ID K2C3_HUMAN Reviewed; 628 AA. AC P12035; A6NIS2; Q701L8; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 3. DT 27-MAR-2024, entry version 208. DE RecName: Full=Keratin, type II cytoskeletal 3; DE AltName: Full=65 kDa cytokeratin; DE AltName: Full=Cytokeratin-3; DE Short=CK-3; DE AltName: Full=Keratin-3; DE Short=K3; DE AltName: Full=Type-II keratin Kb3; GN Name=KRT3; 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 VARIANT GLY-375. RX PubMed=2439698; DOI=10.1007/bf02134130; RA Klinge E.M., Sylvestre Y.R., Freedberg I.M., Blumenberg M.; RT "Evolution of keratin genes: different protein domains evolve by different RT pathways."; RL J. Mol. Evol. 24:319-329(1987). 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 [MRNA] OF 16-628. RC TISSUE=Eye; RX PubMed=15737194; DOI=10.1111/j.0022-202x.2004.23530.x; RA Rogers M.A., Edler L., Winter H., Langbein L., Beckmann I., Schweizer J.; RT "Characterization of new members of the human type II keratin gene family RT and a general evaluation of the keratin gene domain on chromosome RT 12q13.13."; RL J. Invest. Dermatol. 124:536-544(2005). RN [4] RP VARIANT MECD2 LYS-509, AND INVOLVEMENT IN MECD2. RX PubMed=9171831; DOI=10.1038/ng0697-184; RA Irvine A.D., Corden L.D., Swensson O., Swensson B., Moore J.E., RA Frazer D.G., Smith F.J.D., Knowlton R.G., Christophers E., Rochels R., RA Uitto J., McLean W.H.I.; RT "Mutations in cornea-specific keratin K3 or K12 genes cause Meesmann's RT corneal dystrophy."; RL Nat. Genet. 16:184-187(1997). RN [5] RP VARIANT MECD2 PRO-503, AND INVOLVEMENT IN MECD2. RX PubMed=16227835; DOI=10.1097/01.ico.0000159732.29930.26; RA Chen Y.T., Tseng S.H., Chao S.C.; RT "Novel mutations in the helix termination motif of keratin 3 and keratin 12 RT in 2 Taiwanese families with Meesmann corneal dystrophy."; RL Cornea 24:928-932(2005). CC -!- SUBUNIT: Heterotetramer of two type I and two type II keratins. CC Keratin-3 associates with keratin-12. CC -!- INTERACTION: CC P12035; Q9NP55: BPIFA1; NbExp=3; IntAct=EBI-2430095, EBI-953896; CC P12035; Q6ZUJ4: C3orf62; NbExp=3; IntAct=EBI-2430095, EBI-2837036; CC P12035; Q8NCU1: CCDC197; NbExp=3; IntAct=EBI-2430095, EBI-750686; CC P12035; Q05D60: DEUP1; NbExp=3; IntAct=EBI-2430095, EBI-748597; CC P12035; Q96CS2: HAUS1; NbExp=3; IntAct=EBI-2430095, EBI-2514791; CC P12035; O14964: HGS; NbExp=3; IntAct=EBI-2430095, EBI-740220; CC P12035; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-2430095, EBI-14069005; CC P12035; P02533: KRT14; NbExp=3; IntAct=EBI-2430095, EBI-702178; CC P12035; P08779: KRT16; NbExp=3; IntAct=EBI-2430095, EBI-356410; CC P12035; P08727: KRT19; NbExp=3; IntAct=EBI-2430095, EBI-742756; CC P12035; P35900: KRT20; NbExp=3; IntAct=EBI-2430095, EBI-742094; CC P12035; Q2M2I5: KRT24; NbExp=3; IntAct=EBI-2430095, EBI-2952736; CC P12035; Q7Z3Z0: KRT25; NbExp=3; IntAct=EBI-2430095, EBI-11980019; CC P12035; Q7Z3Y9: KRT26; NbExp=3; IntAct=EBI-2430095, EBI-12084444; CC P12035; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-2430095, EBI-3044087; CC P12035; Q7Z3Y7: KRT28; NbExp=5; IntAct=EBI-2430095, EBI-11980489; CC P12035; Q15323: KRT31; NbExp=3; IntAct=EBI-2430095, EBI-948001; CC P12035; Q14525: KRT33B; NbExp=3; IntAct=EBI-2430095, EBI-1049638; CC P12035; O76011: KRT34; NbExp=5; IntAct=EBI-2430095, EBI-1047093; CC P12035; Q92764: KRT35; NbExp=3; IntAct=EBI-2430095, EBI-1058674; CC P12035; O76013-2: KRT36; NbExp=5; IntAct=EBI-2430095, EBI-11958506; CC P12035; O76014: KRT37; NbExp=3; IntAct=EBI-2430095, EBI-1045716; CC P12035; O76015: KRT38; NbExp=3; IntAct=EBI-2430095, EBI-1047263; CC P12035; Q6A163: KRT39; NbExp=3; IntAct=EBI-2430095, EBI-11958242; CC P12035; O95678: KRT75; NbExp=3; IntAct=EBI-2430095, EBI-2949715; CC P12035; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-2430095, EBI-11953846; CC P12035; Q9UBR4-2: LHX3; NbExp=3; IntAct=EBI-2430095, EBI-12039345; CC P12035; Q96LR2: LURAP1; NbExp=3; IntAct=EBI-2430095, EBI-741355; CC P12035; P37198: NUP62; NbExp=3; IntAct=EBI-2430095, EBI-347978; CC P12035; O43482: OIP5; NbExp=3; IntAct=EBI-2430095, EBI-536879; CC P12035; Q58EX7: PLEKHG4; NbExp=3; IntAct=EBI-2430095, EBI-949255; CC P12035; Q86UD0: SAPCD2; NbExp=3; IntAct=EBI-2430095, EBI-2561646; CC P12035; Q96R06: SPAG5; NbExp=3; IntAct=EBI-2430095, EBI-413317; CC P12035; Q13077: TRAF1; NbExp=3; IntAct=EBI-2430095, EBI-359224; CC P12035; P14373: TRIM27; NbExp=3; IntAct=EBI-2430095, EBI-719493; CC P12035; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-2430095, EBI-2130429; CC P12035; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-2430095, EBI-12040603; CC P12035; Q9BUY5: ZNF426; NbExp=3; IntAct=EBI-2430095, EBI-743265; CC P12035; G4XUV3; NbExp=3; IntAct=EBI-2430095, EBI-10177989; CC -!- TISSUE SPECIFICITY: Cornea specific. CC -!- DISEASE: Corneal dystrophy, Meesmann 2 (MECD2) [MIM:618767]: A form of CC Meesmann corneal dystrophy, a corneal disease characterized by CC fragility of the anterior corneal epithelium. Histological examination CC shows a disorganized and thickened epithelium with widespread CC cytoplasmic vacuolation and numerous small, round, debris-laden CC intraepithelial cysts. Patients are usually asymptomatic until CC adulthood when rupture of the corneal microcysts may cause erosions, CC producing clinical symptoms such as photophobia, contact lens CC intolerance and intermittent diminution of visual acuity. Rarely, CC subepithelial scarring causes irregular corneal astigmatism and CC permanent visual impairment. MECD2 inheritance is autosomal dominant. CC {ECO:0000269|PubMed:16227835, ECO:0000269|PubMed:9171831}. 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 -!- SIMILARITY: Belongs to the intermediate filament family. CC {ECO:0000255|PROSITE-ProRule:PRU01188}. CC -!- SEQUENCE CAUTION: CC Sequence=CAF31522.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Keratin-3 entry; CC URL="https://en.wikipedia.org/wiki/Keratin_3"; 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; X05418; CAA28991.1; -; Genomic_DNA. DR EMBL; X05419; CAA28992.1; -; Genomic_DNA. DR EMBL; X05420; CAA28993.1; -; Genomic_DNA. DR EMBL; X05420; CAA28994.1; -; Genomic_DNA. DR EMBL; X05420; CAA28995.1; -; Genomic_DNA. DR EMBL; X05421; CAA28996.1; -; Genomic_DNA. DR EMBL; AC107016; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJ628418; CAF31522.1; ALT_INIT; mRNA. DR CCDS; CCDS44895.1; -. DR PIR; A29666; A29666. DR RefSeq; NP_476429.2; NM_057088.2. DR AlphaFoldDB; P12035; -. DR SMR; P12035; -. DR BioGRID; 110048; 86. DR IntAct; P12035; 51. DR STRING; 9606.ENSP00000413479; -. DR GlyGen; P12035; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P12035; -. DR PhosphoSitePlus; P12035; -. DR SwissPalm; P12035; -. DR BioMuta; KRT3; -. DR DMDM; 313104225; -. DR jPOST; P12035; -. DR MassIVE; P12035; -. DR PaxDb; 9606-ENSP00000413479; -. DR PeptideAtlas; P12035; -. DR PRIDE; P12035; -. DR ProteomicsDB; 52820; -. DR Antibodypedia; 7889; 217 antibodies from 28 providers. DR DNASU; 3850; -. DR Ensembl; ENST00000417996.2; ENSP00000413479.2; ENSG00000186442.7. DR GeneID; 3850; -. DR KEGG; hsa:3850; -. DR MANE-Select; ENST00000417996.2; ENSP00000413479.2; NM_057088.3; NP_476429.2. DR UCSC; uc001say.4; human. DR AGR; HGNC:6440; -. DR CTD; 3850; -. DR DisGeNET; 3850; -. DR GeneCards; KRT3; -. DR HGNC; HGNC:6440; KRT3. DR HPA; ENSG00000186442; Group enriched (esophagus, salivary gland). DR MalaCards; KRT3; -. DR MIM; 148043; gene. DR MIM; 618767; phenotype. DR neXtProt; NX_P12035; -. DR OpenTargets; ENSG00000186442; -. DR Orphanet; 98954; Meesmann corneal dystrophy. DR PharmGKB; PA30228; -. DR VEuPathDB; HostDB:ENSG00000186442; -. DR eggNOG; ENOG502QURK; Eukaryota. DR GeneTree; ENSGT00940000162629; -. DR HOGENOM; CLU_012560_6_0_1; -. DR InParanoid; P12035; -. DR OMA; XLGELQT; -. DR OrthoDB; 4640531at2759; -. DR PhylomeDB; P12035; -. DR TreeFam; TF332742; -. DR PathwayCommons; P12035; -. DR Reactome; R-HSA-6805567; Keratinization. DR Reactome; R-HSA-6809371; Formation of the cornified envelope. DR SignaLink; P12035; -. DR BioGRID-ORCS; 3850; 11 hits in 1143 CRISPR screens. DR GeneWiki; Keratin_3; -. DR GenomeRNAi; 3850; -. DR Pharos; P12035; Tbio. DR PRO; PR:P12035; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P12035; Protein. DR Bgee; ENSG00000186442; Expressed in gingiva and 23 other cell types or tissues. 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:0030280; F:structural constituent of skin epidermis; IBA:GO_Central. DR GO; GO:0030855; P:epithelial cell differentiation; ISS:UniProtKB. DR GO; GO:0045104; P:intermediate filament cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0045109; P:intermediate filament organization; IBA:GO_Central. DR GO; GO:0031424; P:keratinization; IBA:GO_Central. 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; IPR032444; Keratin_2_head. DR InterPro; IPR003054; Keratin_II. DR PANTHER; PTHR45616; GATA-TYPE DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR45616:SF38; KERATIN, TYPE II CYTOSKELETAL 3; 1. DR Pfam; PF00038; Filament; 1. DR Pfam; PF16208; Keratin_2_head; 2. DR PRINTS; PR01276; TYPE2KERATIN. DR SMART; SM01391; Filament; 1. DR SUPFAM; SSF64593; Intermediate filament protein, coiled coil region; 3. DR PROSITE; PS00226; IF_ROD_1; 1. DR PROSITE; PS51842; IF_ROD_2; 1. DR Genevisible; P12035; HS. PE 1: Evidence at protein level; KW Coiled coil; Corneal dystrophy; Disease variant; Intermediate filament; KW Keratin; Methylation; Phosphoprotein; Reference proteome. FT CHAIN 1..628 FT /note="Keratin, type II cytoskeletal 3" FT /id="PRO_0000063716" FT DOMAIN 198..513 FT /note="IF rod" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188" FT REGION 1..197 FT /note="Head" FT REGION 1..21 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 198..233 FT /note="Coil 1A" FT REGION 234..254 FT /note="Linker 1" FT REGION 255..346 FT /note="Coil 1B" FT REGION 347..370 FT /note="Linker 12" FT REGION 371..509 FT /note="Coil 2" FT REGION 510..628 FT /note="Tail" FT REGION 605..628 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 13 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04264" FT MOD_RES 56 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04264" FT MOD_RES 296 FT /note="N6,N6-dimethyllysine" FT /evidence="ECO:0000250|UniProtKB:P04264" FT MOD_RES 364 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04264" FT VARIANT 44 FT /note="G -> A (in dbSNP:rs28721426)" FT /id="VAR_061297" FT VARIANT 375 FT /note="R -> G (in dbSNP:rs3887954)" FT /evidence="ECO:0000269|PubMed:2439698" FT /id="VAR_056023" FT VARIANT 503 FT /note="R -> P (in MECD2; dbSNP:rs60410063)" FT /evidence="ECO:0000269|PubMed:16227835" FT /id="VAR_031327" FT VARIANT 509 FT /note="E -> K (in MECD2; dbSNP:rs57872071)" FT /evidence="ECO:0000269|PubMed:9171831" FT /id="VAR_003868" FT CONFLICT 162 FT /note="G -> A (in Ref. 1; CAA28991)" FT /evidence="ECO:0000305" FT CONFLICT 175 FT /note="I -> T (in Ref. 1; CAA28991)" FT /evidence="ECO:0000305" FT CONFLICT 184 FT /note="N -> K (in Ref. 1; CAA28991)" FT /evidence="ECO:0000305" FT CONFLICT 187 FT /note="I -> T (in Ref. 1; CAA28991)" FT /evidence="ECO:0000305" FT CONFLICT 298 FT /note="T -> Y (in Ref. 1; CAA28993)" FT /evidence="ECO:0000305" FT CONFLICT 397 FT /note="L -> M (in Ref. 1; CAA28996)" FT /evidence="ECO:0000305" FT CONFLICT 409 FT /note="D -> G (in Ref. 3; CAF31522)" FT /evidence="ECO:0000305" FT CONFLICT 448 FT /note="E -> Q (in Ref. 1; CAA28996)" FT /evidence="ECO:0000305" FT CONFLICT 511 FT /note="Y -> YS (in Ref. 1; CAA28996)" FT /evidence="ECO:0000305" FT CONFLICT 562 FT /note="S -> I (in Ref. 1; CAA28996)" FT /evidence="ECO:0000305" FT CONFLICT 580 FT /note="S -> T (in Ref. 1; CAA28996)" FT /evidence="ECO:0000305" SQ SEQUENCE 628 AA; 64417 MW; 65FDB8CAA7F3C960 CRC64; MSRQASKTSG GGSQGFSGRS AVVSGSSRMS CVAHSGGAGG GAYGFRSGAG GFGSRSLYNL GGNKSISISV AAGGSRAGGF GGGRSSCAFA GGYGGGFGSG YGGGFGGGFG GGRGMGGGFG GAGGFGGAGG FGGAGGFGGP GGFGGSGGFG GPGSLGSPGG FGPGGFPGGI QEVTINQSLL QPLNVEIDPQ IGQVKAQERE QIKTLNNKFA SFIDKVRFLE QQNKVLETKW NLLQQQGTSS ISGTNNLEPL FENHINYLRS YLDNILGERG RLDSELKNME DLVEDFKKKY EDEINKRTAA ENEFVTLKKD VDSAYMNKVE LQAKVDALID EIDFLRTLYD AELSQMQSHI SDTSVVLSMD NNRSLDLDSI IAEVRAQYED IAQRSKAEAE ALYQTKLGEL QTTAGRHGDD LRNTKSEIIE LNRMIQRLRA EIEGVKKQNA NLQTAIAEAE QHGEMALKDA NAKLQELQAA LQQAKDDLAR LLRDYQELMN VKLALDVEIA TYRKLLEGEE YRMSGECPSA VSISVVSSST TSASAGGYGG GYGGGMGGGL GGGFSAGGGS GSGFGRGGGG GIGGGFGGGS SGFSGGSGFG SISGARYGVS GGGFSSASNR GGSIKFSQSS QSSQRYSR //