K2C3_HUMAN
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 03-AUG-2022, entry version 199.
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=Human Intermediate Filament Mutation Database;
CC URL="http://www.interfil.org";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Keratin-3 entry;
CC URL="https://en.wikipedia.org/wiki/Keratin_3";
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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; 85.
DR IntAct; P12035; 46.
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; P12035; -.
DR PeptideAtlas; P12035; -.
DR PRIDE; P12035; -.
DR ProteomicsDB; 52820; -.
DR Antibodypedia; 7889; 180 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 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; DSEMRNM; -.
DR OrthoDB; 824246at2759; -.
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; 10 hits in 1065 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 tissues.
DR Genevisible; P12035; HS.
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 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; 2.
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; 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
