O75792 (RNH2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	299 AA.
Sequence status	Complete.
Protein existence	Evidence 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.7 Ref.8
Catalytic activity	Endonucleolytic cleavage to 5'-phosphomonoester. Ref.7
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.7
Subunit structure	The RNase H2 complex is a heterotrimer composed of the catalytic subunit RNASEH2A and the non-catalytic subunits RNASEH2B and RNASEH2C. Ref.7
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.8
Sequence similarities	Belongs to the RNase HII family. Eukaryotic subfamily.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Aicardi-Goutieres syndrome Disease mutation
Ligand	Metal-binding
Molecular function	Endonuclease Hydrolase Nuclease
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication Traceable author statement Ref.7. Source: UniProtKB RNA catabolic process Inferred from direct assay Ref.7. Source: UniProtKB
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell ribonuclease H2 complex Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	RNA binding Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW ribonuclease H activity Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 299

299

Ribonuclease H2 subunit A

PRO_0000111710

Sites

Metal binding

34

1

Divalent metal cation By similarity

Metal binding

35

1

Divalent metal cation By similarity

Metal binding

141

1

Divalent metal cation By similarity

Amino acid modifications

Modified residue

204

1

Phosphothreonine Ref.5

Modified residue

216

1

Phosphothreonine Ref.5

Modified residue

257

1

Phosphoserine By similarity

Natural variations

Natural variant

37

1

G → S in AGS4; strongly impairs enzyme activity but not interaction with RNASEH2B and RNASEH2C. Ref.8

VAR_027377

Natural variant

202

1

L → S.
Corresponds to variant rs7247284 [ dbSNP | Ensembl ].

VAR_024617

Natural variant

258

1

A → G.
Corresponds to variant rs15389 [ dbSNP | Ensembl ].

VAR_027378

Experimental info

Mutagenesis

67

1

D → A: Loss of enzyme activity. Ref.7

Mutagenesis

69

1

K → A: Strongly reduced enzyme activity. Ref.7

Mutagenesis

112

1

N → A: Reduced enzyme activity. Ref.7

Mutagenesis

210

1

Y → A: Strongly reduced enzyme activity. Ref.7

Mutagenesis

210

1

Y → F: Loss of enzyme activity. Ref.7

Mutagenesis

240

1

T → A: Strongly reduced enzyme activity. Ref.7

Sequence conflict

152

1

R → Q in CAB09725. Ref.1

Secondary structure

1

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299

Helix Strand Turn

Details...

Helix

4 – 7

4

Beta strand

15 – 17

3

Helix

23 – 26

4

Beta strand

29 – 36

8

Beta strand

41 – 43

3

Beta strand

45 – 54

10

Helix

57 – 62

6

Helix

73 – 84

12

Beta strand

86 – 88

3

Beta strand

90 – 96

7

Helix

98 – 105

8

Beta strand

107 – 109

3

Helix

113 – 130

18

Beta strand

135 – 144

10

Helix

146 – 156

11

Beta strand

160 – 166

7

Helix

168 – 171

4

Helix

173 – 191

19

Helix

214 – 222

9

Turn

226 – 228

3

Helix

239 – 248

10

Helix

286 – 290

5

Beta strand

293 – 295

3

Sequences

	Sequence		Length	Mass (Da)
	O75792 [UniParc]. Last modified May 15, 2002. Version 2. Checksum: 34992FE85130157B	FASTA	299	33,395
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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]	"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.
[8]	"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. , 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.
+	Additional computationally mapped references.

Web resources

GeneReviews

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.

IPI

IPI00290192.

RefSeq

NP_006388.2. NM_006397.2.

UniGene

Hs.532851.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3P56	X-ray	4.06	A/D	1-299	[»]
3PUF	X-ray	3.10	A/D/G/J/M/P	1-299	[»]

ProteinModelPortal

O75792.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000221486.

PTM databases

PhosphoSite

O75792.

Proteomic databases

PaxDb

O75792.

PRIDE

O75792.

Protocols and materials databases

DNASU

10535.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000221486; ENSP00000221486; ENSG00000104889.

GeneID

10535.

KEGG

hsa:10535.

UCSC

uc002mvg.1. human.

Organism-specific databases

CTD

10535.

GeneCards

GC19P012918.

HGNC

HGNC:18518. RNASEH2A.

HPA

HPA042692.

MIM

606034. gene.
610333. phenotype.

neXtProt

NX_O75792.

Orphanet

51. Aicardi-Goutieres syndrome.

PharmGKB

PA38565.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0164.

HOGENOM

HOG000100290.

HOVERGEN

HBG023585.

InParanoid

O75792.

KO

K10743.

OMA

WRTAQTI.

OrthoDB

EOG4PNXHM.

PhylomeDB

O75792.

Gene expression databases

Bgee

O75792.

CleanEx

HS_RNASEH2A.

Genevestigator

O75792.

GermOnline

ENSG00000104889. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.460. 1 hit.

InterPro

IPR004649. 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]

PANTHER

PTHR10954. PTHR10954. 1 hit.

Pfam

PF01351. RNase_HII. 1 hit.
[Graphical view]

SUPFAM

SSF53098. RNaseH_fold. 1 hit.

TIGRFAMs

TIGR00729. TIGR00729. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

O75792.

GenomeRNAi

10535.

NextBio

39969.

SOURCE

Search...

Entry information

Entry name

RNH2A_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 124 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.