Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Ribonuclease H2 subunit A

Gene

RNASEH2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

Endonucleolytic cleavage to 5'-phosphomonoester.1 Publication

Cofactori

Mn2+By similarity, Mg2+By similarityNote: 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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi34Divalent metal cationBy similarity1
Metal bindingi35Divalent metal cationBy similarity1
Metal bindingi141Divalent metal cationBy similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • ribonuclease activity Source: ProtInc
  • RNA binding Source: InterPro
  • RNA-DNA hybrid ribonuclease activity Source: UniProtKB

GO - Biological processi

  • DNA replication Source: UniProtKB
  • DNA replication, removal of RNA primer Source: GO_Central
  • mismatch repair Source: MGI
  • RNA catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Hydrolase, Nuclease

Keywords - Ligandi

Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS02645-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Ribonuclease H2 subunit A (EC:3.1.26.4)
Short name:
RNase H2 subunit A
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 namesi
Name:RNASEH2A
Synonyms:RNASEHI, RNHIA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:18518. RNASEH2A.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • nucleoplasm Source: HPA
  • ribonuclease H2 complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Aicardi-Goutieres syndrome 4 (AGS4)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:610333
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0706232 – 3DL → YP in AGS4. 2
Natural variantiVAR_02737737G → S in AGS4; strongly impairs enzyme activity but not interaction with RNASEH2B and RNASEH2C. 2 PublicationsCorresponds to variant rs76857106dbSNPEnsembl.1
Natural variantiVAR_070625108R → W in AGS4. 1 PublicationCorresponds to variant rs76436818dbSNPEnsembl.1
Natural variantiVAR_070626186R → W in AGS4. 2 PublicationsCorresponds to variant rs77103971dbSNPEnsembl.1
Natural variantiVAR_070628230F → L in AGS4. 1 PublicationCorresponds to variant rs79767407dbSNPEnsembl.1
Natural variantiVAR_070629235R → Q in AGS4. 1 PublicationCorresponds to variant rs75718910dbSNPEnsembl.1
Natural variantiVAR_070630240T → M in AGS4. 1 PublicationCorresponds to variant rs79843600dbSNPEnsembl.1
Natural variantiVAR_070632291R → H in AGS4. 1 PublicationCorresponds to variant rs75037667dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi67D → A: Loss of enzyme activity. 1 Publication1
Mutagenesisi69K → A: Strongly reduced enzyme activity. 1 Publication1
Mutagenesisi112N → A: Reduced enzyme activity. 1 Publication1
Mutagenesisi210Y → A: Strongly reduced enzyme activity. 1 Publication1
Mutagenesisi210Y → F: Loss of enzyme activity. 1 Publication1
Mutagenesisi240T → A: Strongly reduced enzyme activity. 1 Publication1

Keywords - Diseasei

Aicardi-Goutieres syndrome, Disease mutation

Organism-specific databases

DisGeNETi10535.
MalaCardsiRNASEH2A.
MIMi610333. phenotype.
OpenTargetsiENSG00000104889.
Orphaneti51. Aicardi-Goutieres syndrome.
PharmGKBiPA38565.

Polymorphism and mutation databases

BioMutaiRNASEH2A.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001117101 – 299Ribonuclease H2 subunit AAdd BLAST299

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei204PhosphothreonineCombined sources1
Modified residuei216PhosphothreonineCombined sources1
Modified residuei257PhosphoserineBy similarity1
Modified residuei277PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO75792.
MaxQBiO75792.
PaxDbiO75792.
PeptideAtlasiO75792.
PRIDEiO75792.

PTM databases

iPTMnetiO75792.
PhosphoSitePlusiO75792.

Expressioni

Gene expression databases

BgeeiENSG00000104889.
CleanExiHS_RNASEH2A.
GenevisibleiO75792. HS.

Organism-specific databases

HPAiHPA042692.

Interactioni

Subunit structurei

The RNase H2 complex is a heterotrimer composed of the catalytic subunit RNASEH2A and the non-catalytic subunits RNASEH2B and RNASEH2C.1 Publication

Protein-protein interaction databases

BioGridi115789. 44 interactors.
IntActiO75792. 26 interactors.
STRINGi9606.ENSP00000221486.

Structurei

Secondary structure

1299
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 7Combined sources4
Beta strandi15 – 17Combined sources3
Helixi23 – 26Combined sources4
Beta strandi29 – 36Combined sources8
Beta strandi41 – 43Combined sources3
Beta strandi45 – 54Combined sources10
Helixi57 – 62Combined sources6
Helixi73 – 84Combined sources12
Beta strandi86 – 88Combined sources3
Beta strandi90 – 96Combined sources7
Helixi98 – 105Combined sources8
Beta strandi107 – 109Combined sources3
Helixi113 – 130Combined sources18
Beta strandi135 – 144Combined sources10
Helixi146 – 156Combined sources11
Beta strandi160 – 166Combined sources7
Helixi168 – 171Combined sources4
Helixi173 – 191Combined sources19
Helixi214 – 222Combined sources9
Turni226 – 228Combined sources3
Helixi239 – 248Combined sources10
Helixi286 – 290Combined sources5
Beta strandi293 – 295Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3P56X-ray4.06A/D1-299[»]
3PUFX-ray3.10A/D/G/J/M/P1-299[»]
ProteinModelPortaliO75792.
SMRiO75792.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75792.

Family & Domainsi

Sequence similaritiesi

Belongs to the RNase HII family. Eukaryotic subfamily.Curated

Phylogenomic databases

eggNOGiKOG2299. Eukaryota.
COG0164. LUCA.
GeneTreeiENSGT00390000010768.
HOGENOMiHOG000100290.
HOVERGENiHBG023585.
InParanoidiO75792.
KOiK10743.
OMAiREECRFF.
OrthoDBiEOG091G0E06.
PhylomeDBiO75792.
TreeFamiTF314302.

Family and domain databases

Gene3Di1.10.10.460. 1 hit.
3.30.420.10. 1 hit.
InterProiIPR004649. 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]
PANTHERiPTHR10954. PTHR10954. 1 hit.
PfamiPF01351. RNase_HII. 1 hit.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.
TIGRFAMsiTIGR00729. TIGR00729. 1 hit.

Sequencei

Sequence statusi: Complete.

O75792-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLSELERDN TGRCRLSSPV PAVCRKEPCV LGVDEAGRGP VLGPMVYAIC
60 70 80 90 100
YCPLPRLADL EALKVADSKT LLESERERLF AKMEDTDFVG WALDVLSPNL
110 120 130 140 150
ISTSMLGRVK YNLNSLSHDT ATGLIQYALD QGVNVTQVFV DTVGMPETYQ
160 170 180 190 200
ARLQQSFPGI EVTVKAKADA LYPVVSAASI CAKVARDQAV KKWQFVEKLQ
210 220 230 240 250
DLDTDYGSGY PNDPKTKAWL KEHVEPVFGF PQFVRFSWRT AQTILEKEAE
260 270 280 290
DVIWEDSASE NQEGLRKITS YFLNEGSQAR PRSSHRYFLE RGLESATSL
Length:299
Mass (Da):33,395
Last modified:May 15, 2002 - v2
Checksum:i34992FE85130157B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti152R → Q in CAB09725 (PubMed:9789007).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0706232 – 3DL → YP in AGS4. 2
Natural variantiVAR_02737737G → S in AGS4; strongly impairs enzyme activity but not interaction with RNASEH2B and RNASEH2C. 2 PublicationsCorresponds to variant rs76857106dbSNPEnsembl.1
Natural variantiVAR_07062499N → D.1 Publication1
Natural variantiVAR_070625108R → W in AGS4. 1 PublicationCorresponds to variant rs76436818dbSNPEnsembl.1
Natural variantiVAR_070626186R → W in AGS4. 2 PublicationsCorresponds to variant rs77103971dbSNPEnsembl.1
Natural variantiVAR_024617202L → S.1 PublicationCorresponds to variant rs7247284dbSNPEnsembl.1
Natural variantiVAR_070627205D → E.1 PublicationCorresponds to variant rs62619782dbSNPEnsembl.1
Natural variantiVAR_070628230F → L in AGS4. 1 PublicationCorresponds to variant rs79767407dbSNPEnsembl.1
Natural variantiVAR_070629235R → Q in AGS4. 1 PublicationCorresponds to variant rs75718910dbSNPEnsembl.1
Natural variantiVAR_070630240T → M in AGS4. 1 PublicationCorresponds to variant rs79843600dbSNPEnsembl.1
Natural variantiVAR_027378258A → G.Corresponds to variant rs15389dbSNPEnsembl.1
Natural variantiVAR_070631260E → G.1 PublicationCorresponds to variant rs770898096dbSNPEnsembl.1
Natural variantiVAR_070632291R → H in AGS4. 1 PublicationCorresponds to variant rs75037667dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z97029 mRNA. Translation: CAB09725.1.
AK315327 mRNA. Translation: BAG37728.1.
CH471106 Genomic DNA. Translation: EAW84313.1.
BC011748 mRNA. Translation: AAH11748.1.
CCDSiCCDS12282.1.
RefSeqiNP_006388.2. NM_006397.2.
UniGeneiHs.532851.

Genome annotation databases

EnsembliENST00000221486; ENSP00000221486; ENSG00000104889.
GeneIDi10535.
KEGGihsa:10535.
UCSCiuc002mvg.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z97029 mRNA. Translation: CAB09725.1.
AK315327 mRNA. Translation: BAG37728.1.
CH471106 Genomic DNA. Translation: EAW84313.1.
BC011748 mRNA. Translation: AAH11748.1.
CCDSiCCDS12282.1.
RefSeqiNP_006388.2. NM_006397.2.
UniGeneiHs.532851.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3P56X-ray4.06A/D1-299[»]
3PUFX-ray3.10A/D/G/J/M/P1-299[»]
ProteinModelPortaliO75792.
SMRiO75792.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115789. 44 interactors.
IntActiO75792. 26 interactors.
STRINGi9606.ENSP00000221486.

PTM databases

iPTMnetiO75792.
PhosphoSitePlusiO75792.

Polymorphism and mutation databases

BioMutaiRNASEH2A.

Proteomic databases

EPDiO75792.
MaxQBiO75792.
PaxDbiO75792.
PeptideAtlasiO75792.
PRIDEiO75792.

Protocols and materials databases

DNASUi10535.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000221486; ENSP00000221486; ENSG00000104889.
GeneIDi10535.
KEGGihsa:10535.
UCSCiuc002mvg.2. human.

Organism-specific databases

CTDi10535.
DisGeNETi10535.
GeneCardsiRNASEH2A.
GeneReviewsiRNASEH2A.
HGNCiHGNC:18518. RNASEH2A.
HPAiHPA042692.
MalaCardsiRNASEH2A.
MIMi606034. gene.
610333. phenotype.
neXtProtiNX_O75792.
OpenTargetsiENSG00000104889.
Orphaneti51. Aicardi-Goutieres syndrome.
PharmGKBiPA38565.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2299. Eukaryota.
COG0164. LUCA.
GeneTreeiENSGT00390000010768.
HOGENOMiHOG000100290.
HOVERGENiHBG023585.
InParanoidiO75792.
KOiK10743.
OMAiREECRFF.
OrthoDBiEOG091G0E06.
PhylomeDBiO75792.
TreeFamiTF314302.

Enzyme and pathway databases

BioCyciZFISH:HS02645-MONOMER.

Miscellaneous databases

EvolutionaryTraceiO75792.
GeneWikiiRNASEH2A.
GenomeRNAii10535.
PROiO75792.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104889.
CleanExiHS_RNASEH2A.
GenevisibleiO75792. HS.

Family and domain databases

Gene3Di1.10.10.460. 1 hit.
3.30.420.10. 1 hit.
InterProiIPR004649. 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]
PANTHERiPTHR10954. PTHR10954. 1 hit.
PfamiPF01351. RNase_HII. 1 hit.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.
TIGRFAMsiTIGR00729. TIGR00729. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiRNH2A_HUMAN
AccessioniPrimary (citable) accession number: O75792
Secondary accession number(s): B2RCY1, Q96F11
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 15, 2002
Last modified: November 2, 2016
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.