ID RINI_HUMAN Reviewed; 461 AA. AC P13489; Q8IZK8; Q96FD7; Q9BQ80; Q9UDK6; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 236. DE RecName: Full=Ribonuclease inhibitor; DE AltName: Full=Placental ribonuclease inhibitor; DE Short=Placental RNase inhibitor; DE AltName: Full=Ribonuclease/angiogenin inhibitor 1; DE Short=RAI; GN Name=RNH1; Synonyms=PRI, RNH; 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], PROTEIN SEQUENCE OF 20-28; 35-44; 47-62; 65-72; RP 87-130; 147-181; 189-200; 206-226; 231-235; 239-268; 272-276; 288-295; RP 297-299; 303-316; 353-364; 374-394; 402-412; 424-449 AND 453-461, AND RP OXIDATION STATE OF THE CYSTEINES. RC TISSUE=Placenta; RX PubMed=3219362; DOI=10.1021/bi00423a007; RA Lee F.S., Fox E.A., Zhou H.-M., Strydom D.J., Vallee B.L.; RT "Primary structure of human placental ribonuclease inhibitor."; RL Biochemistry 27:8545-8553(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 444-462. RX PubMed=3243277; DOI=10.1002/j.1460-2075.1988.tb03310.x; RA Schneider R., Schneider-Scherzer E., Thurnher M., Auer B., Schweiger M.; RT "The primary structure of human ribonuclease/angiogenin inhibitor (RAI) RT discloses a novel highly diversified protein superfamily with a common RT repetitive module."; RL EMBO J. 7:4151-4156(1988). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RX PubMed=14515218; RA Huang G.H., Yang G.Z., Chen J.Y., Wu X.F.; RT "Expression of a human ribonuclease inhibitor variant in Escherichia coli RT and silkworm insect cell (Bombyx mori)."; RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 35:960-963(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, Colon, Lymph, and Ovary; 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 [6] RP PROTEIN SEQUENCE OF 2-14. RC TISSUE=Brain; RX PubMed=8037455; DOI=10.1006/abbi.1994.1328; RA Nadano D., Yasuda T., Takeshita H., Uchide K., Kishi K.; RT "Purification and characterization of human brain ribonuclease inhibitor."; RL Arch. Biochem. Biophys. 312:421-428(1994). RN [7] RP PROTEIN SEQUENCE OF 174-195 AND 288-302, AND INTERACTION WITH RNASE1. RX PubMed=1633192; DOI=10.1016/0167-4838(92)90134-y; RA Crevel-Thieffry I., Cotterill S., Schuller E.; RT "Characterisation of a tryptic peptide from human placental ribonuclease RT inhibitor which inhibits ribonuclease activity."; RL Biochim. Biophys. Acta 1122:107-112(1992). RN [8] RP MUTAGENESIS OF SER-461, AND INTERACTION WITH ANG AND RNASE1. RX PubMed=9050852; DOI=10.1073/pnas.94.5.1761; RA Chen C.Z., Shapiro R.; RT "Site-specific mutagenesis reveals differences in the structural bases for RT tight binding of RNase inhibitor to angiogenin and RNase A."; RL Proc. Natl. Acad. Sci. U.S.A. 94:1761-1766(1997). RN [9] RP MUTAGENESIS OF 435-TYR-ASP-436, AND INTERACTION WITH ANG AND RNASE1. RX PubMed=10413501; DOI=10.1021/bi990762a; RA Chen C.Z., Shapiro R.; RT "Superadditive and subadditive effects of 'hot spot' mutations within the RT interfaces of placental ribonuclease inhibitor with angiogenin and RT ribonuclease A."; RL Biochemistry 38:9273-9285(1999). RN [10] RP FUNCTION, MUTAGENESIS OF TRP-262; TRP-264; TRP-319; 435-TYR-ASP-436 AND RP SER-461, AND INTERACTION WITH RNASE2. RX PubMed=12578357; DOI=10.1021/bi026852o; RA Teufel D.P., Kao R.Y., Acharya K.R., Shapiro R.; RT "Mutational analysis of the complex of human RNase inhibitor and human RT eosinophil-derived neurotoxin (RNase 2)."; RL Biochemistry 42:1451-1459(2003). RN [11] RP FUNCTION. RX PubMed=17292889; DOI=10.1016/j.febslet.2007.01.072; RA Monti D.M., Montesano Gesualdi N., Matousek J., Esposito F., D'Alessio G.; RT "The cytosolic ribonuclease inhibitor contributes to intracellular redox RT homeostasis."; RL FEBS Lett. 581:930-934(2007). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-82, AND IDENTIFICATION BY RP 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 [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-91, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [15] 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 [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [20] RP INVOLVEMENT IN IIAE12. RX PubMed=36935417; DOI=10.1038/s41431-023-01327-7; RA Hedberg-Oldfors C., Mitra S., Molinaro A., Visuttijai K., Fogelstrand L., RA Oldfors A., Sterky F.H., Darin N.; RT "Ribonuclease inhibitor 1 (RNH1) deficiency cause congenital cataracts and RT global developmental delay with infection-induced psychomotor regression RT and anemia."; RL Eur. J. Hum. Genet. 31:887-894(2023). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2-461 IN COMPLEX WITH ANG, RP INTERACTION WITH ANG, AND DOMAIN. RX PubMed=9311977; DOI=10.1093/emboj/16.17.5162; RA Papageorgiou A.C., Shapiro R., Acharya K.R.; RT "Molecular recognition of human angiogenin by placental ribonuclease RT inhibitor -- an X-ray crystallographic study at 2.0-A resolution."; RL EMBO J. 16:5162-5177(1997). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2-461 IN COMPLEX WITH RNASE2, RP DOMAIN, INTERACTION WITH RNASE2, AND MUTAGENESIS OF TRP-376 AND ARG-458. RX PubMed=15755456; DOI=10.1016/j.jmb.2005.01.035; RA Iyer S., Holloway D.E., Kumar K., Shapiro R., Acharya K.R.; RT "Molecular recognition of human eosinophil-derived neurotoxin (RNase 2) by RT placental ribonuclease inhibitor."; RL J. Mol. Biol. 347:637-655(2005). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH RNASE1, DOMAIN, AND RP INTERACTION WITH RNASE1. RX PubMed=17350650; DOI=10.1016/j.jmb.2007.02.005; RA Johnson R.J., McCoy J.G., Bingman C.A., Phillips G.N. Jr., Raines R.T.; RT "Inhibition of human pancreatic ribonuclease by the human ribonuclease RT inhibitor protein."; RL J. Mol. Biol. 368:434-449(2007). RN [24] RP VARIANTS IIAE12 14-GLU--SER-461 DEL; HIS-93; TYR-209; PRO-296 AND TRP-373, RP AND INVOLVEMENT IN IIAE12. RX PubMed=37191094; DOI=10.1016/j.gim.2023.100897; RG Undiagnosed Diseases Network; RA Shashi V., Schoch K., Ganetzky R., Kranz P.G., Sondheimer N., Markert M.L., RA Cope H., Sadeghpour A., Roehrs P., Arbogast T., Muraresku C., Tyndall A.V., RA Esser M.J., Woodward K.E., Ping-Yee Au B., Parboosingh J.S., Lamont R.E., RA Bernier F.P., Wright N.A.M., Benseler S.M., Parsons S.J., El-Dairi M., RA Smith E.C., Valdez P., Tennison M., Innes A.M., Davis E.E.; RT "Biallelic variants in ribonuclease inhibitor (RNH1), an inflammasome RT modulator, are associated with a distinctive subtype of acute, necrotizing RT encephalopathy."; RL Genet. Med. 25:100897-100897(2023). CC -!- FUNCTION: Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and ANG. CC May play a role in redox homeostasis. {ECO:0000269|PubMed:12578357, CC ECO:0000269|PubMed:14515218, ECO:0000269|PubMed:17292889}. CC -!- SUBUNIT: Forms high-affinity heterodimers with RNASE1, ANG and RNASE2. CC {ECO:0000269|PubMed:15755456, ECO:0000269|PubMed:17350650, CC ECO:0000269|PubMed:9311977}. CC -!- INTERACTION: CC P13489; P03950: ANG; NbExp=3; IntAct=EBI-1237106, EBI-525291; CC P13489; P07998: RNASE1; NbExp=8; IntAct=EBI-1237106, EBI-2823523; CC P13489; O00560: SDCBP; NbExp=8; IntAct=EBI-1237106, EBI-727004; CC P13489; O76024: WFS1; NbExp=3; IntAct=EBI-1237106, EBI-720609; CC P13489; P61823: RNASE1; Xeno; NbExp=3; IntAct=EBI-1237106, EBI-908364; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- DOMAIN: The LRR domain forms a horseshoe-shaped structure that CC interacts tightly with target RNases via a large protein interaction CC surface on its interior side. {ECO:0000269|PubMed:15755456, CC ECO:0000269|PubMed:17350650, ECO:0000269|PubMed:9311977}. CC -!- PTM: The N-terminus is blocked. CC -!- PTM: At least 30 of the 32 cysteine residues are in the reduced form. CC -!- DISEASE: Encephalitis, acute, infection-induced, 12 (IIAE12) CC [MIM:620461]: An autosomal recessive disorder apparent in infancy or CC early childhood, and characterized by acute encephalopathy triggered by CC viral infections and febrile illness. Neurologic features of the acute CC episodes include seizures, hemiplegia, decreased consciousness, CC hypotonia, abnormal posturing, feeding problems, and respiratory CC insufficiency. Disease severity is variable, ranging from death to CC normal neurologic outcomes. {ECO:0000269|PubMed:36935417, CC ECO:0000269|PubMed:37191094}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. 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; M22414; AAA59130.1; -; mRNA. DR EMBL; M36717; AAA60249.1; -; mRNA. DR EMBL; X13973; CAA32151.1; -; mRNA. DR EMBL; AY071904; AAL60586.1; -; mRNA. DR EMBL; AL161967; CAB82310.1; -; mRNA. DR EMBL; BC000677; AAH00677.1; -; mRNA. DR EMBL; BC003506; AAH03506.1; -; mRNA. DR EMBL; BC011186; AAH11186.1; -; mRNA. DR EMBL; BC011500; AAH11500.1; -; mRNA. DR EMBL; BC014629; AAH14629.1; -; mRNA. DR EMBL; BC024037; AAH24037.1; -; mRNA. DR EMBL; BC047730; AAH47730.1; -; mRNA. DR CCDS; CCDS7697.1; -. DR PIR; A31858; A31858. DR RefSeq; NP_002930.2; NM_002939.3. DR RefSeq; NP_976317.1; NM_203383.1. DR RefSeq; NP_976318.1; NM_203384.1. DR RefSeq; NP_976319.1; NM_203385.1. DR RefSeq; NP_976320.1; NM_203386.2. DR RefSeq; NP_976321.1; NM_203387.2. DR RefSeq; NP_976322.1; NM_203388.2. DR RefSeq; NP_976323.1; NM_203389.2. DR RefSeq; XP_011518557.1; XM_011520255.1. DR RefSeq; XP_011518559.1; XM_011520257.2. DR RefSeq; XP_011518560.1; XM_011520258.2. DR RefSeq; XP_011518561.1; XM_011520259.2. DR RefSeq; XP_011518562.1; XM_011520260.2. DR RefSeq; XP_011518563.1; XM_011520261.2. DR RefSeq; XP_011518564.1; XM_011520262.2. DR RefSeq; XP_011518565.1; XM_011520263.1. DR RefSeq; XP_016873595.1; XM_017018106.1. DR PDB; 1A4Y; X-ray; 2.00 A; A/D=2-461. DR PDB; 1Z7X; X-ray; 1.95 A; W/Y=1-461. DR PDB; 2BEX; X-ray; 1.99 A; A/B=2-461. DR PDB; 2Q4G; X-ray; 1.95 A; W/Y=1-461. DR PDBsum; 1A4Y; -. DR PDBsum; 1Z7X; -. DR PDBsum; 2BEX; -. DR PDBsum; 2Q4G; -. DR AlphaFoldDB; P13489; -. DR SMR; P13489; -. DR BioGRID; 111977; 210. DR CORUM; P13489; -. DR IntAct; P13489; 58. DR MINT; P13489; -. DR STRING; 9606.ENSP00000433999; -. DR GlyGen; P13489; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P13489; -. DR PhosphoSitePlus; P13489; -. DR SwissPalm; P13489; -. DR BioMuta; RNH1; -. DR DMDM; 132573; -. DR REPRODUCTION-2DPAGE; IPI00550069; -. DR EPD; P13489; -. DR jPOST; P13489; -. DR MassIVE; P13489; -. DR MaxQB; P13489; -. DR PaxDb; 9606-ENSP00000433999; -. DR PeptideAtlas; P13489; -. DR PRIDE; P13489; -. DR ProteomicsDB; 52913; -. DR Pumba; P13489; -. DR Antibodypedia; 22490; 537 antibodies from 31 providers. DR DNASU; 6050; -. DR Ensembl; ENST00000354420.7; ENSP00000346402.2; ENSG00000023191.17. DR Ensembl; ENST00000356187.9; ENSP00000348515.5; ENSG00000023191.17. DR Ensembl; ENST00000397604.7; ENSP00000380729.3; ENSG00000023191.17. DR Ensembl; ENST00000397614.5; ENSP00000380738.1; ENSG00000023191.17. DR Ensembl; ENST00000397615.6; ENSP00000380739.2; ENSG00000023191.17. DR Ensembl; ENST00000438658.6; ENSP00000416589.2; ENSG00000023191.17. DR Ensembl; ENST00000533410.5; ENSP00000435594.1; ENSG00000023191.17. DR Ensembl; ENST00000534797.5; ENSP00000433999.1; ENSG00000023191.17. DR Ensembl; ENST00000612988.4; ENSP00000479004.1; ENSG00000276230.4. DR Ensembl; ENST00000617351.4; ENSP00000484572.1; ENSG00000276230.4. DR Ensembl; ENST00000618184.3; ENSP00000478664.1; ENSG00000276230.4. DR Ensembl; ENST00000619599.4; ENSP00000479966.1; ENSG00000276230.4. DR Ensembl; ENST00000621211.2; ENSP00000480036.1; ENSG00000276230.4. DR Ensembl; ENST00000632527.1; ENSP00000487940.1; ENSG00000276230.4. DR Ensembl; ENST00000632954.1; ENSP00000487753.1; ENSG00000276230.4. DR Ensembl; ENST00000633287.1; ENSP00000488734.1; ENSG00000276230.4. DR GeneID; 6050; -. DR KEGG; hsa:6050; -. DR MANE-Select; ENST00000354420.7; ENSP00000346402.2; NM_203387.3; NP_976321.1. DR UCSC; uc001lpk.1; human. DR AGR; HGNC:10074; -. DR CTD; 6050; -. DR DisGeNET; 6050; -. DR GeneCards; RNH1; -. DR HGNC; HGNC:10074; RNH1. DR HPA; ENSG00000023191; Low tissue specificity. DR MalaCards; RNH1; -. DR MIM; 173320; gene. DR MIM; 620461; phenotype. DR neXtProt; NX_P13489; -. DR OpenTargets; ENSG00000023191; -. DR PharmGKB; PA34447; -. DR VEuPathDB; HostDB:ENSG00000023191; -. DR eggNOG; KOG4308; Eukaryota. DR GeneTree; ENSGT00940000161492; -. DR HOGENOM; CLU_002274_4_6_1; -. DR InParanoid; P13489; -. DR OMA; CQLECLW; -. DR OrthoDB; 55870at2759; -. DR PhylomeDB; P13489; -. DR PathwayCommons; P13489; -. DR SignaLink; P13489; -. DR BioGRID-ORCS; 6050; 71 hits in 1152 CRISPR screens. DR ChiTaRS; RNH1; human. DR EvolutionaryTrace; P13489; -. DR GeneWiki; RNH1; -. DR GenomeRNAi; 6050; -. DR Pharos; P13489; Tbio. DR PRO; PR:P13489; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P13489; Protein. DR Bgee; ENSG00000023191; Expressed in skin of leg and 100 other cell types or tissues. DR ExpressionAtlas; P13489; baseline and differential. DR GO; GO:0032311; C:angiogenin-PRI complex; IPI:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0030027; C:lamellipodium; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0008428; F:ribonuclease inhibitor activity; IDA:UniProtKB. DR GO; GO:0016477; P:cell migration; IBA:GO_Central. DR GO; GO:0006402; P:mRNA catabolic process; NAS:UniProtKB. DR GO; GO:0045765; P:regulation of angiogenesis; IDA:UniProtKB. DR GO; GO:0034315; P:regulation of Arp2/3 complex-mediated actin nucleation; IBA:GO_Central. DR CDD; cd00116; LRR_RI; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR006553; Leu-rich_rpt_Cys-con_subtyp. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR041302; LRR_RI_cap. DR PANTHER; PTHR45690; NACHT, LRR AND PYD DOMAINS-CONTAINING PROTEIN 12; 1. DR PANTHER; PTHR45690:SF15; NACHT, LRR AND PYD DOMAINS-CONTAINING PROTEIN 14; 1. DR Pfam; PF13516; LRR_6; 6. DR Pfam; PF18779; LRR_RI_capping; 1. DR SMART; SM00367; LRR_CC; 5. DR SMART; SM00368; LRR_RI; 13. DR SUPFAM; SSF52047; RNI-like; 2. DR Genevisible; P13489; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; KW Disease variant; Leucine-rich repeat; Phosphoprotein; Reference proteome; KW Repeat. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:8037455, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT CHAIN 2..461 FT /note="Ribonuclease inhibitor" FT /id="PRO_0000097343" FT REPEAT 20..48 FT /note="LRR 1" FT REPEAT 49..76 FT /note="LRR 2" FT REPEAT 77..105 FT /note="LRR 3" FT REPEAT 106..133 FT /note="LRR 4" FT REPEAT 134..162 FT /note="LRR 5" FT REPEAT 163..190 FT /note="LRR 6" FT REPEAT 191..219 FT /note="LRR 7" FT REPEAT 220..247 FT /note="LRR 8" FT REPEAT 248..276 FT /note="LRR 9" FT REPEAT 277..304 FT /note="LRR 10" FT REPEAT 305..333 FT /note="LRR 11" FT REPEAT 334..361 FT /note="LRR 12" FT REPEAT 362..390 FT /note="LRR 13" FT REPEAT 391..418 FT /note="LRR 14" FT REPEAT 419..447 FT /note="LRR 15" FT REGION 2..11 FT /note="2 X 5 AA tandem repeats of S-L-D-I-Q" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT MOD_RES 82 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 91 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT VARIANT 14..461 FT /note="Missing (in IIAE12; risk factor)" FT /evidence="ECO:0000269|PubMed:37191094" FT /id="VAR_088810" FT VARIANT 93 FT /note="Q -> H (in IIAE12; uncertain significance)" FT /evidence="ECO:0000269|PubMed:37191094" FT /id="VAR_088811" FT VARIANT 170 FT /note="P -> L (in dbSNP:rs17585)" FT /id="VAR_014726" FT VARIANT 209 FT /note="C -> Y (in IIAE12; uncertain significance)" FT /evidence="ECO:0000269|PubMed:37191094" FT /id="VAR_088812" FT VARIANT 296 FT /note="L -> P (in IIAE12; uncertain significance)" FT /evidence="ECO:0000269|PubMed:37191094" FT /id="VAR_088813" FT VARIANT 373 FT /note="R -> W (in IIAE12; risk factor)" FT /evidence="ECO:0000269|PubMed:37191094" FT /id="VAR_088814" FT MUTAGEN 262 FT /note="W->A: Binding affinity decreased 5000-fold over the FT wild type for RNASE2; when associated with A-264 and FT A-319." FT /evidence="ECO:0000269|PubMed:12578357" FT MUTAGEN 264 FT /note="W->A: Substantially decreased binding affinity for FT RNASE2. Binding affinity decreased 5000-fold over the wild FT type for RNASE2; when associated with A-262 and A-319." FT /evidence="ECO:0000269|PubMed:12578357" FT MUTAGEN 319 FT /note="W->A: Substantially decreased binding affinity for FT RNASE2. Binding affinity decreased 5000-fold over the wild FT type for RNASE2; when associated with A-262 and A-264." FT /evidence="ECO:0000269|PubMed:12578357" FT MUTAGEN 376 FT /note="W->A: 40-fold reduction in binding affinity for FT RNASE2." FT /evidence="ECO:0000269|PubMed:15755456" FT MUTAGEN 435..436 FT /note="YD->AA: Substantially decreases binding affinity for FT RNASE1, ANG and RNASE2." FT /evidence="ECO:0000269|PubMed:10413501, FT ECO:0000269|PubMed:12578357" FT MUTAGEN 458 FT /note="R->A: 25-fold reduction in binding affinity for FT RNASE2." FT /evidence="ECO:0000269|PubMed:15755456" FT MUTAGEN 461 FT /note="Missing: A significant decrease in binding affinity FT with RNASE1, slight decrease for the ANG ligand, no real FT change in binding affinity for RNASE2." FT /evidence="ECO:0000269|PubMed:12578357, FT ECO:0000269|PubMed:9050852" FT CONFLICT 188 FT /note="R -> H (in Ref. 5; AAH03506)" FT /evidence="ECO:0000305" FT CONFLICT 359 FT /note="R -> A (in Ref. 3; AAL60586)" FT /evidence="ECO:0000305" FT CONFLICT 365 FT /note="L -> P (in Ref. 3; AAL60586)" FT /evidence="ECO:0000305" FT CONFLICT 423..424 FT /note="RQ -> SE (in Ref. 2; CAA32151/AAA60249)" FT /evidence="ECO:0000305" FT STRAND 3..12 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 17..27 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 31..38 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 42..53 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 60..62 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 69..78 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 89..91 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 99..101 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 102..108 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 117..119 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 122..124 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 126..137 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 146..148 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 156..158 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 159..168 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 174..176 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 179..181 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 183..196 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 203..205 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 215..225 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 231..233 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 236..238 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 240..251 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 260..262 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 270..282 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 288..290 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 297..308 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 310..312 FT /evidence="ECO:0007829|PDB:2Q4G" FT STRAND 317..319 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 327..329 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 330..339 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 345..347 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 350..352 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 354..365 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 374..376 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 384..396 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 402..404 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 407..409 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 412..422 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 431..433 FT /evidence="ECO:0007829|PDB:1Z7X" FT HELIX 441..453 FT /evidence="ECO:0007829|PDB:1Z7X" FT STRAND 457..460 FT /evidence="ECO:0007829|PDB:1Z7X" SQ SEQUENCE 461 AA; 49973 MW; 5E88CDAC95BAE5B3 CRC64; MSLDIQSLDI QCEELSDARW AELLPLLQQC QVVRLDDCGL TEARCKDISS ALRVNPALAE LNLRSNELGD VGVHCVLQGL QTPSCKIQKL SLQNCCLTGA GCGVLSSTLR TLPTLQELHL SDNLLGDAGL QLLCEGLLDP QCRLEKLQLE YCSLSAASCE PLASVLRAKP DFKELTVSNN DINEAGVRVL CQGLKDSPCQ LEALKLESCG VTSDNCRDLC GIVASKASLR ELALGSNKLG DVGMAELCPG LLHPSSRLRT LWIWECGITA KGCGDLCRVL RAKESLKELS LAGNELGDEG ARLLCETLLE PGCQLESLWV KSCSFTAACC SHFSSVLAQN RFLLELQISN NRLEDAGVRE LCQGLGQPGS VLRVLWLADC DVSDSSCSSL AATLLANHSL RELDLSNNCL GDAGILQLVE SVRQPGCLLE QLVLYDIYWS EEMEDRLQAL EKDKPSLRVI S //