Multifunctional protein ADE2 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P22234 (PUR6_HUMAN)

Last modified February 9, 2010. Version 107. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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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.

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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 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate: step 1/2. Purine metabolism; IMP biosynthesis via de novo pathway; 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate from 5-amino-1-(5-phospho-D-ribosyl)imidazole (carboxylase route): step 1/1.
Subunit structure	Homooctamer. Ref.14
Sequence similarities	In the N-terminal section; belongs to the SAICAR synthetase family. In the C-terminal section; belongs to the AIR carboxylase family.

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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 Complete proteome Direct protein sequencing Multifunctional enzyme
Gene Ontology (GO)
Biological process	'de novo' IMP biosynthetic process Inferred from Experiment. Source: Reactome 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...

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Binary interactions

With	Entry	#Exp.	IntAct
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
FXR2	P51116	2	EBI-712261,EBI-740459
GNAS	P63092	1	EBI-712261,EBI-1047114
HLA-B	P30480	1	EBI-712261,EBI-1054175
MCC	P23508	1	EBI-712261,EBI-307531
NUDT18	Q6ZVK8	2	EBI-712261,EBI-740486
PSMC4	P43686	1	EBI-712261,EBI-743997
TRAF6	Q9Y4K3	1	EBI-712261,EBI-359276

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed Ref.4

Chain

2 – 425

424

Multifunctional protein ADE2

PRO_0000075030

Regions

Region

2 – 260

259

SAICAR synthetase

Region

261 – 266

Linker

Region

267 – 425

159

AIR carboxylase

Sites

Active site

101

For SAICAR synthetase activity Ref.14

Active site

107

For SAICAR synthetase activity Ref.14

Active site

215

For SAICAR synthetase activity Ref.14

Active site

303

For AIR carboxylase activity Ref.14

Active site

332

For AIR carboxylase activity Ref.14

Site

334

Essential for AIR carboxylase activity

Amino acid modifications

Modified residue

N-acetylalanine Ref.4 Ref.10

Modified residue

Phosphotyrosine By similarity

Modified residue

Phosphoserine Ref.10 Ref.5 Ref.6 Ref.7 Ref.8 Ref.12

Modified residue

N6-acetyllysine Ref.13

Modified residue

105

Phosphothreonine

Modified residue

107

Phosphoserine Ref.8

Modified residue

238

Phosphothreonine Ref.10 Ref.7 Ref.8

Modified residue

247

N6-acetyllysine Ref.13

Natural variations

Natural variant

201

K → N: dbSNP rs11549976.

VAR_051884

Experimental info

Mutagenesis

303

H → Y: Loss of AIR carboxylase activity. Ref.14

Mutagenesis

332

S → A: Loss of AIR carboxylase activity. Ref.14

Mutagenesis

334

G → A: Loss of AIR carboxylase activity. Ref.14

Mutagenesis

400

S → A: No change of AIR carboxylase activity.

Secondary structure

425

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P22234-1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: E08CF19BC8898F29
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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

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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]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27 AND THR-238, MASS SPECTROMETRY.
[11]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27; THR-105; SER-107 AND THR-238, MASS SPECTROMETRY.
[12]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, MASS SPECTROMETRY. Tissue: T-cell.
[13]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-53 AND LYS-247, MASS SPECTROMETRY.
[14]	"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.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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

PDBe
RCSB PDB
PDBj

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

ModBase

Search...

Protein-protein interaction databases

IntAct

P22234. 22 interactions.

STRING

P22234.

PTM databases

PhosphoSite

P22234.

Proteomic databases

PRIDE

P22234.

Genome annotation databases

Ensembl

ENST00000264221; ENSP00000264221; ENSG00000128050; Homo sapiens. [Genome view]

GeneID

10606.

KEGG

hsa:10606.

NMPDR

fig|9606.3.peg.24135.

UCSC

uc003hbs.1. human.

Organism-specific databases

CTD

10606.

GeneCards

GC04P056996.

H-InvDB

HIX0004234.

HGNC

HGNC:8587. PAICS.

MIM

172439. gene.

PharmGKB

PA32914.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04677.

HOVERGEN

P22234.

InParanoid

P22234.

OrthoDB

EOG9X6FVP.

PhylomeDB

P22234.

Enzyme and pathway databases

BRENDA

4.1.1.21. 247.
6.3.2.6. 247.

Reactome

REACT_1698. Metabolism of nucleotides.

Gene expression databases

ArrayExpress

P22234.

Bgee

P22234.

CleanEx

HS_PAICS.

Genevestigator

P22234.

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]

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...

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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:	February 9, 2010
This is version 107 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents