UniProt Accession

 PUR8_HUMAN; P30566; B0QY76; O75495; Q5TI34 

Genbank Protein ID

 X65867; X65867; AF067853; AF067854; CR456368; AL022238; AL022238; CH471095; BC000253; S60710 

Genbank Nucleotide ID

 CAA46696.1; CAA46697.1; AAC21560.1; AAC21561.1; CAG30254.1; CAI18983.1; CAQ08930.1; EAW60375.1; AAH00253.1; AAC60603.1 

Protein Name

 Adenylosuccinate lyase 

Protein Synonyms/Alias

 ASL; Adenylosuccinase; ASase 

Gene Name

 ADSL 

Gene Synonyms/Alias

 AMPS 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
75	NLENIDFKMAAEEEK	ubiquitination	[1]
134	ALDLLLPKLARVISR	ubiquitination	[1, 2]
147	SRLADFAKERASLPT	acetylation	[3]
147	SRLADFAKERASLPT	ubiquitination	[1]
170	AQLTTVGKRCCLWIQ	ubiquitination	[1, 4]
199	DLRFRGVKGTTGTQA	ubiquitination	[1]
218	LFEGDDHKVEQLDKM	ubiquitination	[1]
229	LDKMVTEKAGFKRAF	ubiquitination	[1]
276	IRLLANLKEMEEPFE	ubiquitination	[1]
284	EMEEPFEKQQIGSSA	ubiquitination	[1]
295	GSSAMPYKRNPMRSE	acetylation	[3]
295	GSSAMPYKRNPMRSE	ubiquitination	[1]
391	NIIMAMVKAGGSRQD	ubiquitination	[1]
415	QQAASVVKQEGGDND	ubiquitination	[1]
470	EEVYPLLKPYESVMK	ubiquitination	[1]
479	YESVMKVKAELCL**	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [3] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473] 

Functional Description

 Catalyzes two non-sequential steps in de novo AMP synthesis: converts (S)-2-(5-amino-1-(5-phospho-D- ribosyl)imidazole-4-carboxamido)succinate (SAICAR) to fumarate plus 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, and thereby also contributes to de novo IMP synthesis, and converts succinyladenosine monophosphate (SAMP) to AMP and fumarate. 

Sequence Annotation

 REGION 20 21 Substrate binding; shared with
 REGION 85 87 Substrate binding.
 REGION 111 112 Substrate binding.
 ACT_SITE 159 159 Proton donor/acceptor.
 ACT_SITE 289 289 Proton donor/acceptor.
 BINDING 241 241 Substrate.
 BINDING 303 303 Substrate; shared with neighboring
 BINDING 329 329 Substrate.
 BINDING 334 334 Substrate.
 BINDING 338 338 Substrate.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 147 147 N6-acetyllysine.
 MOD_RES 295 295 N6-acetyllysine.  

Keyword

 3D-structure; Acetylation; Alternative splicing; Complete proteome; Direct protein sequencing; Disease mutation; Epilepsy; Lyase; Purine biosynthesis; Reference proteome. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 484 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005739; C:mitochondrion; IEA:Compara.
 GO:0070626; F:(S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate AMP-lyase (fumarate-forming) activity; IEA:EC.
 GO:0004018; F:N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity; IDA:UniProtKB.
 GO:0044208; P:'de novo' AMP biosynthetic process; IEA:UniProtKB-UniPathway.
 GO:0006189; P:'de novo' IMP biosynthetic process; IEA:UniProtKB-UniPathway.
 GO:0009060; P:aerobic respiration; IEA:Compara.
 GO:0006167; P:AMP biosynthetic process; IDA:UniProtKB.
 GO:0051262; P:protein tetramerization; IDA:UniProtKB.
 GO:0006144; P:purine nucleobase metabolic process; TAS:Reactome.
 GO:0001666; P:response to hypoxia; IEA:Compara.
 GO:0014850; P:response to muscle activity; IEA:Compara.
 GO:0007584; P:response to nutrient; IEA:Compara.
 GO:0042594; P:response to starvation; IEA:Compara. 

Interpro

 IPR019468; AdenyloSucc_lyase_C.
 IPR003031; D_crystallin.
 IPR024083; Fumarase/histidase_N.
 IPR000362; Fumarate_lyase.
 IPR020557; Fumarate_lyase_CS.
 IPR022761; Fumarate_lyase_N.
 IPR008948; L-Aspartase-like.
 IPR004769; Pur_lyase. 

Pfam

 PF10397; ADSL_C
 PF00206; Lyase_1 

SMART

 SM00998; ADSL_C 

PROSITE

 PS00163; FUMARATE_LYASES 

PRINTS

 PR00145; ARGSUCLYASE.
 PR00149; FUMRATELYASE.