ID RPC1_HUMAN Reviewed; 1390 AA. AC O14802; Q8IW34; Q8TCW5; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 23-SEP-2008, sequence version 2. DT 27-MAR-2024, entry version 195. DE RecName: Full=DNA-directed RNA polymerase III subunit RPC1; DE Short=RNA polymerase III subunit C1; DE EC=2.7.7.6 {ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:33335104, ECO:0000269|PubMed:33558764, ECO:0000269|PubMed:34675218, ECO:0000269|PubMed:9331371}; DE AltName: Full=DNA-directed RNA polymerase III largest subunit; DE AltName: Full=DNA-directed RNA polymerase III subunit A; DE AltName: Full=RNA polymerase III 155 kDa subunit; DE Short=RPC155 {ECO:0000303|PubMed:9331371}; DE AltName: Full=RNA polymerase III subunit C160; GN Name=POLR3A {ECO:0000312|HGNC:HGNC:30074}; 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], FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=9331371; DOI=10.1101/gr.7.10.1006; RA Sepehri S., Hernandez N.; RT "The largest subunit of human RNA polymerase III is closely related to the RT largest subunit of yeast and trypanosome RNA polymerase III."; RL Genome Res. 7:1006-1019(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterus; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 1-374. RX PubMed=12384934; DOI=10.1002/art.10521; RA Kuwana M., Kimura K., Kawakami Y.; RT "Identification of an immunodominant epitope on RNA polymerase III RT recognized by systemic sclerosis sera: application to enzyme-linked RT immunosorbent assay."; RL Arthritis Rheum. 46:2742-2747(2002). RN [6] RP INTERACTION WITH PKP2, AND SUBCELLULAR LOCATION. RX PubMed=11416169; DOI=10.1073/pnas.141219498; RA Mertens C., Hofmann I., Wang Z., Teichmann M., Sepehri Chong S., RA Schnoelzer M., Franke W.W.; RT "Nuclear particles containing RNA polymerase III complexes associated with RT the junctional plaque protein plakophilin 2."; RL Proc. Natl. Acad. Sci. U.S.A. 98:7795-7800(2001). RN [7] RP IDENTIFICATION IN THE RNA POL III COMPLEX, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=12391170; DOI=10.1128/mcb.22.22.8044-8055.2002; RA Hu P., Wu S., Sun Y., Yuan C.-C., Kobayashi R., Myers M.P., Hernandez N.; RT "Characterization of human RNA polymerase III identifies orthologues for RT Saccharomyces cerevisiae RNA polymerase III subunits."; RL Mol. Cell. Biol. 22:8044-8055(2002). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=19631370; DOI=10.1016/j.cell.2009.06.015; RA Chiu Y.-H., Macmillan J.B., Chen Z.J.; RT "RNA polymerase III detects cytosolic DNA and induces type I interferons RT through the RIG-I pathway."; RL Cell 138:576-591(2009). RN [9] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=19609254; DOI=10.1038/ni.1779; RA Ablasser A., Bauernfeind F., Hartmann G., Latz E., Fitzgerald K.A., RA Hornung V.; RT "RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA RT polymerase III-transcribed RNA intermediate."; RL Nat. Immunol. 10:1065-1072(2009). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-445, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [11] RP FUNCTION OF POL III. RX PubMed=20413673; DOI=10.1101/gr.101337.109; RA Canella D., Praz V., Reina J.H., Cousin P., Hernandez N.; RT "Defining the RNA polymerase III transcriptome: Genome-wide localization of RT the RNA polymerase III transcription machinery in human cells."; RL Genome Res. 20:710-721(2010). 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 FUNCTION OF POL III, AND SUBUNIT. RX PubMed=35637192; DOI=10.1038/s41467-022-30323-6; RA Van Bortle K., Marciano D.P., Liu Q., Chou T., Lipchik A.M., Gollapudi S., RA Geller B.S., Monte E., Kamakaka R.T., Snyder M.P.; RT "A cancer-associated RNA polymerase III identity drives robust RT transcription and expression of snaR-A non-coding RNA."; RL Nat. Commun. 13:3007-3007(2022). RN [14] RP STRUCTURE BY ELECTRON MICROSCOPY (4.00 ANGSTROMS), FUNCTION, CATALYTIC RP ACTIVITY, SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=33335104; DOI=10.1038/s41467-020-20262-5; RA Ramsay E.P., Abascal-Palacios G., Daiss J.L., King H., Gouge J., Pilsl M., RA Beuron F., Morris E., Gunkel P., Engel C., Vannini A.; RT "Structure of human RNA polymerase III."; RL Nat. Commun. 11:6409-6421(2020). RN [15] RP STRUCTURE BY ELECTRON MICROSCOPY (3.35 ANGSTROMS) IN COMPLEX WITH DNA-RNA RP HYBRID; MG(2+) AND ZN(2+), FUNCTION, AND SUBUNIT. RX PubMed=33674783; DOI=10.1038/s41422-021-00472-2; RA Li L., Yu Z., Zhao D., Ren Y., Hou H., Xu Y.; RT "Structure of human RNA polymerase III elongation complex."; RL Cell Res. 31:791-800(2021). RN [16] RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) IN COMPLEX WITH DNA-RNA RP HYBRID; MG(2+) AND ZN(2+), FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND RP SUBUNIT. RX PubMed=34675218; DOI=10.1038/s41467-021-26402-9; RA Hou H., Li Y., Wang M., Liu A., Yu Z., Chen K., Zhao D., Xu Y.; RT "Structural insights into RNA polymerase III-mediated transcription RT termination through trapping poly-deoxythymidine."; RL Nat. Commun. 12:6135-6146(2021). RN [17] RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) IN COMPLEX WITH DNA-RNA RP HYBRID; MG(2+) AND ZN(2+), FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND RP SUBUNIT. RX PubMed=33558764; DOI=10.1038/s41594-020-00555-5; RA Girbig M., Misiaszek A.D., Vorlander M.K., Lafita A., Grotsch H., RA Baudin F., Bateman A., Muller C.W.; RT "Cryo-EM structures of human RNA polymerase III in its unbound and RT transcribing states."; RL Nat. Struct. Mol. Biol. 28:210-219(2021). RN [18] RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) IN COMPLEX WITH DNA-RNA RP HYBRID; MG(2+) AND ZN(2+), FUNCTION, AND SUBUNIT. RX PubMed=33558766; DOI=10.1038/s41594-021-00557-x; RA Wang Q., Li S., Wan F., Xu Y., Wu Z., Cao M., Lan P., Lei M., Wu J.; RT "Structural insights into transcriptional regulation of human RNA RT polymerase III."; RL Nat. Struct. Mol. Biol. 28:220-227(2021). RN [19] RP VARIANTS HLD7 ASN-372; LEU-558; TYR-636; GLU-672; TYR-724; ILE-775; VAL-852 RP AND THR-1247 INS, INVOLVEMENT IN HLD7, AND TISSUE SPECIFICITY. RX PubMed=21855841; DOI=10.1016/j.ajhg.2011.07.014; RA Bernard G., Chouery E., Putorti M.L., Tetreault M., Takanohashi A., RA Carosso G., Clement I., Boespflug-Tanguy O., Rodriguez D., Delague V., RA Abou Ghoch J., Jalkh N., Dorboz I., Fribourg S., Teichmann M., RA Megarbane A., Schiffmann R., Vanderver A., Brais B.; RT "Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III RT cause a recessive hypomyelinating leukodystrophy."; RL Am. J. Hum. Genet. 89:415-423(2011). RN [20] RP VARIANTS HLD7 ASN-897 AND CYS-1005. RX PubMed=22036171; DOI=10.1016/j.ajhg.2011.10.003; RA Saitsu H., Osaka H., Sasaki M., Takanashi J., Hamada K., Yamashita A., RA Shibayama H., Shiina M., Kondo Y., Nishiyama K., Tsurusaki Y., Miyake N., RA Doi H., Ogata K., Inoue K., Matsumoto N.; RT "Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause RT an autosomal-recessive hypomyelinating leukoencephalopathy."; RL Am. J. Hum. Genet. 89:644-651(2011). RN [21] RP VARIANTS HLD7 LEU-91; GLY-387; ARG-602; VAL-852; CYS-1005 AND LYS-1261. RX PubMed=23355746; DOI=10.1136/jmedgenet-2012-101357; RA Daoud H., Tetreault M., Gibson W., Guerrero K., Cohen A., RA Gburek-Augustat J., Synofzik M., Brais B., Stevens C.A., RA Sanchez-Carpintero R., Goizet C., Naidu S., Vanderver A., Bernard G.; RT "Mutations in POLR3A and POLR3B are a major cause of hypomyelinating RT leukodystrophies with or without dental abnormalities and/or RT hypogonadotropic hypogonadism."; RL J. Med. Genet. 50:194-197(2013). RN [22] RP VARIANTS HLD7 CYS-310 AND THR-804. RX PubMed=23694757; DOI=10.1016/j.braindev.2013.04.011; RA Shimojima K., Shimada S., Tamasaki A., Akaboshi S., Komoike Y., Saito A., RA Furukawa T., Yamamoto T.; RT "Novel compound heterozygous mutations of POLR3A revealed by whole-exome RT sequencing in a patient with hypomyelination."; RL Brain Dev. 36:315-321(2014). RN [23] RP VARIANT WDRTS 873-ARG--THR-1390 DEL, AND INVOLVEMENT IN WDRTS. RX PubMed=27612211; DOI=10.1002/ajmg.a.37960; RA Jay A.M., Conway R.L., Thiffault I., Saunders C., Farrow E., Adams J., RA Toriello H.V.; RT "Neonatal progeriod syndrome associated with biallelic truncating variants RT in POLR3A."; RL Am. J. Med. Genet. A 170:3343-3346(2016). RN [24] RP VARIANTS WDRTS 254-ARG--THR-1390 DEL AND 669-ARG--THR-1390 DEL, AND RP INVOLVEMENT IN WDRTS. RX PubMed=30414627; DOI=10.1016/j.ajhg.2018.10.010; RA Wambach J.A., Wegner D.J., Patni N., Kircher M., Willing M.C., RA Baldridge D., Xing C., Agarwal A.K., Vergano S.A.S., Patel C., Grange D.K., RA Kenney A., Najaf T., Nickerson D.A., Bamshad M.J., Cole F.S., Garg A.; RT "Bi-allelic POLR3A loss-of-function variants cause autosomal-recessive RT Wiedemann-Rautenstrauch syndrome."; RL Am. J. Hum. Genet. 103:968-975(2018). RN [25] RP VARIANT WDRTS 254-ARG--THR-1390 DEL, AND INVOLVEMENT IN WDRTS. RX PubMed=30450527; DOI=10.1007/s00439-018-1957-1; RA Lessel D., Ozel A.B., Campbell S.E., Saadi A., Arlt M.F., McSweeney K.M., RA Plaiasu V., Szakszon K., Szollos A., Rusu C., Rojas A.J., Lopez-Valdez J., RA Thiele H., Nuernberg P., Nickerson D.A., Bamshad M.J., Li J.Z., Kubisch C., RA Glover T.W., Gordon L.B.; RT "Analyses of LMNA-negative juvenile progeroid cases confirms biallelic RT POLR3A mutations in Wiedemann-Rautenstrauch-like syndrome and expands the RT phenotypic spectrum of PYCR1 mutations."; RL Hum. Genet. 137:921-939(2018). RN [26] RP VARIANTS WDRTS 825-SER--THR-1390 DEL; ARG-903; GLN-1069; ARG-1131; ASN-1292 RP AND ARG-1335, AND INVOLVEMENT IN WDRTS. RX PubMed=30323018; DOI=10.1136/jmedgenet-2018-105528; RA Paolacci S., Li Y., Agolini E., Bellacchio E., Arboleda-Bustos C.E., RA Carrero D., Bertola D., Al-Gazali L., Alders M., Altmueller J., RA Arboleda G., Beleggia F., Bruselles A., Ciolfi A., Gillessen-Kaesbach G., RA Krieg T., Mohammed S., Mueller C., Novelli A., Ortega J., Sandoval A., RA Velasco G., Yigit G., Arboleda H., Lopez-Otin C., Wollnik B., Tartaglia M., RA Hennekam R.C.; RT "Specific combinations of biallelic POLR3A variants cause Wiedemann- RT Rautenstrauch syndrome."; RL J. Med. Genet. 55:837-846(2018). CC -!- FUNCTION: Catalytic core component of RNA polymerase III (Pol III), a CC DNA-dependent RNA polymerase which synthesizes small non-coding RNAs CC using the four ribonucleoside triphosphates as substrates. Synthesizes CC 5S rRNA, snRNAs, tRNAs and miRNAs from at least 500 distinct genomic CC loci (PubMed:9331371, PubMed:20413673, PubMed:33558766, CC PubMed:35637192, PubMed:19609254, PubMed:19631370, PubMed:33335104, CC PubMed:34675218, PubMed:33558764). Pol III-mediated transcription cycle CC proceeds through transcription initiation, transcription elongation and CC transcription termination stages. During transcription initiation, Pol CC III is recruited to DNA promoters type I, II or III with the help of CC general transcription factors and other specific initiation factors. CC Once the polymerase has escaped from the promoter it enters the CC elongation phase during which RNA is actively polymerized, based on CC complementarity with the template DNA strand. Transcription termination CC involves the release of the RNA transcript and polymerase from the DNA CC (PubMed:20413673, PubMed:33335104, PubMed:33674783, PubMed:34675218, CC PubMed:33558764, PubMed:33558766). Forms Pol III active center together CC with the second largest subunit POLR3B/RPC2. Appends one nucleotide at CC a time to the 3' end of the nascent RNA, with POLR3A/RPC1 contributing CC a Mg(2+)-coordinating DxDGD motif, and POLR3B/RPC2 participating in the CC coordination of a second Mg(2+) ion and providing lysine residues CC believed to facilitate Watson-Crick base pairing between the incoming CC nucleotide and template base. Typically, Mg(2+) ions direct a 5' CC nucleoside triphosphate to form a phosphodiester bond with the 3' CC hydroxyl of the preceding nucleotide of the nascent RNA, with the CC elimination of pyrophosphate (PubMed:9331371, PubMed:19609254, CC PubMed:33335104, PubMed:33674783, PubMed:34675218, PubMed:33558764, CC PubMed:20413673). Pol III plays a key role in sensing and limiting CC infection by intracellular bacteria and DNA viruses. Acts as a nuclear CC and cytosolic DNA sensor involved in innate immune response. Can sense CC non-self dsDNA that serves as template for transcription into dsRNA. CC The non-self RNA polymerase III transcripts, such as Epstein-Barr CC virus-encoded RNAs (EBERs) induce type I interferon and NF-kappa-B CC through the RIG-I pathway. {ECO:0000250, ECO:0000269|PubMed:19609254, CC ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:20413673, CC ECO:0000269|PubMed:33335104, ECO:0000269|PubMed:33558764, CC ECO:0000269|PubMed:33558766, ECO:0000269|PubMed:33674783, CC ECO:0000269|PubMed:34675218, ECO:0000269|PubMed:35637192, CC ECO:0000269|PubMed:9331371}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA- CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; CC EC=2.7.7.6; Evidence={ECO:0000269|PubMed:19609254, CC ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:33335104, CC ECO:0000269|PubMed:33558764, ECO:0000269|PubMed:34675218, CC ECO:0000269|PubMed:9331371}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21249; CC Evidence={ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, CC ECO:0000269|PubMed:33335104, ECO:0000269|PubMed:33558764, CC ECO:0000269|PubMed:34675218, ECO:0000269|PubMed:9331371}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:33558764, ECO:0000269|PubMed:34675218}; CC Note=Two Mg(2+) ions are coordinated by both the catalytic residues and CC the nucleic acid substrate to enhance substrate recognition and CC catalytic efficiency. {ECO:0000250|UniProtKB:P24928, CC ECO:0000269|PubMed:33558764, ECO:0000269|PubMed:34675218}; CC -!- SUBUNIT: Component of the RNA polymerase III (Pol III) (Pol III) CC complex consisting of 17 subunits: a ten-subunit catalytic core CC composed of POLR3A/RPC1, POLR3B/RPC2, POLR1C/RPAC1, POLR1D/RPAC2, CC POLR3K/RPC10, POLR2E/RPABC1, POLR2F/RPABC2, POLR2H/RPABC3, CC POLR2K/RPABC4 and POLR2L/RPABC5; a mobile stalk composed of two CC subunits POLR3H/RPC8 and CRCP/RPC9, protruding from the core and CC functioning primarily in transcription initiation; and additional CC subunits homologous to general transcription factors of the RNA CC polymerase II machinery, POLR3C/RPC3-POLR3F/RPC6-POLR3G/RPC7 CC heterotrimer required for transcription initiation and POLR3D/RPC4- CC POLR3E/RPC5 heterodimer involved in both transcription initiation and CC termination (PubMed:12391170, PubMed:33335104, PubMed:33674783, CC PubMed:34675218, PubMed:19631370). Pol III exists as two alternative CC complexes defined by the mutually exclusive incorporation of subunit CC POLR3G/RPC7alpha or POLR3GL/RPC7beta. The presence of POLR3G/RPC7alpha CC or POLR3GL/RPC7beta differentially modulates the transcription CC potential of Pol III, with POLR3G/RPC7alpha specifically associated CC with transcription of snaR-A non-coding RNAs (PubMed:35637192, CC PubMed:33558764, PubMed:33558766). As part of the RNA polymerase III CC complex, interacts with PKP2 (PubMed:11416169). {ECO:0000250, CC ECO:0000269|PubMed:11416169, ECO:0000269|PubMed:12391170, CC ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:33335104, CC ECO:0000269|PubMed:33558764, ECO:0000269|PubMed:33558766, CC ECO:0000269|PubMed:33674783, ECO:0000269|PubMed:34675218, CC ECO:0000269|PubMed:35637192}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11416169, CC ECO:0000269|PubMed:33335104}. Cytoplasm, cytosol CC {ECO:0000269|PubMed:33335104}. CC -!- TISSUE SPECIFICITY: Expressed in the brain, in the cortex and the white CC matter (at protein level). {ECO:0000269|PubMed:21855841}. CC -!- DISEASE: Leukodystrophy, hypomyelinating, 7, with or without CC oligodontia and/or hypogonadotropic hypogonadism (HLD7) [MIM:607694]: CC An autosomal recessive neurodegenerative disorder characterized by CC childhood onset of progressive motor decline manifest as spasticity, CC ataxia, tremor, and cerebellar signs, as well as mild cognitive CC regression. Other features may include hypodontia or oligodontia and CC hypogonadotropic hypogonadism. There is considerable inter- and CC intrafamilial variability. {ECO:0000269|PubMed:21855841, CC ECO:0000269|PubMed:22036171, ECO:0000269|PubMed:23355746, CC ECO:0000269|PubMed:23694757}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Wiedemann-Rautenstrauch syndrome (WDRTS) [MIM:264090]: An CC autosomal recessive, neonatal progeroid disorder characterized by CC intrauterine growth retardation, failure to thrive, short stature, CC hypotonia, variable mental impairment, and a progeroid appearance. CC Clinical features include apparent macrocephaly, sparse hair, prominent CC scalp veins, entropion, greatly widened anterior fontanelles, malar CC hypoplasia, and generalized lipoatrophy. Death usually occurs in early CC childhood but survival to third decade has been reported. CC {ECO:0000269|PubMed:27612211, ECO:0000269|PubMed:30323018, CC ECO:0000269|PubMed:30414627, ECO:0000269|PubMed:30450527}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the RNA polymerase beta' chain family. CC {ECO:0000305}. 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; AF021351; AAB86536.1; -; mRNA. DR EMBL; AL512628; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471083; EAW54617.1; -; Genomic_DNA. DR EMBL; BC041089; AAH41089.1; -; mRNA. DR EMBL; AY091459; AAM12029.1; -; mRNA. DR CCDS; CCDS7354.1; -. DR RefSeq; NP_008986.2; NM_007055.3. DR PDB; 7A6H; EM; 3.30 A; A=1-1390. DR PDB; 7AE1; EM; 2.80 A; A=1-1390. DR PDB; 7AE3; EM; 3.10 A; A=1-1390. DR PDB; 7AEA; EM; 3.40 A; A=1-1390. DR PDB; 7AST; EM; 4.00 A; N=1-1390. DR PDB; 7D58; EM; 2.90 A; A=1-1390. DR PDB; 7D59; EM; 3.10 A; A=1-1390. DR PDB; 7DN3; EM; 3.50 A; A=1-1390. DR PDB; 7DU2; EM; 3.35 A; A=1-1390. DR PDB; 7FJI; EM; 3.60 A; A=1-1390. DR PDB; 7FJJ; EM; 3.60 A; A=1-1390. DR PDB; 8ITY; EM; 3.90 A; A=1-1390. DR PDB; 8IUE; EM; 4.10 A; A=1-1390. DR PDB; 8IUH; EM; 3.40 A; A=1-1390. DR PDBsum; 7A6H; -. DR PDBsum; 7AE1; -. DR PDBsum; 7AE3; -. DR PDBsum; 7AEA; -. DR PDBsum; 7AST; -. DR PDBsum; 7D58; -. DR PDBsum; 7D59; -. DR PDBsum; 7DN3; -. DR PDBsum; 7DU2; -. DR PDBsum; 7FJI; -. DR PDBsum; 7FJJ; -. DR PDBsum; 8ITY; -. DR PDBsum; 8IUE; -. DR PDBsum; 8IUH; -. DR AlphaFoldDB; O14802; -. DR EMDB; EMD-11673; -. DR EMDB; EMD-11736; -. DR EMDB; EMD-11738; -. DR EMDB; EMD-11742; -. DR EMDB; EMD-11904; -. DR EMDB; EMD-30577; -. DR EMDB; EMD-30578; -. DR EMDB; EMD-30779; -. DR EMDB; EMD-30865; -. DR EMDB; EMD-31621; -. DR EMDB; EMD-31622; -. DR EMDB; EMD-35712; -. DR EMDB; EMD-35719; -. DR EMDB; EMD-35722; -. DR SMR; O14802; -. DR BioGRID; 116301; 180. DR ComplexPortal; CPX-2393; DNA-directed RNA polymerase III complex, POLR3G variant. DR ComplexPortal; CPX-7482; DNA-directed RNA polymerase III complex, POLR3GL variant. DR IntAct; O14802; 49. DR MINT; O14802; -. DR STRING; 9606.ENSP00000361446; -. DR ChEMBL; CHEMBL4665582; -. DR GlyGen; O14802; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O14802; -. DR MetOSite; O14802; -. DR PhosphoSitePlus; O14802; -. DR SwissPalm; O14802; -. DR BioMuta; POLR3A; -. DR EPD; O14802; -. DR jPOST; O14802; -. DR MassIVE; O14802; -. DR MaxQB; O14802; -. DR PaxDb; 9606-ENSP00000361446; -. DR PeptideAtlas; O14802; -. DR ProteomicsDB; 48248; -. DR Pumba; O14802; -. DR Antibodypedia; 29822; 181 antibodies from 29 providers. DR DNASU; 11128; -. DR Ensembl; ENST00000372371.8; ENSP00000361446.3; ENSG00000148606.15. DR GeneID; 11128; -. DR KEGG; hsa:11128; -. DR MANE-Select; ENST00000372371.8; ENSP00000361446.3; NM_007055.4; NP_008986.2. DR UCSC; uc001jzn.4; human. DR AGR; HGNC:30074; -. DR CTD; 11128; -. DR DisGeNET; 11128; -. DR GeneCards; POLR3A; -. DR GeneReviews; POLR3A; -. DR HGNC; HGNC:30074; POLR3A. DR HPA; ENSG00000148606; Low tissue specificity. DR MalaCards; POLR3A; -. DR MIM; 264090; phenotype. DR MIM; 607694; phenotype. DR MIM; 614258; gene. DR neXtProt; NX_O14802; -. DR OpenTargets; ENSG00000148606; -. DR Orphanet; 137639; Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome. DR Orphanet; 447893; Hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome. DR Orphanet; 88637; Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome. DR Orphanet; 77295; Odontoleukodystrophy. DR Orphanet; 447896; Tremor-ataxia-central hypomyelination syndrome. DR Orphanet; 3455; Wiedemann-Rautenstrauch syndrome. DR PharmGKB; PA134900426; -. DR VEuPathDB; HostDB:ENSG00000148606; -. DR eggNOG; KOG0261; Eukaryota. DR GeneTree; ENSGT00930000151028; -. DR HOGENOM; CLU_000487_3_0_1; -. DR InParanoid; O14802; -. DR OMA; AVCPPYN; -. DR OrthoDB; 169836at2759; -. DR PhylomeDB; O14802; -. DR TreeFam; TF103054; -. DR PathwayCommons; O14802; -. DR Reactome; R-HSA-1834949; Cytosolic sensors of pathogen-associated DNA. DR Reactome; R-HSA-73780; RNA Polymerase III Chain Elongation. DR Reactome; R-HSA-73980; RNA Polymerase III Transcription Termination. DR Reactome; R-HSA-749476; RNA Polymerase III Abortive And Retractive Initiation. DR Reactome; R-HSA-76061; RNA Polymerase III Transcription Initiation From Type 1 Promoter. DR Reactome; R-HSA-76066; RNA Polymerase III Transcription Initiation From Type 2 Promoter. DR Reactome; R-HSA-76071; RNA Polymerase III Transcription Initiation From Type 3 Promoter. DR SignaLink; O14802; -. DR SIGNOR; O14802; -. DR BioGRID-ORCS; 11128; 855 hits in 1176 CRISPR screens. DR ChiTaRS; POLR3A; human. DR GenomeRNAi; 11128; -. DR Pharos; O14802; Tbio. DR PRO; PR:O14802; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; O14802; Protein. DR Bgee; ENSG00000148606; Expressed in buccal mucosa cell and 185 other cell types or tissues. DR ExpressionAtlas; O14802; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005666; C:RNA polymerase III complex; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; IEA:InterPro. DR GO; GO:0003899; F:DNA-directed 5'-3' RNA polymerase activity; NAS:UniProtKB. DR GO; GO:0071667; F:DNA/RNA hybrid binding; IDA:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW. DR GO; GO:0006351; P:DNA-templated transcription; NAS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB. DR GO; GO:0032728; P:positive regulation of interferon-beta production; IMP:UniProtKB. DR GO; GO:0042797; P:tRNA transcription by RNA polymerase III; IDA:UniProtKB. DR CDD; cd02736; RNAP_III_Rpc1_C; 1. DR CDD; cd02583; RNAP_III_RPC1_N; 1. DR Gene3D; 1.10.132.30; -; 1. DR Gene3D; 1.10.150.390; -; 1. DR Gene3D; 2.40.40.20; -; 1. DR Gene3D; 6.10.250.2940; -; 1. DR Gene3D; 6.20.50.80; -; 1. DR Gene3D; 3.30.1490.180; RNA polymerase ii; 1. DR Gene3D; 4.10.860.120; RNA polymerase II, clamp domain; 1. DR Gene3D; 1.10.274.100; RNA polymerase Rpb1, domain 3; 1. DR InterPro; IPR045867; DNA-dir_RpoC_beta_prime. DR InterPro; IPR000722; RNA_pol_asu. DR InterPro; IPR006592; RNA_pol_N. DR InterPro; IPR007080; RNA_pol_Rpb1_1. DR InterPro; IPR007066; RNA_pol_Rpb1_3. DR InterPro; IPR042102; RNA_pol_Rpb1_3_sf. DR InterPro; IPR007083; RNA_pol_Rpb1_4. DR InterPro; IPR007081; RNA_pol_Rpb1_5. DR InterPro; IPR044893; RNA_pol_Rpb1_clamp_domain. DR InterPro; IPR035698; RNAP_III_Rpc1_C. DR InterPro; IPR035697; RNAP_III_RPC1_N. DR InterPro; IPR038120; Rpb1_funnel_sf. DR PANTHER; PTHR19376; DNA-DIRECTED RNA POLYMERASE; 1. DR PANTHER; PTHR19376:SF32; DNA-DIRECTED RNA POLYMERASE III SUBUNIT RPC1; 1. DR Pfam; PF04997; RNA_pol_Rpb1_1; 1. DR Pfam; PF00623; RNA_pol_Rpb1_2; 1. DR Pfam; PF04983; RNA_pol_Rpb1_3; 1. DR Pfam; PF05000; RNA_pol_Rpb1_4; 1. DR Pfam; PF04998; RNA_pol_Rpb1_5; 1. DR SMART; SM00663; RPOLA_N; 1. DR SUPFAM; SSF64484; beta and beta-prime subunits of DNA dependent RNA-polymerase; 1. DR Genevisible; O14802; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Antiviral defense; Cytoplasm; Disease variant; KW DNA-directed RNA polymerase; Immunity; Innate immunity; Leukodystrophy; KW Magnesium; Metal-binding; Nucleotidyltransferase; Nucleus; KW Reference proteome; Transcription; Transferase; Zinc. FT CHAIN 1..1390 FT /note="DNA-directed RNA polymerase III subunit RPC1" FT /id="PRO_0000073947" FT REGION 843..884 FT /note="Bridging helix" FT /evidence="ECO:0000250|UniProtKB:G3MZY8" FT REGION 1029..1070 FT /note="Trigger loop" FT /evidence="ECO:0000250|UniProtKB:G3MZY8" FT BINDING 69 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33558766, ECO:0000269|PubMed:33674783, FT ECO:0000269|PubMed:34675218, ECO:0007744|PDB:7AE1, FT ECO:0007744|PDB:7D58, ECO:0007744|PDB:7DN3, FT ECO:0007744|PDB:7FJJ" FT BINDING 72 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33558766, ECO:0000269|PubMed:33674783, FT ECO:0000269|PubMed:34675218, ECO:0007744|PDB:7AE1, FT ECO:0007744|PDB:7D58, ECO:0007744|PDB:7DN3, FT ECO:0007744|PDB:7FJJ" FT BINDING 79 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33674783, ECO:0000269|PubMed:34675218, FT ECO:0007744|PDB:7AE1, ECO:0007744|PDB:7DN3, FT ECO:0007744|PDB:7FJJ" FT BINDING 82 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:33558766, FT ECO:0000269|PubMed:33674783, ECO:0000269|PubMed:34675218, FT ECO:0007744|PDB:7D58, ECO:0007744|PDB:7DN3, FT ECO:0007744|PDB:7FJJ" FT BINDING 109 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33558766, ECO:0007744|PDB:7AE1, FT ECO:0007744|PDB:7D58" FT BINDING 112 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33558766, ECO:0007744|PDB:7AE1, FT ECO:0007744|PDB:7D58" FT BINDING 144 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="nontemplate strand" FT /evidence="ECO:0000269|PubMed:33674783, FT ECO:0007744|PDB:7DN3" FT BINDING 156 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33674783, ECO:0007744|PDB:7AE1, FT ECO:0007744|PDB:7DN3" FT BINDING 159 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33674783, ECO:0007744|PDB:7AE1, FT ECO:0007744|PDB:7DN3" FT BINDING 167 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="nontemplate strand" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0007744|PDB:7AE1" FT BINDING 326 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="template strand" FT /evidence="ECO:0000269|PubMed:33558766, FT ECO:0007744|PDB:7D58" FT BINDING 348 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="template strand" FT /evidence="ECO:0000269|PubMed:33558766, FT ECO:0007744|PDB:7D58" FT BINDING 353 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="template strand" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33674783, ECO:0007744|PDB:7A6H, FT ECO:0007744|PDB:7DN3" FT BINDING 360 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="template strand" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33674783, ECO:0000269|PubMed:34675218, FT ECO:0007744|PDB:7AE1, ECO:0007744|PDB:7DN3, FT ECO:0007744|PDB:7FJJ" FT BINDING 366 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="template strand" FT /evidence="ECO:0000269|PubMed:33674783, FT ECO:0007744|PDB:7DN3" FT BINDING 464 FT /ligand="RNA" FT /ligand_id="ChEBI:CHEBI:33697" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33558766, ECO:0000269|PubMed:33674783, FT ECO:0007744|PDB:7AE1, ECO:0007744|PDB:7D58, FT ECO:0007744|PDB:7DN3" FT BINDING 499 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33674783, ECO:0000269|PubMed:34675218, FT ECO:0007744|PDB:7AE1, ECO:0007744|PDB:7DN3, FT ECO:0007744|PDB:7FJJ" FT BINDING 499 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /ligand_note="ligand shared with POLR3B/RPC2" FT /evidence="ECO:0000250|UniProtKB:P24928" FT BINDING 501 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33674783, ECO:0000269|PubMed:34675218, FT ECO:0007744|PDB:7AE1, ECO:0007744|PDB:7DN3, FT ECO:0007744|PDB:7FJJ" FT BINDING 501 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /ligand_note="ligand shared with POLR3B/RPC2" FT /evidence="ECO:0000250|UniProtKB:P04050" FT BINDING 503 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33674783, ECO:0000269|PubMed:34675218, FT ECO:0007744|PDB:7AE1, ECO:0007744|PDB:7DN3, FT ECO:0007744|PDB:7FJJ" FT BINDING 503 FT /ligand="RNA" FT /ligand_id="ChEBI:CHEBI:33697" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:33558766, ECO:0000269|PubMed:33674783, FT ECO:0007744|PDB:7AE1, ECO:0007744|PDB:7D58, FT ECO:0007744|PDB:7DN3" FT BINDING 1159 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="nontemplate strand" FT /evidence="ECO:0000269|PubMed:33558764, FT ECO:0000269|PubMed:34675218, ECO:0007744|PDB:7AE1, FT ECO:0007744|PDB:7FJJ" FT BINDING 1305 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="template strand" FT /evidence="ECO:0000269|PubMed:33558766, FT ECO:0007744|PDB:7D58" FT BINDING 1323 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /ligand_label="template strand" FT /evidence="ECO:0000269|PubMed:33674783, FT ECO:0007744|PDB:7DN3" FT MOD_RES 445 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VARIANT 91 FT /note="P -> L (in HLD7; dbSNP:rs1375717376)" FT /evidence="ECO:0000269|PubMed:23355746" FT /id="VAR_072338" FT VARIANT 254..1390 FT /note="Missing (in WDRTS)" FT /evidence="ECO:0000269|PubMed:30414627, FT ECO:0000269|PubMed:30450527" FT /id="VAR_081999" FT VARIANT 310 FT /note="W -> C (in HLD7; dbSNP:rs1217230904)" FT /evidence="ECO:0000269|PubMed:23694757" FT /id="VAR_072339" FT VARIANT 372 FT /note="D -> N (in HLD7; dbSNP:rs267608673)" FT /evidence="ECO:0000269|PubMed:21855841" FT /id="VAR_066516" FT VARIANT 387 FT /note="A -> G (in HLD7; dbSNP:rs1307896663)" FT /evidence="ECO:0000269|PubMed:23355746" FT /id="VAR_072340" FT VARIANT 558 FT /note="F -> L (in HLD7; dbSNP:rs267608668)" FT /evidence="ECO:0000269|PubMed:21855841" FT /id="VAR_066517" FT VARIANT 582 FT /note="R -> L (in dbSNP:rs34588967)" FT /id="VAR_051873" FT VARIANT 602 FT /note="S -> R (in HLD7; dbSNP:rs762708292)" FT /evidence="ECO:0000269|PubMed:23355746" FT /id="VAR_072341" FT VARIANT 636 FT /note="S -> Y (in HLD7; dbSNP:rs267608676)" FT /evidence="ECO:0000269|PubMed:21855841" FT /id="VAR_066518" FT VARIANT 669..1390 FT /note="Missing (in WDRTS)" FT /evidence="ECO:0000269|PubMed:30414627" FT /id="VAR_082000" FT VARIANT 672 FT /note="G -> E (in HLD7; dbSNP:rs267608670)" FT /evidence="ECO:0000269|PubMed:21855841" FT /id="VAR_066519" FT VARIANT 713 FT /note="K -> N (in dbSNP:rs35354908)" FT /id="VAR_051874" FT VARIANT 724 FT /note="C -> Y (in HLD7; dbSNP:rs267608679)" FT /evidence="ECO:0000269|PubMed:21855841" FT /id="VAR_066520" FT VARIANT 775 FT /note="N -> I (in HLD7; dbSNP:rs267608672)" FT /evidence="ECO:0000269|PubMed:21855841" FT /id="VAR_066521" FT VARIANT 804 FT /note="I -> T (in HLD7)" FT /evidence="ECO:0000269|PubMed:23694757" FT /id="VAR_072342" FT VARIANT 825..1390 FT /note="Missing (in WDRTS)" FT /evidence="ECO:0000269|PubMed:30323018" FT /id="VAR_082001" FT VARIANT 852 FT /note="M -> V (in HLD7; dbSNP:rs267608671)" FT /evidence="ECO:0000269|PubMed:21855841, FT ECO:0000269|PubMed:23355746" FT /id="VAR_066522" FT VARIANT 873..1390 FT /note="Missing (in WDRTS)" FT /evidence="ECO:0000269|PubMed:27612211" FT /id="VAR_082002" FT VARIANT 897 FT /note="I -> N (in HLD7; dbSNP:rs267608681)" FT /evidence="ECO:0000269|PubMed:22036171" FT /id="VAR_067004" FT VARIANT 903 FT /note="G -> R (in WDRTS; uncertain significance; FT dbSNP:rs1399429058)" FT /evidence="ECO:0000269|PubMed:30323018" FT /id="VAR_082003" FT VARIANT 1005 FT /note="R -> C (in HLD7; dbSNP:rs267608682)" FT /evidence="ECO:0000269|PubMed:22036171, FT ECO:0000269|PubMed:23355746" FT /id="VAR_066523" FT VARIANT 1069 FT /note="R -> Q (in WDRTS; uncertain significance; FT dbSNP:rs778985686)" FT /evidence="ECO:0000269|PubMed:30323018" FT /id="VAR_082004" FT VARIANT 1131 FT /note="K -> R (in WDRTS; uncertain significance; FT dbSNP:rs138305578)" FT /evidence="ECO:0000269|PubMed:30323018" FT /id="VAR_082005" FT VARIANT 1247 FT /note="T -> TT (in HLD7)" FT /evidence="ECO:0000269|PubMed:21855841" FT /id="VAR_066524" FT VARIANT 1261 FT /note="E -> K (in HLD7; dbSNP:rs371703979)" FT /evidence="ECO:0000269|PubMed:23355746" FT /id="VAR_072343" FT VARIANT 1292 FT /note="D -> N (in WDRTS; uncertain significance; FT dbSNP:rs757209071)" FT /evidence="ECO:0000269|PubMed:30323018" FT /id="VAR_082006" FT VARIANT 1335 FT /note="G -> R (in WDRTS; uncertain significance; FT dbSNP:rs768222183)" FT /evidence="ECO:0000269|PubMed:30323018" FT /id="VAR_082007" FT CONFLICT 15 FT /note="I -> T (in Ref. 1; AAB86536)" FT /evidence="ECO:0000305" FT CONFLICT 262 FT /note="I -> F (in Ref. 1; AAB86536)" FT /evidence="ECO:0000305" FT CONFLICT 283 FT /note="L -> P (in Ref. 5; AAM12029)" FT /evidence="ECO:0000305" FT CONFLICT 1056 FT /note="A -> G (in Ref. 1; AAB86536)" FT /evidence="ECO:0000305" FT CONFLICT 1275 FT /note="M -> MV (in Ref. 1; AAB86536)" FT /evidence="ECO:0000305" FT STRAND 12..21 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 25..31 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 33..35 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 44..47 FT /evidence="ECO:0007829|PDB:7D58" FT STRAND 54..56 FT /evidence="ECO:0007829|PDB:7D58" FT HELIX 58..60 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 64..67 FT /evidence="ECO:0007829|PDB:7D58" FT STRAND 70..72 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 76..78 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 84..93 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 95..97 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 98..107 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 110..112 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 119..128 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 131..133 FT /evidence="ECO:0007829|PDB:7AE3" FT HELIX 136..151 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 157..159 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 166..168 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 170..172 FT /evidence="ECO:0007829|PDB:7D58" FT STRAND 174..176 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 183..185 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 188..195 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 198..203 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 207..210 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 211..213 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 216..218 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 220..227 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 232..234 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 236..238 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 242..244 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 247..250 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 251..257 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 260..262 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 266..268 FT /evidence="ECO:0007829|PDB:7D58" FT TURN 269..272 FT /evidence="ECO:0007829|PDB:7D58" FT STRAND 273..275 FT /evidence="ECO:0007829|PDB:7D58" FT HELIX 278..299 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 303..321 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 330..332 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 341..345 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 347..349 FT /evidence="ECO:0007829|PDB:7DU2" FT HELIX 351..354 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 355..357 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 358..371 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 379..383 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 384..387 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 390..395 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 398..400 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 401..410 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 411..413 FT /evidence="ECO:0007829|PDB:7AE3" FT STRAND 414..416 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 418..422 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 424..426 FT /evidence="ECO:0007829|PDB:7D58" FT STRAND 429..435 FT /evidence="ECO:0007829|PDB:7D58" FT HELIX 437..442 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 449..453 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 459..463 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 470..472 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 473..488 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 490..492 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 493..496 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 500..502 FT /evidence="ECO:0007829|PDB:7D58" FT STRAND 504..508 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 513..523 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 525..527 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 532..534 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 539..541 FT /evidence="ECO:0007829|PDB:7AE3" FT TURN 543..545 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 547..552 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 553..555 FT /evidence="ECO:0007829|PDB:7D58" FT HELIX 561..568 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 569..571 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 574..578 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 590..592 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 594..596 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 597..605 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 608..611 FT /evidence="ECO:0007829|PDB:7D58" FT STRAND 616..620 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 627..631 FT /evidence="ECO:0007829|PDB:7D58" FT STRAND 637..641 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 644..647 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 652..655 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 656..661 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 663..671 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 673..694 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 700..702 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 707..732 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 739..741 FT /evidence="ECO:0007829|PDB:7D58" FT HELIX 744..770 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 776..782 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 783..786 FT /evidence="ECO:0007829|PDB:7DU2" FT HELIX 789..796 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 804..807 FT /evidence="ECO:0007829|PDB:7D59" FT STRAND 812..815 FT /evidence="ECO:0007829|PDB:7D58" FT STRAND 816..818 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 829..831 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 838..840 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 844..879 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 893..895 FT /evidence="ECO:0007829|PDB:7AE3" FT STRAND 897..901 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 902..905 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 909..911 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 913..918 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 921..931 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 935..937 FT /evidence="ECO:0007829|PDB:7D59" FT HELIX 942..952 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 956..960 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 963..987 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 991..993 FT /evidence="ECO:0007829|PDB:7D59" FT HELIX 998..1002 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1008..1023 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1033..1047 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 1056..1059 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1067..1075 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 1085..1091 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1095..1105 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1110..1112 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 1114..1121 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 1126..1132 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1134..1140 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1146..1152 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 1153..1157 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 1162..1164 FT /evidence="ECO:0007829|PDB:7AE3" FT STRAND 1165..1169 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 1172..1175 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 1181..1183 FT /evidence="ECO:0007829|PDB:7D58" FT TURN 1186..1188 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1189..1195 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1196..1198 FT /evidence="ECO:0007829|PDB:7AE3" FT STRAND 1199..1203 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 1209..1214 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 1223..1230 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1232..1235 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1243..1245 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 1247..1249 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1251..1258 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1260..1277 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1284..1295 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 1296..1299 FT /evidence="ECO:0007829|PDB:7D58" FT HELIX 1305..1311 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1315..1318 FT /evidence="ECO:0007829|PDB:7AE1" FT TURN 1319..1321 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1324..1334 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 1337..1339 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1343..1349 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1356..1358 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 1359..1364 FT /evidence="ECO:0007829|PDB:7AE1" FT STRAND 1378..1380 FT /evidence="ECO:0007829|PDB:7AE1" FT HELIX 1382..1384 FT /evidence="ECO:0007829|PDB:7AE1" SQ SEQUENCE 1390 AA; 155641 MW; 56F30900848E3DB9 CRC64; MVKEQFRETD VAKKISHICF GMKSPEEMRQ QAHIQVVSKN LYSQDNQHAP LLYGVLDHRM GTSEKDRPCE TCGKNLADCL GHYGYIDLEL PCFHVGYFRA VIGILQMICK TCCHIMLSQE EKKQFLDYLK RPGLTYLQKR GLKKKISDKC RKKNICHHCG AFNGTVKKCG LLKIIHEKYK TNKKVVDPIV SNFLQSFETA IEHNKEVEPL LGRAQENLNP LVVLNLFKRI PAEDVPLLLM NPEAGKPSDL ILTRLLVPPL CIRPSVVSDL KSGTNEDDLT MKLTEIIFLN DVIKKHRISG AKTQMIMEDW DFLQLQCALY INSELSGIPL NMAPKKWTRG FVQRLKGKQG RFRGNLSGKR VDFSGRTVIS PDPNLRIDEV AVPVHVAKIL TFPEKVNKAN INFLRKLVQN GPEVHPGANF IQQRHTQMKR FLKYGNREKM AQELKYGDIV ERHLIDGDVV LFNRQPSLHK LSIMAHLARV KPHRTFRFNE CVCTPYNADF DGDEMNLHLP QTEEAKAEAL VLMGTKANLV TPRNGEPLIA AIQDFLTGAY LLTLKDTFFD RAKACQIIAS ILVGKDEKIK VRLPPPTILK PVTLWTGKQI FSVILRPSDD NPVRANLRTK GKQYCGKGED LCANDSYVTI QNSELMSGSM DKGTLGSGSK NNIFYILLRD WGQNEAADAM SRLARLAPVY LSNRGFSIGI GDVTPGQGLL KAKYELLNAG YKKCDEYIEA LNTGKLQQQP GCTAEETLEA LILKELSVIR DHAGSACLRE LDKSNSPLTM ALCGSKGSFI NISQMIACVG QQAISGSRVP DGFENRSLPH FEKHSKLPAA KGFVANSFYS GLTPTEFFFH TMAGREGLVD TAVKTAETGY MQRRLVKSLE DLCSQYDLTV RSSTGDIIQF IYGGDGLDPA AMEGKDEPLE FKRVLDNIKA VFPCPSEPAL SKNELILTTE SIMKKSEFLC CQDSFLQEIK KFIKGVSEKI KKTRDKYGIN DNGTTEPRVL YQLDRITPTQ VEKFLETCRD KYMRAQMEPG SAVGALCAQS IGEPGTQMTL KTFHFAGVAS MNITLGVPRI KEIINASKAI STPIITAQLD KDDDADYARL VKGRIEKTLL GEISEYIEEV FLPDDCFILV KLSLERIRLL RLEVNAETVR YSICTSKLRV KPGDVAVHGE AVVCVTPREN SKSSMYYVLQ FLKEDLPKVV VQGIPEVSRA VIHIDEQSGK EKYKLLVEGD NLRAVMATHG VKGTRTTSNN TYEVEKTLGI EAARTTIINE IQYTMVNHGM SIDRRHVMLL SDLMTYKGEV LGITRFGLAK MKESVLMLAS FEKTADHLFD AAYFGQKDSV CGVSECIIMG IPMNIGTGLF KLLHKADRDP NPPKRPLIFD TNEFHIPLVT //