K2C74_HUMAN
ID K2C74_HUMAN Reviewed; 529 AA.
AC Q7RTS7; B5MD61; Q86Y45;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Keratin, type II cytoskeletal 74;
DE AltName: Full=Cytokeratin-74;
DE Short=CK-74;
DE AltName: Full=Keratin-5c;
DE Short=K5C;
DE AltName: Full=Keratin-74;
DE Short=K74;
DE AltName: Full=Type II inner root sheath-specific keratin-K6irs4;
DE AltName: Full=Type-II keratin Kb37;
GN Name=KRT74; Synonyms=K6IRS4, KB37, KRT5C, KRT6IRS4;
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]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT ASP-271.
RC TISSUE=Scalp;
RX PubMed=12648212; DOI=10.1046/j.1523-1747.2003.12087.x;
RA Langbein L., Rogers M.A., Praetzel S., Winter H., Schweizer J.;
RT "K6irs1, K6irs2, K6irs3, and K6irs4 represent the inner-root-sheath-
RT specific type II epithelial keratins of the human hair follicle.";
RL J. Invest. Dermatol. 120:512-522(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [3]
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 [4]
RP IDENTIFICATION, AND VARIANT ASP-271.
RX PubMed=11683385; DOI=10.1242/jcs.114.14.2569;
RA Hesse M., Magin T.M., Weber K.;
RT "Genes for intermediate filament proteins and the draft sequence of the
RT human genome: novel keratin genes and a surprisingly high number of
RT pseudogenes related to keratin genes 8 and 18.";
RL J. Cell Sci. 114:2569-2575(2001).
RN [5]
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-513, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [7]
RP VARIANT ADWH LYS-148, AND CHARACTERIZATION OF VARIANT ADWH LYS-148.
RX PubMed=20346438; DOI=10.1016/j.ajhg.2010.02.025;
RA Shimomura Y., Wajid M., Petukhova L., Kurban M., Christiano A.M.;
RT "Autosomal-dominant woolly hair resulting from disruption of keratin 74
RT (KRT74), a potential determinant of human hair texture.";
RL Am. J. Hum. Genet. 86:632-638(2010).
RN [8]
RP VARIANT HYPT3 ASN-482.
RX PubMed=21188418; DOI=10.1007/s00439-010-0938-9;
RA Wasif N., Naqvi S.K., Basit S., Ali N., Ansar M., Ahmad W.;
RT "Novel mutations in the keratin-74 (KRT74) gene underlie autosomal dominant
RT woolly hair/hypotrichosis in Pakistani families.";
RL Hum. Genet. 129:419-424(2011).
RN [9]
RP INVOLVEMENT IN ECTD7, VARIANT ECTD7 SER-274, AND TISSUE SPECIFICITY.
RX PubMed=24714551; DOI=10.1371/journal.pone.0093607;
RA Raykova D., Klar J., Azhar A., Khan T.N., Malik N.A., Iqbal M., Tariq M.,
RA Baig S.M., Dahl N.;
RT "Autosomal recessive transmission of a rare KRT74 variant causes hair and
RT nail ectodermal dysplasia: allelism with dominant woolly
RT hair/hypotrichosis.";
RL PLoS ONE 9:E93607-E93607(2014).
CC -!- FUNCTION: Has a role in hair formation. Specific component of keratin
CC intermediate filaments in the inner root sheath (IRS) of the hair
CC follicle (Probable). {ECO:0000305}.
CC -!- SUBUNIT: Heterotetramer of two type I and two type II keratins.
CC -!- INTERACTION:
CC Q7RTS7; P13646: KRT13; NbExp=3; IntAct=EBI-968660, EBI-1223876;
CC Q7RTS7; P19012: KRT15; NbExp=3; IntAct=EBI-968660, EBI-739566;
CC Q7RTS7; P08779: KRT16; NbExp=3; IntAct=EBI-968660, EBI-356410;
CC Q7RTS7; P08727: KRT19; NbExp=3; IntAct=EBI-968660, EBI-742756;
CC Q7RTS7; Q7Z3Z0: KRT25; NbExp=5; IntAct=EBI-968660, EBI-11980019;
CC Q7RTS7; Q7Z3Y9: KRT26; NbExp=3; IntAct=EBI-968660, EBI-12084444;
CC Q7RTS7; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-968660, EBI-3044087;
CC Q7RTS7; Q15323: KRT31; NbExp=3; IntAct=EBI-968660, EBI-948001;
CC Q7RTS7; O76011: KRT34; NbExp=3; IntAct=EBI-968660, EBI-1047093;
CC Q7RTS7; Q92764: KRT35; NbExp=3; IntAct=EBI-968660, EBI-1058674;
CC Q7RTS7; O76014: KRT37; NbExp=7; IntAct=EBI-968660, EBI-1045716;
CC Q7RTS7; O76015: KRT38; NbExp=3; IntAct=EBI-968660, EBI-1047263;
CC Q7RTS7; Q6A163: KRT39; NbExp=3; IntAct=EBI-968660, EBI-11958242;
CC Q7RTS7; P61968: LMO4; NbExp=3; IntAct=EBI-968660, EBI-2798728;
CC -!- TISSUE SPECIFICITY: Highly expressed in hair follicles from scalp. In
CC hair, it is specifically present in the inner root sheath (IRS) of the
CC hair follicle. Present in the IRS Huxley layer, but not in Henle layer
CC or cuticle of the IRS. In the IRS Huxley layer, it is expressed in
CC specialized Huxley cells, termed 'Fluegelzellen, along the area of
CC differentiated Henle cells (at protein level).
CC {ECO:0000269|PubMed:12648212, ECO:0000269|PubMed:16874310,
CC ECO:0000269|PubMed:24714551}.
CC -!- DISEASE: Woolly hair autosomal dominant (ADWH) [MIM:194300]: 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. {ECO:0000269|PubMed:20346438}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Hypotrichosis 3 (HYPT3) [MIM:613981]: A condition
CC characterized by the presence of less than the normal amount of hair.
CC Affected individuals have normal hair in early childhood but experience
CC progressive hair loss limited to the scalp beginning in the middle of
CC the first decade and almost complete baldness by the third decade. Body
CC hair, beard, eyebrows, axillary hair, teeth, and nails develop
CC normally. HYPT3 inheritance is autosomal dominant.
CC {ECO:0000269|PubMed:21188418}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Ectodermal dysplasia 7, hair/nail type (ECTD7) [MIM:614929]: A
CC form of ectodermal dysplasia, a heterogeneous group of disorders due to
CC abnormal development of two or more ectodermal structures such as hair,
CC teeth, nails and sweat glands, with or without any additional clinical
CC sign. Each combination of clinical features represents a different type
CC of ectodermal dysplasia. Ectodermal dysplasia of the hair/nail type is
CC characterized by hypotrichosis and nail dystrophy without non-
CC ectodermal or other ectodermal manifestations.
CC {ECO:0000269|PubMed:24714551}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=DAA00404.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Human Intermediate Filament Mutation Database;
CC URL="http://www.interfil.org";
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DR EMBL; AJ508777; CAD48514.1; -; mRNA.
DR EMBL; AC055715; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW96637.1; -; Genomic_DNA.
DR EMBL; BK000977; DAA00404.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS8832.1; -.
DR RefSeq; NP_778223.2; NM_175053.3.
DR AlphaFoldDB; Q7RTS7; -.
DR SMR; Q7RTS7; -.
DR BioGRID; 125727; 20.
DR IntAct; Q7RTS7; 18.
DR STRING; 9606.ENSP00000307240; -.
DR GlyGen; Q7RTS7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q7RTS7; -.
DR PhosphoSitePlus; Q7RTS7; -.
DR SwissPalm; Q7RTS7; -.
DR BioMuta; KRT74; -.
DR DMDM; 166218812; -.
DR jPOST; Q7RTS7; -.
DR MassIVE; Q7RTS7; -.
DR PaxDb; Q7RTS7; -.
DR PeptideAtlas; Q7RTS7; -.
DR PRIDE; Q7RTS7; -.
DR ProteomicsDB; 68895; -.
DR Antibodypedia; 56742; 49 antibodies from 16 providers.
DR DNASU; 121391; -.
DR Ensembl; ENST00000305620.3; ENSP00000307240.2; ENSG00000170484.10.
DR GeneID; 121391; -.
DR KEGG; hsa:121391; -.
DR MANE-Select; ENST00000305620.3; ENSP00000307240.2; NM_175053.4; NP_778223.2.
DR UCSC; uc001sap.1; human.
DR CTD; 121391; -.
DR DisGeNET; 121391; -.
DR GeneCards; KRT74; -.
DR HGNC; HGNC:28929; KRT74.
DR HPA; ENSG00000170484; Group enriched (epididymis, skin).
DR MalaCards; KRT74; -.
DR MIM; 194300; phenotype.
DR MIM; 608248; gene.
DR MIM; 613981; phenotype.
DR MIM; 614929; phenotype.
DR neXtProt; NX_Q7RTS7; -.
DR OpenTargets; ENSG00000170484; -.
DR Orphanet; 90368; Hypotrichosis simplex of the scalp.
DR Orphanet; 69084; Pure hair and nail ectodermal dysplasia.
DR Orphanet; 170; Woolly hair.
DR PharmGKB; PA147357741; -.
DR VEuPathDB; HostDB:ENSG00000170484; -.
DR eggNOG; ENOG502RNQG; Eukaryota.
DR GeneTree; ENSGT00940000162774; -.
DR InParanoid; Q7RTS7; -.
DR OrthoDB; 671547at2759; -.
DR PhylomeDB; Q7RTS7; -.
DR TreeFam; TF317854; -.
DR PathwayCommons; Q7RTS7; -.
DR Reactome; R-HSA-6805567; Keratinization.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; Q7RTS7; -.
DR BioGRID-ORCS; 121391; 14 hits in 1059 CRISPR screens.
DR GenomeRNAi; 121391; -.
DR Pharos; Q7RTS7; Tbio.
DR PRO; PR:Q7RTS7; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q7RTS7; protein.
DR Bgee; ENSG00000170484; Expressed in upper arm skin and 41 other tissues.
DR ExpressionAtlas; Q7RTS7; baseline and differential.
DR Genevisible; Q7RTS7; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0045095; C:keratin filament; IBA:GO_Central.
DR GO; GO:1990254; F:keratin filament binding; IPI:UniProtKB.
DR GO; GO:0030280; F:structural constituent of skin epidermis; IBA:GO_Central.
DR GO; GO:0045104; P:intermediate filament cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0045109; P:intermediate filament organization; IBA:GO_Central.
DR GO; GO:0031424; P:keratinization; IBA:GO_Central.
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; Disease variant; Ectodermal dysplasia; Hypotrichosis;
KW Intermediate filament; Keratin; Phosphoprotein; Reference proteome.
FT CHAIN 1..529
FT /note="Keratin, type II cytoskeletal 74"
FT /id="PRO_0000314885"
FT DOMAIN 140..453
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT REGION 1..139
FT /note="Head"
FT REGION 140..175
FT /note="Coil 1A"
FT REGION 176..194
FT /note="Linker 1"
FT REGION 195..286
FT /note="Coil 1B"
FT REGION 287..310
FT /note="Linker 12"
FT REGION 311..449
FT /note="Coil 2"
FT REGION 450..529
FT /note="Tail"
FT REGION 484..529
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 488..504
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 514..529
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 391
FT /note="Stutter"
FT MOD_RES 513
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT VARIANT 148
FT /note="N -> K (in ADWH; results in disruption of keratin
FT intermediate filament formation in cultured cells;
FT dbSNP:rs267607205)"
FT /evidence="ECO:0000269|PubMed:20346438"
FT /id="VAR_063587"
FT VARIANT 165
FT /note="N -> K (in dbSNP:rs11170177)"
FT /id="VAR_038096"
FT VARIANT 178
FT /note="L -> Q (in dbSNP:rs11170176)"
FT /id="VAR_049806"
FT VARIANT 271
FT /note="E -> D (in dbSNP:rs670741)"
FT /evidence="ECO:0000269|PubMed:11683385,
FT ECO:0000269|PubMed:12648212"
FT /id="VAR_038097"
FT VARIANT 274
FT /note="F -> S (in ECTD7; autosomal recessive;
FT dbSNP:rs147962513)"
FT /evidence="ECO:0000269|PubMed:24714551"
FT /id="VAR_071383"
FT VARIANT 392
FT /note="R -> Q (in dbSNP:rs57387512)"
FT /id="VAR_061299"
FT VARIANT 424
FT /note="E -> K (in dbSNP:rs57711382)"
FT /id="VAR_061300"
FT VARIANT 482
FT /note="D -> N (in HYPT3; dbSNP:rs267607477)"
FT /evidence="ECO:0000269|PubMed:21188418"
FT /id="VAR_065951"
SQ SEQUENCE 529 AA; 57865 MW; CE81527DD4825CBF CRC64;
MSRQLNIKSS GDKGNFSVHS AVVPRKAVGS LASYCAAGRG AGAGFGSRSL YSLGGNRRIS
FNVAGGGVRA GGYGFRPGSG YGGGRASGFA GSMFGSVALG PACLSVCPPG GIHQVTVNKS
LLAPLNVELD PEIQKVRAQE REQIKVLNDK FASFIDKVRF LEQQNQVLET KWELLQQLDL
NNCKKNLEPI LEGYISNLRK QLETLSGDRV RLDSELRSMR DLVEDYKKRY EVEINRRTTA
ENEFVVLKKD ADAAYAVKVE LQAKVDSLDK EIKFLKCLYD AEIAQIQTHA SETSVILSMD
NNRDLDLDSI IAEVRMHYEE IALKSKAEAE ALYQTKIQEL QLAASRHGDD LKHTRSEMVE
LNRLIQRIRC EIGNVKKQRA SLETAIADAE QRGDNALKDA QAKLDELEGA LHQAKEELAR
MLREYQELMS LKLALDMEIA TYRKLLEGEE CRMSGENPSS VSISVISSSS YSYHHPSSAG
VDLGASAVAG SSGSTQSGQT KTTEARGGDL KDTQGKSTPA SIPARKATR
