Reviewed, UniProtKB/Swiss-Prot P22234 (PUR6_HUMAN)

Names and origin

Protein names

Recommended name:
    Multifunctional protein ADE2
Including the following 2 domains:
    1- Recommended name:
            Phosphoribosylaminoimidazole-succinocarboxamide synthase
              EC=6.3.2.6
        Alternative name(s):
            SAICAR synthetase
    2- Recommended name:
            Phosphoribosylaminoimidazole carboxylase
              EC=4.1.1.21
        Alternative name(s):
            AIR carboxylase
              Short name=AIRC

Gene names

Name:	PAICS
Synonyms:	ADE2, AIRC, PAIS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	425 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)

Catalytic activity	ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate = ADP + phosphate + (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate. 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO2.
Pathway	Purine metabolism; IMP biosynthesis via de novo pathway; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 3/5. Purine metabolism; IMP biosynthesis via de novo pathway; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide: step 4/5.
Subunit structure	Homooctamer. Ref.10
Sequence similarities	In the N-terminal section; belongs to the SAICAR synthetase family. In the C-terminal section; belongs to the AIR carboxylase family.

Ontologies

Keywords
Biological process	Purine biosynthesis
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Decarboxylase Ligase Lyase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing Multifunctional enzyme
Gene Ontology (GO)
Biological process	'de novo' IMP biosynthetic process Inferred from electronic annotation. Source: InterPro purine base biosynthetic process Ref.1 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW identical protein binding Inferred from physical interaction. Source: IntAct phosphoribosylaminoimidazole carboxylase activity Inferred from electronic annotation. Source: EC phosphoribosylaminoimidazolesuccinocarboxamide synthase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-712261,EBI-712261
DGKE	P52429	1	EBI-712261,EBI-1057499
EIF6	P56537	1	EBI-712261,EBI-372243
EPB41	P11171	1	EBI-712261,EBI-1050906
GNAS	P63092	1	EBI-712261,EBI-1047114
HLA-B	P30480	1	EBI-712261,EBI-1054175
MCC	P23508	1	EBI-712261,EBI-307531
PSMC4	P43686	1	EBI-712261,EBI-743997
TRAF6	Q9Y4K3	1	EBI-712261,EBI-359276

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.4

Chain

2 – 425

424

Multifunctional protein ADE2

PRO_0000075030

Regions

Region

2 – 260

259

SAICAR synthetase

Region

261 – 266

6

Linker

Region

267 – 425

159

AIR carboxylase

Sites

Active site

101

1

For SAICAR synthetase activity Ref.10

Active site

107

1

For SAICAR synthetase activity Ref.10

Active site

215

1

For SAICAR synthetase activity Ref.10

Active site

303

1

For AIR carboxylase activity Ref.10

Active site

332

1

For AIR carboxylase activity Ref.10

Site

334

1

Essential for AIR carboxylase activity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.4

Modified residue

22

1

Phosphotyrosine By similarity

Modified residue

27

1

Phosphoserine Ref.5 Ref.6 Ref.7 Ref.8

Modified residue

107

1

Phosphoserine Ref.8

Modified residue

238

1

Phosphothreonine Ref.7 Ref.8

Natural variations

Natural variant

201

1

K → N: dbSNP rs11549976.

VAR_051884

Experimental info

Mutagenesis

303

1

H → Y: Loss of AIR carboxylase activity. Ref.10

Mutagenesis

332

1

S → A: Loss of AIR carboxylase activity. Ref.10

Mutagenesis

334

1

G → A: Loss of AIR carboxylase activity. Ref.10

Mutagenesis

400

1

S → A: No change of AIR carboxylase activity.

Secondary structure

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425

Helix Strand Turn

Details...

Beta strand

20 – 22

3

Beta strand

32 – 35

4

Helix

54 – 71

18

Beta strand

82 – 88

7

Beta strand

91 – 93

3

Beta strand

97 – 103

7

Helix

106 – 111

6

Beta strand

126 – 130

5

Helix

142 – 146

5

Turn

147 – 149

3

Helix

159 – 180

22

Helix

181 – 183

3

Beta strand

186 – 192

7

Beta strand

194 – 197

4

Turn

198 – 200

3

Beta strand

203 – 205

3

Beta strand

213 – 217

5

Beta strand

241 – 243

3

Helix

249 – 253

5

Helix

256 – 260

5

Beta strand

267 – 273

7

Helix

275 – 277

3

Helix

278 – 290

13

Beta strand

295 – 299

5

Turn

302 – 304

3

Helix

306 – 317

12

Beta strand

323 – 328

6

Helix

335 – 342

8

Beta strand

347 – 349

3

Turn

355 – 357

3

Helix

358 – 361

4

Helix

362 – 364

3

Helix

380 – 392

13

Helix

396 – 421

26

Sequences

	Sequence		Length	Mass (Da)
	P22234-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: E08CF19BC8898F29	FASTA	425	47,079
	10 20 30 40 50 60 MATAEVLNIG KKLYEGKTKE VYELLDSPGK VLLQSKDQIT AGNAARKNHL EGKAAISNKI 70 80 90 100 110 120 TSCIFQLLQE AGIKTAFTRK CGETAFIAPQ CEMIPIEWVC RRIATGSFLK RNPGVKEGYK 130 140 150 160 170 180 FYPPKVELFF KDDANNDPQW SEEQLIAAKF CFAGLLIGQT EVDIMSHATQ AIFEILEKSW 190 200 210 220 230 240 LPQNCTLVDM KIEFGVDVTT KEIVLADVID NDSWRLWPSG DRSQQKDKQS YRDLKEVTPE 250 260 270 280 290 300 GLQMVKKNFE WVAERVELLL KSESQCRVVV LMGSTSDLGH CEKIKKACGN FGIPCELRVT 310 320 330 340 350 360 SAHKGPDETL RIKAEYEGDG IPTVFVAVAG RSNGLGPVMS GNTAYPVISC PPLTPDWGVQ 370 380 390 400 410 420 DVWSSLRLPS GLGCSTVLSP EGSAQFAAQI FGLSNHLVWS KLRASILNTW ISLKQADKKI RECNL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of a human cDNA coding for a multifunctional polypeptide of the purine pathway by complementation of the ade2-101 mutant in Saccharomyces cerevisiae." Minet M., Lacroute F. Curr. Genet. 18:287-291(1990) [PubMed: 2253271] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung and Placenta.
[4]	Bienvenut W.V., Potts A., Brablan J., Quadroni M. Submitted (JUL-2004) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-11, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[5]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27 AND THR-238, MASS SPECTROMETRY.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27; SER-107 AND THR-238, MASS SPECTROMETRY.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"Octameric structure of the human bifunctional enzyme PAICS in purine biosynthesis." Li S.-X., Tong Y.-P., Xie X.-C., Wang Q.-H., Zhou H.-N., Han Y., Zhang Z.-Y., Gao W., Li S.-G., Zhang X.C., Bi R.-C. J. Mol. Biol. 366:1603-1614(2007) [PubMed: 17224163] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), SUBUNIT, ACTIVE SITE, MUTAGENESIS OF HIS-303; SER-332 AND GLY-334.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X53793 mRNA. Translation: CAA37801.1.
BT006988 mRNA. Translation: AAP35634.1.
BC010273 mRNA. Translation: AAH10273.1.
BC019255 mRNA. Translation: AAH19255.1.

IPI

IPI00217223.

PIR

S14147.

RefSeq

NP_001072992.1.
NP_006443.1.

UniGene

Hs.518774
Hs.709570

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2H31	X-ray	2.80	A	1-425	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P22234. 21 interactions.

PTM databases

PhosphoSite

P22234.

Proteomic databases

PRIDE

P22234.

Genome annotation databases

Ensembl

ENSG00000128050. Homo sapiens. [Contig view]

GeneID

10606.

KEGG

hsa:10606.

NMPDR

fig|9606.3.peg.24135.

Organism-specific databases

GeneCards

GC04P056996.

H-InvDB

HIX0004234.

HGNC

HGNC:8587. PAICS.

MIM

172439. gene.

PharmGKB

PA32914.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P22234.

Enzyme and pathway databases

BRENDA

4.1.1.21. 247.
6.3.2.6. 247.

Reactome

REACT_1698. Nucleotide metabolism.

Gene expression databases

ArrayExpress

P22234.

Bgee

P22234.

CleanEx

HS_PAICS.

GermOnline

ENSG00000128050. Homo sapiens.

Family and domain databases

InterPro

IPR000031. AIR_COase_core.
IPR013816. ATP_grasp_subdomain_2.
IPR001636. SAICAR_synt.
IPR018236. SAICAR_synthetase_CS.
[Graphical view]

Gene3D

G3DSA:3.40.50.7700. AIR_carboxyl. 1 hit.
G3DSA:3.30.470.20. ATP_grasp_subdomain_2. 1 hit.

PANTHER

PTHR11609. SAICAR_synt. 1 hit.

Pfam

PF00731. AIRC. 1 hit.
PF01259. SAICAR_synt. 1 hit.
[Graphical view]

ProDom

PD002193. AIR_carboxyl. 1 hit.
PD003043. SAICAR_synt. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR01162. purE. 1 hit.

PROSITE

PS01057. SAICAR_SYNTHETASE_1. 1 hit.
PS01058. SAICAR_SYNTHETASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00128. L-Aspartic Acid.

NextBio

40280.

SOURCE

Search...

Entry information

Entry name

PUR6_HUMAN

Accession

Primary (citable) accession number: P22234

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 98 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)