ID SYA_YEAST Reviewed; 983 AA. AC P40825; D6W330; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 3. DT 04-NOV-2026, entry version 201. DE RecName: Full=Alanine--tRNA ligase, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03133}; DE EC=6.1.1.7 {ECO:0000255|HAMAP-Rule:MF_03133}; DE AltName: Full=Alanyl-tRNA synthetase {ECO:0000255|HAMAP-Rule:MF_03133}; DE Short=AlaRS {ECO:0000255|HAMAP-Rule:MF_03133}; DE Flags: Precursor; GN Name=ALA1 {ECO:0000255|HAMAP-Rule:MF_03133}; Synonyms=CDC64; GN OrderedLocusNames=YOR335C; 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 [GENOMIC DNA]. RX PubMed=8896263; RX DOI=10.1002/(sici)1097-0061(199609)12:10b%3c999::aid-yea976%3e3.0.co;2-e; RA Parle-McDermott A.G., Hand N.J., Goulding S.E., Wolfe K.H.; RT "Sequence of 29 kb around the PDR10 locus on the right arm of Saccharomyces RT cerevisiae chromosome XV: similarity to part of chromosome I."; RL Yeast 12:999-1004(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169874; DOI=10.1038/387s098; RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J., RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A., RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B., RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H., RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E., RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U., RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B., RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A., RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C., RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G., RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B., RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B., RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F., RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E., RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I., RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H., RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV."; RL Nature 387:98-102(1997). RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 4-983, AND FUNCTION. RX PubMed=7761427; DOI=10.1073/pnas.92.11.4932; RA Ripmaster T.L., Shiba K., Schimmel P.; RT "Wide cross-species aminoacyl-tRNA synthetase replacement in vivo: yeast RT cytoplasmic alanine enzyme replaced by human polymyositis serum antigen."; RL Proc. Natl. Acad. Sci. U.S.A. 92:4932-4936(1995). RN [5] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=14562095; DOI=10.1038/nature02026; RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., RA Weissman J.S., O'Shea E.K.; RT "Global analysis of protein localization in budding yeast."; RL Nature 425:686-691(2003). RN [6] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., RA O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [7] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=14576278; DOI=10.1073/pnas.2135385100; RA Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E., RA Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P., RA Pfanner N., Meisinger C.; RT "The proteome of Saccharomyces cerevisiae mitochondria."; RL Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003). RN [8] RP ALTERNATIVE INITIATION. RX PubMed=15358761; DOI=10.1074/jbc.m408081200; RA Tang H.L., Yeh L.S., Chen N.K., Ripmaster T., Schimmel P., Wang C.C.; RT "Translation of a yeast mitochondrial tRNA synthetase initiated at RT redundant non-AUG codons."; RL J. Biol. Chem. 279:49656-49663(2004). RN [9] RP SUBCELLULAR LOCATION. RX PubMed=16556230; DOI=10.1111/j.1365-2958.2006.05083.x; RA Huang H.Y., Tang H.L., Chao H.Y., Yeh L.S., Wang C.C.; RT "An unusual pattern of protein expression and localization of yeast alanyl- RT tRNA synthetase isoforms."; RL Mol. Microbiol. 60:189-198(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-504, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200; RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; RT "A multidimensional chromatography technology for in-depth phosphoproteome RT analysis."; RL Mol. Cell. Proteomics 7:1389-1396(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-975, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19779198; DOI=10.1126/science.1172867; RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.; RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights RT into evolution."; RL Science 325:1682-1686(2009). CC -!- FUNCTION: Catalyzes the attachment of alanine to tRNA(Ala) in a two- CC step reaction: alanine is first activated by ATP to form Ala-AMP and CC then transferred to the acceptor end of tRNA(Ala). Also edits CC incorrectly charged tRNA(Ala) via its editing domain. CC {ECO:0000255|HAMAP-Rule:MF_03133, ECO:0000269|PubMed:7761427}. CC -!- CATALYTIC ACTIVITY: CC Reaction=tRNA(Ala) + L-alanine + ATP = L-alanyl-tRNA(Ala) + AMP + CC diphosphate; Xref=Rhea:RHEA:12540, Rhea:RHEA-COMP:9657, Rhea:RHEA- CC COMP:9923, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57972, CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78497, ChEBI:CHEBI:456215; EC=6.1.1.7; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03133}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000255|HAMAP- CC Rule:MF_03133}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_03133}; CC -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_03133}. CC -!- SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm. CC -!- SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=Mitochondrial; CC IsoId=P40825-1; Sequence=Displayed; CC Name=Cytoplasmic; CC IsoId=P40825-2; Sequence=VSP_040236; CC -!- DOMAIN: Consists of three domains; the N-terminal catalytic domain, the CC editing domain and the C-terminal C-Ala domain. The editing domain CC removes incorrectly charged amino acids, while the C-Ala domain, along CC with tRNA(Ala), serves as a bridge to cooperatively bring together the CC editing and aminoacylation centers thus stimulating deacylation of CC misacylated tRNAs. {ECO:0000255|HAMAP-Rule:MF_03133}. CC -!- MISCELLANEOUS: Present with 33800 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. CC -!- MISCELLANEOUS: [Isoform Mitochondrial]: Produced by alternative CC initiation at 2 upstream redundant non-AUG codons in-frame of the first CC AUG used for isoform Cytoplasmic. CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family. CC {ECO:0000255|HAMAP-Rule:MF_03133}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC49007.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA89980.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA99658.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=DAA11096.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; Z49821; CAA89980.1; ALT_INIT; Genomic_DNA. DR EMBL; Z75243; CAA99658.1; ALT_INIT; Genomic_DNA. DR EMBL; U18672; AAC49007.1; ALT_INIT; Genomic_DNA. DR EMBL; BK006948; DAA11096.1; ALT_INIT; Genomic_DNA. DR PIR; S62065; S62065. DR RefSeq; NP_014980.3; NM_001183755.3. [P40825-2] DR AlphaFoldDB; P40825; -. DR SMR; P40825; -. DR BioGRID; 34718; 385. DR DIP; DIP-6286N; -. DR FunCoup; P40825; 1196. DR IntAct; P40825; 13. DR STRING; 4932.YOR335C; -. DR CarbonylDB; P40825; -. DR iPTMnet; P40825; -. DR PaxDb; 4932-YOR335C; -. DR PeptideAtlas; P40825; -. DR EnsemblFungi; YOR335C_mRNA; YOR335C; YOR335C. [P40825-2] DR GeneID; 854513; -. DR KEGG; sce:YOR335C; -. DR AGR; SGD:S000005862; -. DR SGD; S000005862; ALA1. DR eggNOG; KOG0188; Eukaryota. DR HOGENOM; CLU_004485_5_0_1; -. DR InParanoid; P40825; -. DR OMA; AAAKWMY; -. DR OrthoDB; 2423964at2759; -. DR BioCyc; YEAST:G3O-33810-MONOMER; -. DR BRENDA; 6.1.1.7; 984. DR BioGRID-ORCS; 854513; 0 hits in 10 CRISPR screens. DR CD-CODE; E03F929F; Stress granule. DR PRO; PR:P40825; -. DR Proteomes; UP000002311; Chromosome XV. DR RNAct; P40825; protein. DR GO; GO:0005737; C:cytoplasm; IDA:SGD. DR GO; GO:0005739; C:mitochondrion; IDA:SGD. DR GO; GO:0004813; F:alanine-tRNA ligase activity; IMP:SGD. DR GO; GO:0002161; F:aminoacyl-tRNA deacylase activity; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule. DR GO; GO:1990825; F:sequence-specific mRNA binding; IDA:SGD. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0006419; P:alanyl-tRNA aminoacylation; IMP:SGD. DR GO; GO:0070143; P:mitochondrial alanyl-tRNA aminoacylation; IEA:UniProtKB-UniRule. DR CDD; cd00673; AlaRS_core; 1. DR FunFam; 2.40.30.130:FF:000004; Alanine--tRNA ligase; 1. DR FunFam; 3.10.310.40:FF:000003; Alanine--tRNA ligase; 1. DR FunFam; 3.30.930.10:FF:000011; Alanine--tRNA ligase, cytoplasmic; 1. DR FunFam; 3.30.980.10:FF:000004; Alanine--tRNA ligase, cytoplasmic; 1. DR Gene3D; 2.40.30.130; -; 1. DR Gene3D; 3.10.310.40; -; 1. DR Gene3D; 3.30.930.10; Bira Bifunctional Protein, Domain 2; 1. DR Gene3D; 3.30.980.10; Threonyl-trna Synthetase, Chain A, domain 2; 1. DR HAMAP; MF_00036_B; Ala_tRNA_synth_B; 1. DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL. DR InterPro; IPR002318; Ala-tRNA-lgiase_IIc. DR InterPro; IPR018162; Ala-tRNA-ligase_IIc_anticod-bd. DR InterPro; IPR018165; Ala-tRNA-synth_IIc_core. DR InterPro; IPR018164; Ala-tRNA-synth_IIc_N. DR InterPro; IPR059090; ALA1_helical. DR InterPro; IPR023033; Ala_tRNA_ligase_euk/bac. DR InterPro; IPR003156; DHHA1_dom. DR InterPro; IPR018163; Thr/Ala-tRNA-synth_IIc_edit. DR InterPro; IPR009000; Transl_B-barrel_sf. DR InterPro; IPR012947; tRNA_SAD. DR NCBIfam; TIGR00344; alaS; 1. DR PANTHER; PTHR11777:SF9; ALANINE--TRNA LIGASE, CYTOPLASMIC; 1. DR PANTHER; PTHR11777; ALANYL-TRNA SYNTHETASE; 1. DR Pfam; PF26023; ALA1; 1. DR Pfam; PF02272; DHHA1; 1. DR Pfam; PF01411; tRNA-synt_2c; 1. DR Pfam; PF07973; tRNA_SAD; 1. DR PRINTS; PR00980; TRNASYNTHALA. DR SMART; SM00863; tRNA_SAD; 1. DR SUPFAM; SSF55681; Class II aaRS and biotin synthetases; 1. DR SUPFAM; SSF101353; Putative anticodon-binding domain of alanyl-tRNA synthetase (AlaRS); 1. DR SUPFAM; SSF55186; ThrRS/AlaRS common domain; 1. DR SUPFAM; SSF50447; Translation proteins; 1. DR PROSITE; PS50860; AA_TRNA_LIGASE_II_ALA; 1. PE 1: Evidence at protein level; KW Alternative initiation; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; KW Ligase; Metal-binding; Mitochondrion; Nucleotide-binding; Phosphoprotein; KW Protein biosynthesis; Reference proteome; RNA-binding; Transit peptide; KW tRNA-binding; Zinc. FT TRANSIT 1..24 FT /note="Mitochondrion" FT CHAIN 25..983 FT /note="Alanine--tRNA ligase, mitochondrial" FT /id="PRO_0000075287" FT BINDING 625 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03133" FT BINDING 629 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03133" FT BINDING 744 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03133" FT BINDING 748 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03133" FT MOD_RES 504 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18407956" FT MOD_RES 975 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19779198" FT VAR_SEQ 1..25 FT /note="Missing (in isoform Cytoplasmic)" FT /evidence="ECO:0000305" FT /id="VSP_040236" FT CONFLICT 4..7 FT /note="TTGL -> NYRI (in Ref. 4; AAC49007)" FT /evidence="ECO:0000305" FT CONFLICT 16 FT /note="Missing (in Ref. 4; AAC49007)" FT /evidence="ECO:0000305" FT CONFLICT 161 FT /note="R -> S (in Ref. 4; AAC49007)" FT /evidence="ECO:0000305" FT CONFLICT 490..492 FT /note="KDQ -> RTK (in Ref. 4; AAC49007)" FT /evidence="ECO:0000305" FT CONFLICT 865..866 FT /note="FE -> LQ (in Ref. 4; AAC49007)" FT /evidence="ECO:0000305" SQ SEQUENCE 983 AA; 110059 MW; DC0F50DB6409F11F CRC64; MTSTTGLRNL TLSFKKQLTT STRTIMTIGD KQKWTATNVR NTFLDYFKSK EHKFVKSSPV VPFDDPTLLF ANAGMNQYKP IFLGTVDPAS DFYTLKRAYN SQKCIRAGGK HNDLEDVGKD SYHHTFFEML GNWSFGDYFK KEAITYSWTL LTEVYGIPKD RLYVTYFEGD EKLGLEPDTE ARELWKNVGV PDDHILPGNA KDNFWEMGDQ GPCGPCSEIH YDRIGGRNAA SLVNMDDPDV LEVWNLVFIQ FNREQDGSLK PLPAKHIDTG MGFERLVSVL QDVRSNYDTD VFTPLFERIQ EITSVRPYSG NFGENDKDGI DTAYRVLADH VRTLTFALAD GGVPNNEGRG YVLRRILRRG ARYARKYMNY PIGNFFSTLA PTLISQVQDI FPELAKDPAF LFEILDEEEA SFAKTLDRGE RLFEKYASAA SKTESKTLDG KQVWRLYDTY GFPVDLTELM AEEQGLKIDG PGFEKAKQES YEASKRGGKK DQSDLIKLNV HELSELNDAK VPKTNDEFKY GSANVEGTIL KLHDGTNFVD EITEPGKKYG IILDKTCFYA EQGGQEYDTG KIVIDDAAEF NVENVQLYNG FVFHTGSLEE GKLSVGDKII ASFDELRRFP IKNNHTGTHI LNFALKETLG NDVDQKGSLV APEKLRFDFS HKKAVSNEEL KKVEDICNEQ IKENLQVFYK EIPLDLAKSI DGVRAVFGET YPDPVRVVSV GKPIEELLAN PANEEWTKYS IEFCGGTHVN KTGDIKYFVI LEESGIAKGI RRIVAVTGTE AFEAQRLAEQ FAADLDAADK LPFSPIKEKK LKELGVKLGQ LSISVITKNE LKQKFNKIEK AVKDEVKSRA KKENKQTLDE VKTFFETNEN APYLVKFIDI SPNAKAITEA INYMKSNDSV KDKSIYLLAG NDPEGRVAHG CYISNAALAK GIDGSALAKK VSSIIGGKAG GKGNVFQGMG DKPAAIKDAV DDLESLFKEK LSI //