P30566 (PUR8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Adenylosuccinate lyase
Short name=ASL
EC=4.3.2.2

Alternative name(s):
Adenylosuccinase
Short name=ASase

Gene names

Name:	ADSL
Synonyms:	AMPS

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	484 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Catalytic activity	N(6)-(1,2-dicarboxyethyl)AMP = fumarate + AMP. Ref.9 Ref.13 (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate = fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide. Ref.9 Ref.13
Enzyme regulation	The enzyme reaction kinetics indicate cooperativity between subunits. Ref.13 Ref.20
Pathway	Purine metabolism; AMP biosynthesis via de novo pathway; AMP from IMP: step 2/2. Purine metabolism; IMP biosynthesis via de novo pathway; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate: step 2/2.
Subunit structure	Homotetramer. Residues from neighboring subunits contribute catalytic and substrate-binding residues to each active site. Ref.9 Ref.13
Tissue specificity	Ubiquitously expressed. Both isoforms are produced by all tissues. Isoform 2 is 10-fold less abundant than isoform 1.
Involvement in disease	Adenylosuccinase deficiency (ADSL deficiency) [MIM:103050]: An autosomal recessive disorder characterized by the accumulation in the body fluids of succinylaminoimidazole-carboxamide riboside (SAICA-riboside) and succinyladenosine (S-Ado). Most children display marked psychomotor delay, often accompanied by epilepsy or autistic features, or both, although some patients may be less profoundly retarded. Occasionally, growth retardation and muscular wasting are also present. Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities	Belongs to the lyase 1 family. Adenylosuccinate lyase subfamily.
Sequence caution	The sequence AAC60603.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence CAA46697.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Purine biosynthesis
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Epilepsy
Molecular function	Lyase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	'de novo' AMP biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway 'de novo' IMP biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway AMP biosynthetic process Inferred from direct assay PubMed 11428554. Source: UniProtKB aerobic respiration Inferred from electronic annotation. Source: Compara protein tetramerization Inferred from direct assay Ref.9. Source: UniProtKB purine nucleobase metabolic process Traceable author statement. Source: Reactome response to hypoxia Inferred from electronic annotation. Source: Compara response to muscle activity Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara response to starvation Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	(S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate AMP-lyase (fumarate-forming) activity Inferred from electronic annotation. Source: EC N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity Inferred from direct assay Ref.9Ref.2. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P30566-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P30566-2)

Also known as: Delta-ADSL;

The sequence of this isoform differs from the canonical sequence as follows:
     398-456: Missing.

Note: Lacks enzymatic activity.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 484

483

Adenylosuccinate lyase

PRO_0000137892

Regions

Region

20 – 21

2

Substrate binding; shared with neighboring subunit

Region

85 – 87

3

Substrate binding

Region

111 – 112

2

Substrate binding

Sites

Active site

159

1

Proton donor/acceptor Ref.13

Active site

289

1

Proton donor/acceptor Ref.13

Binding site

241

1

Substrate

Binding site

303

1

Substrate; shared with neighboring subunit

Binding site

329

1

Substrate

Binding site

334

1

Substrate

Binding site

338

1

Substrate

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.8

Modified residue

147

1

N6-acetyllysine Ref.10

Modified residue

295

1

N6-acetyllysine Ref.10

Natural variations

Alternative sequence

398 – 456

59

Missing in isoform 2.

VSP_000318

Natural variant

2

1

A → V in ADSL deficiency; severe. Ref.17

VAR_016930

Natural variant

3

1

A → V in ADSL deficiency; severe. Ref.2

VAR_017078

Natural variant

26

1

M → L in ADSL deficiency; severe. Ref.17

VAR_016931

Natural variant

31

1

S → N.
Corresponds to variant rs5757921 [ dbSNP | Ensembl ].

VAR_037883

Natural variant

72

1

I → V in ADSL deficiency; severe. Ref.16

VAR_007972

Natural variant

100

1

P → A in ADSL deficiency; moderate. Ref.15

VAR_017079

Natural variant

114

1

Y → H in ADSL deficiency; severe. Total loss of activity. Ref.2

VAR_017080

Natural variant

141

1

R → W in ADSL deficiency; severe. Ref.16 Ref.17

VAR_007973

Natural variant

147

1

K → M.
Corresponds to variant rs11089991 [ dbSNP | Ensembl ].

VAR_037884

Natural variant

190

1

R → Q in ADSL deficiency; moderate. Ref.2 Ref.16
Corresponds to variant rs28941471 [ dbSNP | Ensembl ].

VAR_007974

Natural variant

194

1

R → C in ADSL deficiency; severe. Reduces protein stability. Ref.2 Ref.20

VAR_017081

Natural variant

246

1

K → E in ADSL deficiency; moderate. Strongly reduced catalytic activity. Ref.16 Ref.20

VAR_007975

Natural variant

268

1

D → N in ADSL deficiency; severe. Total loss of activity. Ref.2

VAR_017082

Natural variant

303

1

R → C in ADSL deficiency; mild. Strongly reduced activity with SAMP, but only slightly reduced activity with SAICAR. Abolishes cooperativity. Ref.13 Ref.16 Ref.17

VAR_007976

Natural variant

311

1

L → V in ADSL deficiency; severe. Slightly reduced enzyme activity. Ref.18 Ref.20

VAR_017083

Natural variant

318

1

P → L in ADSL deficiency; severe.

VAR_017084

Natural variant

364

1

V → M in ADSL deficiency; severe. Ref.18

VAR_017085

Natural variant

374

1

R → W in ADSL deficiency; severe.

VAR_017086

Natural variant

395

1

S → R in ADSL deficiency; severe. Ref.16 Ref.17

VAR_007977

Natural variant

396

1

R → C in ADSL deficiency; severe. Abolishes cooperativity and reduces enzyme activity. Ref.20

VAR_017087

Natural variant

396

1

R → H in ADSL deficiency; severe. Abolishes cooperativity and reduces enzyme activity. Ref.18 Ref.20

VAR_017088

Natural variant

422

1

D → Y in ADSL deficiency; moderate. Ref.15

VAR_017089

Natural variant

423

1

L → V in ADSL deficiency; moderate.

VAR_017090

Natural variant

426

1

R → H in ADSL deficiency; severe. Most frequent mutation. Ref.2 Ref.14 Ref.16 Ref.17 Ref.19

VAR_007978

Natural variant

430

1

D → N in ADSL deficiency; mild. Ref.2

VAR_017091

Natural variant

438

1

S → P in ADSL deficiency; severe. Ref.7

VAR_000680

Natural variant

447

1

S → P in ADSL deficiency; severe.

VAR_017092

Natural variant

450

1

T → S in ADSL deficiency; moderate. Ref.17

VAR_016932

Natural variant

452

1

R → P in ADSL deficiency; severe. Ref.18

VAR_017093

Secondary structure

1

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484

Helix Strand Turn

Details...

Helix

16 – 19

4

Helix

24 – 29

6

Helix

32 – 53

22

Helix

59 – 66

8

Beta strand

68 – 70

3

Helix

74 – 84

11

Helix

87 – 98

12

Turn

100 – 102

3

Helix

103 – 105

3

Turn

106 – 109

4

Helix

113 – 148

36

Turn

149 – 151

3

Beta strand

153 – 158

6

Beta strand

161 – 167

7

Helix

168 – 192

25

Beta strand

201 – 204

4

Helix

206 – 211

6

Turn

212 – 214

3

Helix

216 – 229

14

Beta strand

240 – 242

3

Helix

246 – 274

29

Beta strand

277 – 279

3

Helix

299 – 313

15

Helix

316 – 323

8

Helix

331 – 333

3

Helix

334 – 360

27

Helix

366 – 380

15

Helix

382 – 389

8

Helix

396 – 416

21

Helix

423 – 429

7

Helix

431 – 433

3

Helix

434 – 437

4

Helix

440 – 443

4

Helix

446 – 449

4

Helix

453 – 463

11

Helix

465 – 469

5

Helix

470 – 472

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 30, 2000. Version 2. Checksum: 7AA3A0A2C681FD94	FASTA	484	54,889
	10 20 30 40 50 60 MAAGGDHGSP DSYRSPLASR YASPEMCFVF SDRYKFRTWR QLWLWLAEAE QTLGLPITDE 70 80 90 100 110 120 QIQEMKSNLE NIDFKMAAEE EKRLRHDVMA HVHTFGHCCP KAAGIIHLGA TSCYVGDNTD 130 140 150 160 170 180 LIILRNALDL LLPKLARVIS RLADFAKERA SLPTLGFTHF QPAQLTTVGK RCCLWIQDLC 190 200 210 220 230 240 MDLQNLKRVR DDLRFRGVKG TTGTQASFLQ LFEGDDHKVE QLDKMVTEKA GFKRAFIITG 250 260 270 280 290 300 QTYTRKVDIE VLSVLASLGA SVHKICTDIR LLANLKEMEE PFEKQQIGSS AMPYKRNPMR 310 320 330 340 350 360 SERCCSLARH LMTLVMDPLQ TASVQWFERT LDDSANRRIC LAEAFLTADT ILNTLQNISE 370 380 390 400 410 420 GLVVYPKVIE RRIRQELPFM ATENIIMAMV KAGGSRQDCH EKIRVLSQQA ASVVKQEGGD 430 440 450 460 470 480 NDLIERIQVD AYFSPIHSQL DHLLDPSSFT GRASQQVQRF LEEEVYPLLK PYESVMKVKA ELCL
	Isoform 2 (Delta-ADSL) [UniParc]. Checksum: 66356963E46FDA3D	FASTA	425	48,328
	10 20 30 40 50 60 MAAGGDHGSP DSYRSPLASR YASPEMCFVF SDRYKFRTWR QLWLWLAEAE QTLGLPITDE 70 80 90 100 110 120 QIQEMKSNLE NIDFKMAAEE EKRLRHDVMA HVHTFGHCCP KAAGIIHLGA TSCYVGDNTD 130 140 150 160 170 180 LIILRNALDL LLPKLARVIS RLADFAKERA SLPTLGFTHF QPAQLTTVGK RCCLWIQDLC 190 200 210 220 230 240 MDLQNLKRVR DDLRFRGVKG TTGTQASFLQ LFEGDDHKVE QLDKMVTEKA GFKRAFIITG 250 260 270 280 290 300 QTYTRKVDIE VLSVLASLGA SVHKICTDIR LLANLKEMEE PFEKQQIGSS AMPYKRNPMR 310 320 330 340 350 360 SERCCSLARH LMTLVMDPLQ TASVQWFERT LDDSANRRIC LAEAFLTADT ILNTLQNISE 370 380 390 400 410 420 GLVVYPKVIE RRIRQELPFM ATENIIMAMV KAGGSRQVQR FLEEEVYPLL KPYESVMKVK AELCL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mapping of the human adenylosuccinate lyase (ADSL) gene to chromosome 22q13.1-->q13.2." Fon E.A., Demczuk S., Delattre O., Thomas G., Rouleau G.A. Cytogenet. Cell Genet. 64:201-203(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Human adenylosuccinate lyase (ADSL), cloning and characterization of full-length cDNA and its isoform, gene structure and molecular basis for ADSL deficiency in six patients." Kmoch S., Hartmannova H., Stiburkova B., Krijt J., Zikanova M., Sebesta I. Hum. Mol. Genet. 9:1501-1513(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS ADSL DEFICIENCY VAL-3; HIS-114; GLN-190; CYS-194; ASN-268; HIS-426 AND ASN-430. Tissue: Skeletal muscle.
[3]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Eye.
[7]	"A mutation in adenylosuccinate lyase associated with mental retardation and autistic features." Stone R.L., Aimi J., Barshop B.A., Jaeken J., van den Berghe G., Zalkin H., Dixon J.E. Nat. Genet. 1:59-63(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-484 (ISOFORM 1), VARIANT ADSL DEFICIENCY PRO-438.
[8]	Bienvenut W.V., Ramsay A., Leung H.Y. Submitted (JUN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-20 AND 235-245, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[9]	"Expression, purification, and characterization of stable, recombinant human adenylosuccinate lyase." Lee P., Colman R.F. Protein Expr. Purif. 51:227-234(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, SUBUNIT.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-147 AND LYS-295, MASS SPECTROMETRY.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"Human adenylosuccinate lyase in complex with its substrate N6-(1,2-dicarboxyethyl)-AMP, and its products AMP and fumarate." Structural genomics consortium (SGC) Submitted (SEP-2007) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE; FUMARATE AND AMP.
[13]	"Structural and biochemical characterization of human adenylosuccinate lyase (ADSL) and the R303C ADSL deficiency-associated mutation." Ray S.P., Deaton M.K., Capodagli G.C., Calkins L.A., Sawle L., Ghosh K., Patterson D., Pegan S.D. Biochemistry 51:6701-6713(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF WILD-TYPE AND VARIANT ADSL DEFICIENCY CYS-303, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANT ADSL DEFICIENCY CYS-303, ACTIVE SITE, ENZYME REGULATION, SUBUNIT.
[14]	"Adenylosuccinase deficiency presenting with epilepsy in early infancy." Maaswinkel-Mooij P.D., Laan L.A.E.M., Onkenhout W., Brouwer O.F., Jaeken J., Poorthuis B.J.H.M. J. Inherit. Metab. Dis. 20:606-607(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ADSL DEFICIENCY HIS-426.
[15]	"Identification of new mutations in the adenylosuccinate lyase gene associated with impaired enzyme activity in lymphocytes and red blood cells." Verginelli D., Luckow B., Crifo C., Salerno C., Gross M. Biochim. Biophys. Acta 1406:81-84(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ADSL DEFICIENCY ALA-100 AND TYR-422.
[16]	"Mutation analysis in adenylosuccinate lyase deficiency: eight novel mutations in the re-evaluated full ADSL coding sequence." Marie S., Cuppens H., Heuterspreute M., Jaspers M., Tola E.Z., Gu X.X., Legius E., Vincent M.-F., Jaeken J., Cassiman J.-J., van den Berghe G. Hum. Mutat. 13:197-202(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ADSL DEFICIENCY VAL-72; TRP-141; GLN-190; GLU-246; CYS-303; ARG-395 AND HIS-426.
[17]	"Clinical, biochemical and molecular genetic correlations in adenylosuccinate lyase deficiency." Race V., Marie S., Vincent M.-F., Van den Berghe G. Hum. Mol. Genet. 9:2159-2165(2000) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS ADSL DEFICIENCY VAL-2; LEU-26; TRP-141; CYS-303; ARG-395; HIS-426 AND SER-450.
[18]	"Screening for adenylosuccinate lyase deficiency: clinical, biochemical and molecular findings in four patients." Castro M., Perez-Cerda C., Merinero B., Garcia M.J., Bernar J., Gil Nagel A., Torres J., Bermudez M., Garavito P., Marie S., Vincent F., Van den Berghe G., Ugarte M. Neuropediatrics 33:186-189(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ADSL DEFICIENCY VAL-311; MET-364; HIS-396 AND PRO-452.
[19]	"Intrafamilial variability in the phenotypic expression of adenylosuccinate lyase deficiency: a report on three patients." Edery P., Chabrier S., Ceballos-Picot I., Marie S., Vincent M.-F., Tardieu M. Am. J. Med. Genet. A 120:185-190(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ADSL DEFICIENCY HIS-426.
[20]	"Biochemical and biophysical analysis of five disease-associated human adenylosuccinate lyase mutants." Ariyananda Lde Z., Lee P., Antonopoulos C., Colman R.F. Biochemistry 48:5291-5302(2009) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS ADSL DEFICIENCY CYS-194; GLU-246; VAL-311; CYS-396 AND HIS-396, ENZYME REGULATION.
+	Additional computationally mapped references.

Web resources

ADSLdb

Adenylosuccinate lyase mutations database

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X65867 mRNA. Translation: CAA46696.1.
X65867 mRNA. Translation: CAA46697.1. Different initiation.
AF067853 mRNA. Translation: AAC21560.1.
AF067854 mRNA. Translation: AAC21561.1.
CR456368 mRNA. Translation: CAG30254.1.
AL022238 Genomic DNA. Translation: CAI18983.1.
AL022238 Genomic DNA. Translation: CAQ08930.1.
CH471095 Genomic DNA. Translation: EAW60375.1.
BC000253 mRNA. Translation: AAH00253.1.
S60710 mRNA. Translation: AAC60603.1. Different initiation.

IPI

IPI00220887.
IPI00942092.

RefSeq

NP_000017.1. NM_000026.2.
NP_001116850.1. NM_001123378.1.

UniGene

Hs.75527.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2J91	X-ray	1.80	A/B/C/D	1-481	[»]
2VD6	X-ray	2.00	A/B/C/D	1-481	[»]
4FFX	X-ray	2.70	A/B/C/D	1-484	[»]
4FLC	X-ray	2.60	A/B/C/D	1-484	[»]

ProteinModelPortal

P30566.

ModBase

Search...

Protein-protein interaction databases

IntAct

P30566. 4 interactions.

STRING

9606.ENSP00000216194.

PTM databases

PhosphoSite

P30566.

Polymorphism databases

DMDM

6686318.

Proteomic databases

PaxDb

P30566.

PeptideAtlas

P30566.

PRIDE

P30566.

Protocols and materials databases

DNASU

158.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000216194; ENSP00000216194; ENSG00000239900.
ENST00000342312; ENSP00000341429; ENSG00000239900.

GeneID

158.

KEGG

hsa:158.

UCSC

uc003ayp.4. human.
uc003ays.4. human.

Organism-specific databases

CTD

158.

GeneCards

GC22P040742.

HGNC

HGNC:291. ADSL.

HPA

CAB019285.
HPA000525.

MIM

103050. phenotype.
608222. gene.

neXtProt

NX_P30566.

Orphanet

46. Adenylosuccinate lyase deficiency.

PharmGKB

PA24600.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0015.

HOGENOM

HOG000033915.

HOVERGEN

HBG000214.

InParanoid

P30566.

KO

K01756.

OrthoDB

EOG4QJRN2.

PhylomeDB

P30566.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00074; UER00132.
UPA00075; UER00336.

Gene expression databases

ArrayExpress

P30566.

Bgee

P30566.

CleanEx

HS_ADSL.

Genevestigator

P30566.

GermOnline

ENSG00000100357. Homo sapiens.

Family and domain databases

Gene3D

1.10.275.10. 1 hit.

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.
[Graphical view]

PANTHER

PTHR11444:SF2. PTHR11444:SF2. 1 hit.

Pfam

PF10397. ADSL_C. 1 hit.
PF00206. Lyase_1. 1 hit.
[Graphical view]

PRINTS

PR00145. ARGSUCLYASE.
PR00149. FUMRATELYASE.

SMART

SM00998. ADSL_C. 1 hit.
[Graphical view]

SUPFAM

SSF48557. L-Aspartase-like. 1 hit.

TIGRFAMs

TIGR00928. purB. 1 hit.

PROSITE

PS00163. FUMARATE_LYASES. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P30566.

GenomeRNAi

158.

NextBio

629.

SOURCE

Search...

Entry information

Entry name

PUR8_HUMAN

Accession

Primary (citable) accession number: P30566
Secondary accession number(s): B0QY76, O75495, Q5TI34

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	May 30, 2000
Last modified:	May 1, 2013
This is version 147 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.