ID ASSY_BOVIN Reviewed; 412 AA. AC P14568; Q3T0A7; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1990, sequence version 1. DT 27-MAR-2024, entry version 167. DE RecName: Full=Argininosuccinate synthase {ECO:0000305}; DE EC=6.3.4.5 {ECO:0000250|UniProtKB:P00966}; DE AltName: Full=Citrulline--aspartate ligase; GN Name=ASS1 {ECO:0000250|UniProtKB:P00966}; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND INVOLVEMENT IN CITRULLINEMIA. RX PubMed=2813370; DOI=10.1073/pnas.86.20.7947; RA Dennis J.A., Healy P.J., Beaudet A.L., O'Brien W.E.; RT "Molecular definition of bovine argininosuccinate synthetase deficiency."; RL Proc. Natl. Acad. Sci. U.S.A. 86:7947-7951(1989). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Crossbred X Angus; TISSUE=Ileum; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: One of the enzymes of the urea cycle, the metabolic pathway CC transforming neurotoxic amonia produced by protein catabolism into CC inocuous urea in the liver of ureotelic animals. Catalyzes the CC formation of arginosuccinate from aspartate, citrulline and ATP and CC together with ASL it is responsible for the biosynthesis of arginine in CC most body tissues. {ECO:0000250|UniProtKB:P00966}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-aspartate + L-citrulline = 2-(N(omega)-L- CC arginino)succinate + AMP + diphosphate + H(+); Xref=Rhea:RHEA:10932, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29991, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57472, ChEBI:CHEBI:57743, CC ChEBI:CHEBI:456215; EC=6.3.4.5; CC Evidence={ECO:0000250|UniProtKB:P00966}; CC -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine CC from L-ornithine and carbamoyl phosphate: step 2/3. CC {ECO:0000250|UniProtKB:P00966}. CC -!- PATHWAY: Nitrogen metabolism; urea cycle; (N(omega)-L- CC arginino)succinate from L-aspartate and L-citrulline: step 1/1. CC {ECO:0000250|UniProtKB:P00966}. CC -!- SUBUNIT: Homotetramer. Interacts with NMRAL1. Interacts with CLOCK; in CC a circadian manner (By similarity). Forms tissue-specific complexes CC with ASL, SLC7A1, HSP90AA1 and nitric oxide synthase NOS1, NOS2 or CC NOS3; the complex regulates cell-autonomous L-arginine synthesis and CC citrulline recycling while channeling extracellular L-arginine to CC nitric oxide synthesis pathway (By similarity). CC {ECO:0000250|UniProtKB:P00966, ECO:0000250|UniProtKB:P16460}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P00966}. CC -!- PTM: Acetylated by CLOCK in a circadian manner which negatively CC regulates its enzyme activity. Deacetylated by histone deacetylases. CC {ECO:0000250|UniProtKB:P00966}. CC -!- DISEASE: Note=Defects in ASS1 are the cause of a bovine form of CC citrullinemia. {ECO:0000269|PubMed:2813370}. CC -!- SIMILARITY: Belongs to the argininosuccinate synthase family. Type 1 CC subfamily. {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; M26198; AAA30388.1; -; mRNA. DR EMBL; BC102474; AAI02475.1; -; mRNA. DR PIR; A33986; AJBORS. DR RefSeq; NP_776317.1; NM_173892.4. DR AlphaFoldDB; P14568; -. DR SMR; P14568; -. DR STRING; 9913.ENSBTAP00000072835; -. DR iPTMnet; P14568; -. DR PaxDb; 9913-ENSBTAP00000027649; -. DR PeptideAtlas; P14568; -. DR Ensembl; ENSBTAT00000027649.4; ENSBTAP00000027649.3; ENSBTAG00000020747.4. DR Ensembl; ENSBTAT00000071866.1; ENSBTAP00000074521.1; ENSBTAG00000020747.4. DR GeneID; 280726; -. DR KEGG; bta:280726; -. DR CTD; 445; -. DR VEuPathDB; HostDB:ENSBTAG00000020747; -. DR VGNC; VGNC:26224; ASS1. DR eggNOG; KOG1706; Eukaryota. DR GeneTree; ENSGT00390000004524; -. DR HOGENOM; CLU_032784_4_2_1; -. DR InParanoid; P14568; -. DR OMA; ACGAFHI; -. DR OrthoDB; 350199at2759; -. DR TreeFam; TF300736; -. DR Reactome; R-BTA-70635; Urea cycle. DR SABIO-RK; P14568; -. DR UniPathway; UPA00068; UER00113. DR UniPathway; UPA00158; UER00272. DR Proteomes; UP000009136; Chromosome 11. DR Bgee; ENSBTAG00000020747; Expressed in cortex of kidney and 105 other cell types or tissues. DR ExpressionAtlas; P14568; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl. DR GO; GO:0016597; F:amino acid binding; IEA:Ensembl. DR GO; GO:0004055; F:argininosuccinate synthase activity; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0006526; P:arginine biosynthetic process; ISS:UniProtKB. DR GO; GO:0000053; P:argininosuccinate metabolic process; IBA:GO_Central. DR GO; GO:0006531; P:aspartate metabolic process; IEA:Ensembl. DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; IEA:Ensembl. DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB. DR GO; GO:0000052; P:citrulline metabolic process; IEA:Ensembl. DR GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; IEA:Ensembl. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl. DR GO; GO:0000050; P:urea cycle; ISS:UniProtKB. DR CDD; cd01999; Argininosuccinate_Synthase; 1. DR Gene3D; 3.90.1260.10; Argininosuccinate synthetase, chain A, domain 2; 1. DR Gene3D; 3.40.50.620; HUPs; 1. DR Gene3D; 1.20.5.470; Single helix bin; 1. DR HAMAP; MF_00005; Arg_succ_synth_type1; 1. DR InterPro; IPR048268; Arginosuc_syn_C. DR InterPro; IPR048267; Arginosuc_syn_N. DR InterPro; IPR001518; Arginosuc_synth. DR InterPro; IPR018223; Arginosuc_synth_CS. DR InterPro; IPR023434; Arginosuc_synth_type_1_subfam. DR InterPro; IPR024074; AS_cat/multimer_dom_body. DR InterPro; IPR014729; Rossmann-like_a/b/a_fold. DR NCBIfam; TIGR00032; argG; 1. DR PANTHER; PTHR11587; ARGININOSUCCINATE SYNTHASE; 1. DR PANTHER; PTHR11587:SF2; ARGININOSUCCINATE SYNTHASE; 1. DR Pfam; PF20979; Arginosuc_syn_C; 1. DR Pfam; PF00764; Arginosuc_synth; 1. DR SUPFAM; SSF52402; Adenine nucleotide alpha hydrolases-like; 1. DR SUPFAM; SSF69864; Argininosuccinate synthetase, C-terminal domain; 1. DR PROSITE; PS00564; ARGININOSUCCIN_SYN_1; 1. DR PROSITE; PS00565; ARGININOSUCCIN_SYN_2; 1. PE 2: Evidence at transcript level; KW Acetylation; Amino-acid biosynthesis; Arginine biosynthesis; ATP-binding; KW Cytoplasm; Ligase; Nucleotide-binding; Phosphoprotein; Reference proteome; KW Urea cycle. FT CHAIN 1..412 FT /note="Argininosuccinate synthase" FT /id="PRO_0000148553" FT BINDING 10..18 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P00966" FT BINDING 36 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P00966" FT BINDING 87 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000250|UniProtKB:P00966" FT BINDING 92 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000250|UniProtKB:P00966" FT BINDING 115..123 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P00966" FT BINDING 119 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000250|UniProtKB:P00966" FT BINDING 123 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000250|UniProtKB:P00966" FT BINDING 123 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000250|UniProtKB:P00966" FT BINDING 124 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000250|UniProtKB:P00966" FT BINDING 127 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000250|UniProtKB:P00966" FT BINDING 180 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000250|UniProtKB:P00966" FT BINDING 189 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000250|UniProtKB:P00966" FT BINDING 270 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000250|UniProtKB:P00966" FT BINDING 282 FT /ligand="L-citrulline" FT /ligand_id="ChEBI:CHEBI:57743" FT /evidence="ECO:0000250|UniProtKB:P00966" FT MOD_RES 87 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P09034" FT MOD_RES 112 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P16460" FT MOD_RES 113 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P00966" FT MOD_RES 165 FT /note="N6-acetyllysine; by CLOCK" FT /evidence="ECO:0000250|UniProtKB:P00966" FT MOD_RES 176 FT /note="N6-acetyllysine; by CLOCK" FT /evidence="ECO:0000250|UniProtKB:P00966" FT MOD_RES 180 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00966" FT MOD_RES 219 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P16460" SQ SEQUENCE 412 AA; 46417 MW; 6F74C7F445EE0D86 CRC64; MSGKGSVVLA YSGGLDTSCI LVWLKEQGYD VIAYLANIGQ KEDFEEARKK ALKLGAKKVF IEDISKEFVE EFIWPAIQSS ALYEDRYLLG TSLARPCIAR KQVEIAQREG AKYVSHGATG KGNDQIRFEL TCYSLAPQIK VIAPWRMPEF YNRFQGRNDL MEYAKQHGIP VPVTPKNPWS MDENLMHISY EAGILENPKN QAPPGLYTKT QDPAKAPNSP DMLEIEFKKG VPVKVTNVGD GTTHSTALEL FLYLNEVAGK HGVGRIDIVE NRFIGMKSRG IYETPAGTIL YHAHLDIEAF TMDREVRKIK QGLGLKFAEL VYTGFWHSPE CEFVRHCIAK SQERVEGKVQ VSVFKGQVYI LGRESPLSLY NEELVSMNVQ GDYEPVDATG FININSLRLK EYHRLQNKVT AK //