Q5TBB1 (RNH2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ribonuclease H2 subunit B
Short name=RNase H2 subunit B

Alternative name(s):
Aicardi-Goutieres syndrome 2 protein
Short name=AGS2
Deleted in lymphocytic leukemia 8
Ribonuclease HI subunit B

Gene names

Name:	RNASEH2B
Synonyms:	DLEU8

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	312 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Non catalytic subunit of RNase H2, 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.8 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.8
Subcellular location	Nucleus Probable.
Tissue specificity	Widely expressed. Ref.9
Involvement in disease	Aicardi-Goutieres syndrome 2 (AGS2) [MIM:610181]: 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 Ref.9
Sequence similarities	Belongs to the RNase H2 subunit B family.
Sequence caution	The sequence AAH01397.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence. The sequence AAH07332.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence. The sequence AAH10174.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
Cellular component	Nucleus
Disease	Aicardi-Goutieres syndrome Disease mutation
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	RNA catabolic process Inferred from direct assay Ref.8. Source: UniProtKB
Cellular_component	nucleus Inferred from direct assay. Source: HPA ribonuclease H2 complex Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 312

312

Ribonuclease H2 subunit B

PRO_0000248378

Amino acid modifications

Modified residue

295

1

N6-acetyllysine Ref.6

Natural variations

Natural variant

60

1

L → R in AGS2; heterozygous compound with T-177. Ref.9

VAR_027280

Natural variant

86

1

H → R in AGS2; heterozygous compound with T-177; reduces stability of the RNase complex. Ref.8 Ref.9

VAR_027281

Natural variant

162

1

K → T in AGS2. Ref.9

VAR_027282

Natural variant

163

1

T → I in AGS2; heterozygous compound with T-177. Ref.9

VAR_027283

Natural variant

177

1

A → T in AGS2; frequent mutation. Ref.9

VAR_027284

Natural variant

185

1

V → G in AGS2. Ref.9

VAR_027285

Natural variant

219

1

Y → H in AGS2; heterozygous compound with a nonsense mutation; reduces stability of the RNase complex. Ref.8 Ref.9

VAR_027286

Experimental info

Mutagenesis

73

1

W → L: Reduces stability of the RNase complex. Ref.8

Mutagenesis

83

1

G → S: Reduces stability of the RNase complex. Ref.8

Sequence conflict

61

1

F → L in AAX13343. Ref.1

Sequence conflict

61

1

F → L in BAB13892. Ref.2

Secondary structure

1

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312

Helix Strand Turn

Details...

Beta strand

14 – 21

8

Beta strand

36 – 41

6

Turn

43 – 45

3

Beta strand

47 – 54

8

Turn

55 – 58

4

Beta strand

59 – 66

8

Beta strand

72 – 75

4

Beta strand

78 – 81

4

Beta strand

85 – 90

6

Helix

94 – 107

14

Helix

113 – 116

4

Helix

123 – 130

8

Helix

134 – 138

5

Turn

139 – 141

3

Beta strand

142 – 145

4

Beta strand

155 – 158

4

Helix

160 – 181

22

Helix

206 – 216

11

Turn

217 – 219

3

Helix

222 – 230

9

Helix

297 – 299

3

Sequences

	Sequence		Length	Mass (Da)
	Q5TBB1 [UniParc]. Last modified April 12, 2005. Version 1. Checksum: 98B1A8E073A50D68	FASTA	312	35,139
	10 20 30 40 50 60 MAAGVDCGDG VGARQHVFLV SEYLKDASKK MKNGLMFVKL VNPCSGEGAI YLFNMCLQQL 70 80 90 100 110 120 FEVKVFKEKH HSWFINQSVQ SGGLLHFATP VDPLFLLLHY LIKADKEGKF QPLDQVVVDN 130 140 150 160 170 180 VFPNCILLLK LPGLEKLLHH VTEEKGNPEI DNKKYYKYSK EKTLKWLEKK VNQTVAALKT 190 200 210 220 230 240 NNVNVSSRVQ STAFFSGDQA STDKEEDYIR YAHGLISDYI PKELSDDLSK YLKLPEPSAS 250 260 270 280 290 300 LPNPPSKKIK LSDEPVEAKE DYTKFNTKDL KTEKKNSKMT AAQKALAKVD KSGMKSIDTF 310 FGVKNKKKIG KV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"DLEU8, a novel conserved gene located in the CLL 13q14 deletion locus." Corcoran M.M. Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases 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].
[3]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[4]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] OF 1-304. Tissue: Skin.
[6]	"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-295, MASS SPECTROMETRY.
[7]	"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].
[8]	"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) OF 14-233, SUBUNIT, FUNCTION, CHARACTERIZATION OF VARIANTS AGS2 ARG-86 AND HIS-219, MUTAGENESIS OF TRP-73 AND GLY-83.
[9]	"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: VARIANTS AGS2 ARG-60; ARG-86; THR-162; ILE-163; THR-177; GLY-185 AND HIS-219, FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH RNASEH2A AND RNASEH2C.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY764036 mRNA. Translation: AAX13343.1.
AK021774 mRNA. Translation: BAB13892.1.
AK223340 mRNA. Translation: BAD97060.1.
AL137881 Genomic DNA. Translation: CAI13913.1.
BC001397 mRNA. Translation: AAH01397.1. Sequence problems.
BC007332 mRNA. Translation: AAH07332.1. Sequence problems.
BC010174 mRNA. Translation: AAH10174.1. Sequence problems.

IPI

IPI01010943.

RefSeq

NP_078846.2. NM_024570.3.

UniGene

Hs.306291.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3P56	X-ray	4.06	B/E	2-226	[»]
3P87	X-ray	2.99	G/H/I/J/K/L	290-312	[»]
3PUF	X-ray	3.10	B/E/H/K/N/Q	14-233	[»]

ProteinModelPortal

Q5TBB1.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000337623.

PTM databases

PhosphoSite

Q5TBB1.

Polymorphism databases

DMDM

74745929.

Proteomic databases

PaxDb

Q5TBB1.

PRIDE

Q5TBB1.

Protocols and materials databases

DNASU

79621.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000336617; ENSP00000337623; ENSG00000136104.

GeneID

79621.

KEGG

hsa:79621.

UCSC

uc001vfa.4. human.

Organism-specific databases

CTD

79621.

GeneCards

GC13P051483.

HGNC

HGNC:25671. RNASEH2B.

HPA

HPA040084.

MIM

610181. phenotype.
610326. gene.

neXtProt

NX_Q5TBB1.

Orphanet

51. Aicardi-Goutieres syndrome.

PharmGKB

PA162401418.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG320404.

HOVERGEN

HBG056010.

InParanoid

Q5TBB1.

KO

K10744.

OrthoDB

EOG4BRWMG.

Gene expression databases

ArrayExpress

Q5TBB1.

Bgee

Q5TBB1.

CleanEx

HS_RNASEH2B.

Genevestigator

Q5TBB1.

GermOnline

ENSG00000136104. Homo sapiens.

Family and domain databases

InterPro

IPR019024. RNase_H2_suB.
[Graphical view]

Pfam

PF09468. RNase_H2-Ydr279. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q5TBB1.

GenomeRNAi

79621.

NextBio

68689.

SOURCE

Search...

Entry information

Entry name

RNH2B_HUMAN

Accession

Primary (citable) accession number: Q5TBB1
Secondary accession number(s): Q6PK48, Q9HAF7

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
Last sequence update:	April 12, 2005
Last modified:	May 1, 2013
This is version 73 of the entry and version 1 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.