ID RNH2A_HUMAN Reviewed; 299 AA. AC O75792; B2RCY1; Q96F11; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 15-MAY-2002, sequence version 2. DT 27-MAR-2024, entry version 194. DE RecName: Full=Ribonuclease H2 subunit A; DE Short=RNase H2 subunit A; DE EC=3.1.26.4; DE AltName: Full=Aicardi-Goutieres syndrome 4 protein; DE Short=AGS4; DE AltName: Full=RNase H(35); DE AltName: Full=Ribonuclease HI large subunit; DE Short=RNase HI large subunit; DE AltName: Full=Ribonuclease HI subunit A; GN Name=RNASEH2A; Synonyms=RNASEHI, RNHIA; 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]. RX PubMed=9789007; DOI=10.1073/pnas.95.22.12872; RA Frank P., Braunshofer-Reiter C., Wintersberger U., Grimm R., Buesen W.; RT "Cloning of the cDNA encoding the large subunit of human RNase HI, a RT homologue of the prokaryotic RNase HII."; RL Proc. Natl. Acad. Sci. U.S.A. 95:12872-12877(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Thalamus; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-204 AND THR-216, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). 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-277, AND IDENTIFICATION BY RP MASS 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), SUBUNIT, FUNCTION, CATALYTIC RP ACTIVITY, COFACTOR, AND MUTAGENESIS OF ASP-67; LYS-69; ASN-112; TYR-210 AND RP THR-240. 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 VARIANT AGS4 SER-37, CHARACTERIZATION OF VARIANT AGS4 SER-37, FUNCTION, AND RP INTERACTION WITH RNASEH2B AND RNASEH2C. 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 [12] RP VARIANTS AGS4 SER-37; TRP-108; TRP-186; LEU-230; GLN-235; MET-240 AND RP HIS-291, AND VARIANTS ASP-99; SER-202; GLU-205 AND GLY-260. 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 [13] RP VARIANTS AGS4 2-ASP-LEU-3 DELINS TYR-PRO AND TRP-186. 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: Catalytic subunit of RNase HII, 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 -!- CATALYTIC ACTIVITY: CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4; CC Evidence={ECO:0000269|PubMed:21177858}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC Note=Manganese or magnesium. Binds 1 divalent metal ion per monomer in CC the absence of substrate. May bind a second metal ion after substrate CC binding. {ECO:0000250}; 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 -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- DISEASE: Aicardi-Goutieres syndrome 4 (AGS4) [MIM:610333]: 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 -!- SIMILARITY: Belongs to the RNase HII family. Eukaryotic subfamily. CC {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; Z97029; CAB09725.1; -; mRNA. DR EMBL; AK315327; BAG37728.1; -; mRNA. DR EMBL; CH471106; EAW84313.1; -; Genomic_DNA. DR EMBL; BC011748; AAH11748.1; -; mRNA. DR CCDS; CCDS12282.1; -. DR RefSeq; NP_006388.2; NM_006397.2. DR PDB; 3P56; X-ray; 4.06 A; A/D=1-299. DR PDB; 3PUF; X-ray; 3.10 A; A/D/G/J/M/P=1-299. DR PDBsum; 3P56; -. DR PDBsum; 3PUF; -. DR AlphaFoldDB; O75792; -. DR SMR; O75792; -. DR BioGRID; 115789; 74. DR ComplexPortal; CPX-745; RNase H2 complex. DR IntAct; O75792; 38. DR MINT; O75792; -. DR STRING; 9606.ENSP00000221486; -. DR GlyGen; O75792; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O75792; -. DR PhosphoSitePlus; O75792; -. DR BioMuta; RNASEH2A; -. DR EPD; O75792; -. DR jPOST; O75792; -. DR MassIVE; O75792; -. DR MaxQB; O75792; -. DR PaxDb; 9606-ENSP00000221486; -. DR PeptideAtlas; O75792; -. DR ProteomicsDB; 50197; -. DR Pumba; O75792; -. DR Antibodypedia; 13379; 199 antibodies from 28 providers. DR CPTC; O75792; 1 antibody. DR DNASU; 10535; -. DR Ensembl; ENST00000221486.6; ENSP00000221486.4; ENSG00000104889.7. DR GeneID; 10535; -. DR KEGG; hsa:10535; -. DR MANE-Select; ENST00000221486.6; ENSP00000221486.4; NM_006397.3; NP_006388.2. DR UCSC; uc002mvg.2; human. DR AGR; HGNC:18518; -. DR CTD; 10535; -. DR DisGeNET; 10535; -. DR GeneCards; RNASEH2A; -. DR GeneReviews; RNASEH2A; -. DR HGNC; HGNC:18518; RNASEH2A. DR HPA; ENSG00000104889; Low tissue specificity. DR MalaCards; RNASEH2A; -. DR MIM; 606034; gene. DR MIM; 610333; phenotype. DR neXtProt; NX_O75792; -. DR OpenTargets; ENSG00000104889; -. DR Orphanet; 51; Aicardi-Goutieres syndrome. DR PharmGKB; PA38565; -. DR VEuPathDB; HostDB:ENSG00000104889; -. DR eggNOG; KOG2299; Eukaryota. DR GeneTree; ENSGT00390000010768; -. DR HOGENOM; CLU_036532_0_3_1; -. DR InParanoid; O75792; -. DR OMA; REECRFF; -. DR OrthoDB; 117476at2759; -. DR PhylomeDB; O75792; -. DR TreeFam; TF314302; -. DR BioCyc; MetaCyc:HS02645-MONOMER; -. DR BRENDA; 3.1.26.4; 2681. DR PathwayCommons; O75792; -. DR SignaLink; O75792; -. DR BioGRID-ORCS; 10535; 245 hits in 1164 CRISPR screens. DR ChiTaRS; RNASEH2A; human. DR EvolutionaryTrace; O75792; -. DR GeneWiki; RNASEH2A; -. DR GenomeRNAi; 10535; -. DR Pharos; O75792; Tbio. DR PRO; PR:O75792; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; O75792; Protein. DR Bgee; ENSG00000104889; Expressed in ganglionic eminence and 101 other cell types or tissues. DR ExpressionAtlas; O75792; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0032299; C:ribonuclease H2 complex; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0003723; F:RNA binding; IEA:InterPro. DR GO; GO:0004540; F:RNA nuclease activity; TAS:ProtInc. DR GO; GO:0004523; F:RNA-DNA hybrid ribonuclease activity; IDA:UniProtKB. DR GO; GO:0006260; P:DNA replication; TAS:UniProtKB. DR GO; GO:0043137; P:DNA replication, removal of RNA primer; IBA:GO_Central. DR GO; GO:0006298; P:mismatch repair; IDA:MGI. DR GO; GO:0006401; P:RNA catabolic process; IDA:UniProtKB. DR CDD; cd07181; RNase_HII_eukaryota_like; 1. DR Gene3D; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 1. DR Gene3D; 1.10.10.460; Ribonuclease hii. Domain 2; 1. DR IDEAL; IID00601; -. DR InterPro; IPR004649; RNase_H2_suA. DR InterPro; IPR001352; RNase_HII/HIII. DR InterPro; IPR024567; RNase_HII/HIII_dom. DR InterPro; IPR023160; RNase_HII_hlx-loop-hlx_cap_dom. DR InterPro; IPR012337; RNaseH-like_sf. DR InterPro; IPR036397; RNaseH_sf. DR NCBIfam; TIGR00729; ribonuclease HII; 1. DR PANTHER; PTHR10954; RIBONUCLEASE H2 SUBUNIT A; 1. DR PANTHER; PTHR10954:SF7; RIBONUCLEASE H2 SUBUNIT A; 1. DR Pfam; PF01351; RNase_HII; 1. DR SUPFAM; SSF53098; Ribonuclease H-like; 1. DR PROSITE; PS51975; RNASE_H_2; 1. DR Genevisible; O75792; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Aicardi-Goutieres syndrome; Disease variant; KW Endonuclease; Hydrolase; Metal-binding; Nuclease; Nucleus; Phosphoprotein; KW Reference proteome. FT CHAIN 1..299 FT /note="Ribonuclease H2 subunit A" FT /id="PRO_0000111710" FT DOMAIN 28..250 FT /note="RNase H type-2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01319" FT BINDING 34 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /evidence="ECO:0000250" FT BINDING 35 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /evidence="ECO:0000250" FT BINDING 141 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /evidence="ECO:0000250" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT MOD_RES 204 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 216 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 257 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9CWY8" FT MOD_RES 277 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VARIANT 2..3 FT /note="DL -> YP (in AGS4)" FT /evidence="ECO:0000269|PubMed:20131292" FT /id="VAR_070623" FT VARIANT 37 FT /note="G -> S (in AGS4; strongly impairs enzyme activity FT but not interaction with RNASEH2B and RNASEH2C; FT dbSNP:rs76857106)" FT /evidence="ECO:0000269|PubMed:16845400, FT ECO:0000269|PubMed:17846997" FT /id="VAR_027377" FT VARIANT 99 FT /note="N -> D" FT /evidence="ECO:0000269|PubMed:17846997" FT /id="VAR_070624" FT VARIANT 108 FT /note="R -> W (in AGS4; dbSNP:rs76436818)" FT /evidence="ECO:0000269|PubMed:17846997" FT /id="VAR_070625" FT VARIANT 186 FT /note="R -> W (in AGS4; dbSNP:rs77103971)" FT /evidence="ECO:0000269|PubMed:17846997, FT ECO:0000269|PubMed:20131292" FT /id="VAR_070626" FT VARIANT 202 FT /note="L -> S (in dbSNP:rs7247284)" FT /evidence="ECO:0000269|PubMed:17846997" FT /id="VAR_024617" FT VARIANT 205 FT /note="D -> E (in dbSNP:rs62619782)" FT /evidence="ECO:0000269|PubMed:17846997" FT /id="VAR_070627" FT VARIANT 230 FT /note="F -> L (in AGS4; dbSNP:rs79767407)" FT /evidence="ECO:0000269|PubMed:17846997" FT /id="VAR_070628" FT VARIANT 235 FT /note="R -> Q (in AGS4; dbSNP:rs75718910)" FT /evidence="ECO:0000269|PubMed:17846997" FT /id="VAR_070629" FT VARIANT 240 FT /note="T -> M (in AGS4; dbSNP:rs79843600)" FT /evidence="ECO:0000269|PubMed:17846997" FT /id="VAR_070630" FT VARIANT 258 FT /note="A -> G (in dbSNP:rs15389)" FT /id="VAR_027378" FT VARIANT 260 FT /note="E -> G (in dbSNP:rs770898096)" FT /evidence="ECO:0000269|PubMed:17846997" FT /id="VAR_070631" FT VARIANT 291 FT /note="R -> H (in AGS4; dbSNP:rs75037667)" FT /evidence="ECO:0000269|PubMed:17846997" FT /id="VAR_070632" FT MUTAGEN 67 FT /note="D->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:21177858" FT MUTAGEN 69 FT /note="K->A: Strongly reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:21177858" FT MUTAGEN 112 FT /note="N->A: Reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:21177858" FT MUTAGEN 210 FT /note="Y->A: Strongly reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:21177858" FT MUTAGEN 210 FT /note="Y->F: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:21177858" FT MUTAGEN 240 FT /note="T->A: Strongly reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:21177858" FT CONFLICT 152 FT /note="R -> Q (in Ref. 1; CAB09725)" FT /evidence="ECO:0000305" FT HELIX 4..7 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 15..17 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 23..26 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 29..36 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 41..43 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 45..54 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 57..62 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 73..84 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 90..96 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 98..105 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 113..130 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 135..144 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 146..156 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 160..166 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 168..171 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 173..191 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 214..222 FT /evidence="ECO:0007829|PDB:3PUF" FT TURN 226..228 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 239..248 FT /evidence="ECO:0007829|PDB:3PUF" FT HELIX 286..290 FT /evidence="ECO:0007829|PDB:3PUF" FT STRAND 293..295 FT /evidence="ECO:0007829|PDB:3PUF" SQ SEQUENCE 299 AA; 33395 MW; 34992FE85130157B CRC64; MDLSELERDN TGRCRLSSPV PAVCRKEPCV LGVDEAGRGP VLGPMVYAIC YCPLPRLADL EALKVADSKT LLESERERLF AKMEDTDFVG WALDVLSPNL ISTSMLGRVK YNLNSLSHDT ATGLIQYALD QGVNVTQVFV DTVGMPETYQ ARLQQSFPGI EVTVKAKADA LYPVVSAASI CAKVARDQAV KKWQFVEKLQ DLDTDYGSGY PNDPKTKAWL KEHVEPVFGF PQFVRFSWRT AQTILEKEAE DVIWEDSASE NQEGLRKITS YFLNEGSQAR PRSSHRYFLE RGLESATSL //