P07741 (APT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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	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	Adenine phosphoribosyltransferase deficiency (APRTD) [MIM:614723]: An enzymatic deficiency that can lead to urolithiasis and renal failure. Patients have 2,8-dihydroxyadenine (DHA) urinary stones. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21
Sequence similarities	Belongs to the purine/pyrimidine phosphoribosyltransferase family.

Ontologies

Keywords
Biological process	Purine salvage
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Molecular function	Glycosyltransferase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	AMP salvage Inferred from electronic annotation. Source: UniProtKB-UniPathway adenine salvage Inferred from electronic annotation. Source: Compara cellular response to insulin stimulus Inferred from electronic annotation. Source: Compara grooming behavior Inferred from electronic annotation. Source: Compara lactation Inferred from electronic annotation. Source: Compara purine nucleobase metabolic process Traceable author statement. Source: Reactome purine ribonucleoside salvage Inferred from electronic annotation. Source: UniProtKB-KW purine-containing compound salvage Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA
Molecular_function	AMP binding Inferred from direct assay Ref.13. Source: MGI adenine binding Inferred from electronic annotation. Source: Compara adenine phosphoribosyltransferase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P07741-1)

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: P07741-2)

The sequence of this isoform differs from the canonical sequence as follows:
     134-180: GTMNAACELLGRLQAEVLECVSLVELTSLKGREKLAPVPFFSLLQYE → V

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8 Ref.9

Chain

2 – 180

179

Adenine phosphoribosyltransferase

PRO_0000149504

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.9 Ref.10

Modified residue

4

1

Phosphoserine Ref.10

Modified residue

15

1

Phosphoserine Ref.10

Modified residue

60

1

Phosphotyrosine Ref.10

Modified residue

66

1

Phosphoserine Ref.10

Modified residue

114

1

N6-acetyllysine Ref.11

Modified residue

135

1

Phosphothreonine Ref.10

Natural variations

Alternative sequence

134 – 180

47

GTMNA…LLQYE → V in isoform 2.

VSP_045705

Natural variant

33

1

L → P in APRTD. Ref.21

VAR_069049

Natural variant

65

1

D → V in APRTD; Icelandic type. Ref.14

VAR_006747

Natural variant

84

1

V → M in APRTD. Ref.20
Corresponds to variant rs200392753 [ dbSNP | Ensembl ].

VAR_069050

Natural variant

110

1

L → P in APRTD; Newfoundland type. Ref.15

VAR_006748

Natural variant

121

1

Q → R. Ref.4
Corresponds to variant rs8191494 [ dbSNP | Ensembl ].

VAR_019055

Natural variant

133

1

G → D in APRTD. Ref.20

VAR_069051

Natural variant

136

1

M → T in APRTD; Japanese type; allele APRT*J; most common mutation. Ref.16 Ref.17 Ref.18 Ref.21
Corresponds to variant rs28999113 [ dbSNP | Ensembl ].

VAR_006749

Natural variant

150

1

V → F in APRTD. Ref.19

VAR_022608

Natural variant

153

1

C → R in APRTD. Ref.19

VAR_022609

Natural variant

173

1

Missing in APRTD. Ref.17

VAR_037575

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

180

Helix Strand Turn

Details...

Helix

4 – 10

7

Beta strand

14 – 17

4

Beta strand

19 – 21

3

Beta strand

25 – 28

4

Helix

30 – 34

5

Helix

36 – 54

19

Beta strand

60 – 64

5

Turn

65 – 67

3

Helix

68 – 79

12

Beta strand

82 – 88

7

Beta strand

94 – 103

10

Beta strand

106 – 113

8

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)
	Isoform 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
	Isoform 2 [UniParc]. Checksum: 404EC4ACAE4C29DE	FASTA	134	14,557
	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 QRVVVVDDLL ATGV

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORMS 1 AND 2). Tissue: Astrocytoma.
[8]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-180.
[9]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-12, ACETYLATION AT ALA-2. Tissue: Platelet.
[10]	"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] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-15; TYR-60; SER-66 AND THR-135, MASS SPECTROMETRY.
[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.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-114, MASS SPECTROMETRY.
[12]	"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].
[13]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[14]	"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] [Europe PMC] [Abstract] Cited for: VARIANT APRTD VAL-65.
[15]	"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] [Europe PMC] [Abstract] Cited for: VARIANT APRTD PRO-110.
[16]	"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] [Europe PMC] [Abstract] Cited for: VARIANT APRTD THR-136.
[17]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS APRTD THR-136 AND PHE-173 DEL.
[18]	"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] [Europe PMC] [Abstract] Cited for: VARIANT APRTD THR-136.
[19]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS APRTD PHE-150 AND ARG-153.
[20]	"Identification of two novel mutations in adenine phosphoribosyltransferase gene in patients with 2,8-dihydroxyadenine urolithiasis." Taniguchi A., Tsuchida S., Kuno S., Mita M., Machida T., Ioritani N., Terai C., Yamanaka H., Kamatani N. Nucleosides Nucleotides Nucleic Acids 23:1141-1145(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS APRTD MET-84 AND ASP-133.
[21]	"A Japanese boy with adenine phosphoribosyltransferase (APRT) deficiency caused by compound heterozygosity including a novel missense mutation in APRT gene." Nozue H., Kamoda T., Saitoh H., Ichikawa K., Taniguchi A. Acta Paediatr. 100:E285-E288(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS APRTD PRO-33 AND THR-136.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Wikipedia

Adenine phosphoribosyltransferase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y00486 Genomic DNA. Translation: CAA68543.1.
M16446 Genomic DNA. Translation: AAA51769.1.
CR749423 mRNA. Translation: CAH18261.1.
AY306126 Genomic DNA. Translation: AAP45051.1.
AC092384 Genomic DNA. No translation available.
CH471184 Genomic DNA. Translation: EAW66761.1.
BC107151 mRNA. Translation: AAI07152.1.
BM550173 mRNA. No translation available.

IPI

IPI00218693.

PIR

RTHUA. S06232.

RefSeq

NP_000476.1. NM_000485.2.
NP_001025189.1. NM_001030018.1.

UniGene

Hs.28914.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P07741.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07741. 2 interactions.

STRING

9606.ENSP00000367615.

PTM databases

PhosphoSite

P07741.

Polymorphism databases

DMDM

114074.

2D gel databases

SWISS-2DPAGE

P07741.

Proteomic databases

PaxDb

P07741.

PRIDE

P07741.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000378364; ENSP00000367615; ENSG00000198931.
ENST00000426324; ENSP00000397007; ENSG00000198931.

GeneID

353.

KEGG

hsa:353.

UCSC

uc002flv.3. human.

Organism-specific databases

CTD

353.

GeneCards

GC16M088875.

HGNC

HGNC:626. APRT.

HPA

HPA026681.

MIM

102600. gene.
614723. phenotype.

neXtProt

NX_P07741.

Orphanet

976. 2,8 dihydroxyadenine urolithiasis.

PharmGKB

PA24914.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0503.

HOGENOM

HOG000036776.

HOVERGEN

HBG003144.

InParanoid

P07741.

KO

K00759.

OMA

DYALEYG.

OrthoDB

EOG48KRCC.

PhylomeDB

P07741.

Enzyme and pathway databases

BRENDA

2.4.2.7. 2681.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P07741.

UniPathway

UPA00588; UER00646.

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_dom.
[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

DrugBank

DB00173. Adenine.
DB00131. Adenosine monophosphate.

EvolutionaryTrace

P07741.

GenomeRNAi

353.

NextBio

1453.

SOURCE

Search...

Entry information

Entry name

APT_HUMAN

Accession

Primary (citable) accession number: P07741
Secondary accession number(s): G5E9J2, Q3KP55, Q68DF9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 151 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.