Reviewed, UniProtKB/Swiss-Prot P07741 (APT_HUMAN)

Names and origin

Protein names

Recommended name:
    Adenine phosphoribosyltransferase
      Short name=APRT
    EC=2.4.2.7

Gene names

Name:

APRT

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

Protein attributes

Sequence length	180 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 a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.
Catalytic activity	AMP + diphosphate = adenine + 5-phospho-alpha-D-ribose 1-diphosphate.
Pathway	Purine metabolism; AMP biosynthesis via salvage pathway; AMP from adenine: step 1/1.
Subunit structure	Homodimer.
Subcellular location	Cytoplasm.
Involvement in disease	Defects in APRT are the cause of APRT deficiency [MIM:102600]; also known as 2,8-dihydroxyadenine urolithiasis. It is an autosomal recessive disease characterized by renal failure. Patients have 2,8-dihydroxyadenine (DHA) urinary stones.
Sequence similarities	Belongs to the purine/pyrimidine phosphoribosyltransferase family.

Ontologies

Keywords
Biological process	Purine salvage
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Molecular function	Glycosyltransferase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	purine ribonucleoside salvage Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from Experiment. Source: Reactome
Molecular function	AMP binding Ref.12 Inferred from direct assay. Source: MGI adenine phosphoribosyltransferase activity Ref.6 Inferred from Experiment. Source: Reactome protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
VHL	P40337	1	EBI-1047565,EBI-301246

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6 Ref.7

Chain

2 – 180

179

Adenine phosphoribosyltransferase

PRO_0000149504

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.7

Modified residue

66

1

Phosphoserine

Modified residue

114

1

N6-acetyllysine Ref.11

Natural variations

Natural variant

65

1

D → V in APRT deficiency; Icelandic type. Ref.13

VAR_006747

Natural variant

110

1

L → P in APRT deficiency; Newfoundland type. Ref.14

VAR_006748

Natural variant

121

1

Q → R: dbSNP rs8191494. Ref.4

VAR_019055

Natural variant

136

1

M → T in APRT deficiency; Japanese type; allele APRT*J; most common mutation. dbSNP rs28999113. Ref.15 Ref.16 Ref.17

VAR_006749

Natural variant

150

1

V → F in APRT deficiency. Ref.18

VAR_022608

Natural variant

153

1

C → R in APRT deficiency. Ref.18

VAR_022609

Natural variant

173

1

Missing in APRT deficiency.

VAR_037575

Secondary structure

1

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180

Helix Strand Turn

Details...

Helix

5 – 10

6

Beta strand

14 – 16

3

Beta strand

26 – 28

3

Helix

30 – 34

5

Helix

36 – 54

19

Beta strand

60 – 64

5

Turn

65 – 67

3

Helix

68 – 70

3

Helix

72 – 78

7

Beta strand

82 – 88

7

Beta strand

94 – 102

9

Beta strand

107 – 113

7

Beta strand

122 – 133

12

Helix

134 – 145

12

Beta strand

149 – 159

11

Helix

160 – 162

3

Helix

164 – 168

5

Beta strand

173 – 179

7

Sequences

	Sequence		Length	Mass (Da)
	P07741-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: CDC7703337A6E453	FASTA	180	19,608
	10 20 30 40 50 60 MADSELQLVE QRIRSFPDFP TPGVVFRDIS PVLKDPASFR AAIGLLARHL KATHGGRIDY 70 80 90 100 110 120 IAGLDSRGFL FGPSLAQELG LGCVLIRKRG KLPGPTLWAS YSLEYGKAEL EIQKDALEPG 130 140 150 160 170 180 QRVVVVDDLL ATGGTMNAAC ELLGRLQAEV LECVSLVELT SLKGREKLAP VPFFSLLQYE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of the human APRT gene." Hidaka Y., Tarle S.A., Toole T.E.O., Kelley W.N., Palella T.D. Nucleic Acids Res. 15:9086-9086(1987) [PubMed: 3684585] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Liver.
[2]	"Comparative anatomy of the human APRT gene and enzyme: nucleotide sequence divergence and conservation of a nonrandom CpG dinucleotide arrangement." Broderick T.P., Schaff D.A., Bertino A.M., Dush M.K., Tischfield J.A., Stambrook P.J. Proc. Natl. Acad. Sci. U.S.A. 84:3349-3353(1987) [PubMed: 3554238] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Uterine endothelium.
[4]	NIEHS SNPs program Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-121.
[5]	"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].
[6]	"Human adenine phosphoribosyltransferase. Complete amino acid sequence of the erythrocyte enzyme." Wilson J.M., O'Toole T.E., Argos P., Shewach D.S., Daddona P.E., Kelley W.N. J. Biol. Chem. 261:13677-13683(1986) [PubMed: 3531209] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-180.
[7]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-12, ACETYLATION AT ALA-2. Tissue: Platelet.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"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, MASS SPECTROMETRY.
[10]	"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-66, MASS SPECTROMETRY. Tissue: T-cell.
[11]	"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-114, MASS SPECTROMETRY.
[12]	"Three-dimensional structure of human adenine phosphoribosyltransferase and its relation to DHA-urolithiasis." Silva M., Silva C.H., Iulek J., Thiemann O.H. Biochemistry 43:7663-7671(2004) [PubMed: 15196008] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[13]	"Identification of a single missense mutation in the adenine phosphoribosyltransferase (APRT) gene from five Icelandic patients and a British patient." Chen J., Sahota A., Laxdal T., Scrine M., Bowman S., Cui C., Stambrook P.J., Tischfield J.A. Am. J. Hum. Genet. 49:1306-1311(1991) [PubMed: 1746557] [Abstract] Cited for: VARIANT APRT DEFICIENCY VAL-65.
[14]	"Missense mutation in the adenine phosphoribosyltransferase gene causing 2,8-dihydroxyadenine urolithiasis." Sahota A., Chen J., Boyadjiev S.A., Gault M.H., Tischfield J.A. Hum. Mol. Genet. 3:817-818(1994) [PubMed: 7915931] [Abstract] Cited for: VARIANT APRT DEFICIENCY PRO-110.
[15]	"Human adenine phosphoribosyltransferase. Identification of allelic mutations at the nucleotide level as a cause of complete deficiency of the enzyme." Hidaka Y., Palella T.D., O'Toole T.E., Tarle S.A., Kelley W.N. J. Clin. Invest. 80:1409-1415(1987) [PubMed: 3680503] [Abstract] Cited for: VARIANT APRT DEFICIENCY THR-136.
[16]	"Human adenine phosphoribosyltransferase deficiency. Demonstration of a single mutant allele common to the Japanese." Hidaka Y., Tarle S.A., Fujimori S., Kamatani N., Kelley W.N. J. Clin. Invest. 81:945-950(1988) [PubMed: 3343350] [Abstract] Cited for: VARIANTS APRT DEFICIENCY THR-136 AND PHE-173 DEL.
[17]	"Only three mutations account for almost all defective alleles causing adenine phosphoribosyltransferase deficiency in Japanese patients." Kamatani N., Hakoda M., Otsuka S., Yoshikawa H., Kashiwazaki S. J. Clin. Invest. 90:130-135(1992) [PubMed: 1353080] [Abstract] Cited for: VARIANT APRT DEFICIENCY THR-136.
[18]	"2,8-Dihydroxyadenine urolithiasis in a patient with considerable residual adenine phosphoribosyltransferase activity in cell extracts but with mutations in both copies of APRT." Deng L., Yang M., Fruend S., Wessel T., De Abreu R.A., Tischfield J.A., Sahota A. Mol. Genet. Metab. 72:260-264(2001) [PubMed: 11243733] [Abstract] Cited for: VARIANTS APRT DEFICIENCY PHE-150 AND ARG-153.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Wikipedia

Adenine phosphoribosyltransferase entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

Y00486 Genomic DNA. Translation: CAA68543.1.
M16446 Genomic DNA. Translation: AAA51769.1.
CR749423 mRNA. Translation: CAH18261.1.
AY306126 Genomic DNA. Translation: AAP45051.1.
BC107151 mRNA. Translation: AAI07152.1.

IPI

IPI00218693.

PIR

RTHUA. S06232.

RefSeq

NP_000476.1.

UniGene

Hs.271383
Hs.28914

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1OPU	model	-	A	1-180	[»]
1ORE	X-ray	2.10	A	1-180	[»]
1ZN7	X-ray	1.83	A/B	1-180	[»]
1ZN8	X-ray	1.76	A/B	1-180	[»]
1ZN9	X-ray	2.05	A/B	1-180	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P07741. 6 interactions.

STRING

P07741.

PTM databases

PhosphoSite

P07741.

2-D gel databases

SWISS-2DPAGE

P07741.

Proteomic databases

PRIDE

P07741.

Genome annotation databases

Ensembl

ENST00000378364; ENSP00000367615; ENSG00000198931; Homo sapiens. [Genome view]

GeneID

353.

KEGG

hsa:353.

NMPDR

fig|9606.3.peg.12727.

UCSC

uc002flv.1. human.

Organism-specific databases

CTD

353.

GeneCards

GC16M087403.

H-InvDB

HIX0038644.

HGNC

HGNC:626. APRT.

HPA

HPA026681.

MIM

102600. gene+phenotype.

Orphanet

976. 2,8 dihydroxyadenine urolithiasis.

PharmGKB

PA24914.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P07741.

OMA

YILEYGR

OrthoDB

EOG9KD96F

Enzyme and pathway databases

BRENDA

2.4.2.7. 247.

Reactome

REACT_1698. Metablism of nucleotides.

Gene expression databases

ArrayExpress

P07741.

Bgee

P07741.

CleanEx

HS_APRT.

Genevestigator

P07741.

GermOnline

ENSG00000198931. Homo sapiens.

Family and domain databases

InterPro

IPR005764. Ade_phspho_trans.
IPR000836. PRibTrfase.
[Graphical view]

Pfam

PF00156. Pribosyltran. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01090. apt. 1 hit.

PROSITE

PS00103. PUR_PYR_PR_TRANSFER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00173. Adenine.
DB00131. Adenosine monophosphate.

NextBio

1453.

SOURCE

Search...

Entry information

Entry name

APT_HUMAN

Accession

Primary (citable) accession number: P07741
Secondary accession number(s): Q3KP55, Q68DF9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 23, 2007
Last modified:	November 24, 2009
This is version 118 of the entry and version 2 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.