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O75792 (RNH2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ribonuclease H2 subunit A

Short name=RNase H2 subunit A
EC=3.1.26.4
Alternative name(s):
Aicardi-Goutieres syndrome 4 protein
Short name=AGS4
RNase H(35)
Ribonuclease HI large subunit
Short name=RNase HI large subunit
Ribonuclease HI subunit A
Gene names
Name:RNASEH2A
Synonyms:RNASEHI, RNHIA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length299 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes. Ref.9 Ref.10

Catalytic activity

Endonucleolytic cleavage to 5'-phosphomonoester. Ref.9

Cofactor

Manganese or magnesium. Binds 1 divalent metal ion per monomer in the absence of substrate. May bind a second metal ion after substrate binding By similarity. Ref.9

Subunit structure

The RNase H2 complex is a heterotrimer composed of the catalytic subunit RNASEH2A and the non-catalytic subunits RNASEH2B and RNASEH2C. Ref.9

Subcellular location

Nucleus Probable.

Involvement in disease

Aicardi-Goutieres syndrome 4 (AGS4) [MIM:610333]: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.12

Sequence similarities

Belongs to the RNase HII family. Eukaryotic subfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 299299Ribonuclease H2 subunit A
PRO_0000111710

Sites

Metal binding341Divalent metal cation By similarity
Metal binding351Divalent metal cation By similarity
Metal binding1411Divalent metal cation By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.7 Ref.8
Modified residue2041Phosphothreonine Ref.5
Modified residue2161Phosphothreonine Ref.5
Modified residue2571Phosphoserine By similarity

Natural variations

Natural variant2 – 32DL → YP in AGS4.
VAR_070623
Natural variant371G → S in AGS4; strongly impairs enzyme activity but not interaction with RNASEH2B and RNASEH2C. Ref.10 Ref.11
VAR_027377
Natural variant991N → D. Ref.11
VAR_070624
Natural variant1081R → W in AGS4. Ref.11
VAR_070625
Natural variant1861R → W in AGS4. Ref.11 Ref.12
VAR_070626
Natural variant2021L → S. Ref.11
Corresponds to variant rs7247284 [ dbSNP | Ensembl ].
VAR_024617
Natural variant2051D → E. Ref.11
VAR_070627
Natural variant2301F → L in AGS4. Ref.11
VAR_070628
Natural variant2351R → Q in AGS4. Ref.11
VAR_070629
Natural variant2401T → M in AGS4. Ref.11
VAR_070630
Natural variant2581A → G.
Corresponds to variant rs15389 [ dbSNP | Ensembl ].
VAR_027378
Natural variant2601E → G. Ref.11
VAR_070631
Natural variant2911R → H in AGS4. Ref.11
VAR_070632

Experimental info

Mutagenesis671D → A: Loss of enzyme activity. Ref.9
Mutagenesis691K → A: Strongly reduced enzyme activity. Ref.9
Mutagenesis1121N → A: Reduced enzyme activity. Ref.9
Mutagenesis2101Y → A: Strongly reduced enzyme activity. Ref.9
Mutagenesis2101Y → F: Loss of enzyme activity. Ref.9
Mutagenesis2401T → A: Strongly reduced enzyme activity. Ref.9
Sequence conflict1521R → Q in CAB09725. Ref.1

Secondary structure

............................................... 299
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O75792 [UniParc].

Last modified May 15, 2002. Version 2.
Checksum: 34992FE85130157B

FASTA29933,395
        10         20         30         40         50         60 
MDLSELERDN TGRCRLSSPV PAVCRKEPCV LGVDEAGRGP VLGPMVYAIC YCPLPRLADL 

        70         80         90        100        110        120 
EALKVADSKT LLESERERLF AKMEDTDFVG WALDVLSPNL ISTSMLGRVK YNLNSLSHDT 

       130        140        150        160        170        180 
ATGLIQYALD QGVNVTQVFV DTVGMPETYQ ARLQQSFPGI EVTVKAKADA LYPVVSAASI 

       190        200        210        220        230        240 
CAKVARDQAV KKWQFVEKLQ DLDTDYGSGY PNDPKTKAWL KEHVEPVFGF PQFVRFSWRT 

       250        260        270        280        290 
AQTILEKEAE DVIWEDSASE NQEGLRKITS YFLNEGSQAR PRSSHRYFLE RGLESATSL 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of the cDNA encoding the large subunit of human RNase HI, a homologue of the prokaryotic RNase HII."
Frank P., Braunshofer-Reiter C., Wintersberger U., Grimm R., Buesen W.
Proc. Natl. Acad. Sci. U.S.A. 95:12872-12877(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Thalamus.
[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: Brain.
[5]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-204 AND THR-216, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[6]"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].
[7]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutieres syndrome defects."
Figiel M., Chon H., Cerritelli S.M., Cybulska M., Crouch R.J., Nowotny M.
J. Biol. Chem. 286:10540-10550(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS), SUBUNIT, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, MUTAGENESIS OF ASP-67; LYS-69; ASN-112; TYR-210 AND THR-240.
[10]"Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutieres syndrome and mimic congenital viral brain infection."
Crow Y.J., Leitch A., Hayward B.E., Garner A., Parmar R., Griffith E., Ali M., Semple C., Aicardi J., Babul-Hirji R., Baumann C., Baxter P., Bertini E., Chandler K.E., Chitayat D., Cau D., Dery C., Fazzi E. expand/collapse author list , Goizet C., King M.D., Klepper J., Lacombe D., Lanzi G., Lyall H., Martinez-Frias M.L., Mathieu M., McKeown C., Monier A., Oade Y., Quarrell O.W., Rittey C.D., Rogers R.C., Sanchis A., Stephenson J.B.P., Tacke U., Till M., Tolmie J.L., Tomlin P., Voit T., Weschke B., Woods C.G., Lebon P., Bonthron D.T., Ponting C.P., Jackson A.P.
Nat. Genet. 38:910-916(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AGS4 SER-37, CHARACTERIZATION OF VARIANT AGS4 SER-37, FUNCTION, INTERACTION WITH RNASEH2B AND RNASEH2C.
[11]"Clinical and molecular phenotype of Aicardi-Goutieres syndrome."
Rice G., Patrick T., Parmar R., Taylor C.F., Aeby A., Aicardi J., Artuch R., Montalto S.A., Bacino C.A., Barroso B., Baxter P., Benko W.S., Bergmann C., Bertini E., Biancheri R., Blair E.M., Blau N., Bonthron D.T. expand/collapse author list , Briggs T., Brueton L.A., Brunner H.G., Burke C.J., Carr I.M., Carvalho D.R., Chandler K.E., Christen H.J., Corry P.C., Cowan F.M., Cox H., D'Arrigo S., Dean J., De Laet C., De Praeter C., Dery C., Ferrie C.D., Flintoff K., Frints S.G., Garcia-Cazorla A., Gener B., Goizet C., Goutieres F., Green A.J., Guet A., Hamel B.C., Hayward B.E., Heiberg A., Hennekam R.C., Husson M., Jackson A.P., Jayatunga R., Jiang Y.H., Kant S.G., Kao A., King M.D., Kingston H.M., Klepper J., van der Knaap M.S., Kornberg A.J., Kotzot D., Kratzer W., Lacombe D., Lagae L., Landrieu P.G., Lanzi G., Leitch A., Lim M.J., Livingston J.H., Lourenco C.M., Lyall E.G., Lynch S.A., Lyons M.J., Marom D., McClure J.P., McWilliam R., Melancon S.B., Mewasingh L.D., Moutard M.L., Nischal K.K., Ostergaard J.R., Prendiville J., Rasmussen M., Rogers R.C., Roland D., Rosser E.M., Rostasy K., Roubertie A., Sanchis A., Schiffmann R., Scholl-Burgi S., Seal S., Shalev S.A., Corcoles C.S., Sinha G.P., Soler D., Spiegel R., Stephenson J.B., Tacke U., Tan T.Y., Till M., Tolmie J.L., Tomlin P., Vagnarelli F., Valente E.M., Van Coster R.N., Van der Aa N., Vanderver A., Vles J.S., Voit T., Wassmer E., Weschke B., Whiteford M.L., Willemsen M.A., Zankl A., Zuberi S.M., Orcesi S., Fazzi E., Lebon P., Crow Y.J.
Am. J. Hum. Genet. 81:713-725(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AGS4 SER-37; TRP-108; TRP-186; LEU-230; GLN-235; MET-240 AND HIS-291, VARIANTS ASP-99; SER-202; GLU-205 AND GLY-260.
[12]"Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutieres syndrome."
Ramantani G., Kohlhase J., Hertzberg C., Innes A.M., Engel K., Hunger S., Borozdin W., Mah J.K., Ungerath K., Walkenhorst H., Richardt H.H., Buckard J., Bevot A., Siegel C., von Stuelpnagel C., Ikonomidou C., Thomas K., Proud V. expand/collapse author list , Niemann F., Wieczorek D., Haeusler M., Niggemann P., Baltaci V., Conrad K., Lebon P., Lee-Kirsch M.A.
Arthritis Rheum. 62:1469-1477(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AGS4 2-TYR-PRO-3 AND TRP-186.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z97029 mRNA. Translation: CAB09725.1.
AK315327 mRNA. Translation: BAG37728.1.
CH471106 Genomic DNA. Translation: EAW84313.1.
BC011748 mRNA. Translation: AAH11748.1.
RefSeqNP_006388.2. NM_006397.2.
UniGeneHs.532851.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3P56X-ray4.06A/D1-299[»]
3PUFX-ray3.10A/D/G/J/M/P1-299[»]
ProteinModelPortalO75792.
SMRO75792. Positions 2-299.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115789. 7 interactions.
STRING9606.ENSP00000221486.

PTM databases

PhosphoSiteO75792.

Proteomic databases

PaxDbO75792.
PRIDEO75792.

Protocols and materials databases

DNASU10535.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000221486; ENSP00000221486; ENSG00000104889.
GeneID10535.
KEGGhsa:10535.
UCSCuc002mvg.1. human.

Organism-specific databases

CTD10535.
GeneCardsGC19P012918.
HGNCHGNC:18518. RNASEH2A.
HPAHPA042692.
HPA051652.
MIM606034. gene.
610333. phenotype.
neXtProtNX_O75792.
Orphanet51. Aicardi-Goutieres syndrome.
PharmGKBPA38565.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0164.
HOGENOMHOG000100290.
HOVERGENHBG023585.
InParanoidO75792.
KOK10743.
OMAGPPEKYQ.
OrthoDBEOG7KM5T4.
PhylomeDBO75792.
TreeFamTF314302.

Gene expression databases

BgeeO75792.
CleanExHS_RNASEH2A.
GenevestigatorO75792.

Family and domain databases

Gene3D1.10.10.460. 1 hit.
3.30.420.10. 1 hit.
InterProIPR004649. RNase_H2_suA.
IPR001352. RNase_HII/HIII.
IPR024567. RNase_HII/HIII_dom.
IPR023160. RNase_HII_hlx-loop-hlx_cap_dom.
IPR012337. RNaseH-like_dom.
[Graphical view]
PANTHERPTHR10954. PTHR10954. 1 hit.
PfamPF01351. RNase_HII. 1 hit.
[Graphical view]
SUPFAMSSF53098. SSF53098. 1 hit.
TIGRFAMsTIGR00729. TIGR00729. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceO75792.
GeneWikiRNASEH2A.
GenomeRNAi10535.
NextBio39969.
PROO75792.
SOURCESearch...

Entry information

Entry nameRNH2A_HUMAN
AccessionPrimary (citable) accession number: O75792
Secondary accession number(s): B2RCY1, Q96F11
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 15, 2002
Last modified: April 16, 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 19

Human chromosome 19: entries, gene names and cross-references to MIM