PUR8_HUMAN
ID PUR8_HUMAN Reviewed; 484 AA.
AC P30566; B0QY76; O75495; Q5TI34;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Adenylosuccinate lyase {ECO:0000303|PubMed:8404037};
DE Short=ADSL {ECO:0000303|PubMed:8404037};
DE Short=ASL;
DE EC=4.3.2.2 {ECO:0000269|PubMed:16973378, ECO:0000269|PubMed:22812634};
DE AltName: Full=Adenylosuccinase {ECO:0000303|PubMed:9266401};
DE Short=ASase;
GN Name=ADSL; Synonyms=AMPS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8404037; DOI=10.1159/000133575;
RA Fon E.A., Demczuk S., Delattre O., Thomas G., Rouleau G.A.;
RT "Mapping of the human adenylosuccinate lyase (ADSL) gene to chromosome
RT 22q13.1-->q13.2.";
RL Cytogenet. Cell Genet. 64:201-203(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND VARIANTS ADSLD
RP VAL-3; HIS-114; GLN-190; CYS-194; ASN-268; HIS-426 AND ASN-430.
RC TISSUE=Skeletal muscle;
RX PubMed=10888601; DOI=10.1093/hmg/9.10.1501;
RA Kmoch S., Hartmannova H., Stiburkova B., Krijt J., Zikanova M., Sebesta I.;
RT "Human adenylosuccinate lyase (ADSL), cloning and characterization of full-
RT length cDNA and its isoform, gene structure and molecular basis for ADSL
RT deficiency in six patients.";
RL Hum. Mol. Genet. 9:1501-1513(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-484 (ISOFORM 1), AND VARIANT ADSLD PRO-438.
RX PubMed=1302001; DOI=10.1038/ng0492-59;
RA Stone R.L., Aimi J., Barshop B.A., Jaeken J., van den Berghe G., Zalkin H.,
RA Dixon J.E.;
RT "A mutation in adenylosuccinate lyase associated with mental retardation
RT and autistic features.";
RL Nat. Genet. 1:59-63(1992).
RN [8]
RP PROTEIN SEQUENCE OF 2-20 AND 235-245, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Ramsay A., Leung H.Y.;
RL Submitted (JUN-2009) to UniProtKB.
RN [9]
RP CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=16973378; DOI=10.1016/j.pep.2006.07.023;
RA Lee P., Colman R.F.;
RT "Expression, purification, and characterization of stable, recombinant
RT human adenylosuccinate lyase.";
RL Protein Expr. Purif. 51:227-234(2007).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-147 AND LYS-295, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-415, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE;
RP FUMARATE AND AMP.
RG Structural genomics consortium (SGC);
RT "Human adenylosuccinate lyase in complex with its substrate N6-(1,2-
RT dicarboxyethyl)-AMP, and its products AMP and fumarate.";
RL Submitted (SEP-2007) to the PDB data bank.
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF WILD-TYPE AND VARIANT ADSLD
RP CYS-303, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANT ADSLD CYS-303,
RP ACTIVE SITE, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=22812634; DOI=10.1021/bi300796y;
RA Ray S.P., Deaton M.K., Capodagli G.C., Calkins L.A., Sawle L., Ghosh K.,
RA Patterson D., Pegan S.D.;
RT "Structural and biochemical characterization of human adenylosuccinate
RT lyase (ADSL) and the R303C ADSL deficiency-associated mutation.";
RL Biochemistry 51:6701-6713(2012).
RN [16]
RP VARIANT ADSLD HIS-426.
RX PubMed=9266401; DOI=10.1023/a:1005323512982;
RA Maaswinkel-Mooij P.D., Laan L.A.E.M., Onkenhout W., Brouwer O.F.,
RA Jaeken J., Poorthuis B.J.H.M.;
RT "Adenylosuccinase deficiency presenting with epilepsy in early infancy.";
RL J. Inherit. Metab. Dis. 20:606-607(1997).
RN [17]
RP VARIANTS ADSLD ALA-100 AND TYR-422.
RX PubMed=9545543; DOI=10.1016/s0925-4439(97)00086-0;
RA Verginelli D., Luckow B., Crifo C., Salerno C., Gross M.;
RT "Identification of new mutations in the adenylosuccinate lyase gene
RT associated with impaired enzyme activity in lymphocytes and red blood
RT cells.";
RL Biochim. Biophys. Acta 1406:81-84(1998).
RN [18]
RP VARIANTS ADSLD VAL-72; TRP-141; GLN-190; GLU-246; CYS-303; ARG-395 AND
RP HIS-426.
RX PubMed=10090474;
RX DOI=10.1002/(sici)1098-1004(1999)13:3<197::aid-humu3>3.0.co;2-d;
RA Marie S., Cuppens H., Heuterspreute M., Jaspers M., Tola E.Z., Gu X.X.,
RA Legius E., Vincent M.-F., Jaeken J., Cassiman J.-J., van den Berghe G.;
RT "Mutation analysis in adenylosuccinate lyase deficiency: eight novel
RT mutations in the re-evaluated full ADSL coding sequence.";
RL Hum. Mutat. 13:197-202(1999).
RN [19]
RP CHARACTERIZATION OF VARIANTS ADSLD VAL-2; LEU-26; TRP-141; CYS-303;
RP ARG-395; HIS-426 AND SER-450.
RX PubMed=10958654; DOI=10.1093/hmg/9.14.2159;
RA Race V., Marie S., Vincent M.-F., Van den Berghe G.;
RT "Clinical, biochemical and molecular genetic correlations in
RT adenylosuccinate lyase deficiency.";
RL Hum. Mol. Genet. 9:2159-2165(2000).
RN [20]
RP VARIANTS ADSLD VAL-311; MET-364; HIS-396 AND PRO-452.
RX PubMed=12368987; DOI=10.1055/s-2002-34493;
RA Castro M., Perez-Cerda C., Merinero B., Garcia M.J., Bernar J.,
RA Gil Nagel A., Torres J., Bermudez M., Garavito P., Marie S., Vincent F.,
RA Van den Berghe G., Ugarte M.;
RT "Screening for adenylosuccinate lyase deficiency: clinical, biochemical and
RT molecular findings in four patients.";
RL Neuropediatrics 33:186-189(2002).
RN [21]
RP VARIANT ADSLD HIS-426.
RX PubMed=12833398; DOI=10.1002/ajmg.a.20176;
RA Edery P., Chabrier S., Ceballos-Picot I., Marie S., Vincent M.-F.,
RA Tardieu M.;
RT "Intrafamilial variability in the phenotypic expression of adenylosuccinate
RT lyase deficiency: a report on three patients.";
RL Am. J. Med. Genet. A 120:185-190(2003).
RN [22]
RP CHARACTERIZATION OF VARIANTS ADSLD CYS-194; GLU-246; VAL-311; CYS-396 AND
RP HIS-396, AND ACTIVITY REGULATION.
RX PubMed=19405474; DOI=10.1021/bi802321m;
RA Ariyananda Lde Z., Lee P., Antonopoulos C., Colman R.F.;
RT "Biochemical and biophysical analysis of five disease-associated human
RT adenylosuccinate lyase mutants.";
RL Biochemistry 48:5291-5302(2009).
CC -!- FUNCTION: Catalyzes two non-sequential steps in de novo AMP synthesis:
CC converts (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-
CC carboxamido)succinate (SAICAR) to fumarate plus 5-amino-1-(5-phospho-D-
CC ribosyl)imidazole-4-carboxamide, and thereby also contributes to de
CC novo IMP synthesis, and converts succinyladenosine monophosphate (SAMP)
CC to AMP and fumarate. {ECO:0000269|PubMed:10888601}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-(1,2-dicarboxyethyl)-AMP = AMP + fumarate;
CC Xref=Rhea:RHEA:16853, ChEBI:CHEBI:29806, ChEBI:CHEBI:57567,
CC ChEBI:CHEBI:456215; EC=4.3.2.2;
CC Evidence={ECO:0000269|PubMed:16973378, ECO:0000269|PubMed:22812634};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S)-2-[5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-
CC carboxamido]succinate = 5-amino-1-(5-phospho-beta-D-
CC ribosyl)imidazole-4-carboxamide + fumarate; Xref=Rhea:RHEA:23920,
CC ChEBI:CHEBI:29806, ChEBI:CHEBI:58443, ChEBI:CHEBI:58475; EC=4.3.2.2;
CC Evidence={ECO:0000269|PubMed:16973378, ECO:0000269|PubMed:22812634};
CC -!- ACTIVITY REGULATION: The enzyme reaction kinetics indicate
CC cooperativity between subunits. {ECO:0000269|PubMed:19405474,
CC ECO:0000269|PubMed:22812634}.
CC -!- PATHWAY: Purine metabolism; AMP biosynthesis via de novo pathway; AMP
CC from IMP: step 2/2.
CC -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; 5-
CC amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-
CC phospho-D-ribosyl)imidazole-4-carboxylate: step 2/2.
CC -!- SUBUNIT: Homotetramer. Residues from neighboring subunits contribute
CC catalytic and substrate-binding residues to each active site.
CC {ECO:0000269|PubMed:16973378, ECO:0000269|PubMed:22812634}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P30566-1; Sequence=Displayed;
CC Name=2; Synonyms=Delta-ADSL;
CC IsoId=P30566-2; Sequence=VSP_000318;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Both isoforms are produced
CC by all tissues. Isoform 2 is 10-fold less abundant than isoform 1.
CC -!- DISEASE: Adenylosuccinase deficiency (ADSLD) [MIM:103050]: An autosomal
CC recessive disorder characterized by the accumulation in the body fluids
CC of succinylaminoimidazole-carboxamide riboside (SAICA-riboside) and
CC succinyladenosine (S-Ado). Most children display marked psychomotor
CC delay, often accompanied by epilepsy or autistic features, or both,
CC although some patients may be less profoundly retarded. Occasionally,
CC growth retardation and muscular wasting are also present.
CC {ECO:0000269|PubMed:10090474, ECO:0000269|PubMed:10888601,
CC ECO:0000269|PubMed:10958654, ECO:0000269|PubMed:12368987,
CC ECO:0000269|PubMed:12833398, ECO:0000269|PubMed:1302001,
CC ECO:0000269|PubMed:19405474, ECO:0000269|PubMed:22812634,
CC ECO:0000269|PubMed:9266401, ECO:0000269|PubMed:9545543}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Lacks enzymatic activity. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the lyase 1 family. Adenylosuccinate lyase
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC60603.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA46697.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=ADSLdb; Note=Adenylosuccinate lyase mutations
CC database;
CC URL="http://www.icp.ucl.ac.be/adsldb/";
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DR EMBL; X65867; CAA46696.1; -; mRNA.
DR EMBL; X65867; CAA46697.1; ALT_INIT; mRNA.
DR EMBL; AF067853; AAC21560.1; -; mRNA.
DR EMBL; AF067854; AAC21561.1; -; mRNA.
DR EMBL; CR456368; CAG30254.1; -; mRNA.
DR EMBL; AL022238; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471095; EAW60375.1; -; Genomic_DNA.
DR EMBL; BC000253; AAH00253.1; -; mRNA.
DR EMBL; S60710; AAC60603.1; ALT_INIT; mRNA.
DR CCDS; CCDS14001.1; -. [P30566-1]
DR CCDS; CCDS46714.1; -. [P30566-2]
DR RefSeq; NP_000017.1; NM_000026.3. [P30566-1]
DR RefSeq; NP_001116850.1; NM_001123378.2. [P30566-2]
DR RefSeq; NP_001304852.1; NM_001317923.1.
DR PDB; 2J91; X-ray; 1.80 A; A/B/C/D=1-481.
DR PDB; 2VD6; X-ray; 2.00 A; A/B/C/D=1-481.
DR PDB; 4FFX; X-ray; 2.70 A; A/B/C/D=1-484.
DR PDB; 4FLC; X-ray; 2.60 A; A/B/C/D=1-484.
DR PDBsum; 2J91; -.
DR PDBsum; 2VD6; -.
DR PDBsum; 4FFX; -.
DR PDBsum; 4FLC; -.
DR AlphaFoldDB; P30566; -.
DR SASBDB; P30566; -.
DR SMR; P30566; -.
DR BioGRID; 106667; 250.
DR IntAct; P30566; 33.
DR MINT; P30566; -.
DR STRING; 9606.ENSP00000485525; -.
DR GlyGen; P30566; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P30566; -.
DR PhosphoSitePlus; P30566; -.
DR SwissPalm; P30566; -.
DR BioMuta; ADSL; -.
DR DMDM; 6686318; -.
DR EPD; P30566; -.
DR jPOST; P30566; -.
DR MassIVE; P30566; -.
DR MaxQB; P30566; -.
DR PaxDb; P30566; -.
DR PeptideAtlas; P30566; -.
DR PRIDE; P30566; -.
DR ProteomicsDB; 54723; -. [P30566-1]
DR ProteomicsDB; 54724; -. [P30566-2]
DR Antibodypedia; 34889; 253 antibodies from 27 providers.
DR DNASU; 158; -.
DR Ensembl; ENST00000342312.9; ENSP00000341429.6; ENSG00000239900.14. [P30566-2]
DR Ensembl; ENST00000623063.3; ENSP00000485525.1; ENSG00000239900.14. [P30566-1]
DR GeneID; 158; -.
DR KEGG; hsa:158; -.
DR MANE-Select; ENST00000623063.3; ENSP00000485525.1; NM_000026.4; NP_000017.1.
DR UCSC; uc003ays.5; human. [P30566-1]
DR CTD; 158; -.
DR DisGeNET; 158; -.
DR GeneCards; ADSL; -.
DR HGNC; HGNC:291; ADSL.
DR HPA; ENSG00000239900; Group enriched (skeletal muscle, tongue).
DR MalaCards; ADSL; -.
DR MIM; 103050; phenotype.
DR MIM; 608222; gene.
DR neXtProt; NX_P30566; -.
DR OpenTargets; ENSG00000239900; -.
DR Orphanet; 46; Adenylosuccinate lyase deficiency.
DR PharmGKB; PA24600; -.
DR VEuPathDB; HostDB:ENSG00000239900; -.
DR eggNOG; KOG2700; Eukaryota.
DR GeneTree; ENSGT00950000183122; -.
DR HOGENOM; CLU_030949_1_1_1; -.
DR InParanoid; P30566; -.
DR OMA; ASSCEKI; -.
DR OrthoDB; 904932at2759; -.
DR PhylomeDB; P30566; -.
DR TreeFam; TF106385; -.
DR BioCyc; MetaCyc:HS02059-MON; -.
DR BRENDA; 4.3.2.2; 2681.
DR PathwayCommons; P30566; -.
DR Reactome; R-HSA-73817; Purine ribonucleoside monophosphate biosynthesis.
DR SABIO-RK; P30566; -.
DR SignaLink; P30566; -.
DR SIGNOR; P30566; -.
DR UniPathway; UPA00074; UER00132.
DR UniPathway; UPA00075; UER00336.
DR BioGRID-ORCS; 158; 564 hits in 1087 CRISPR screens.
DR ChiTaRS; ADSL; human.
DR EvolutionaryTrace; P30566; -.
DR GeneWiki; Adenylosuccinate_lyase; -.
DR GenomeRNAi; 158; -.
DR Pharos; P30566; Tbio.
DR PRO; PR:P30566; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P30566; protein.
DR Bgee; ENSG00000239900; Expressed in hindlimb stylopod muscle and 98 other tissues.
DR ExpressionAtlas; P30566; baseline and differential.
DR Genevisible; P30566; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0070626; F:(S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido) succinate lyase (fumarate-forming) activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0004018; F:N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity; IDA:UniProtKB.
DR GO; GO:0044208; P:'de novo' AMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0006189; P:'de novo' IMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0097294; P:'de novo' XMP biosynthetic process; IEA:Ensembl.
DR GO; GO:0009060; P:aerobic respiration; IEA:Ensembl.
DR GO; GO:0006167; P:AMP biosynthetic process; IDA:UniProtKB.
DR GO; GO:0044209; P:AMP salvage; IEA:Ensembl.
DR GO; GO:0006177; P:GMP biosynthetic process; IEA:Ensembl.
DR GO; GO:0006164; P:purine nucleotide biosynthetic process; IC:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0014850; P:response to muscle activity; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0042594; P:response to starvation; IEA:Ensembl.
DR InterPro; IPR019468; AdenyloSucc_lyase_C.
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 InterPro; IPR004769; Pur_lyase.
DR Pfam; PF10397; ADSL_C; 1.
DR Pfam; PF00206; Lyase_1; 1.
DR PRINTS; PR00149; FUMRATELYASE.
DR SMART; SM00998; ADSL_C; 1.
DR SUPFAM; SSF48557; SSF48557; 1.
DR TIGRFAMs; TIGR00928; purB; 1.
DR PROSITE; PS00163; FUMARATE_LYASES; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing;
KW Disease variant; Epilepsy; Isopeptide bond; Lyase; Purine biosynthesis;
KW Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8"
FT CHAIN 2..484
FT /note="Adenylosuccinate lyase"
FT /id="PRO_0000137892"
FT ACT_SITE 159
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000269|PubMed:22812634"
FT ACT_SITE 289
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000269|PubMed:22812634"
FT BINDING 20..21
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT BINDING 85..87
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT BINDING 111..112
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT BINDING 241
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT BINDING 303
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT BINDING 329
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT BINDING 334
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT BINDING 338
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.8"
FT MOD_RES 147
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 295
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CROSSLNK 415
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0007744|PubMed:25114211"
FT VAR_SEQ 398..456
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10888601,
FT ECO:0000303|PubMed:15461802"
FT /id="VSP_000318"
FT VARIANT 2
FT /note="A -> V (in ADSLD; severe; dbSNP:rs143083947)"
FT /evidence="ECO:0000269|PubMed:10958654"
FT /id="VAR_016930"
FT VARIANT 3
FT /note="A -> V (in ADSLD; severe)"
FT /evidence="ECO:0000269|PubMed:10888601"
FT /id="VAR_017078"
FT VARIANT 26
FT /note="M -> L (in ADSLD; severe; dbSNP:rs1311171245)"
FT /evidence="ECO:0000269|PubMed:10958654"
FT /id="VAR_016931"
FT VARIANT 31
FT /note="S -> N (in dbSNP:rs5757921)"
FT /id="VAR_037883"
FT VARIANT 72
FT /note="I -> V (in ADSLD; severe)"
FT /evidence="ECO:0000269|PubMed:10090474"
FT /id="VAR_007972"
FT VARIANT 100
FT /note="P -> A (in ADSLD; moderate; dbSNP:rs119450942)"
FT /evidence="ECO:0000269|PubMed:9545543"
FT /id="VAR_017079"
FT VARIANT 114
FT /note="Y -> H (in ADSLD; severe; total loss of activity;
FT dbSNP:rs374259530)"
FT /evidence="ECO:0000269|PubMed:10888601"
FT /id="VAR_017080"
FT VARIANT 141
FT /note="R -> W (in ADSLD; severe; dbSNP:rs756210458)"
FT /evidence="ECO:0000269|PubMed:10090474,
FT ECO:0000269|PubMed:10958654"
FT /id="VAR_007973"
FT VARIANT 147
FT /note="K -> M (in dbSNP:rs11089991)"
FT /id="VAR_037884"
FT VARIANT 190
FT /note="R -> Q (in ADSLD; moderate; dbSNP:rs28941471)"
FT /evidence="ECO:0000269|PubMed:10090474,
FT ECO:0000269|PubMed:10888601"
FT /id="VAR_007974"
FT VARIANT 194
FT /note="R -> C (in ADSLD; severe; reduces protein stability;
FT dbSNP:rs1465152683)"
FT /evidence="ECO:0000269|PubMed:10888601,
FT ECO:0000269|PubMed:19405474"
FT /id="VAR_017081"
FT VARIANT 246
FT /note="K -> E (in ADSLD; moderate; strongly reduced
FT catalytic activity; dbSNP:rs119450944)"
FT /evidence="ECO:0000269|PubMed:10090474,
FT ECO:0000269|PubMed:19405474"
FT /id="VAR_007975"
FT VARIANT 268
FT /note="D -> N (in ADSLD; severe; total loss of activity;
FT dbSNP:rs746501563)"
FT /evidence="ECO:0000269|PubMed:10888601"
FT /id="VAR_017082"
FT VARIANT 303
FT /note="R -> C (in ADSLD; mild; strongly reduced activity
FT with SAMP, but only slightly reduced activity with SAICAR;
FT abolishes cooperativity; dbSNP:rs373458753)"
FT /evidence="ECO:0000269|PubMed:10090474,
FT ECO:0000269|PubMed:10958654, ECO:0000269|PubMed:22812634"
FT /id="VAR_007976"
FT VARIANT 311
FT /note="L -> V (in ADSLD; severe; slightly reduced enzyme
FT activity)"
FT /evidence="ECO:0000269|PubMed:12368987,
FT ECO:0000269|PubMed:19405474"
FT /id="VAR_017083"
FT VARIANT 318
FT /note="P -> L (in ADSLD; severe; dbSNP:rs202064195)"
FT /id="VAR_017084"
FT VARIANT 364
FT /note="V -> M (in ADSLD; severe; dbSNP:rs370851726)"
FT /evidence="ECO:0000269|PubMed:12368987"
FT /id="VAR_017085"
FT VARIANT 374
FT /note="R -> W (in ADSLD; severe; dbSNP:rs376533026)"
FT /id="VAR_017086"
FT VARIANT 395
FT /note="S -> R (in ADSLD; severe)"
FT /evidence="ECO:0000269|PubMed:10090474,
FT ECO:0000269|PubMed:10958654"
FT /id="VAR_007977"
FT VARIANT 396
FT /note="R -> C (in ADSLD; severe; abolishes cooperativity
FT and reduces enzyme activity; dbSNP:rs755492501)"
FT /evidence="ECO:0000269|PubMed:19405474"
FT /id="VAR_017087"
FT VARIANT 396
FT /note="R -> H (in ADSLD; severe; abolishes cooperativity
FT and reduces enzyme activity; dbSNP:rs763542069)"
FT /evidence="ECO:0000269|PubMed:12368987,
FT ECO:0000269|PubMed:19405474"
FT /id="VAR_017088"
FT VARIANT 422
FT /note="D -> Y (in ADSLD; moderate; dbSNP:rs119450943)"
FT /evidence="ECO:0000269|PubMed:9545543"
FT /id="VAR_017089"
FT VARIANT 423
FT /note="L -> V (in ADSLD; moderate)"
FT /id="VAR_017090"
FT VARIANT 426
FT /note="R -> H (in ADSLD; severe; most frequent mutation;
FT dbSNP:rs119450941)"
FT /evidence="ECO:0000269|PubMed:10090474,
FT ECO:0000269|PubMed:10888601, ECO:0000269|PubMed:10958654,
FT ECO:0000269|PubMed:12833398, ECO:0000269|PubMed:9266401"
FT /id="VAR_007978"
FT VARIANT 430
FT /note="D -> N (in ADSLD; mild; dbSNP:rs554254383)"
FT /evidence="ECO:0000269|PubMed:10888601"
FT /id="VAR_017091"
FT VARIANT 438
FT /note="S -> P (in ADSLD; severe; dbSNP:rs119450940)"
FT /evidence="ECO:0000269|PubMed:1302001"
FT /id="VAR_000680"
FT VARIANT 447
FT /note="S -> P (in ADSLD; severe; dbSNP:rs777821034)"
FT /id="VAR_017092"
FT VARIANT 450
FT /note="T -> S (in ADSLD; moderate; dbSNP:rs372895468)"
FT /evidence="ECO:0000269|PubMed:10958654"
FT /id="VAR_016932"
FT VARIANT 452
FT /note="R -> P (in ADSLD; severe)"
FT /evidence="ECO:0000269|PubMed:12368987"
FT /id="VAR_017093"
FT HELIX 16..19
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 24..29
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 32..53
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 59..66
FT /evidence="ECO:0007829|PDB:2J91"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:4FFX"
FT HELIX 74..84
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 87..98
FT /evidence="ECO:0007829|PDB:2J91"
FT TURN 100..102
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:2J91"
FT TURN 106..109
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 113..148
FT /evidence="ECO:0007829|PDB:2J91"
FT TURN 149..151
FT /evidence="ECO:0007829|PDB:2J91"
FT STRAND 153..158
FT /evidence="ECO:0007829|PDB:2J91"
FT STRAND 161..167
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 168..192
FT /evidence="ECO:0007829|PDB:2J91"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:4FLC"
FT HELIX 206..211
FT /evidence="ECO:0007829|PDB:2J91"
FT TURN 212..214
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 216..229
FT /evidence="ECO:0007829|PDB:2J91"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 246..274
FT /evidence="ECO:0007829|PDB:2J91"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 299..313
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 316..323
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 331..333
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 334..360
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 366..380
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 382..389
FT /evidence="ECO:0007829|PDB:2J91"
FT TURN 391..393
FT /evidence="ECO:0007829|PDB:4FLC"
FT HELIX 396..416
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 423..429
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 431..433
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 434..437
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 440..443
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 446..449
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 453..463
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 465..469
FT /evidence="ECO:0007829|PDB:2J91"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:2J91"
SQ SEQUENCE 484 AA; 54889 MW; 7AA3A0A2C681FD94 CRC64;
MAAGGDHGSP DSYRSPLASR YASPEMCFVF SDRYKFRTWR QLWLWLAEAE QTLGLPITDE
QIQEMKSNLE NIDFKMAAEE EKRLRHDVMA HVHTFGHCCP KAAGIIHLGA TSCYVGDNTD
LIILRNALDL LLPKLARVIS RLADFAKERA SLPTLGFTHF QPAQLTTVGK RCCLWIQDLC
MDLQNLKRVR DDLRFRGVKG TTGTQASFLQ LFEGDDHKVE QLDKMVTEKA GFKRAFIITG
QTYTRKVDIE VLSVLASLGA SVHKICTDIR LLANLKEMEE PFEKQQIGSS AMPYKRNPMR
SERCCSLARH LMTLVMDPLQ TASVQWFERT LDDSANRRIC LAEAFLTADT ILNTLQNISE
GLVVYPKVIE RRIRQELPFM ATENIIMAMV KAGGSRQDCH EKIRVLSQQA ASVVKQEGGD
NDLIERIQVD AYFSPIHSQL DHLLDPSSFT GRASQQVQRF LEEEVYPLLK PYESVMKVKA
ELCL
