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O14802 (RPC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1390 AA.
Sequence statusComplete.
Protein existenceEvidence 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 processAntiviral defense
Immunity
Innate immunity
Transcription
   Cellular componentDNA-directed RNA polymerase
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseLeukodystrophy
   LigandMagnesium
Metal-binding
Zinc
   Molecular functionNucleotidyltransferase
Transferase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdefense response to virus

Inferred from electronic annotation. Source: UniProtKB-KW

gene expression

Traceable author statement. Source: Reactome

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

positive regulation of type I interferon production

Traceable author statement. Source: Reactome

termination of RNA polymerase III transcription

Traceable author statement. Source: Reactome

transcription elongation from RNA polymerase III promoter

Traceable author statement. Source: Reactome

transcription from RNA polymerase III promoter

Traceable author statement. Source: Reactome

transcription, DNA-templated

Non-traceable author statement Ref.1. Source: UniProtKB

   Cellular_componentDNA-directed RNA polymerase III complex

Inferred from direct assay PubMed 24107381. Source: MGI

cytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

   Molecular_functionDNA 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: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13901390DNA-directed RNA polymerase III subunit RPC1
PRO_0000073947

Regions

Region844 – 85613Bridging helix By similarity

Sites

Metal binding691Zinc 1 By similarity
Metal binding721Zinc 1 By similarity
Metal binding791Zinc 1 By similarity
Metal binding821Zinc 1 By similarity
Metal binding1091Zinc 2 By similarity
Metal binding1121Zinc 2 By similarity
Metal binding1561Zinc 2 By similarity
Metal binding4991Magnesium; catalytic By similarity
Metal binding5011Magnesium; catalytic By similarity
Metal binding5031Magnesium; catalytic By similarity

Amino acid modifications

Modified residue4451N6-acetyllysine Ref.9

Natural variations

Natural variant3721D → N in HLD7. Ref.11
VAR_066516
Natural variant5581F → L in HLD7. Ref.11
VAR_066517
Natural variant5821R → L.
Corresponds to variant rs34588967 [ dbSNP | Ensembl ].
VAR_051873
Natural variant6361S → Y in HLD7. Ref.11
VAR_066518
Natural variant6721G → E in HLD7. Ref.11
VAR_066519
Natural variant7131K → N.
Corresponds to variant rs35354908 [ dbSNP | Ensembl ].
VAR_051874
Natural variant7241C → Y in HLD7. Ref.11
VAR_066520
Natural variant7751N → I in HLD7. Ref.11
VAR_066521
Natural variant8521M → V in HLD7. Ref.11
VAR_066522
Natural variant8971I → N in HLD7. Ref.12
VAR_067004
Natural variant10051R → C in HLD7. Ref.12
VAR_066523
Natural variant12471T → TT in HLD7. Ref.11
VAR_066524

Experimental info

Sequence conflict151I → T in AAB86536. Ref.1
Sequence conflict2621I → F in AAB86536. Ref.1
Sequence conflict2831L → P in AAM12029. Ref.5
Sequence conflict10561A → G in AAB86536. Ref.1
Sequence conflict12751M → MV in AAB86536. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O14802 [UniParc].

Last modified September 23, 2008. Version 2.
Checksum: 56F30900848E3DB9

FASTA1,390155,641
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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.
CCDSCCDS7354.1.
RefSeqNP_008986.2. NM_007055.3.
UniGeneHs.436896.

3D structure databases

ProteinModelPortalO14802.
SMRO14802. Positions 13-1363.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116301. 26 interactions.
IntActO14802. 3 interactions.
STRING9606.ENSP00000361446.

PTM databases

PhosphoSiteO14802.

Proteomic databases

MaxQBO14802.
PaxDbO14802.
PRIDEO14802.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000372371; ENSP00000361446; ENSG00000148606.
GeneID11128.
KEGGhsa:11128.
UCSCuc001jzn.3. human.

Organism-specific databases

CTD11128.
GeneCardsGC10M079729.
GeneReviewsPOLR3A.
HGNCHGNC:30074. POLR3A.
HPAHPA037926.
HPA037927.
MIM607694. phenotype.
614258. gene.
neXtProtNX_O14802.
Orphanet88637. Hypomyelination - hypogonadotropic hypogonadism - hypodontia.
77295. Odontoleukodystrophy.
PharmGKBPA134900426.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0086.
HOGENOMHOG000222974.
HOVERGENHBG004339.
InParanoidO14802.
KOK03018.
OMAHKADRDP.
OrthoDBEOG761BSV.
PhylomeDBO14802.
TreeFamTF103054.

Enzyme and pathway databases

ReactomeREACT_1788. Transcription.
REACT_6900. Immune System.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressO14802.
BgeeO14802.
CleanExHS_POLR3A.
GenevestigatorO14802.

Family and domain databases

InterProIPR000722. RNA_pol_asu.
IPR006592. RNA_pol_N.
IPR007080. RNA_pol_Rpb1_1.
IPR007066. RNA_pol_Rpb1_3.
IPR007083. RNA_pol_Rpb1_4.
IPR007081. RNA_pol_Rpb1_5.
IPR015700. RPC1.
[Graphical view]
PANTHERPTHR19376:SF31. PTHR19376:SF31. 1 hit.
PfamPF04997. 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]
SMARTSM00663. RPOLA_N. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPOLR3A. human.
GenomeRNAi11128.
NextBio42292.
PROO14802.
SOURCESearch...

Entry information

Entry nameRPC1_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM