O14802 (RPC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA-directed RNA polymerase III subunit RPC1
Short name=RNA polymerase III subunit C1
EC=2.7.7.6

Alternative name(s):
DNA-directed RNA polymerase III largest subunit
DNA-directed RNA polymerase III subunit A
RNA polymerase III 155 kDa subunit
Short name=RPC155
RNA polymerase III subunit C160

Gene names

Name:

POLR3A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1390 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic core component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. Forms the polymerase active center together with the second largest subunit. A single stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol III. A bridging helix emanates from RPC1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol III by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition By similarity. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF- Kappa-B through the RIG-I pathway. Ref.7 Ref.8
Catalytic activity	Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
Subunit structure	Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits By similarity. Ref.6
Subcellular location	Nucleus.
Tissue specificity	Expressed in the brain, in the cortex and the white matter (at protein level). Ref.11
Involvement in disease	Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism (HLD7) [MIM:607694]: An autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression. Other features may include hypodontia or oligodontia and hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12
Sequence similarities	Belongs to the RNA polymerase beta' chain family.

Ontologies

Keywords
Biological process	Antiviral defense Immunity Innate immunity Transcription
Cellular component	DNA-directed RNA polymerase Nucleus
Coding sequence diversity	Polymorphism
Disease	Leukodystrophy
Ligand	Magnesium Metal-binding Zinc
Molecular function	Nucleotidyltransferase Transferase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from mutant phenotype Ref.8. Source: UniProtKB positive regulation of interferon-beta production Inferred from mutant phenotype Ref.8. Source: UniProtKB termination of RNA polymerase III transcription Traceable author statement. Source: Reactome transcription elongation from RNA polymerase III promoter Traceable author statement. Source: Reactome
Cellular_component	DNA-directed RNA polymerase III complex Non-traceable author statement. Source: UniProtKB
Molecular_function	DNA binding Inferred from electronic annotation. Source: InterPro DNA-directed RNA polymerase activity Non-traceable author statement Ref.1. Source: UniProtKB chromatin binding Inferred from electronic annotation. Source: Compara ribonucleoside binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1390	1390	DNA-directed RNA polymerase III subunit RPC1		PRO_0000073947
Regions
	Region	844 – 856	13	Bridging helix By similarity
Sites
	Metal binding	69	1	Zinc 1 By similarity
	Metal binding	72	1	Zinc 1 By similarity
	Metal binding	79	1	Zinc 1 By similarity
	Metal binding	82	1	Zinc 1 By similarity
	Metal binding	109	1	Zinc 2 By similarity
	Metal binding	112	1	Zinc 2 By similarity
	Metal binding	156	1	Zinc 2 By similarity
	Metal binding	499	1	Magnesium; catalytic By similarity
	Metal binding	501	1	Magnesium; catalytic By similarity
	Metal binding	503	1	Magnesium; catalytic By similarity
Amino acid modifications
	Modified residue	445	1	N6-acetyllysine Ref.9
Natural variations
	Natural variant	372	1	D → N in HLD7. Ref.11		VAR_066516
	Natural variant	558	1	F → L in HLD7. Ref.11		VAR_066517
	Natural variant	582	1	R → L. Corresponds to variant rs34588967 [ dbSNP | Ensembl ].		VAR_051873
	Natural variant	636	1	S → Y in HLD7. Ref.11		VAR_066518
	Natural variant	672	1	G → E in HLD7. Ref.11		VAR_066519
	Natural variant	713	1	K → N. Corresponds to variant rs35354908 [ dbSNP | Ensembl ].		VAR_051874
	Natural variant	724	1	C → Y in HLD7. Ref.11		VAR_066520
	Natural variant	775	1	N → I in HLD7. Ref.11		VAR_066521
	Natural variant	852	1	M → V in HLD7. Ref.11		VAR_066522
	Natural variant	897	1	I → N in HLD7. Ref.12		VAR_067004
	Natural variant	1005	1	R → C in HLD7. Ref.12		VAR_066523
	Natural variant	1247	1	T → TT in HLD7. Ref.11		VAR_066524
Experimental info
	Sequence conflict	15	1	I → T in AAB86536. Ref.1
	Sequence conflict	262	1	I → F in AAB86536. Ref.1
	Sequence conflict	283	1	L → P in AAM12029. Ref.5
	Sequence conflict	1056	1	A → G in AAB86536. Ref.1
	Sequence conflict	1275	1	M → MV in AAB86536. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O14802 [UniParc]. Last modified September 23, 2008. Version 2. Checksum: 56F30900848E3DB9	FASTA	1,390	155,641
	10 20 30 40 50 60 MVKEQFRETD VAKKISHICF GMKSPEEMRQ QAHIQVVSKN LYSQDNQHAP LLYGVLDHRM 70 80 90 100 110 120 GTSEKDRPCE TCGKNLADCL GHYGYIDLEL PCFHVGYFRA VIGILQMICK TCCHIMLSQE 130 140 150 160 170 180 EKKQFLDYLK RPGLTYLQKR GLKKKISDKC RKKNICHHCG AFNGTVKKCG LLKIIHEKYK 190 200 210 220 230 240 TNKKVVDPIV SNFLQSFETA IEHNKEVEPL LGRAQENLNP LVVLNLFKRI PAEDVPLLLM 250 260 270 280 290 300 NPEAGKPSDL ILTRLLVPPL CIRPSVVSDL KSGTNEDDLT MKLTEIIFLN DVIKKHRISG 310 320 330 340 350 360 AKTQMIMEDW DFLQLQCALY INSELSGIPL NMAPKKWTRG FVQRLKGKQG RFRGNLSGKR 370 380 390 400 410 420 VDFSGRTVIS PDPNLRIDEV AVPVHVAKIL TFPEKVNKAN INFLRKLVQN GPEVHPGANF 430 440 450 460 470 480 IQQRHTQMKR FLKYGNREKM AQELKYGDIV ERHLIDGDVV LFNRQPSLHK LSIMAHLARV 490 500 510 520 530 540 KPHRTFRFNE CVCTPYNADF DGDEMNLHLP QTEEAKAEAL VLMGTKANLV TPRNGEPLIA 550 560 570 580 590 600 AIQDFLTGAY LLTLKDTFFD RAKACQIIAS ILVGKDEKIK VRLPPPTILK PVTLWTGKQI 610 620 630 640 650 660 FSVILRPSDD NPVRANLRTK GKQYCGKGED LCANDSYVTI QNSELMSGSM DKGTLGSGSK 670 680 690 700 710 720 NNIFYILLRD WGQNEAADAM SRLARLAPVY LSNRGFSIGI GDVTPGQGLL KAKYELLNAG 730 740 750 760 770 780 YKKCDEYIEA LNTGKLQQQP GCTAEETLEA LILKELSVIR DHAGSACLRE LDKSNSPLTM 790 800 810 820 830 840 ALCGSKGSFI NISQMIACVG QQAISGSRVP DGFENRSLPH FEKHSKLPAA KGFVANSFYS 850 860 870 880 890 900 GLTPTEFFFH TMAGREGLVD TAVKTAETGY MQRRLVKSLE DLCSQYDLTV RSSTGDIIQF 910 920 930 940 950 960 IYGGDGLDPA AMEGKDEPLE FKRVLDNIKA VFPCPSEPAL SKNELILTTE SIMKKSEFLC 970 980 990 1000 1010 1020 CQDSFLQEIK KFIKGVSEKI KKTRDKYGIN DNGTTEPRVL YQLDRITPTQ VEKFLETCRD 1030 1040 1050 1060 1070 1080 KYMRAQMEPG SAVGALCAQS IGEPGTQMTL KTFHFAGVAS MNITLGVPRI KEIINASKAI 1090 1100 1110 1120 1130 1140 STPIITAQLD KDDDADYARL VKGRIEKTLL GEISEYIEEV FLPDDCFILV KLSLERIRLL 1150 1160 1170 1180 1190 1200 RLEVNAETVR YSICTSKLRV KPGDVAVHGE AVVCVTPREN SKSSMYYVLQ FLKEDLPKVV 1210 1220 1230 1240 1250 1260 VQGIPEVSRA VIHIDEQSGK EKYKLLVEGD NLRAVMATHG VKGTRTTSNN TYEVEKTLGI 1270 1280 1290 1300 1310 1320 EAARTTIINE IQYTMVNHGM SIDRRHVMLL SDLMTYKGEV LGITRFGLAK MKESVLMLAS 1330 1340 1350 1360 1370 1380 FEKTADHLFD AAYFGQKDSV CGVSECIIMG IPMNIGTGLF KLLHKADRDP NPPKRPLIFD 1390 TNEFHIPLVT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The largest subunit of human RNA polymerase III is closely related to the largest subunit of yeast and trypanosome RNA polymerase III." Sepehri S., Hernandez N. Genome Res. 7:1006-1019(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Uterus.
[5]	"Identification of an immunodominant epitope on RNA polymerase III recognized by systemic sclerosis sera: application to enzyme-linked immunosorbent assay." Kuwana M., Kimura K., Kawakami Y. Arthritis Rheum. 46:2742-2747(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-374.
[6]	"Characterization of human RNA polymerase III identifies orthologues for Saccharomyces cerevisiae RNA polymerase III subunits." Hu P., Wu S., Sun Y., Yuan C.-C., Kobayashi R., Myers M.P., Hernandez N. Mol. Cell. Biol. 22:8044-8055(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE RNA POL III COMPLEX, MASS SPECTROMETRY.
[7]	"RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway." Chiu Y.-H., Macmillan J.B., Chen Z.J. Cell 138:576-591(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate." Ablasser A., Bauernfeind F., Hartmann G., Latz E., Fitzgerald K.A., Hornung V. Nat. Immunol. 10:1065-1072(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-445, MASS SPECTROMETRY.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy." Bernard G., Chouery E., Putorti M.L., Tetreault M., Takanohashi A., Carosso G., Clement I., Boespflug-Tanguy O., Rodriguez D., Delague V., Abou Ghoch J., Jalkh N., Dorboz I., Fribourg S., Teichmann M., Megarbane A., Schiffmann R., Vanderver A., Brais B. Am. J. Hum. Genet. 89:415-423(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HLD7 ASN-372; LEU-558; TYR-636; GLU-672; TYR-724; ILE-775; VAL-852 AND THR-1247 INS, TISSUE SPECIFICITY.
[12]	"Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy." Saitsu H., Osaka H., Sasaki M., Takanashi J., Hamada K., Yamashita A., Shibayama H., Shiina M., Kondo Y., Nishiyama K., Tsurusaki Y., Miyake N., Doi H., Ogata K., Inoue K., Matsumoto N. Am. J. Hum. Genet. 89:644-651(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HLD7 ASN-897 AND CYS-1005.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF021351 mRNA. Translation: AAB86536.1. AL512628 Genomic DNA. Translation: CAI16466.1. CH471083 Genomic DNA. Translation: EAW54617.1. BC041089 mRNA. Translation: AAH41089.1. AY091459 mRNA. Translation: AAM12029.1.
IPI	IPI00024163.
RefSeq	NP_008986.2. NM_007055.3.
UniGene	Hs.436896.
3D structure databases
ProteinModelPortal	O14802.
ModBase	Search...
Protein-protein interaction databases
IntAct	O14802. 3 interactions.
STRING	9606.ENSP00000361446.
PTM databases
PhosphoSite	O14802.
Proteomic databases
PaxDb	O14802.
PRIDE	O14802.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000372371; ENSP00000361446; ENSG00000148606.
GeneID	11128.
KEGG	hsa:11128.
UCSC	uc001jzn.3. human.
Organism-specific databases
CTD	11128.
GeneCards	GC10M079729.
HGNC	HGNC:30074. POLR3A.
HPA	HPA037926.
MIM	607694. phenotype. 614258. gene.
neXtProt	NX_O14802.
Orphanet	88637. Hypomyelination - hypogonadotropic hypogonadism - hypodontia. 77295. Odontoleukodystrophy.
PharmGKB	PA134900426.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0086.
HOGENOM	HOG000222974.
HOVERGEN	HBG004339.
InParanoid	O14802.
KO	K03018.
OMA	PRRPLIF.
OrthoDB	EOG4QVCB4.
PhylomeDB	O14802.
Enzyme and pathway databases
Reactome	REACT_1788. Transcription. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	O14802.
Bgee	O14802.
CleanEx	HS_POLR3A.
Genevestigator	O14802.
GermOnline	ENSG00000148606. Homo sapiens.
Family and domain databases
Gene3D	2.40.40.20. 2 hits.
InterPro	IPR009010. Asp_de-COase-like_dom. IPR000722. RNA_pol_asu. IPR015700. RNA_pol_III_lsu. IPR006592. RNA_pol_N. IPR007080. RNA_pol_Rpb1_1. IPR007066. RNA_pol_Rpb1_3. IPR007083. RNA_pol_Rpb1_4. IPR007081. RNA_pol_Rpb1_5. [Graphical view]
PANTHER	PTHR19376:SF15. PTHR19376:SF15. 1 hit.
Pfam	PF04997. RNA_pol_Rpb1_1. 1 hit. PF00623. RNA_pol_Rpb1_2. 1 hit. PF04983. RNA_pol_Rpb1_3. 1 hit. PF05000. RNA_pol_Rpb1_4. 1 hit. PF04998. RNA_pol_Rpb1_5. 1 hit. [Graphical view]
SMART	SM00663. RPOLA_N. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	POLR3A. human.
GenomeRNAi	11128.
NextBio	42292.
SOURCE	Search...

Entry information

Entry name

RPC1_HUMAN

Accession

Primary (citable) accession number: O14802
Secondary accession number(s): Q8IW34, Q8TCW5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	September 23, 2008
Last modified:	May 1, 2013
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.