT00940000161994; -.
DR HOGENOM; CLU_012560_8_3_1; -.
DR InParanoid; Q7Z3Z0; -.
DR OMA; KGWYEQF; -.
DR OrthoDB; 805081at2759; -.
DR PhylomeDB; Q7Z3Z0; -.
DR TreeFam; TF332742; -.
DR PathwayCommons; Q7Z3Z0; -.
DR Reactome; R-HSA-6805567; Keratinization.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; Q7Z3Z0; -.
DR BioGRID-ORCS; 147183; 10 hits in 1062 CRISPR screens.
DR GenomeRNAi; 147183; -.
DR Pharos; Q7Z3Z0; Tbio.
DR PRO; PR:Q7Z3Z0; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q7Z3Z0; protein.
DR Bgee; ENSG00000204897; Expressed in upper arm skin and 56 other tissues.
DR Genevisible; Q7Z3Z0; HS.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0045095; C:keratin filament; IPI:ComplexPortal.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0007568; P:aging; IDA:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0042633; P:hair cycle; IDA:UniProtKB.
DR GO; GO:0031069; P:hair follicle morphogenesis; IBA:GO_Central.
DR GO; GO:0045109; P:intermediate filament organization; IBA:GO_Central.
DR InterPro; IPR039008; IF_rod_dom.
DR InterPro; IPR002957; Keratin_I.
DR PANTHER; PTHR23239; PTHR23239; 1.
DR Pfam; PF00038; Filament; 1.
DR PRINTS; PR01248; TYPE1KERATIN.
DR SMART; SM01391; Filament; 1.
DR PROSITE; PS51842; IF_ROD_2; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; Disease variant; Hypotrichosis;
KW Intermediate filament; Keratin; Phosphoprotein; Reference proteome.
FT CHAIN 1..450
FT /note="Keratin, type I cytoskeletal 25"
FT /id="PRO_0000312691"
FT DOMAIN 79..394
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT REGION 1..78
FT /note="Head"
FT /evidence="ECO:0000255"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 79..114
FT /note="Coil 1A"
FT /evidence="ECO:0000255"
FT REGION 115..136
FT /note="Linker 1"
FT /evidence="ECO:0000255"
FT REGION 137..228
FT /note="Coil 1B"
FT /evidence="ECO:0000255"
FT REGION 229..251
FT /note="Linker 12"
FT /evidence="ECO:0000255"
FT REGION 252..390
FT /note="Coil 2"
FT /evidence="ECO:0000255"
FT REGION 391..450
FT /note="Tail"
FT /evidence="ECO:0000255"
FT MOD_RES 442
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VARIANT 54
FT /note="S -> L (in dbSNP:rs12951399)"
FT /id="VAR_049786"
FT VARIANT 238
FT /note="V -> L (in ARWH3; reduces keratin intermediate
FT filamen formation; impairs cytoskeleton assembly;
FT dbSNP:rs879253749)"
FT /evidence="ECO:0000269|PubMed:26902920"
FT /id="VAR_076303"
FT VARIANT 317
FT /note="L -> P (in ARWH3; dbSNP:rs766783183)"
FT /evidence="ECO:0000269|PubMed:26160856"
FT /id="VAR_076304"
FT VARIANT 376
FT /note="L -> R (in ARWH3; disruption of keratin intermediate
FT filament formation formed via heterodimerization with
FT KRT5)"
FT /evidence="ECO:0000269|PubMed:28899683"
FT /id="VAR_079711"
SQ SEQUENCE 450 AA; 49318 MW; 12AB5BF74BA426FF CRC64;
MSLRLSSASR RSCPRPTTGS LRLYGGGTSF GTGNSCGISG IGSGFSSAFG GSSSGGNTGG
GNPCAGFTVN ERGLLSGNEK VTMQNLNDRL ASYLDSVHAL EEANADLEQK IKGWYEKFGP
GSCRGLDHDY SRYFPIIDDL KNQIIASTTS NANAVLQIDN ARLTADDFRL KYENELALHQ
SVEADVNGLR RVLDEITLCR TDLEIQYETL SEEMTYLKKN HKEEMQVLQC AAGGNVNVEM
NAAPGVDLTV LLNNMRAEYE ALAEQNRRDA EAWFNEKSAS LQQQISEDVG ATTSARNELT
EMKRTLQTLE IELQSLLATK HSLECSLTET ESNYCAQLAQ IQAQIGALEE QLHQVRTETE
GQKLEYEQLL DIKLHLEKEI ETYCLLIGGD DGACKSGGYK SKDYGSGNVG SQVKDPAKAI
VVKKVLEEVD QRSKILTTRL HSLEEKSQSN
