ASSY_RAT
ID ASSY_RAT Reviewed; 412 AA.
AC P09034;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Argininosuccinate synthase {ECO:0000305};
DE EC=6.3.4.5 {ECO:0000269|PubMed:19491403};
DE AltName: Full=Citrulline--aspartate ligase;
GN Name=Ass1 {ECO:0000312|RGD:2163};
GN Synonyms=Ass {ECO:0000303|PubMed:3174461};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=3174461; DOI=10.1093/nar/16.19.9352;
RA Surh L.C., Morris S.M., O'Brien W.E., Beaudet A.L.;
RT "Nucleotide sequence of the cDNA encoding the rat argininosuccinate
RT synthetase.";
RL Nucleic Acids Res. 16:9352-9352(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary;
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 FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MISCELLANEOUS.
RX PubMed=19491403; DOI=10.1074/jbc.m109.021089;
RA Guerreiro J.R., Lameu C., Oliveira E.F., Klitzke C.F., Melo R.L.,
RA Linares E., Augusto O., Fox J.W., Lebrun I., Serrano S.M., Camargo A.C.;
RT "Argininosuccinate synthetase is a functional target for a snake venom
RT anti-hypertensive peptide: role in arginine and nitric oxide production.";
RL J. Biol. Chem. 284:20022-20033(2009).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-87 AND THR-219, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (Probable). Catalyzes
CC the 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 (Probable). Indirectly, may be involved in the
CC control of blood pressure (PubMed:19491403).
CC {ECO:0000269|PubMed:19491403, ECO:0000305|PubMed:19491403}.
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:0000269|PubMed:19491403};
CC -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine
CC from L-ornithine and carbamoyl phosphate: step 2/3.
CC {ECO:0000305|PubMed:19491403}.
CC -!- PATHWAY: Nitrogen metabolism; urea cycle; (N(omega)-L-
CC arginino)succinate from L-aspartate and L-citrulline: step 1/1.
CC {ECO:0000305|PubMed:19491403}.
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 {ECO:0000305|PubMed:19491403}.
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 -!- MISCELLANEOUS: Binds and is activated by Bj-BPP-10c, a bioactive anti-
CC hypertensive proline-rich decapeptide, part of the C-type natriuretic
CC peptide precursor. {ECO:0000269|PubMed:19491403}.
CC -!- SIMILARITY: Belongs to the argininosuccinate synthase family. Type 1
CC subfamily. {ECO:0000305}.
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DR EMBL; X12459; CAA30999.1; -; mRNA.
DR EMBL; M36708; AAA40771.1; -; mRNA.
DR EMBL; BC063146; AAH63146.1; -; mRNA.
DR PIR; S01440; AJRTRS.
DR RefSeq; NP_037289.1; NM_013157.3.
DR RefSeq; XP_006233973.1; XM_006233911.3.
DR AlphaFoldDB; P09034; -.
DR SMR; P09034; -.
DR BioGRID; 247727; 2.
DR IntAct; P09034; 1.
DR STRING; 10116.ENSRNOP00000012075; -.
DR iPTMnet; P09034; -.
DR PhosphoSitePlus; P09034; -.
DR jPOST; P09034; -.
DR PaxDb; P09034; -.
DR PRIDE; P09034; -.
DR Ensembl; ENSRNOT00000093365; ENSRNOP00000076301; ENSRNOG00000008837.
DR GeneID; 25698; -.
DR KEGG; rno:25698; -.
DR UCSC; RGD:2163; rat.
DR CTD; 445; -.
DR RGD; 2163; Ass1.
DR eggNOG; KOG1706; Eukaryota.
DR GeneTree; ENSGT00390000004524; -.
DR HOGENOM; CLU_032784_4_2_1; -.
DR InParanoid; P09034; -.
DR OMA; GRAYFNT; -.
DR OrthoDB; 1459745at2759; -.
DR PhylomeDB; P09034; -.
DR TreeFam; TF300736; -.
DR SABIO-RK; P09034; -.
DR UniPathway; UPA00068; UER00113.
DR UniPathway; UPA00158; UER00272.
DR PRO; PR:P09034; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000008837; Expressed in liver and 18 other tissues.
DR Genevisible; P09034; RN.
DR GO; GO:0070852; C:cell body fiber; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR GO; GO:0005764; C:lysosome; IDA:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0016597; F:amino acid binding; ISO:RGD.
DR GO; GO:0004055; F:argininosuccinate synthase activity; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0015643; F:toxic substance binding; IPI:RGD.
DR GO; GO:0006953; P:acute-phase response; IEP:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0006526; P:arginine biosynthetic process; IDA:RGD.
DR GO; GO:0000053; P:argininosuccinate metabolic process; IDA:RGD.
DR GO; GO:0006531; P:aspartate metabolic process; ISO:RGD.
DR GO; GO:0071418; P:cellular response to amine stimulus; IEP:RGD.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEP:RGD.
DR GO; GO:0071242; P:cellular response to ammonium ion; IEP:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0071377; P:cellular response to glucagon stimulus; IEP:RGD.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEP:RGD.
DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; ISO:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0071400; P:cellular response to oleic acid; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR GO; GO:0000052; P:citrulline metabolic process; ISO:RGD.
DR GO; GO:0060539; P:diaphragm development; IEP:RGD.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0007494; P:midgut development; IEP:RGD.
DR GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; ISO:RGD.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:RGD.
DR GO; GO:0014075; P:response to amine; IEP:RGD.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0070542; P:response to fatty acid; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IDA:RGD.
DR GO; GO:0060416; P:response to growth hormone; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0010046; P:response to mycotoxin; IDA:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0010043; P:response to zinc ion; IDA:RGD.
DR GO; GO:0000050; P:urea cycle; IDA:RGD.
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; Ligase; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Urea cycle.
FT CHAIN 1..412
FT /note="Argininosuccinate synthase"
FT /id="PRO_0000148556"
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:0007744|PubMed:22673903"
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 177
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16460"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00966"
FT MOD_RES 219
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 412 AA; 46496 MW; CCA80906F5A3E93D CRC64;
MSSKGSVVLA YSGGLDTSCI LVWLKEQGYD VIAYLANIGQ KEDFEEARKK ALKLGAKKVF
IEDVSKEFVE EFIWPAVQSS ALYEDRYLLG TSLARPCIAR KQVEIAQREG AKYVSHGATG
KGNDQVRFEL TCYSLAPQIK VIAPWRMPEF YNRFKGRNDL MEYAKQHGIP IPVTPKSPWS
MDENLMHISY EAGILENPKN QAPPGLYTKT QDPAKAPNTP DVLEIEFKKG VPVKVTNVKD
GTTHSTSLDL FMYLNEVAGK HGVGRIDIVE NRFIGMKSRG IYETPAGTIL YHAHLDIEAF
TMDREVRKIK QGLGLKFAEL VYTGFWHSPE CEFVRHCIDK SQERVEGKVQ VSVFKGQVYI
LGRESPLSLY NEELVSMNVQ GDYEPIDATG FININSLRLK EYHRLQSKVT AK
