ID RNH2C_HUMAN Reviewed; 164 AA. AC Q8TDP1; Q9H7F5; DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2002, sequence version 1. DT 24-JAN-2024, entry version 149. DE RecName: Full=Ribonuclease H2 subunit C; DE Short=RNase H2 subunit C; DE AltName: Full=Aicardi-Goutieres syndrome 3 protein; DE Short=AGS3; DE AltName: Full=RNase H1 small subunit; DE AltName: Full=Ribonuclease HI subunit C; GN Name=RNASEH2C; Synonyms=AYP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Frank P., Bogusch A., Grimm R., Wintersberger U.; RT "Cloning of the cDNA encoding the small subunit of human RNase HI."; RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RA Lim H.N., Oakenfull E.A., Hawkins J.R.; RT "Evidence that the T6 pseudogene upstream of human SRY is derived from the RT transcript of a novel autosomal gene, AYP1."; RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Adipose tissue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=B-cell; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [7] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [10] RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS), FUNCTION, AND SUBUNIT. RX PubMed=21177858; DOI=10.1074/jbc.m110.181974; RA Figiel M., Chon H., Cerritelli S.M., Cybulska M., Crouch R.J., Nowotny M.; RT "The structural and biochemical characterization of human RNase H2 complex RT reveals the molecular basis for substrate recognition and Aicardi-Goutieres RT syndrome defects."; RL J. Biol. Chem. 286:10540-10550(2011). RN [11] RP VARIANTS AGS3 HIS-13; TRP-69; LEU-76; LEU-138; ILE-143 AND SER-151. RX PubMed=17846997; DOI=10.1086/521373; RA Rice G., Patrick T., Parmar R., Taylor C.F., Aeby A., Aicardi J., RA Artuch R., Montalto S.A., Bacino C.A., Barroso B., Baxter P., Benko W.S., RA Bergmann C., Bertini E., Biancheri R., Blair E.M., Blau N., Bonthron D.T., RA Briggs T., Brueton L.A., Brunner H.G., Burke C.J., Carr I.M., RA Carvalho D.R., Chandler K.E., Christen H.J., Corry P.C., Cowan F.M., RA Cox H., D'Arrigo S., Dean J., De Laet C., De Praeter C., Dery C., RA Ferrie C.D., Flintoff K., Frints S.G., Garcia-Cazorla A., Gener B., RA Goizet C., Goutieres F., Green A.J., Guet A., Hamel B.C., Hayward B.E., RA Heiberg A., Hennekam R.C., Husson M., Jackson A.P., Jayatunga R., RA Jiang Y.H., Kant S.G., Kao A., King M.D., Kingston H.M., Klepper J., RA van der Knaap M.S., Kornberg A.J., Kotzot D., Kratzer W., Lacombe D., RA Lagae L., Landrieu P.G., Lanzi G., Leitch A., Lim M.J., Livingston J.H., RA Lourenco C.M., Lyall E.G., Lynch S.A., Lyons M.J., Marom D., McClure J.P., RA McWilliam R., Melancon S.B., Mewasingh L.D., Moutard M.L., Nischal K.K., RA Ostergaard J.R., Prendiville J., Rasmussen M., Rogers R.C., Roland D., RA Rosser E.M., Rostasy K., Roubertie A., Sanchis A., Schiffmann R., RA Scholl-Burgi S., Seal S., Shalev S.A., Corcoles C.S., Sinha G.P., Soler D., RA Spiegel R., Stephenson J.B., Tacke U., Tan T.Y., Till M., Tolmie J.L., RA Tomlin P., Vagnarelli F., Valente E.M., Van Coster R.N., Van der Aa N., RA Vanderver A., Vles J.S., Voit T., Wassmer E., Weschke B., Whiteford M.L., RA Willemsen M.A., Zankl A., Zuberi S.M., Orcesi S., Fazzi E., Lebon P., RA Crow Y.J.; RT "Clinical and molecular phenotype of Aicardi-Goutieres syndrome."; RL Am. J. Hum. Genet. 81:713-725(2007). RN [12] RP VARIANTS AGS3 TRP-69 AND ILE-143, FUNCTION, TISSUE SPECIFICITY, AND RP INTERACTION WITH RNASEH2A AND RNASEH2B. RX PubMed=16845400; DOI=10.1038/ng1842; RA Crow Y.J., Leitch A., Hayward B.E., Garner A., Parmar R., Griffith E., RA Ali M., Semple C., Aicardi J., Babul-Hirji R., Baumann C., Baxter P., RA Bertini E., Chandler K.E., Chitayat D., Cau D., Dery C., Fazzi E., RA Goizet C., King M.D., Klepper J., Lacombe D., Lanzi G., Lyall H., RA Martinez-Frias M.L., Mathieu M., McKeown C., Monier A., Oade Y., RA Quarrell O.W., Rittey C.D., Rogers R.C., Sanchis A., Stephenson J.B.P., RA Tacke U., Till M., Tolmie J.L., Tomlin P., Voit T., Weschke B., Woods C.G., RA Lebon P., Bonthron D.T., Ponting C.P., Jackson A.P.; RT "Mutations in genes encoding ribonuclease H2 subunits cause Aicardi- RT Goutieres syndrome and mimic congenital viral brain infection."; RL Nat. Genet. 38:910-916(2006). RN [13] RP VARIANTS AGS3 TYR-39 AND TRP-69. RX PubMed=20131292; DOI=10.1002/art.27367; RA Ramantani G., Kohlhase J., Hertzberg C., Innes A.M., Engel K., Hunger S., RA Borozdin W., Mah J.K., Ungerath K., Walkenhorst H., Richardt H.H., RA Buckard J., Bevot A., Siegel C., von Stuelpnagel C., Ikonomidou C., RA Thomas K., Proud V., Niemann F., Wieczorek D., Haeusler M., Niggemann P., RA Baltaci V., Conrad K., Lebon P., Lee-Kirsch M.A.; RT "Expanding the phenotypic spectrum of lupus erythematosus in Aicardi- RT Goutieres syndrome."; RL Arthritis Rheum. 62:1469-1477(2010). CC -!- FUNCTION: Non catalytic subunit of RNase H2, an endonuclease that CC specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA CC replication, possibly by mediating the removal of lagging-strand CC Okazaki fragment RNA primers during DNA replication. Mediates the CC excision of single ribonucleotides from DNA:RNA duplexes. CC {ECO:0000269|PubMed:16845400, ECO:0000269|PubMed:21177858}. CC -!- SUBUNIT: The RNase H2 complex is a heterotrimer composed of the CC catalytic subunit RNASEH2A and the non-catalytic subunits RNASEH2B and CC RNASEH2C. {ECO:0000269|PubMed:21177858}. CC -!- INTERACTION: CC Q8TDP1; P04792: HSPB1; NbExp=3; IntAct=EBI-9027335, EBI-352682; CC Q8TDP1; O60333-2: KIF1B; NbExp=3; IntAct=EBI-9027335, EBI-10975473; CC Q8TDP1; Q08AM6: VAC14; NbExp=3; IntAct=EBI-9027335, EBI-2107455; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:16845400}. CC -!- DISEASE: Aicardi-Goutieres syndrome 3 (AGS3) [MIM:610329]: A form of CC Aicardi-Goutieres syndrome, a genetically heterogeneous disease CC characterized by cerebral atrophy, leukoencephalopathy, intracranial CC calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, CC increased CSF alpha-interferon, and negative serologic investigations CC for common prenatal infection. Clinical features as thrombocytopenia, CC hepatosplenomegaly and elevated hepatic transaminases along with CC intermittent fever may erroneously suggest an infective process. Severe CC neurological dysfunctions manifest in infancy as progressive CC microcephaly, spasticity, dystonic posturing and profound psychomotor CC retardation. Death often occurs in early childhood. CC {ECO:0000269|PubMed:16845400, ECO:0000269|PubMed:17846997, CC ECO:0000269|PubMed:20131292}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: The T6 pseudogene located upstream of SRY on chromosome CC Y is derived from the transcript of this gene. CC -!- SIMILARITY: Belongs to the RNase H2 subunit C family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF312034; AAL87739.1; -; mRNA. DR EMBL; AF346605; AAO49176.1; -; Genomic_DNA. DR EMBL; AF346606; AAO49177.1; -; mRNA. DR EMBL; AK024627; BAB14937.1; -; mRNA. DR EMBL; BC023588; AAH23588.1; -; mRNA. DR CCDS; CCDS8111.1; -. DR RefSeq; NP_115569.2; NM_032193.3. DR PDB; 3P56; X-ray; 4.06 A; C/F=1-164. DR PDB; 3PUF; X-ray; 3.10 A; C/F/I/L/O/R=1-164. DR PDBsum; 3P56; -. DR PDBsum; 3PUF; -. DR AlphaFoldDB; Q8TDP1; -. DR SMR; Q8TDP1; -. DR BioGRID; 123916; 23. DR ComplexPortal; CPX-745; RNase H2 complex. DR IntAct; Q8TDP1; 7. DR STRING; 9606.ENSP00000308193; -. DR iPTMnet; Q8TDP1; -. DR PhosphoSitePlus; Q8TDP1; -. DR BioMuta; RNASEH2C; -. DR DMDM; 74730607; -. DR EPD; Q8TDP1; -. DR jPOST; Q8TDP1; -. DR MassIVE; Q8TDP1; -. DR MaxQB; Q8TDP1; -. DR PaxDb; 9606-ENSP00000308193; -. DR PeptideAtlas; Q8TDP1; -. DR Pumba; Q8TDP1; -. DR Antibodypedia; 44295; 149 antibodies from 24 providers. DR DNASU; 84153; -. DR Ensembl; ENST00000308418.10; ENSP00000308193.5; ENSG00000172922.11. DR Ensembl; ENST00000531596.6; ENSP00000435717.2; ENSG00000172922.11. DR Ensembl; ENST00000534482.6; ENSP00000432081.2; ENSG00000172922.11. DR Ensembl; ENST00000644142.1; ENSP00000493695.1; ENSG00000172922.11. DR GeneID; 84153; -. DR KEGG; hsa:84153; -. DR MANE-Select; ENST00000308418.10; ENSP00000308193.5; NM_032193.4; NP_115569.2. DR UCSC; uc001ofn.4; human. DR AGR; HGNC:24116; -. DR CTD; 84153; -. DR DisGeNET; 84153; -. DR GeneCards; RNASEH2C; -. DR GeneReviews; RNASEH2C; -. DR HGNC; HGNC:24116; RNASEH2C. DR HPA; ENSG00000172922; Low tissue specificity. DR MalaCards; RNASEH2C; -. DR MIM; 610329; phenotype. DR MIM; 610330; gene. DR neXtProt; NX_Q8TDP1; -. DR OpenTargets; ENSG00000172922; -. DR Orphanet; 51; Aicardi-Goutieres syndrome. DR PharmGKB; PA162401445; -. DR VEuPathDB; HostDB:ENSG00000172922; -. DR eggNOG; ENOG502SBKV; Eukaryota. DR GeneTree; ENSGT00390000001568; -. DR InParanoid; Q8TDP1; -. DR OMA; FDQFIGA; -. DR OrthoDB; 89056at2759; -. DR PhylomeDB; Q8TDP1; -. DR TreeFam; TF324370; -. DR BioCyc; MetaCyc:HS16149-MONOMER; -. DR BRENDA; 3.1.26.4; 2681. DR PathwayCommons; Q8TDP1; -. DR SignaLink; Q8TDP1; -. DR BioGRID-ORCS; 84153; 208 hits in 1169 CRISPR screens. DR ChiTaRS; RNASEH2C; human. DR EvolutionaryTrace; Q8TDP1; -. DR GenomeRNAi; 84153; -. DR Pharos; Q8TDP1; Tbio. DR PRO; PR:Q8TDP1; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q8TDP1; Protein. DR Bgee; ENSG00000172922; Expressed in pancreatic ductal cell and 185 other cell types or tissues. DR ExpressionAtlas; Q8TDP1; baseline and differential. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0032299; C:ribonuclease H2 complex; IDA:UniProtKB. DR GO; GO:0006298; P:mismatch repair; NAS:ComplexPortal. DR GO; GO:0006401; P:RNA catabolic process; IDA:UniProtKB. DR CDD; cd09271; RNase_H2-C; 1. DR Gene3D; 2.40.128.680; -; 1. DR IDEAL; IID00602; -. DR InterPro; IPR013924; RNase_H2_suC. DR PANTHER; PTHR47063; RIBONUCLEASE H2 SUBUNIT C; 1. DR PANTHER; PTHR47063:SF1; RIBONUCLEASE H2 SUBUNIT C; 1. DR Pfam; PF08615; RNase_H2_suC; 1. DR Genevisible; Q8TDP1; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Aicardi-Goutieres syndrome; Disease variant; KW Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1..164 FT /note="Ribonuclease H2 subunit C" FT /id="PRO_0000248385" FT REGION 91..112 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT MOD_RES 3 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VARIANT 13 FT /note="R -> H (in AGS3; dbSNP:rs75328625)" FT /evidence="ECO:0000269|PubMed:17846997" FT /id="VAR_070618" FT VARIANT 39 FT /note="D -> Y (in AGS3; dbSNP:rs773527127)" FT /evidence="ECO:0000269|PubMed:20131292" FT /id="VAR_070619" FT VARIANT 69 FT /note="R -> W (in AGS3; dbSNP:rs78635798)" FT /evidence="ECO:0000269|PubMed:16845400, FT ECO:0000269|PubMed:17846997, ECO:0000269|PubMed:20131292" FT /id="VAR_027287" FT VARIANT 76 FT /note="P -> L (in AGS3; dbSNP:rs76091978)" FT /evidence="ECO:0000269|PubMed:17846997" FT /id="VAR_070620" FT VARIANT 138 FT /note="P -> L (in AGS3)" FT /evidence="ECO:0000269|PubMed:17846997" FT /id="VAR_070621" FT VARIANT 143 FT /note="K -> I (in AGS3; dbSNP:rs75146158)" FT /evidence="ECO:0000269|PubMed:16845400, FT ECO:0000269|PubMed:17846997" FT /id="VAR_027288" FT VARIANT 151 FT /note="P -> S (in AGS3; dbSNP:rs78464826)" FT /evidence="ECO:0000269|PubMed:17846997" FT /id="VAR_070622" FT HELIX 9..12 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 13..16 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 19..22 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 29..36 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 39..41 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 44..47 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 49..51 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 56..63 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 66..70 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 72..74 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 79..86 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 119..131 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 133..136 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 143..147 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 150..157 FT /evidence="ECO:0007829|PDB:3PUF" SQ SEQUENCE 164 AA; 17840 MW; 13D0F1D039963671 CRC64; MESGDEAAIE RHRVHLRSAT LRDAVPATLH LLPCEVAVDG PAPVGRFFTP AIRQGPEGLE VSFRGRCLRG EEVAVPPGLV GYVMVTEEKK VSMGKPDPLR DSGTDDQEEE PLERDFDRFI GATANFSRFT LWGLETIPGP DAKVRGALTW PSLAAAIHAQ VPED //