ID K1C16_HUMAN Reviewed; 473 AA. AC P08779; A8K488; P30654; Q16402; Q9UBG8; DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 27-NOV-2024, entry version 226. DE RecName: Full=Keratin, type I cytoskeletal 16; DE AltName: Full=Cytokeratin-16; DE Short=CK-16; DE AltName: Full=Keratin-16; DE Short=K16; GN Name=KRT16; Synonyms=KRT16A; 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 [GENOMIC DNA]. RX PubMed=2431270; DOI=10.1128/mcb.6.2.539-548.1986; RA Raychaudhury A., Marchuk D., Lindhurst M., Fuchs E.; RT "Three tightly linked genes encoding human type I keratins: conservation of RT sequence in the 5'-untranslated leader and 5'-upstream regions of RT coexpressed keratin genes."; RL Mol. Cell. Biol. 6:539-548(1986). RN [2] RP SEQUENCE REVISION. RX PubMed=2451124; DOI=10.1128/mcb.8.2.722-736.1988; RA Rosenberg M., Raychaudhury A., Shows T.B., le Beau M.M., Fuchs E.; RT "A group of type I keratin genes on human chromosome 17: characterization RT and expression."; RL Mol. Cell. Biol. 8:722-736(1988). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Keratinocyte; RX PubMed=7487986; DOI=10.1006/bbrc.1995.2495; RA Paladini R.D., Takahashi K., Gant T.M., Coulombe P.A.; RT "cDNA cloning and bacterial expression of the human type I keratin 16."; RL Biochem. Biophys. Res. Commun. 215:517-523(1995). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RA Smith F.J.D., Fisher M.P., Healy E., Rees J.L., McKusick V.A., RA Bonifas J.M., Epstein E.H. Jr., Tan E., Uitto J., McLean W.H.I.; RT "Cloning of multiple keratin 16 genes: genotype-phenotype correlation and RT protein expression studies in pachyonychia congenita type 1 and focal RT palmoplantar keratoderma."; RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Mammary gland; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin; 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 [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 118-134, AND VARIANT PC1 PRO-132. RX PubMed=7539673; DOI=10.1038/ng0395-273; RA McLean W.H.I., Rugg E.L., Lunny D.P., Morley S.M., Lane E.B., Swensson O., RA Dopping-Hepenstal P.J.C., Griffiths W.A.D., Eady R.A.J., Higgins C., RA Navsaria H.A., Leigh I.M., Strachan T., Kunkeler L., Munro C.S.; RT "Keratin 16 and keratin 17 mutations cause pachyonychia congenita."; RL Nat. Genet. 9:273-278(1995). RN [9] RP PROTEIN SEQUENCE OF 137-148; 178-195 AND 264-283. RC TISSUE=Keratinocyte; RX PubMed=1286667; DOI=10.1002/elps.11501301199; RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., RA Vandekerckhove J.; RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein RT database of normal human epidermal keratinocytes."; RL Electrophoresis 13:960-969(1992). RN [10] RP MASS SPECTROMETRY. RC TISSUE=Mammary cancer; RX PubMed=11840567; RX DOI=10.1002/1615-9861(200202)2:2<212::aid-prot212>3.0.co;2-h; RA Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A., RA Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J., RA Zvelebil M.J.; RT "Cluster analysis of an extensive human breast cancer cell line protein RT expression map database."; RL Proteomics 2:212-223(2002). RN [11] RP INTERACTION WITH TCHP. RX PubMed=15731013; DOI=10.1242/jcs.01667; RA Nishizawa M., Izawa I., Inoko A., Hayashi Y., Nagata K., Yokoyama T., RA Usukura J., Inagaki M.; RT "Identification of trichoplein, a novel keratin filament-binding protein."; RL J. Cell Sci. 118:1081-1090(2005). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [15] 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 [16] RP VARIANTS FNEPPK1 SER-125 AND CYS-127. RX PubMed=8595410; DOI=10.1093/hmg/4.10.1875; RA Shamsheer M.K., Navsaria H.A., Stevens H.P., Ratnavel R.C., Purkis P.E., RA McLean W.H.I., Cook L.J., Griffiths W.A.D., Geschmeissner S., Spurr N., RA Leigh I.M.; RT "Novel mutations in keratin 16 gene underly focal nonepidermolytic RT palmoplantar keratoderma (NEPPK) in two families."; RL Hum. Mol. Genet. 4:1875-1881(1995). RN [17] RP VARIANTS PC1 PRO-122 AND PRO-127. RX PubMed=10606845; DOI=10.1046/j.1365-2133.1999.03198.x; RA Smith F.J.D., Del Monaco M., Steijlen P.M., Munro C.S., Morvay M., RA Coleman C.M., Rietveld F.J.R., Uitto J., McLean W.H.I.; RT "Novel proline substitution mutations in keratin 16 in two cases of RT pachyonychia congenita type 1."; RL Br. J. Dermatol. 141:1010-1016(1999). RN [18] RP VARIANT PC1 SER-130 DEL. RX PubMed=10521820; RX DOI=10.1002/(sici)1097-0223(199910)19:10<941::aid-pd663>3.3.co;2-n; RA Smith F.J., McKusick V.A., Nielsen K., Pfendner E., Uitto J., RA McLean W.H.I.; RT "Cloning of multiple keratin 16 genes facilitates prenatal diagnosis of RT pachyonychia congenita type 1."; RL Prenat. Diagn. 19:941-946(1999). RN [19] RP VARIANT PC1 ARG-124. RX PubMed=10839714; DOI=10.1034/j.1600-0625.2000.009003170.x; RA Smith F.J., Fisher M.P., Healy E., Rees J.L., Bonifas J.M., RA Epstein E.H. Jr., Tan E.M., Uitto J., McLean W.H.I.; RT "Novel keratin 16 mutations and protein expression studies in pachyonychia RT congenita type 1 and focal palmoplantar keratoderma."; RL Exp. Dermatol. 9:170-177(2000). RN [20] RP VARIANT 104-GLY--ALA-107 DEL. RX PubMed=10844556; DOI=10.1046/j.1523-1747.2000.00983.x; RA Terrinoni A., Puddu P., Didona B., De Laurenzi V., Candi E., Smith F.J., RA McLean W.H.I., Melino G.; RT "A mutation in the V1 domain of K16 is responsible for unilateral RT palmoplantar verrucous nevus."; RL J. Invest. Dermatol. 114:1136-1140(2000). RN [21] RP VARIANT PC1 ASN-354. RX PubMed=11359398; DOI=10.1046/j.1365-2133.2001.04199.x; RA Connors J.B., Rahil A.K., Smith F.J.D., McLean W.H.I., Milstone L.M.; RT "Delayed-onset pachyonychia congenita associated with a novel mutation in RT the central 2B domain of keratin 16."; RL Br. J. Dermatol. 144:1058-1062(2001). RN [22] RP VARIANTS PC1 THR-121 AND GLN-128. RX PubMed=11886499; DOI=10.1046/j.0022-202x.2001.01565.x; RA Terrinoni A., Smith F.J.D., Didona B., Canzona F., Paradisi M., Huber M., RA Hohl D., David A., Verloes A., Leigh I.M., Munro C.S., Melino G., RA McLean W.H.I.; RT "Novel and recurrent mutations in the genes encoding keratins K6a, K16 and RT K17 in 13 cases of pachyonychia congenita."; RL J. Invest. Dermatol. 117:1391-1396(2001). RN [23] RP VARIANTS PC1 PRO-124; HIS-124; ASP-125; SER-125; CYS-127 AND PRO-132. RX PubMed=16250206; DOI=10.1111/j.1087-0024.2005.10204.x; RA Smith F.J., Liao H., Cassidy A.J., Stewart A., Hamill K.J., Wood P., RA Joval I., van Steensel M.A., Bjoerck E., Callif-Daley F., Pals G., RA Collins P., Leachman S.A., Munro C.S., McLean W.H.; RT "The genetic basis of pachyonychia congenita."; RL J. Investig. Dermatol. Symp. Proc. 10:21-30(2005). RN [24] RP VARIANTS PC1 SER-125; PRO-127 AND GLN-128. RX PubMed=17719747; DOI=10.1016/j.jdermsci.2007.07.003; RA Liao H., Sayers J.M., Wilson N.J., Irvine A.D., Mellerio J.E., Baselga E., RA Bayliss S.J., Uliana V., Fimiani M., Lane E.B., McLean W.H., Leachman S.A., RA Smith F.J.; RT "A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia RT congenita."; RL J. Dermatol. Sci. 48:199-205(2007). RN [25] RP VARIANTS PC1 SER-125; PRO-127 AND PRO-132. RX PubMed=21326300; DOI=10.1038/jid.2011.20; RA Wilson N.J., Leachman S.A., Hansen C.D., McMullan A.C., Milstone L.M., RA Schwartz M.E., McLean W.H., Hull P.R., Smith F.J.; RT "A large mutational study in pachyonychia congenita."; RL J. Invest. Dermatol. 131:1018-1024(2011). RN [26] RP VARIANTS PC1 SER-125; ASP-125; PRO-127 AND CYS-127. RX PubMed=21160496; DOI=10.1038/jid.2010.373; RA Fu T., Leachman S.A., Wilson N.J., Smith F.J., Schwartz M.E., Tang J.Y.; RT "Genotype-phenotype correlations among pachyonychia congenita patients with RT K16 mutations."; RL J. Invest. Dermatol. 131:1025-1028(2011). RN [27] RP VARIANT PC1 GLY-125. RX PubMed=22668561; DOI=10.1684/ejd.2012.1773; RA Du Z.F., Xu C.M., Zhao Y., Liu W.T., Chen X.L., Chen C.Y., Fang H., RA Ke H.P., Zhang X.N.; RT "Two novel de novo mutations of KRT6A and KRT16 genes in two Chinese RT pachyonychia congenita pedigrees with fissured tongue or diffuse plantar RT keratoderma."; RL Eur. J. Dermatol. 22:476-480(2012). RN [28] RP VARIANT PC1 PRO-421. RX PubMed=24118415; DOI=10.1111/exd.12262; RA Paris F., Hurtado C., Azon A., Aguado L., Vizmanos J.L.; RT "A new KRT16 mutation associated with a phenotype of pachyonychia RT congenita."; RL Exp. Dermatol. 22:838-839(2013). CC -!- FUNCTION: Epidermis-specific type I keratin that plays a key role in CC skin. Acts as a regulator of innate immunity in response to skin CC barrier breach: required for some inflammatory checkpoint for the skin CC barrier maintenance. {ECO:0000250|UniProtKB:Q9Z2K1}. CC -!- SUBUNIT: Heterodimer of a type I and a type II keratin. KRT16 CC associates with KRT6 isomers (KRT6A or KRT6B) (By similarity). CC Interacts with TCHP (PubMed:15731013). Interacts with TRADD (By CC similarity). {ECO:0000250|UniProtKB:Q9Z2K1, CC ECO:0000269|PubMed:15731013}. CC -!- INTERACTION: CC P08779; Q9NX04: AIRIM; NbExp=3; IntAct=EBI-356410, EBI-8643161; CC P08779; A2BDD9: AMOT; NbExp=3; IntAct=EBI-356410, EBI-17286414; CC P08779; P53365: ARFIP2; NbExp=3; IntAct=EBI-356410, EBI-638194; CC P08779; Q8TAB5: C1orf216; NbExp=3; IntAct=EBI-356410, EBI-747505; CC P08779; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-356410, EBI-11530605; CC P08779; Q8IYE0: CCDC146; NbExp=3; IntAct=EBI-356410, EBI-10749669; CC P08779; Q96LX7-5: CCDC17; NbExp=3; IntAct=EBI-356410, EBI-12165781; CC P08779; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-356410, EBI-10175300; CC P08779; P24863: CCNC; NbExp=3; IntAct=EBI-356410, EBI-395261; CC P08779; Q07002: CDK18; NbExp=3; IntAct=EBI-356410, EBI-746238; CC P08779; Q9UIA0: CYTH4; NbExp=3; IntAct=EBI-356410, EBI-11521003; CC P08779; Q7L775: EPM2AIP1; NbExp=3; IntAct=EBI-356410, EBI-6255981; CC P08779; O95995: GAS8; NbExp=3; IntAct=EBI-356410, EBI-1052570; CC P08779; P50151: GNG10; NbExp=3; IntAct=EBI-356410, EBI-10211741; CC P08779; O14964: HGS; NbExp=3; IntAct=EBI-356410, EBI-740220; CC P08779; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-356410, EBI-14069005; CC P08779; Q9NSK0: KLC4; NbExp=3; IntAct=EBI-356410, EBI-949319; CC P08779; P04264: KRT1; NbExp=3; IntAct=EBI-356410, EBI-298429; CC P08779; P35908: KRT2; NbExp=3; IntAct=EBI-356410, EBI-1247312; CC P08779; P12035: KRT3; NbExp=3; IntAct=EBI-356410, EBI-2430095; CC P08779; P19013: KRT4; NbExp=3; IntAct=EBI-356410, EBI-2371606; CC P08779; P13647: KRT5; NbExp=3; IntAct=EBI-356410, EBI-702187; CC P08779; P02538: KRT6A; NbExp=3; IntAct=EBI-356410, EBI-702198; CC P08779; P48668: KRT6C; NbExp=3; IntAct=EBI-356410, EBI-2564105; CC P08779; Q3SY84: KRT71; NbExp=3; IntAct=EBI-356410, EBI-2952676; CC P08779; Q14CN4: KRT72; NbExp=3; IntAct=EBI-356410, EBI-1221280; CC P08779; Q86Y46-2: KRT73; NbExp=3; IntAct=EBI-356410, EBI-12039441; CC P08779; Q7RTS7: KRT74; NbExp=3; IntAct=EBI-356410, EBI-968660; CC P08779; Q01546: KRT76; NbExp=3; IntAct=EBI-356410, EBI-2952745; CC P08779; Q8N1N4: KRT78; NbExp=3; IntAct=EBI-356410, EBI-1056564; CC P08779; Q5XKE5: KRT79; NbExp=3; IntAct=EBI-356410, EBI-2514135; CC P08779; P05787: KRT8; NbExp=3; IntAct=EBI-356410, EBI-297852; CC P08779; Q6KB66-2: KRT80; NbExp=3; IntAct=EBI-356410, EBI-11999246; CC P08779; Q14533: KRT81; NbExp=3; IntAct=EBI-356410, EBI-739648; CC P08779; P78385: KRT83; NbExp=3; IntAct=EBI-356410, EBI-10221390; CC P08779; P78386: KRT85; NbExp=3; IntAct=EBI-356410, EBI-1049371; CC P08779; O43790: KRT86; NbExp=3; IntAct=EBI-356410, EBI-9996498; CC P08779; P25800: LMO1; NbExp=3; IntAct=EBI-356410, EBI-8639312; CC P08779; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-356410, EBI-739832; CC P08779; O95983-2: MBD3; NbExp=3; IntAct=EBI-356410, EBI-11978579; CC P08779; Q16512: PKN1; NbExp=3; IntAct=EBI-356410, EBI-602382; CC P08779; Q9UGP5-2: POLL; NbExp=3; IntAct=EBI-356410, EBI-10320765; CC P08779; Q6NYC8: PPP1R18; NbExp=3; IntAct=EBI-356410, EBI-2557469; CC P08779; P54646: PRKAA2; NbExp=3; IntAct=EBI-356410, EBI-1383852; CC P08779; P41219: PRPH; NbExp=3; IntAct=EBI-356410, EBI-752074; CC P08779; Q3MIT2: PUS10; NbExp=3; IntAct=EBI-356410, EBI-11983583; CC P08779; Q9C0C4: SEMA4C; NbExp=3; IntAct=EBI-356410, EBI-10303490; CC P08779; Q96ES7: SGF29; NbExp=4; IntAct=EBI-356410, EBI-743117; CC P08779; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-356410, EBI-358489; CC P08779; Q969G3: SMARCE1; NbExp=3; IntAct=EBI-356410, EBI-455078; CC P08779; O95295: SNAPIN; NbExp=3; IntAct=EBI-356410, EBI-296723; CC P08779; Q9BT92: TCHP; NbExp=3; IntAct=EBI-356410, EBI-740781; CC P08779; Q99816: TSG101; NbExp=3; IntAct=EBI-356410, EBI-346882; CC P08779; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-356410, EBI-9090990; CC P08779; Q8N3L3: TXLNB; NbExp=3; IntAct=EBI-356410, EBI-6116822; CC P08779; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-356410, EBI-739895; CC -!- TISSUE SPECIFICITY: Expressed in the corneal epithelium (at protein CC level). {ECO:0000269|PubMed:26758872}. CC -!- MASS SPECTROMETRY: Mass=50924.66; Method=MALDI; CC Evidence={ECO:0000269|PubMed:11840567}; CC -!- DISEASE: Pachyonychia congenita 1 (PC1) [MIM:167200]: An autosomal CC dominant ectodermal dysplasia characterized by hypertrophic nail CC dystrophy resulting in onchyogryposis (thickening and increase in CC curvature of the nail), palmoplantar keratoderma, follicular CC hyperkeratosis, and oral leukokeratosis. Hyperhidrosis of the hands and CC feet is usually present. {ECO:0000269|PubMed:10521820, CC ECO:0000269|PubMed:10606845, ECO:0000269|PubMed:10839714, CC ECO:0000269|PubMed:11359398, ECO:0000269|PubMed:11886499, CC ECO:0000269|PubMed:16250206, ECO:0000269|PubMed:17719747, CC ECO:0000269|PubMed:21160496, ECO:0000269|PubMed:21326300, CC ECO:0000269|PubMed:22668561, ECO:0000269|PubMed:24118415, CC ECO:0000269|PubMed:7539673}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Keratoderma, palmoplantar, non-epidermolytic, focal 1 CC (FNEPPK1) [MIM:613000]: A dermatological disorder characterized by non- CC epidermolytic palmoplantar keratoderma limited to the pressure points CC on the balls of the feet, with later mild involvement on the palms. CC Oral, genital and follicular keratotic lesions are often present. CC {ECO:0000269|PubMed:8595410}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Note=KRT16 and KRT17 are coexpressed only in pathological CC situations such as metaplasias and carcinomas of the uterine cervix and CC in psoriasis vulgaris. 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 --------------------------------------------------------------------------- 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; M28439; AAA59460.1; -; Genomic_DNA. DR EMBL; M28432; AAA59460.1; JOINED; Genomic_DNA. DR EMBL; M28433; AAA59460.1; JOINED; Genomic_DNA. DR EMBL; M28434; AAA59460.1; JOINED; Genomic_DNA. DR EMBL; M28435; AAA59460.1; JOINED; Genomic_DNA. DR EMBL; M28436; AAA59460.1; JOINED; Genomic_DNA. DR EMBL; M28437; AAA59460.1; JOINED; Genomic_DNA. DR EMBL; M28438; AAA59460.1; JOINED; Genomic_DNA. DR EMBL; S79867; AAB35421.1; -; mRNA. DR EMBL; AF061809; AAD15829.1; -; Genomic_DNA. DR EMBL; AF061812; AAC99326.1; -; mRNA. DR EMBL; AK290853; BAF83542.1; -; mRNA. DR EMBL; CH471152; EAW60749.1; -; Genomic_DNA. DR EMBL; BC039169; AAH39169.1; -; mRNA. DR EMBL; S78514; AAB34564.1; -; Genomic_DNA. DR CCDS; CCDS11401.1; -. DR PIR; A33652; A33652. DR PIR; JC4313; JC4313. DR RefSeq; NP_005548.2; NM_005557.3. DR AlphaFoldDB; P08779; -. DR SMR; P08779; -. DR BioGRID; 110066; 189. DR IntAct; P08779; 99. DR MINT; P08779; -. DR STRING; 9606.ENSP00000301653; -. DR DrugBank; DB01593; Zinc. DR DrugBank; DB14487; Zinc acetate. DR GlyGen; P08779; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P08779; -. DR PhosphoSitePlus; P08779; -. DR SwissPalm; P08779; -. DR BioMuta; KRT16; -. DR DMDM; 23503075; -. DR jPOST; P08779; -. DR MassIVE; P08779; -. DR PaxDb; 9606-ENSP00000301653; -. DR PeptideAtlas; P08779; -. DR PRIDE; P08779; -. DR ProteomicsDB; 52166; -. DR Antibodypedia; 3602; 651 antibodies from 37 providers. DR DNASU; 3868; -. DR Ensembl; ENST00000301653.9; ENSP00000301653.3; ENSG00000186832.9. DR GeneID; 3868; -. DR KEGG; hsa:3868; -. DR MANE-Select; ENST00000301653.9; ENSP00000301653.3; NM_005557.4; NP_005548.2. DR UCSC; uc002hxg.5; human. DR AGR; HGNC:6423; -. DR CTD; 3868; -. DR DisGeNET; 3868; -. DR GeneCards; KRT16; -. DR GeneReviews; KRT16; -. DR HGNC; HGNC:6423; KRT16. DR HPA; ENSG00000186832; Tissue enhanced (cervix, esophagus, skin, vagina). DR MalaCards; KRT16; -. DR MIM; 148067; gene. DR MIM; 167200; phenotype. DR MIM; 613000; phenotype. DR neXtProt; NX_P08779; -. DR OpenTargets; ENSG00000186832; -. DR Orphanet; 2199; Epidermolytic palmoplantar keratoderma. DR Orphanet; 448264; Isolated focal non-epidermolytic palmoplantar keratoderma. DR Orphanet; 2309; Pachyonychia congenita. DR PharmGKB; PA30210; -. DR VEuPathDB; HostDB:ENSG00000186832; -. DR eggNOG; ENOG502QTM6; Eukaryota. DR GeneTree; ENSGT00940000154602; -. DR HOGENOM; CLU_012560_8_3_1; -. DR InParanoid; P08779; -. DR OMA; GHQTRPI; -. DR OrthoDB; 4640531at2759; -. DR PhylomeDB; P08779; -. DR TreeFam; TF332742; -. DR PathwayCommons; P08779; -. DR Reactome; R-HSA-6805567; Keratinization. DR Reactome; R-HSA-6809371; Formation of the cornified envelope. DR SignaLink; P08779; -. DR SIGNOR; P08779; -. DR BioGRID-ORCS; 3868; 24 hits in 1147 CRISPR screens. DR ChiTaRS; KRT16; human. DR GeneWiki; Keratin_16; -. DR GenomeRNAi; 3868; -. DR Pharos; P08779; Tbio. DR PRO; PR:P08779; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P08779; protein. DR Bgee; ENSG00000186832; Expressed in gingival epithelium and 113 other cell types or tissues. DR ExpressionAtlas; P08779; baseline and differential. DR GO; GO:0001533; C:cornified envelope; IEA:Ensembl. DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005882; C:intermediate filament; NAS:UniProtKB. DR GO; GO:0045095; C:keratin filament; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; HDA:UniProtKB. DR GO; GO:0005200; F:structural constituent of cytoskeleton; NAS:UniProtKB. DR GO; GO:0007010; P:cytoskeleton organization; NAS:UniProtKB. DR GO; GO:0030855; P:epithelial cell differentiation; IBA:GO_Central. DR GO; GO:0061436; P:establishment of skin barrier; ISS:UniProtKB. DR GO; GO:0042633; P:hair cycle; IDA:UniProtKB. DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB. DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB. DR GO; GO:0045109; P:intermediate filament organization; IBA:GO_Central. DR GO; GO:0031424; P:keratinization; ISS:UniProtKB. DR GO; GO:0030216; P:keratinocyte differentiation; ISS:UniProtKB. DR GO; GO:0051546; P:keratinocyte migration; ISS:UniProtKB. DR GO; GO:0002009; P:morphogenesis of an epithelium; ISS:UniProtKB. DR GO; GO:0030336; P:negative regulation of cell migration; IDA:UniProtKB. DR FunFam; 1.20.5.1160:FF:000002; Type I keratin 10; 1. DR FunFam; 1.20.5.170:FF:000002; Type I keratin KA11; 1. DR FunFam; 1.20.5.500:FF:000001; Type II keratin 23; 1. 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; IPR002957; Keratin_I. DR PANTHER; PTHR23239; INTERMEDIATE FILAMENT; 1. DR PANTHER; PTHR23239:SF105; KERATIN, TYPE I CYTOSKELETAL 16; 1. DR Pfam; PF00038; Filament; 1. DR PRINTS; PR01248; TYPE1KERATIN. DR SMART; SM01391; Filament; 1. DR SUPFAM; SSF64593; Intermediate filament protein, coiled coil region; 2. DR PROSITE; PS00226; IF_ROD_1; 1. DR PROSITE; PS51842; IF_ROD_2; 1. PE 1: Evidence at protein level; KW Coiled coil; Direct protein sequencing; Disease variant; KW Ectodermal dysplasia; Intermediate filament; Keratin; KW Palmoplantar keratoderma; Proteomics identification; Reference proteome. FT CHAIN 1..473 FT /note="Keratin, type I cytoskeletal 16" FT /id="PRO_0000063662" FT DOMAIN 117..428 FT /note="IF rod" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188" FT REGION 1..116 FT /note="Head" FT REGION 117..152 FT /note="Coil 1A" FT REGION 153..170 FT /note="Linker 1" FT REGION 171..262 FT /note="Coil 1B" FT REGION 263..285 FT /note="Linker 12" FT REGION 286..424 FT /note="Coil 2" FT REGION 425..473 FT /note="Tail" FT REGION 428..473 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VARIANT 104..107 FT /note="Missing (found in a patient with localized FT epidermolytic hyperkeratosis in the right palm and the FT right sole; uncertain significance; somatic mutation)" FT /evidence="ECO:0000269|PubMed:10844556" FT /id="VAR_012854" FT VARIANT 121 FT /note="M -> T (in PC1; dbSNP:rs28928894)" FT /evidence="ECO:0000269|PubMed:11886499" FT /id="VAR_017065" FT VARIANT 122 FT /note="Q -> P (in PC1; dbSNP:rs59349773)" FT /evidence="ECO:0000269|PubMed:10606845" FT /id="VAR_012855" FT VARIANT 124 FT /note="L -> H (in PC1; dbSNP:rs58293603)" FT /evidence="ECO:0000269|PubMed:16250206" FT /id="VAR_072436" FT VARIANT 124 FT /note="L -> P (in PC1; dbSNP:rs58293603)" FT /evidence="ECO:0000269|PubMed:16250206" FT /id="VAR_072437" FT VARIANT 124 FT /note="L -> R (in PC1; dbSNP:rs58293603)" FT /evidence="ECO:0000269|PubMed:10839714" FT /id="VAR_013837" FT VARIANT 125 FT /note="N -> D (in PC1; dbSNP:rs58608173)" FT /evidence="ECO:0000269|PubMed:16250206, FT ECO:0000269|PubMed:21160496" FT /id="VAR_072438" FT VARIANT 125 FT /note="N -> G (in PC1; requires 2 nucleotide substitutions; FT dbSNP:rs587777717)" FT /evidence="ECO:0000269|PubMed:22668561" FT /id="VAR_072439" FT VARIANT 125 FT /note="N -> S (in FNEPPK1 and PC1; dbSNP:rs60723330)" FT /evidence="ECO:0000269|PubMed:16250206, FT ECO:0000269|PubMed:17719747, ECO:0000269|PubMed:21160496, FT ECO:0000269|PubMed:21326300, ECO:0000269|PubMed:8595410" FT /id="VAR_009183" FT VARIANT 127 FT /note="R -> C (in FNEPPK1 and PC1; dbSNP:rs59856285)" FT /evidence="ECO:0000269|PubMed:16250206, FT ECO:0000269|PubMed:21160496, ECO:0000269|PubMed:8595410" FT /id="VAR_009184" FT VARIANT 127 FT /note="R -> P (in PC1; dbSNP:rs57424749)" FT /evidence="ECO:0000269|PubMed:10606845, FT ECO:0000269|PubMed:17719747, ECO:0000269|PubMed:21160496, FT ECO:0000269|PubMed:21326300" FT /id="VAR_012856" FT VARIANT 128 FT /note="L -> Q (in PC1; dbSNP:rs28928895)" FT /evidence="ECO:0000269|PubMed:11886499, FT ECO:0000269|PubMed:17719747" FT /id="VAR_017066" FT VARIANT 130 FT /note="Missing (in PC1)" FT /evidence="ECO:0000269|PubMed:10521820" FT /id="VAR_035440" FT VARIANT 132 FT /note="L -> P (in PC1; dbSNP:rs60944949)" FT /evidence="ECO:0000269|PubMed:16250206, FT ECO:0000269|PubMed:21326300, ECO:0000269|PubMed:7539673" FT /id="VAR_003846" FT VARIANT 354 FT /note="K -> N (in PC1; late onset; dbSNP:rs59328451)" FT /evidence="ECO:0000269|PubMed:11359398" FT /id="VAR_017067" FT VARIANT 421 FT /note="L -> P (in PC1)" FT /evidence="ECO:0000269|PubMed:24118415" FT /id="VAR_072440" FT CONFLICT 2 FT /note="T -> A (in Ref. 3; AAB35421)" FT /evidence="ECO:0000305" FT CONFLICT 26 FT /note="G -> A (in Ref. 1; AAA59460)" FT /evidence="ECO:0000305" FT CONFLICT 38 FT /note="G -> A (in Ref. 1; AAA59460)" FT /evidence="ECO:0000305" FT CONFLICT 41..43 FT /note="RAP -> PA (in Ref. 1; AAA59460)" FT /evidence="ECO:0000305" FT CONFLICT 49..50 FT /note="GL -> A (in Ref. 1; AAA59460)" FT /evidence="ECO:0000305" FT CONFLICT 187..189 FT /note="QPI -> HAL (in Ref. 1; AAA59460)" FT /evidence="ECO:0000305" FT CONFLICT 208..211 FT /note="HELA -> ARTG (in Ref. 1; AAA59460)" FT /evidence="ECO:0000305" FT CONFLICT 352 FT /note="S -> R (in Ref. 1; AAA59460)" FT /evidence="ECO:0000305" FT CONFLICT 452..460 FT /note="SRQTRPILK -> AVRPGPSS (in Ref. 1; AAA59460)" FT /evidence="ECO:0000305" SQ SEQUENCE 473 AA; 51268 MW; BA8CE9F4716A88A4 CRC64; MTTCSRQFTS SSSMKGSCGI GGGIGGGSSR ISSVLAGGSC RAPSTYGGGL SVSSRFSSGG ACGLGGGYGG GFSSSSSFGS GFGGGYGGGL GAGFGGGLGA GFGGGFAGGD GLLVGSEKVT MQNLNDRLAS YLDKVRALEE ANADLEVKIR DWYQRQRPSE IKDYSPYFKT IEDLRNKIIA ATIENAQPIL QIDNARLAAD DFRTKYEHEL ALRQTVEADV NGLRRVLDEL TLARTDLEMQ IEGLKEELAY LRKNHEEEML ALRGQTGGDV NVEMDAAPGV DLSRILNEMR DQYEQMAEKN RRDAETWFLS KTEELNKEVA SNSELVQSSR SEVTELRRVL QGLEIELQSQ LSMKASLENS LEETKGRYCM QLSQIQGLIG SVEEQLAQLR CEMEQQSQEY QILLDVKTRL EQEIATYRRL LEGEDAHLSS QQASGQSYSS REVFTSSSSS SSRQTRPILK EQSSSSFSQG QSS //