ASSY_MOUSE
ID ASSY_MOUSE Reviewed; 412 AA.
AC P16460;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 181.
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:0000312|MGI:MGI:88090};
GN Synonyms=Ass {ECO:0000303|PubMed:1708740};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=DBA/2J; TISSUE=Liver;
RX PubMed=1708740; DOI=10.1016/0378-1119(91)90125-u;
RA Surh L.C., Beaudet A.L., O'Brien W.E.;
RT "Molecular characterization of the murine argininosuccinate synthetase
RT locus.";
RL Gene 99:181-189(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II, and FVB/N; TISSUE=Colon, and Mammary gland;
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 [3]
RP PROTEIN SEQUENCE OF 128-140.
RC TISSUE=Brain;
RA Lubec G., Yang J.W., Zigmond M.;
RL Submitted (JUL-2007) to UniProtKB.
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177 AND SER-219, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP INTERACTION WITH ASL; SLC7A1; HSP90AA1; NOS1; NOS2; NOS3.
RX PubMed=22081021; DOI=10.1038/nm.2544;
RA Erez A., Nagamani S.C., Shchelochkov O.A., Premkumar M.H., Campeau P.M.,
RA Chen Y., Garg H.K., Li L., Mian A., Bertin T.K., Black J.O., Zeng H.,
RA Tang Y., Reddy A.K., Summar M., O'Brien W.E., Harrison D.G., Mitch W.E.,
RA Marini J.C., Aschner J.L., Bryan N.S., Lee B.;
RT "Requirement of argininosuccinate lyase for systemic nitric oxide
RT production.";
RL Nat. Med. 17:1619-1626(2011).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-112, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
RN [7]
RP ACETYLATION, AND INTERACTION WITH CLOCK.
RX PubMed=28985504; DOI=10.1016/j.molcel.2017.09.008;
RA Lin R., Mo Y., Zha H., Qu Z., Xie P., Zhu Z.J., Xu Y., Xiong Y., Guan K.L.;
RT "CLOCK acetylates ASS1 to drive circadian rhythm of ureagenesis.";
RL Mol. Cell 68:198-209(2017).
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 (By similarity). Interacts
CC with CLOCK; in a circadian manner (PubMed:28985504). Forms tissue-
CC specific complexes with ASL, SLC7A1, HSP90AA1 and nitric oxide synthase
CC NOS1, NOS2 or NOS3; the complex regulates cell-autonomous L-arginine
CC synthesis and citrulline recycling while channeling extracellular L-
CC arginine to nitric oxide synthesis pathway.
CC {ECO:0000250|UniProtKB:P00966, ECO:0000269|PubMed:22081021,
CC ECO:0000269|PubMed:28985504}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P00966}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:1708740}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal liver.
CC {ECO:0000269|PubMed:1708740}.
CC -!- PTM: Acetylated by CLOCK in a circadian manner which negatively
CC regulates its enzyme activity. Deacetylated by histone deacetylases.
CC {ECO:0000269|PubMed:28985504}.
CC -!- SIMILARITY: Belongs to the argininosuccinate synthase family. Type 1
CC subfamily. {ECO:0000305}.
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DR EMBL; M31690; AAA37266.1; -; mRNA.
DR EMBL; M31692; AAB60707.1; -; Genomic_DNA.
DR EMBL; M31694; AAB60708.1; -; Genomic_DNA.
DR EMBL; M31693; AAB60708.1; JOINED; Genomic_DNA.
DR EMBL; M31695; AAB60708.1; JOINED; Genomic_DNA.
DR EMBL; M31702; AAB60706.1; -; Genomic_DNA.
DR EMBL; BC002074; AAH02074.1; -; mRNA.
DR EMBL; BC087556; AAH87556.1; -; mRNA.
DR CCDS; CCDS15898.1; -.
DR PIR; JU0463; AJMSRS.
DR RefSeq; NP_031520.1; NM_007494.3.
DR AlphaFoldDB; P16460; -.
DR SMR; P16460; -.
DR BioGRID; 198226; 15.
DR IntAct; P16460; 2.
DR MINT; P16460; -.
DR STRING; 10090.ENSMUSP00000099904; -.
DR iPTMnet; P16460; -.
DR MetOSite; P16460; -.
DR PhosphoSitePlus; P16460; -.
DR SwissPalm; P16460; -.
DR REPRODUCTION-2DPAGE; P16460; -.
DR EPD; P16460; -.
DR jPOST; P16460; -.
DR PaxDb; P16460; -.
DR PeptideAtlas; P16460; -.
DR PRIDE; P16460; -.
DR ProteomicsDB; 281854; -.
DR Antibodypedia; 4531; 515 antibodies from 38 providers.
DR DNASU; 11898; -.
DR Ensembl; ENSMUST00000102840; ENSMUSP00000099904; ENSMUSG00000076441.
DR GeneID; 11898; -.
DR KEGG; mmu:11898; -.
DR UCSC; uc008jdu.1; mouse.
DR CTD; 445; -.
DR MGI; MGI:88090; Ass1.
DR VEuPathDB; HostDB:ENSMUSG00000076441; -.
DR eggNOG; KOG1706; Eukaryota.
DR GeneTree; ENSGT00390000004524; -.
DR HOGENOM; CLU_032784_4_2_1; -.
DR InParanoid; P16460; -.
DR OMA; GRAYFNT; -.
DR OrthoDB; 1459745at2759; -.
DR PhylomeDB; P16460; -.
DR TreeFam; TF300736; -.
DR BRENDA; 6.3.4.5; 3474.
DR Reactome; R-MMU-70635; Urea cycle.
DR UniPathway; UPA00068; UER00113.
DR UniPathway; UPA00158; UER00272.
DR BioGRID-ORCS; 11898; 6 hits in 73 CRISPR screens.
DR ChiTaRS; Ass1; mouse.
DR PRO; PR:P16460; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P16460; protein.
DR Bgee; ENSMUSG00000076441; Expressed in adult mammalian kidney and 103 other tissues.
DR ExpressionAtlas; P16460; baseline and differential.
DR Genevisible; P16460; MM.
DR GO; GO:0070852; C:cell body fiber; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0016597; F:amino acid binding; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0015643; F:toxic substance binding; ISO:MGI.
DR GO; GO:0006953; P:acute-phase response; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0006526; P:arginine biosynthetic process; ISS:UniProtKB.
DR GO; GO:0000053; P:argininosuccinate metabolic process; ISO:MGI.
DR GO; GO:0006531; P:aspartate metabolic process; ISO:MGI.
DR GO; GO:0071418; P:cellular response to amine stimulus; IEA:Ensembl.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:0071242; P:cellular response to ammonium ion; IEA:Ensembl.
DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0071377; P:cellular response to glucagon stimulus; IEA:Ensembl.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEA:Ensembl.
DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; ISO:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0071400; P:cellular response to oleic acid; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0007623; P:circadian rhythm; IDA:UniProtKB.
DR GO; GO:0000052; P:citrulline metabolic process; ISO:MGI.
DR GO; GO:0060539; P:diaphragm development; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0007494; P:midgut development; IEA:Ensembl.
DR GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; ISO:MGI.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; ISO:MGI.
DR GO; GO:0060416; P:response to growth hormone; IEA:Ensembl.
DR GO; GO:0010046; P:response to mycotoxin; ISO:MGI.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; ISO:MGI.
DR GO; GO:0000050; P:urea cycle; ISS:UniProtKB.
DR CDD; cd01999; Argininosuccinate_Synthase; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR Gene3D; 3.90.1260.10; -; 1.
DR HAMAP; MF_00005; Arg_succ_synth_type1; 1.
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 PANTHER; PTHR11587; PTHR11587; 1.
DR Pfam; PF00764; Arginosuc_synth; 1.
DR SUPFAM; SSF69864; SSF69864; 1.
DR TIGRFAMs; TIGR00032; argG; 1.
DR PROSITE; PS00564; ARGININOSUCCIN_SYN_1; 1.
DR PROSITE; PS00565; ARGININOSUCCIN_SYN_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Amino-acid biosynthesis; Arginine biosynthesis; ATP-binding;
KW Cytoplasm; Direct protein sequencing; Ligase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Urea cycle.
FT CHAIN 1..412
FT /note="Argininosuccinate synthase"
FT /id="PRO_0000148555"
FT BINDING 10..18
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 36
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
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"
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:0007744|PubMed:23576753"
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 177
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00966"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 412 AA; 46584 MW; A8F3AFDDFBDAEF6A CRC64;
MSSKGSVVLA YSGGLDTSCI LVWLKEQGYD VIAYLANIGQ KEDFEEARKK ALKLGAKKVF
IEDVSKEFVE EFIWPAVQSS ALYEDRYLLG TSLARPCIAR RQVEIAQREG AKYVSHGATG
KGNDQVRFEL TCYSLAPQIK VIAPWRMPEF YNRFKGRNDL MEYAKQHGIP IPVTPKSPWS
MDENLMHISY EAGILENPKN QAPPGLYTKT QDPAKAPNSP DVLEIEFKKG VPVKVTNIKD
GTTRTTSLEL FMYLNEVAGK HGVGRIDIVE NRFIGMKSRG IYETPAGTIL YHAHLDIEAF
TMDREVRKIK QGLGLKFAEL VYTGFWHSPE CEFVRHCIQK SQERVEGKVQ VSVFKGQVYI
LGRESPLSLY NEELVSMNVQ GDYEPIDATG FININSLRLK EYHRLQSKVT AK
