ID   SYAC_PONAB              Reviewed;         968 AA.
AC   Q5RC02;
DT   07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   02-SEP-2026, entry version 94.
DE   RecName: Full=Alanine--tRNA ligase, cytoplasmic {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   AltName: Full=Protein lactyltransferase AARS1 {ECO:0000305};
DE            EC=6.-.-.- {ECO:0000255|HAMAP-Rule:MF_03133};
GN   Name=AARS1; Synonyms=AARS {ECO:0000255|HAMAP-Rule:MF_03133};
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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. In presence of
CC       high levels of lactate, also acts as a protein lactyltransferase that
CC       mediates lactylation of lysine residues in target proteins, such as
CC       TEAD1, TP53/p53 and YAP1. Protein lactylation takes place in a two-step
CC       reaction: lactate is first activated by ATP to form lactate-AMP and
CC       then transferred to lysine residues of target proteins. Acts as an
CC       inhibitor of TP53/p53 activity by catalyzing lactylation of TP53/p53.
CC       Acts as a positive regulator of the Hippo pathway by mediating
CC       lactylation of TEAD1 and YAP1. {ECO:0000255|HAMAP-Rule:MF_03133}.
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   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-lactate + ATP + H(+) = (S)-lactoyl-AMP + diphosphate;
CC         Xref=Rhea:RHEA:80271, ChEBI:CHEBI:15378, ChEBI:CHEBI:16651,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:231470;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_03133};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-lactoyl-AMP + L-lysyl-[protein] = N(6)-[(S)-lactoyl]-L-
CC         lysyl-[protein] + AMP + 2 H(+); Xref=Rhea:RHEA:80275, Rhea:RHEA-
CC         COMP:9752, Rhea:RHEA-COMP:19466, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:29969, ChEBI:CHEBI:231470, ChEBI:CHEBI:231527,
CC         ChEBI:CHEBI:456215; 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   -!- ACTIVITY REGULATION: The protein lactyltransferase activity is
CC       inhibited by beta-alanine. {ECO:0000250|UniProtKB:P49588}.
CC   -!- SUBUNIT: Monomer. Interacts with ANKRD16; the interaction is direct.
CC       {ECO:0000255|HAMAP-Rule:MF_03133}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03133}.
CC       Nucleus {ECO:0000255|HAMAP-Rule:MF_03133}. Note=Translocates to the
CC       nucleus in response to increased levels of lactate; nuclear
CC       translocation is dependent on KPNA4. {ECO:0000255|HAMAP-Rule:MF_03133}.
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   -!- PTM: ISGylated. {ECO:0000255|HAMAP-Rule:MF_03133}.
CC   -!- PTM: Methylation at 'Lys-943' by METTL21C.
CC       {ECO:0000250|UniProtKB:P49588}.
CC   -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC       {ECO:0000255|HAMAP-Rule:MF_03133}.
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DR   EMBL; CR858480; CAH90708.1; -; mRNA.
DR   RefSeq; NP_001125391.1; NM_001131919.1.
DR   AlphaFoldDB; Q5RC02; -.
DR   SMR; Q5RC02; -.
DR   FunCoup; Q5RC02; 2439.
DR   STRING; 9601.ENSPPYP00000008517; -.
DR   GeneID; 100172296; -.
DR   KEGG; pon:100172296; -.
DR   CTD; 16; -.
DR   InParanoid; Q5RC02; -.
DR   OrthoDB; 2423964at2759; -.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; IEA:TreeGrafter.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0004813; F:alanine-tRNA ligase activity; ISS:UniProtKB.
DR   GO; GO:0002161; F:aminoacyl-tRNA deacylase activity; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR   GO; GO:0141207; F:peptide lactyltransferase (ATP-dependent) activity; ISS:UniProtKB.
DR   GO; GO:0002196; F:Ser-tRNA(Ala) deacylase activity; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0006419; P:alanyl-tRNA aminoacylation; ISS:UniProtKB.
DR   GO; GO:1901797; P:negative regulation of signal transduction by p53 class mediator; ISS:UniProtKB.
DR   GO; GO:0035332; P:positive regulation of hippo signaling; ISS:UniProtKB.
DR   GO; GO:0006400; P:tRNA modification; ISS:UniProtKB.
DR   CDD; cd00673; AlaRS_core; 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   FunFam; 3.10.310.40:FF:000002; alanine--tRNA ligase, cytoplasmic; 1.
DR   FunFam; 2.40.30.130:FF:000026; Alanyl-tRNA synthetase; 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; 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:SF36; ALANINE--TRNA LIGASE, CYTOPLASMIC; 1.
DR   PANTHER; PTHR11777; ALANYL-TRNA SYNTHETASE; 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   2: Evidence at transcript level;
KW   Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; Ligase;
KW   Metal-binding; Methylation; Nucleotide-binding; Nucleus; Phosphoprotein;
KW   Protein biosynthesis; Reference proteome; RNA-binding; tRNA-binding;
KW   Ubl conjugation; Zinc.
FT   CHAIN           1..968
FT                   /note="Alanine--tRNA ligase, cytoplasmic"
FT                   /id="PRO_0000075283"
FT   MOTIF           750..763
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03133"
FT   BINDING         77
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   BINDING         95
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   BINDING         176
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   BINDING         214..216
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   BINDING         216
FT                   /ligand="L-alanine"
FT                   /ligand_id="ChEBI:CHEBI:57972"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   BINDING         239
FT                   /ligand="L-alanine"
FT                   /ligand_id="ChEBI:CHEBI:57972"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   BINDING         243
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   BINDING         605
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03133"
FT   BINDING         609
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03133"
FT   BINDING         723
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03133"
FT   BINDING         727
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03133"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:P49588, ECO:0000255|HAMAP-
FT                   Rule:MF_03133"
FT   MOD_RES         3
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   MOD_RES         8
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   MOD_RES         19
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   MOD_RES         399
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   MOD_RES         555
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   MOD_RES         876
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   MOD_RES         943
FT                   /note="N6,N6,N6-trimethyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   MOD_RES         943
FT                   /note="N6,N6-dimethyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
FT   MOD_RES         943
FT                   /note="N6-methyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P49588"
SQ   SEQUENCE   968 AA;  106779 MW;  8FB2F1F06ECB1128 CRC64;
     MDSTLTASKI RQRFIDFFKR NEHTYIHSSA TIPLDDPTLL FANAGMNQFK PIFLNTIDPS
     HPMAKPSRAA NTQKCIRAGG KHNDLDDVGK DVYHHTFFEM LGSWSFGDYF KELACKMALE
     LLTQEFGIPI ERLYVTYFGG DEAAGLEPDL ECKQIWQNLG LDDTKILPGN MKDNFWEMGD
     TGPCGPCSEI HYDRIGGRDA AHLVNQDDPN VLEIWNLVFI QYNREADGIL KPLPKKSIDT
     GMGLERLVSV LQNKMSNYDT DLFVPYFEAI QKGTGARPYT GKVGAEDADG IDMAYRVLAD
     HARTITVALA DGGRPDNTGR GYVLRRILRR AVRYAHEKLN ASRGFFATLV DVVVQSLGDA
     FPELKKDPDM VKDIINEEEV QFLKTLSRGR RILDRKIQSL GDSKTIPGDT AWLLYDTYGF
     PVDLTGLIAE EKGLVVDMDG FEEERKLAQL KSQGKGAGGE DLIMLDIYAI EELRARDLEV
     TDDSPKYNYH LDSSGSYVFE NTVATVMALR REKMFVEEVS TGQECGVVLD KTCFYAEQGG
     QIYDEGYLVK VDDSSEDKTE FTVKNAQVRG GYVLHIGTIY GDLKVGDQVW LFIDEPRRRP
     IMSNHTATHI LNFALRSVLG EADQKGSLVA PDRLRFDFTA KGAMSTQQIK KAEEIANEMI
     EAAKPVYTQD CSLAAAKAIQ GLRAVFDETY PDPVRVVSIG VPVSELLDDP SGPAGSLTSV
     EFCGGTHLRN SSHAGAFVIV TEEAIAKGIR RIVAVTGAEA QKALRKAGSL KKPLSVMEAK
     VKAQTAPNKD VQREIADLGE ALATAVIPQW QKDELRETLK SLKKVMDDLD RASKADVQKR
     VLEKTKQLID SNPNQPLVIL EMESGASAKA LNEALKLFKM HSPQTAAMLF TVDNEAGKIT
     CLCQVPQNAA NRGLKASEWV QQVSGLMDGK GGGKDVSAQA TGKNVGCLQE ALQLATSFAQ
     LRLGDVKN
//