K2C6B_HUMAN
ID K2C6B_HUMAN Reviewed; 564 AA.
AC P04259; P48669;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 26-MAY-2009, sequence version 5.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Keratin, type II cytoskeletal 6B;
DE AltName: Full=Cytokeratin-6B;
DE Short=CK-6B;
DE AltName: Full=Keratin-6B;
DE Short=K6B;
DE AltName: Full=Type-II keratin Kb10;
GN Name=KRT6B; Synonyms=K6B, KRTL1;
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], AND VARIANTS SER-21; SER-227 AND
RP VAL-365.
RC TISSUE=Skin;
RX PubMed=7543104; DOI=10.1074/jbc.270.31.18581;
RA Takahashi K., Paladini R.D., Coulombe P.A.;
RT "Cloning and characterization of multiple human genes and cDNAs encoding
RT highly related type II keratin 6 isoforms.";
RL J. Biol. Chem. 270:18581-18592(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-21; SER-227 AND
RP VAL-365.
RX PubMed=2410904; DOI=10.1073/pnas.82.14.4683;
RA Tyner A.L., Eichman M.J., Fuchs E.;
RT "The sequence of a type II keratin gene expressed in human skin:
RT conservation of structure among all intermediate filament genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:4683-4687(1985).
RN [3]
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 [4]
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 [5]
RP PROTEIN SEQUENCE OF 2-9; 16-24; 31-40; 43-86; 169-189; 195-204; 208-369;
RP 376-386; 425-436; 456-475 AND 534-550, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lung carcinoma;
RA Bienvenut W.V., Vousden K.H., Lukashchuk N.;
RL Submitted (MAR-2008) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 195-203 AND 350-356.
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 [7]
RP VARIANT PC4 LYS-472.
RX PubMed=9618173; DOI=10.1093/hmg/7.7.1143;
RA Smith F.J.D., Jonkman M.F., van Goor H., Coleman C.M., Covello S.P.,
RA Uitto J., McLean W.H.I.;
RT "A mutation in human keratin K6b produces a phenocopy of the K17 disorder
RT pachyonychia congenita type 2.";
RL Hum. Mol. Genet. 7:1143-1148(1998).
RN [8]
RP VARIANT PC4 LYS-472.
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 [9]
RP VARIANT PC4 LYS-472.
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).
CC -!- SUBUNIT: Heterodimer of a type I and a type II keratin. KRT6 isomers
CC associate with KRT16 and/or KRT17.
CC -!- INTERACTION:
CC P04259; Q08379: GOLGA2; NbExp=3; IntAct=EBI-740907, EBI-618309;
CC P04259; Q9BVG8: KIFC3; NbExp=3; IntAct=EBI-740907, EBI-2125614;
CC P04259; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-740907, EBI-14069005;
CC P04259; A1A4E9: KRT13; NbExp=3; IntAct=EBI-740907, EBI-10171552;
CC P04259; P13646: KRT13; NbExp=3; IntAct=EBI-740907, EBI-1223876;
CC P04259; P19012: KRT15; NbExp=7; IntAct=EBI-740907, EBI-739566;
CC P04259; P08727: KRT19; NbExp=4; IntAct=EBI-740907, EBI-742756;
CC P04259; Q7Z3Z0: KRT25; NbExp=3; IntAct=EBI-740907, EBI-11980019;
CC P04259; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-740907, EBI-3044087;
CC P04259; Q7Z3Y7: KRT28; NbExp=5; IntAct=EBI-740907, EBI-11980489;
CC P04259; Q15323: KRT31; NbExp=6; IntAct=EBI-740907, EBI-948001;
CC P04259; Q14525: KRT33B; NbExp=5; IntAct=EBI-740907, EBI-1049638;
CC P04259; Q92764: KRT35; NbExp=3; IntAct=EBI-740907, EBI-1058674;
CC P04259; O76014: KRT37; NbExp=3; IntAct=EBI-740907, EBI-1045716;
CC P04259; O76015: KRT38; NbExp=8; IntAct=EBI-740907, EBI-1047263;
CC P04259; Q6A163: KRT39; NbExp=3; IntAct=EBI-740907, EBI-11958242;
CC P04259; Q6A162: KRT40; NbExp=3; IntAct=EBI-740907, EBI-10171697;
CC P04259; O14777: NDC80; NbExp=3; IntAct=EBI-740907, EBI-715849;
CC P04259; P37198: NUP62; NbExp=3; IntAct=EBI-740907, EBI-347978;
CC P04259; O43482: OIP5; NbExp=3; IntAct=EBI-740907, EBI-536879;
CC P04259; Q8IYF3-3: TEX11; NbExp=3; IntAct=EBI-740907, EBI-11523345;
CC P04259; Q9UBB9: TFIP11; NbExp=6; IntAct=EBI-740907, EBI-1105213;
CC P04259; Q9BYV2: TRIM54; NbExp=6; IntAct=EBI-740907, EBI-2130429;
CC P04259; Q9UGJ1-2: TUBGCP4; NbExp=3; IntAct=EBI-740907, EBI-10964469;
CC -!- TISSUE SPECIFICITY: Constitutively expressed in distinct types of
CC epithelia such as those in oral mucosa, esophagus, papillae of tongue
CC and hair follicle outer root sheath.
CC -!- DISEASE: Pachyonychia congenita 4 (PC4) [MIM:615728]: An autosomal
CC dominant genodermatosis characterized by hypertrophic nail dystrophy,
CC painful and highly debilitating plantar keratoderma, oral
CC leukokeratosis, and a variety of epidermal cysts.
CC {ECO:0000269|PubMed:16250206, ECO:0000269|PubMed:21326300,
CC ECO:0000269|PubMed:9618173}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: There are at least six isoforms of human type II
CC keratin-6 (K6).
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 -!- WEB RESOURCE: Name=Human Intermediate Filament Mutation Database;
CC URL="http://www.interfil.org";
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DR EMBL; L42592; AAC41768.1; -; Genomic_DNA.
DR EMBL; L42584; AAC41768.1; JOINED; Genomic_DNA.
DR EMBL; L42585; AAC41768.1; JOINED; Genomic_DNA.
DR EMBL; L42586; AAC41768.1; JOINED; Genomic_DNA.
DR EMBL; L42587; AAC41768.1; JOINED; Genomic_DNA.
DR EMBL; L42588; AAC41768.1; JOINED; Genomic_DNA.
DR EMBL; L42589; AAC41768.1; JOINED; Genomic_DNA.
DR EMBL; L42590; AAC41768.1; JOINED; Genomic_DNA.
DR EMBL; L42612; AAC41771.1; -; mRNA.
DR EMBL; L00205; AAA59466.1; -; Genomic_DNA.
DR EMBL; M11229; AAA59466.1; JOINED; Genomic_DNA.
DR EMBL; L00198; AAA59466.1; JOINED; Genomic_DNA.
DR EMBL; L00199; AAA59466.1; JOINED; Genomic_DNA.
DR EMBL; L00200; AAA59466.1; JOINED; Genomic_DNA.
DR EMBL; L00201; AAA59466.1; JOINED; Genomic_DNA.
DR EMBL; L00202; AAA59466.1; JOINED; Genomic_DNA.
DR EMBL; L00203; AAA59466.1; JOINED; Genomic_DNA.
DR EMBL; L00204; AAA59466.1; JOINED; Genomic_DNA.
DR EMBL; AC055736; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034535; AAH34535.1; -; mRNA.
DR CCDS; CCDS8828.1; -.
DR PIR; I61767; KRHUEB.
DR PIR; I61771; I61771.
DR RefSeq; NP_005546.2; NM_005555.3.
DR AlphaFoldDB; P04259; -.
DR SMR; P04259; -.
DR BioGRID; 110052; 86.
DR IntAct; P04259; 50.
DR MINT; P04259; -.
DR STRING; 9606.ENSP00000252252; -.
DR Allergome; 415; Hom s 5.
DR GlyGen; P04259; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P04259; -.
DR PhosphoSitePlus; P04259; -.
DR SwissPalm; P04259; -.
DR BioMuta; KRT6B; -.
DR DMDM; 238054404; -.
DR EPD; P04259; -.
DR jPOST; P04259; -.
DR MassIVE; P04259; -.
DR PaxDb; P04259; -.
DR PeptideAtlas; P04259; -.
DR PRIDE; P04259; -.
DR ProteomicsDB; 51693; -.
DR TopDownProteomics; P04259; -.
DR Antibodypedia; 43084; 183 antibodies from 22 providers.
DR DNASU; 3854; -.
DR Ensembl; ENST00000252252.4; ENSP00000252252.3; ENSG00000185479.6.
DR GeneID; 3854; -.
DR KEGG; hsa:3854; -.
DR MANE-Select; ENST00000252252.4; ENSP00000252252.3; NM_005555.4; NP_005546.2.
DR UCSC; uc001sak.3; human.
DR CTD; 3854; -.
DR DisGeNET; 3854; -.
DR GeneCards; KRT6B; -.
DR GeneReviews; KRT6B; -.
DR HGNC; HGNC:6444; KRT6B.
DR HPA; ENSG00000185479; Tissue enriched (esophagus).
DR MalaCards; KRT6B; -.
DR MIM; 148042; gene.
DR MIM; 615728; phenotype.
DR neXtProt; NX_P04259; -.
DR OpenTargets; ENSG00000185479; -.
DR Orphanet; 2309; Pachyonychia congenita.
DR PharmGKB; PA30232; -.
DR VEuPathDB; HostDB:ENSG00000185479; -.
DR eggNOG; ENOG502QURK; Eukaryota.
DR GeneTree; ENSGT00940000154600; -.
DR HOGENOM; CLU_012560_6_1_1; -.
DR InParanoid; P04259; -.
DR OMA; XINKRTA; -.
DR OrthoDB; 824246at2759; -.
DR PhylomeDB; P04259; -.
DR TreeFam; TF317854; -.
DR PathwayCommons; P04259; -.
DR Reactome; R-HSA-6805567; Keratinization.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; P04259; -.
DR BioGRID-ORCS; 3854; 14 hits in 998 CRISPR screens.
DR ChiTaRS; KRT6B; human.
DR GenomeRNAi; 3854; -.
DR Pharos; P04259; Tbio.
DR PRO; PR:P04259; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P04259; protein.
DR Bgee; ENSG00000185479; Expressed in gingiva and 105 other tissues.
DR Genevisible; P04259; HS.
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:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0030280; F:structural constituent of skin epidermis; IBA:GO_Central.
DR GO; GO:0007398; P:ectoderm development; TAS:ProtInc.
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 Acetylation; Coiled coil; Direct protein sequencing; Disease variant;
KW Ectodermal dysplasia; Intermediate filament; Keratin;
KW Palmoplantar keratoderma; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.5"
FT CHAIN 2..564
FT /note="Keratin, type II cytoskeletal 6B"
FT /id="PRO_0000063732"
FT DOMAIN 163..476
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..162
FT /note="Head"
FT REGION 163..198
FT /note="Coil 1A"
FT REGION 199..217
FT /note="Linker 1"
FT REGION 218..309
FT /note="Coil 1B"
FT REGION 310..333
FT /note="Linker 12"
FT REGION 334..472
FT /note="Coil 2"
FT REGION 473..564
FT /note="Tail"
FT REGION 533..564
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 414
FT /note="Stutter"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.5"
FT VARIANT 21
FT /note="N -> S (in dbSNP:rs428894)"
FT /evidence="ECO:0000269|PubMed:2410904,
FT ECO:0000269|PubMed:7543104"
FT /id="VAR_021265"
FT VARIANT 227
FT /note="N -> S (in dbSNP:rs652423)"
FT /evidence="ECO:0000269|PubMed:2410904,
FT ECO:0000269|PubMed:7543104"
FT /id="VAR_021266"
FT VARIANT 365
FT /note="I -> V (in dbSNP:rs437014)"
FT /evidence="ECO:0000269|PubMed:2410904,
FT ECO:0000269|PubMed:7543104"
FT /id="VAR_021267"
FT VARIANT 472
FT /note="E -> K (in PC4; dbSNP:rs60627726)"
FT /evidence="ECO:0000269|PubMed:16250206,
FT ECO:0000269|PubMed:21326300, ECO:0000269|PubMed:9618173"
FT /id="VAR_023062"
FT CONFLICT 89..90
FT /note="GS -> AG (in Ref. 2; AAA59466)"
FT /evidence="ECO:0000305"
FT CONFLICT 116..117
FT /note="AG -> PA (in Ref. 2; AAA59466)"
FT /evidence="ECO:0000305"
FT CONFLICT 119..121
FT /note="AGG -> LC (in Ref. 2; AAA59466)"
FT /evidence="ECO:0000305"
FT CONFLICT 159..160
FT /note="VR -> IG (in Ref. 2; AAA59466)"
FT /evidence="ECO:0000305"
FT CONFLICT 255
FT /note="D -> V (in Ref. 2; AAA59466)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 564 AA; 60067 MW; FFA4C351FBF09F09 CRC64;
MASTSTTIRS HSSSRRGFSA NSARLPGVSR SGFSSISVSR SRGSGGLGGA CGGAGFGSRS
LYGLGGSKRI SIGGGSCAIS GGYGSRAGGS YGFGGAGSGF GFGGGAGIGF GLGGGAGLAG
GFGGPGFPVC PPGGIQEVTV NQSLLTPLNL QIDPAIQRVR AEEREQIKTL NNKFASFIDK
VRFLEQQNKV LDTKWTLLQE QGTKTVRQNL EPLFEQYINN LRRQLDNIVG ERGRLDSELR
NMQDLVEDLK NKYEDEINKR TAAENEFVTL KKDVDAAYMN KVELQAKADT LTDEINFLRA
LYDAELSQMQ THISDTSVVL SMDNNRNLDL DSIIAEVKAQ YEEIAQRSRA EAESWYQTKY
EELQITAGRH GDDLRNTKQE IAEINRMIQR LRSEIDHVKK QCANLQAAIA DAEQRGEMAL
KDAKNKLEGL EDALQKAKQD LARLLKEYQE LMNVKLALDV EIATYRKLLE GEECRLNGEG
VGQVNISVVQ STVSSGYGGA SGVGSGLGLG GGSSYSYGSG LGVGGGFSSS SGRATGGGLS
SVGGGSSTIK YTTTSSSSRK SYKH
