Q8TDP1 (RNH2C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Aicardi-Goutieres syndrome 3 protein
Short name=AGS3
RNase H1 small subunit
Ribonuclease HI subunit C

Gene names

Name:	RNASEH2C
Synonyms:	AYP1

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	164 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.6 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.6
Subcellular location	Nucleus Probable.
Tissue specificity	Widely expressed. Ref.7
Involvement in disease	Aicardi-Goutieres syndrome 3 (AGS3) [MIM:610329]: 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.7
Miscellaneous	The T6 pseudogene located upstream of SRY on chromosome Y is derived from the transcript of this gene.
Sequence similarities	Belongs to the RNase H2 subunit C family.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Aicardi-Goutieres syndrome Disease mutation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	RNA catabolic process Inferred from direct assay Ref.6. Source: UniProtKB
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell ribonuclease H2 complex Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8TDP1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8TDP1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     89-89: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 164

164

Ribonuclease H2 subunit C

PRO_0000248385

Natural variations

Alternative sequence

89

1

Missing in isoform 2.

VSP_020258

Natural variant

69

1

R → W in AGS3. Ref.7

VAR_027287

Natural variant

143

1

K → I in AGS3. Ref.7

VAR_027288

Secondary structure

1

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164

Helix Strand Turn

Details...

Helix

9 – 12

4

Beta strand

13 – 16

4

Helix

19 – 22

4

Beta strand

29 – 36

8

Beta strand

39 – 41

3

Helix

44 – 47

4

Helix

49 – 51

3

Beta strand

56 – 63

8

Beta strand

66 – 70

5

Beta strand

72 – 74

3

Beta strand

79 – 86

8

Beta strand

119 – 131

13

Beta strand

133 – 136

4

Helix

143 – 147

5

Helix

150 – 157

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: 13D0F1D039963671	FASTA	164	17,840
	10 20 30 40 50 60 MESGDEAAIE RHRVHLRSAT LRDAVPATLH LLPCEVAVDG PAPVGRFFTP AIRQGPEGLE 70 80 90 100 110 120 VSFRGRCLRG EEVAVPPGLV GYVMVTEEKK VSMGKPDPLR DSGTDDQEEE PLERDFDRFI 130 140 150 160 GATANFSRFT LWGLETIPGP DAKVRGALTW PSLAAAIHAQ VPED
	Isoform 2 [UniParc]. Checksum: 7CD8D8306DE81EDC	FASTA	163	17,712
	10 20 30 40 50 60 MESGDEAAIE RHRVHLRSAT LRDAVPATLH LLPCEVAVDG PAPVGRFFTP AIRQGPEGLE 70 80 90 100 110 120 VSFRGRCLRG EEVAVPPGLV GYVMVTEEKV SMGKPDPLRD SGTDDQEEEP LERDFDRFIG 130 140 150 160 ATANFSRFTL WGLETIPGPD AKVRGALTWP SLAAAIHAQV PED

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the cDNA encoding the small subunit of human RNase HI." Frank P., Bogusch A., Grimm R., Wintersberger U. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Evidence that the T6 pseudogene upstream of human SRY is derived from the transcript of a novel autosomal gene, AYP1." Lim H.N., Oakenfull E.A., Hawkins J.R. Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[3]	"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] (ISOFORM 2). Tissue: Adipose tissue.
[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] (ISOFORM 1). Tissue: B-cell.
[5]	"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].
[6]	"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), FUNCTION, SUBUNIT.
[7]	"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 AGS3 TRP-69 AND ILE-143, FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH RNASEH2A AND RNASEH2B.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF312034 mRNA. Translation: AAL87739.1.
AF346605 Genomic DNA. Translation: AAO49176.1.
AF346606 mRNA. Translation: AAO49177.1.
AK024627 mRNA. Translation: BAB14937.1.
BC023588 mRNA. Translation: AAH23588.1.

IPI

IPI00382985.
IPI00784761.

RefSeq

NP_115569.2. NM_032193.3.

UniGene

Hs.718438.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3P56	X-ray	4.06	C/F	1-164	[»]
3PUF	X-ray	3.10	C/F/I/L/O/R	1-164	[»]

ProteinModelPortal

Q8TDP1.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000308193.

PTM databases

PhosphoSite

Q8TDP1.

Polymorphism databases

DMDM

74730607.

Proteomic databases

PaxDb

Q8TDP1.

PRIDE

Q8TDP1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000308418; ENSP00000308193; ENSG00000172922.

GeneID

84153.

KEGG

hsa:84153.

UCSC

uc001ofn.3. human.

Organism-specific databases

CTD

84153.

GeneCards

GC11M065485.

HGNC

HGNC:24116. RNASEH2C.

MIM

610329. phenotype.
610330. gene.

neXtProt

NX_Q8TDP1.

Orphanet

51. Aicardi-Goutieres syndrome.

PharmGKB

PA162401445.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG72919.

HOGENOM

HOG000230780.

HOVERGEN

HBG093917.

InParanoid

Q8TDP1.

KO

K10745.

OrthoDB

EOG44F6B8.

PhylomeDB

Q8TDP1.

Gene expression databases

ArrayExpress

Q8TDP1.

Bgee

Q8TDP1.

CleanEx

HS_RNASEH2C.

Genevestigator

Q8TDP1.

GermOnline

ENSG00000172922. Homo sapiens.

Family and domain databases

InterPro

IPR013924. RNase_H2_suC.
[Graphical view]

Pfam

PF08615. RNase_H2_suC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

RNASEH2C. human.

EvolutionaryTrace

Q8TDP1.

GenomeRNAi

84153.

NextBio

73488.

SOURCE

Search...

Entry information

Entry name

RNH2C_HUMAN

Accession

Primary (citable) accession number: Q8TDP1
Secondary accession number(s): Q9H7F5

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
Last sequence update:	June 1, 2002
Last modified:	May 1, 2013
This is version 80 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.