ID CUE2_YEAST Reviewed; 443 AA. AC P36075; D6VXJ8; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 27-MAR-2024, entry version 169. DE RecName: Full=Endonuclease CUE2 {ECO:0000305}; DE AltName: Full=Coupling of ubiquitin conjugation to ER degradation protein 2; GN Name=CUE2 {ECO:0000303|PubMed:31219035, ECO:0000312|SGD:S000001573}; GN OrderedLocusNames=YKL090W; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=8196765; DOI=10.1038/369371a0; RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V., RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P., RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L., RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A., RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H., RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L., RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M., RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H., RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J., RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H., RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J., RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S., RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F., RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R., RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W., RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M., RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C., RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H., RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L., RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S., RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M., RA Becker I., Mewes H.-W.; RT "Complete DNA sequence of yeast chromosome XI."; RL Nature 369:371-378(1994). RN [2] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [3] RP FUNCTION, AND MUTAGENESIS OF 348-ASP--HIS-350 AND ARG-402. RX PubMed=31219035; DOI=10.7554/elife.49117; RA D'Orazio K.N., Wu C.C., Sinha N., Loll-Krippleber R., Brown G.W., Green R.; RT "The endonuclease Cue2 cleaves mRNAs at stalled ribosomes during No Go RT Decay."; RL Elife 8:0-0(2019). RN [4] RP FUNCTION, DOMAIN, AND MUTAGENESIS OF 20-PHE-PRO-21; 46-LEU-LEU-47; RP 67-PHE-PRO-68; 93-LEU-LEU-94 AND TRP-122. RX PubMed=36583309; DOI=10.1093/nar/gkac1172; RA Tomomatsu S., Watanabe A., Tesina P., Hashimoto S., Ikeuchi K., Li S., RA Matsuo Y., Beckmann R., Inada T.; RT "Two modes of Cue2-mediated mRNA cleavage with distinct substrate RT recognition initiate no-go decay."; RL Nucleic Acids Res. 51:253-270(2023). RN [5] RP STRUCTURE BY NMR OF 1-54 IN COMPLEX WITH UBIQUITIN. RX PubMed=12787503; DOI=10.1016/s0092-8674(03)00362-3; RA Kang R.S., Daniels C.M., Francis S.A., Shih S.C., Salerno W.J., Hicke L., RA Radhakrishnan I.; RT "Solution structure of a CUE-ubiquitin complex reveals a conserved mode of RT ubiquitin binding."; RL Cell 113:621-630(2003). CC -!- FUNCTION: mRNA endonuclease involved in the No-Go Decay (NGD) pathway, CC which catalyzes mRNA cleavage and degradation in response to ribosome CC collisions (PubMed:31219035, PubMed:36583309). Acts downstream of the CC ribosome collision sensor HEL2 (PubMed:36583309). Specifically CC recognizes and binds RPS7/eS7 polyubiquitinated by MOT2/NOT4 and HEL2, CC promoting CUE2 recruitment to stalled ribosomes, where it mediates mRNA CC cleavage upstream of the colliding ribosome (PubMed:36583309). Also CC mediates mRNA cleavage within colliding ribosomes: recruited to CC colliding ribosomes downstream of the RQT (ribosome quality control CC trigger) complex following disassembly of stalled ribosomes and cleaves CC mRNAs partially released from the colliding ribosome (PubMed:36583309). CC {ECO:0000269|PubMed:31219035, ECO:0000269|PubMed:36583309}. CC -!- DOMAIN: The CUE domains specifically bind RPS7/eS7 polyubiquitinated by CC MOT2/NOT4 and HEL2. {ECO:0000269|PubMed:36583309}. 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; Z28090; CAA81928.1; -; Genomic_DNA. DR EMBL; BK006944; DAA09068.1; -; Genomic_DNA. DR PIR; S37915; S37915. DR RefSeq; NP_012833.1; NM_001179656.1. DR PDB; 1OTR; NMR; -; A=6-54. DR PDBsum; 1OTR; -. DR AlphaFoldDB; P36075; -. DR SMR; P36075; -. DR BioGRID; 34043; 33. DR DIP; DIP-1917N; -. DR IntAct; P36075; 4. DR MINT; P36075; -. DR STRING; 4932.YKL090W; -. DR iPTMnet; P36075; -. DR MaxQB; P36075; -. DR PaxDb; 4932-YKL090W; -. DR PeptideAtlas; P36075; -. DR EnsemblFungi; YKL090W_mRNA; YKL090W; YKL090W. DR GeneID; 853772; -. DR KEGG; sce:YKL090W; -. DR AGR; SGD:S000001573; -. DR SGD; S000001573; CUE2. DR VEuPathDB; FungiDB:YKL090W; -. DR eggNOG; KOG2401; Eukaryota. DR HOGENOM; CLU_590497_0_0_1; -. DR InParanoid; P36075; -. DR OMA; NDDHESK; -. DR OrthoDB; 2728202at2759; -. DR BioCyc; YEAST:G3O-31881-MONOMER; -. DR BioGRID-ORCS; 853772; 1 hit in 10 CRISPR screens. DR EvolutionaryTrace; P36075; -. DR PRO; PR:P36075; -. DR Proteomes; UP000002311; Chromosome XI. DR RNAct; P36075; Protein. DR GO; GO:0022626; C:cytosolic ribosome; IDA:UniProt. DR GO; GO:0004519; F:endonuclease activity; IDA:SGD. DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; TAS:UniProt. DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IDA:UniProtKB. DR GO; GO:0004521; F:RNA endonuclease activity; IDA:UniProtKB. DR GO; GO:0043130; F:ubiquitin binding; IDA:SGD. DR GO; GO:0070966; P:nuclear-transcribed mRNA catabolic process, no-go decay; IDA:SGD. DR GO; GO:0072344; P:rescue of stalled ribosome; IDA:UniProtKB. DR CDD; cd14374; CUE1_Cue2p_like; 1. DR CDD; cd14375; CUE2_Cue2p_like; 1. DR Gene3D; 3.30.1370.110; -; 1. DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 2. DR InterPro; IPR003892; CUE. DR InterPro; IPR041809; CUE2_CUE1. DR InterPro; IPR041810; CUE2_CUE2. DR InterPro; IPR002625; Smr_dom. DR InterPro; IPR036063; Smr_dom_sf. DR InterPro; IPR009060; UBA-like_sf. DR PANTHER; PTHR46535; NEDD4-BINDING PROTEIN 2; 1. DR PANTHER; PTHR46535:SF1; NEDD4-BINDING PROTEIN 2; 1. DR Pfam; PF02845; CUE; 2. DR SMART; SM00546; CUE; 2. DR SMART; SM00463; SMR; 1. DR SUPFAM; SSF160443; SMR domain-like; 1. DR SUPFAM; SSF46934; UBA-like; 2. DR PROSITE; PS51140; CUE; 2. DR PROSITE; PS50828; SMR; 1. PE 1: Evidence at protein level; KW 3D-structure; Reference proteome; Repeat; Ubl conjugation pathway. FT CHAIN 1..443 FT /note="Endonuclease CUE2" FT /id="PRO_0000079558" FT DOMAIN 8..51 FT /note="CUE 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00468" FT DOMAIN 55..98 FT /note="CUE 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00468" FT DOMAIN 347..443 FT /note="Smr" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00321" FT MUTAGEN 20..21 FT /note="FP->AA: In CUE-D1 mutant; impaired ability to bind FT polyubiquitinated RPS7/eS7; when associated with FT 46-A-A-47." FT /evidence="ECO:0000269|PubMed:36583309" FT MUTAGEN 46..47 FT /note="LL->AA: In CUE-D1 mutant; impaired ability to bind FT polyubiquitinated RPS7/eS7; when associated with FT 21-A-A-22." FT /evidence="ECO:0000269|PubMed:36583309" FT MUTAGEN 67..68 FT /note="FP->AA: In CUE-D2 mutant; impaired ability to bind FT polyubiquitinated RPS7/eS7; when associated with FT 93-A-A-94." FT /evidence="ECO:0000269|PubMed:36583309" FT MUTAGEN 93..94 FT /note="LL->AA: In CUE-D2 mutant; impaired ability to bind FT polyubiquitinated RPS7/eS7; when associated with FT 66-A-A-67." FT /evidence="ECO:0000269|PubMed:36583309" FT MUTAGEN 122 FT /note="W->A: Abolished ability to act downstream of the RQT FT (ribosome quality control trigger) complex." FT /evidence="ECO:0000269|PubMed:36583309" FT MUTAGEN 348..350 FT /note="DFH->AAA: Abolished mRNA endonuclease activity." FT /evidence="ECO:0000269|PubMed:31219035" FT MUTAGEN 402 FT /note="R->A: Decreased ability to participate to No-Go FT Decay (NGD) pathway in response to ribosome collision." FT /evidence="ECO:0000269|PubMed:31219035" FT MUTAGEN 402 FT /note="R->K: No effect." FT /evidence="ECO:0000269|PubMed:31219035" FT HELIX 9..19 FT /evidence="ECO:0007829|PDB:1OTR" FT STRAND 21..23 FT /evidence="ECO:0007829|PDB:1OTR" FT HELIX 25..34 FT /evidence="ECO:0007829|PDB:1OTR" FT TURN 35..37 FT /evidence="ECO:0007829|PDB:1OTR" FT HELIX 40..49 FT /evidence="ECO:0007829|PDB:1OTR" SQ SEQUENCE 443 AA; 50874 MW; 8B7BB872C2BDC734 CRC64; MSMDNNDDHE SKLSILMDMF PAISKSKLQV HLLENNNDLD LTIGLLLKEN DDKSTVDNEL HQLYDMFPQL DCSVIKDQFV INEKSVESTI SDLLNYETLQ KLKDNQANSP DSVKRNEKKN NWESTNDHIE SIIKFTDAPK NIAQEYLAEN GFDTVKAIIK IILDYYDKRD FKKDVDTFKV KRSPNTTVRG GRVQSSTGLA HVLKKGKESA NVAQESLKRP RSYKHSLDSP QMVELNELVA DNRDLKAINH EFLQKCLQFY DGDVVKVLNI SSLLIEDDKN ITKTWNFDEG FTLTSRDNCK QHLPKFSTPQ ISRRNEVGNT YKLPLHDKET PEGAVPVINN LFQTYRLDFH GFLPSEAVST LKLALNKWWS KEVAERELNS HNINSYGSKV QFVSPLIVVT GRGIHSIGGI SKVRLQVKSF LEKNHYIFWE ESSYFRIEGK KKK //