ARLY_MOUSE
ID ARLY_MOUSE Reviewed; 464 AA.
AC Q91YI0; Q3UFA2;
DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Argininosuccinate lyase;
DE Short=ASAL;
DE EC=4.3.2.1 {ECO:0000250|UniProtKB:P04424};
DE AltName: Full=Arginosuccinase;
GN Name=Asl;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RC TISSUE=Corpora quadrigemina, Head, Liver, and Sympathetic ganglion;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 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 [4]
RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH ASS1; SLC7A1; HSP90AA1;
RP NOS1; NOS2 AND 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 [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 AND LYS-7, CLEAVAGE OF
RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Catalyzes the reversible cleavage of L-argininosuccinate to
CC fumarate and L-arginine, an intermediate step reaction in the urea
CC cycle mostly providing for hepatic nitrogen detoxification into
CC excretable urea as well as de novo L-arginine synthesis in nonhepatic
CC tissues (By similarity). Essential regulator of intracellular and
CC extracellular L-arginine pools. As part of citrulline-nitric oxide
CC cycle, forms tissue-specific multiprotein complexes with
CC argininosuccinate synthase ASS1, transport protein SLC7A1 and nitric
CC oxide synthase NOS1, NOS2 or NOS3, allowing for cell-autonomous L-
CC arginine synthesis while channeling extracellular L-arginine to nitric
CC oxide synthesis pathway (PubMed:22081021).
CC {ECO:0000250|UniProtKB:P04424, ECO:0000269|PubMed:22081021}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(N(omega)-L-arginino)succinate = fumarate + L-arginine;
CC Xref=Rhea:RHEA:24020, ChEBI:CHEBI:29806, ChEBI:CHEBI:32682,
CC ChEBI:CHEBI:57472; EC=4.3.2.1;
CC Evidence={ECO:0000250|UniProtKB:P04424};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24021;
CC Evidence={ECO:0000250|UniProtKB:P04424};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24022;
CC Evidence={ECO:0000250|UniProtKB:P04424};
CC -!- ACTIVITY REGULATION: Enzyme activity is regulated by acetylation.
CC {ECO:0000250|UniProtKB:P04424}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine
CC from L-ornithine and carbamoyl phosphate: step 3/3.
CC {ECO:0000250|UniProtKB:P04424}.
CC -!- PATHWAY: Nitrogen metabolism; urea cycle; L-arginine and fumarate from
CC (N(omega)-L-arginino)succinate: step 1/1.
CC {ECO:0000250|UniProtKB:P04424}.
CC -!- SUBUNIT: Homotetramer (By similarity). Forms tissue-specific complexes
CC with ASS1, SLC7A1, HSP90AA1 and nitric oxide synthase NOS1, NOS2 or
CC NOS3; the complex maintenance is independent of ASL catalytic function
CC (PubMed:22081021). {ECO:0000250|UniProtKB:P04424,
CC ECO:0000269|PubMed:22081021}.
CC -!- TISSUE SPECIFICITY: Expressed in lung and brain (at protein level).
CC {ECO:0000269|PubMed:22081021}.
CC -!- PTM: Acetylation modifies enzyme activity in response to alterations of
CC extracellular nutrient availability. Acetylation increased with
CC trichostin A (TSA) or with nicotinamide (NAM). Glucose increases
CC acetylation by about a factor of 3 with decreasing enzyme activity.
CC Acetylation on Lys-288 is decreased on the addition of extra amino
CC acids resulting in activation of enzyme activity.
CC {ECO:0000250|UniProtKB:P04424}.
CC -!- SIMILARITY: Belongs to the lyase 1 family. Argininosuccinate lyase
CC subfamily. {ECO:0000305}.
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DR EMBL; AK076453; BAC36348.1; -; mRNA.
DR EMBL; AK140160; BAE24262.1; -; mRNA.
DR EMBL; AK148764; BAE28659.1; -; mRNA.
DR EMBL; AK168739; BAE40580.1; -; mRNA.
DR EMBL; BC016670; AAH16670.1; -; mRNA.
DR CCDS; CCDS51655.1; -.
DR RefSeq; NP_598529.1; NM_133768.5.
DR RefSeq; XP_006504404.1; XM_006504341.3.
DR AlphaFoldDB; Q91YI0; -.
DR SMR; Q91YI0; -.
DR BioGRID; 225136; 6.
DR STRING; 10090.ENSMUSP00000124274; -.
DR CarbonylDB; Q91YI0; -.
DR iPTMnet; Q91YI0; -.
DR MetOSite; Q91YI0; -.
DR PhosphoSitePlus; Q91YI0; -.
DR EPD; Q91YI0; -.
DR jPOST; Q91YI0; -.
DR MaxQB; Q91YI0; -.
DR PaxDb; Q91YI0; -.
DR PRIDE; Q91YI0; -.
DR ProteomicsDB; 282021; -.
DR DNASU; 109900; -.
DR Ensembl; ENSMUST00000159619; ENSMUSP00000123799; ENSMUSG00000025533.
DR Ensembl; ENSMUST00000160129; ENSMUSP00000124579; ENSMUSG00000025533.
DR Ensembl; ENSMUST00000161094; ENSMUSP00000124274; ENSMUSG00000025533.
DR GeneID; 109900; -.
DR KEGG; mmu:109900; -.
DR UCSC; uc008zty.1; mouse.
DR CTD; 435; -.
DR MGI; MGI:88084; Asl.
DR VEuPathDB; HostDB:ENSMUSG00000025533; -.
DR eggNOG; KOG1316; Eukaryota.
DR GeneTree; ENSGT00950000183122; -.
DR HOGENOM; CLU_027272_2_1_1; -.
DR InParanoid; Q91YI0; -.
DR OMA; KKNPDVF; -.
DR OrthoDB; 1074729at2759; -.
DR PhylomeDB; Q91YI0; -.
DR TreeFam; TF300656; -.
DR Reactome; R-MMU-70635; Urea cycle.
DR UniPathway; UPA00068; UER00114.
DR UniPathway; UPA00158; UER00273.
DR BioGRID-ORCS; 109900; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Asl; mouse.
DR PRO; PR:Q91YI0; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q91YI0; protein.
DR Bgee; ENSMUSG00000025533; Expressed in left lobe of liver and 248 other tissues.
DR ExpressionAtlas; Q91YI0; baseline and differential.
DR Genevisible; Q91YI0; 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; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0004056; F:argininosuccinate lyase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019676; P:ammonia assimilation cycle; IMP:MGI.
DR GO; GO:0006526; P:arginine biosynthetic process; IMP:UniProtKB.
DR GO; GO:0042450; P:arginine biosynthetic process via ornithine; IBA:GO_Central.
DR GO; GO:0006525; P:arginine metabolic process; ISO:MGI.
DR GO; GO:0000053; P:argininosuccinate metabolic process; ISO:MGI.
DR GO; GO:0006520; P:cellular amino acid metabolic process; IMP:MGI.
DR GO; GO:0001889; P:liver development; ISO:MGI.
DR GO; GO:0007626; P:locomotory behavior; IMP:MGI.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0000050; P:urea cycle; ISO:MGI.
DR CDD; cd01359; Argininosuccinate_lyase; 1.
DR Gene3D; 1.10.275.10; -; 1.
DR HAMAP; MF_00006; Arg_succ_lyase; 1.
DR InterPro; IPR029419; Arg_succ_lyase_C.
DR InterPro; IPR009049; Argininosuccinate_lyase.
DR InterPro; IPR024083; Fumarase/histidase_N.
DR InterPro; IPR020557; Fumarate_lyase_CS.
DR InterPro; IPR000362; Fumarate_lyase_fam.
DR InterPro; IPR022761; Fumarate_lyase_N.
DR InterPro; IPR008948; L-Aspartase-like.
DR PANTHER; PTHR43814; PTHR43814; 1.
DR Pfam; PF14698; ASL_C2; 1.
DR Pfam; PF00206; Lyase_1; 1.
DR PRINTS; PR00149; FUMRATELYASE.
DR SUPFAM; SSF48557; SSF48557; 1.
DR TIGRFAMs; TIGR00838; argH; 1.
DR PROSITE; PS00163; FUMARATE_LYASES; 1.
PE 1: Evidence at protein level;
KW Acetylation; Amino-acid biosynthesis; Arginine biosynthesis; Lyase;
KW Reference proteome; Urea cycle.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CHAIN 2..464
FT /note="Argininosuccinate lyase"
FT /id="PRO_0000137714"
FT ACT_SITE 160
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P24058"
FT ACT_SITE 281
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P24058"
FT BINDING 27
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain A"
FT /evidence="ECO:0000250|UniProtKB:P24058"
FT BINDING 114
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain A"
FT /evidence="ECO:0000250|UniProtKB:P24058"
FT BINDING 159
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain C"
FT /evidence="ECO:0000250|UniProtKB:P24058"
FT BINDING 289
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain B"
FT /evidence="ECO:0000250|UniProtKB:P24058"
FT BINDING 321
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain A"
FT /evidence="ECO:0000250|UniProtKB:P24058"
FT BINDING 326
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain A"
FT /evidence="ECO:0000250|UniProtKB:P24058"
FT BINDING 329
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain A"
FT /evidence="ECO:0000250|UniProtKB:P24058"
FT SITE 294
FT /note="Increases basicity of active site His"
FT /evidence="ECO:0000250|UniProtKB:P24058"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 7
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 69
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04424"
FT MOD_RES 288
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04424"
SQ SEQUENCE 464 AA; 51739 MW; A78ABC52A9285A59 CRC64;
MASESGKLWG GRFVGAVDPI MEKFNSSISY DRHLWNVDVQ GSKAYSRGLE KAGLLTKAEM
QQILQGLDKV AEEWAQGTFK LHPNDEDIHT ANERRLKELI GEAAGKLHTG RSRNDQVVTD
LRLWMRQTCS KLSALLRVLI GTMVDRAEAE RDVLFPGYTH LQRAQPIRWS HWILSHAVAL
TRDSERLLEV QKRINVLPLG SGAIAGNPLG VDRELLRAEL NFGAITLNSM DATSERDFVA
EFLFWASLCM THLSRMAEDL ILYGTKEFSF VQLSDAYSTG SSLMPQKKNP DSLELIRSKA
GRVFGRCAGL LMTLKGLPST YNKDLQEDKE AVFEVSDTMI AVLQVATGVI STLQIHRENM
KQALSPDMLA TDLAYYLVRK GMPFRQAHEA SGKAVFMAET KGVALNLLSL QELQTISPLF
SGDVSHVWDY SHSVEQYSAL GGTAKSSVEW QIRQVRALLQ AQEP
