Q14117 (DPYS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dihydropyrimidinase
Short name=DHP
Short name=DHPase
EC=3.5.2.2

Alternative name(s):
Dihydropyrimidine amidohydrolase
Hydantoinase

Gene names

Name:

DPYS

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	519 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Can catalyze the ring opening of 5,6-dihydrouracil to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-amino isobutyrate.
Catalytic activity	5,6-dihydrouracil + H2O = 3-ureidopropanoate.
Cofactor	Binds 2 zinc ions per subunit. Ref.4
Subunit structure	Homotetramer Probable.
Tissue specificity	Liver and kidney.
Post-translational modification	Carbamylation allows a single lysine to coordinate two zinc ions By similarity.
Involvement in disease	Dihydropyrimidinase deficiency (DHPD) [MIM:222748]: A disorder characterized by dihydropyrimidinuria and associated with a variable clinical phenotype characterized by epileptic or convulsive attacks, dysmorphic features and severe developmental delay, and congenital microvillous atrophy. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2
Sequence similarities	Belongs to the DHOase family. Hydantoinase/dihydropyrimidinase subfamily.

Ontologies

Keywords
Disease	Disease mutation
Ligand	Metal-binding Zinc
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	beta-alanine metabolic process Inferred from electronic annotation. Source: Compara protein homotetramerization Inferred from sequence or structural similarity. Source: UniProtKB pyrimidine nucleoside catabolic process Traceable author statement. Source: Reactome thymine catabolic process Inferred from sequence or structural similarity. Source: UniProtKB uracil catabolic process Inferred from direct assay PubMed 10410956. Source: UniProtKB
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	amino acid binding Inferred from electronic annotation. Source: Compara dihydropyrimidinase activity Inferred from direct assay PubMed 10410956Ref.2. Source: UniProtKB thymine binding Inferred from electronic annotation. Source: Compara uracil binding Inferred from electronic annotation. Source: Compara zinc ion binding Non-traceable author statement Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 519

519

Dihydropyrimidinase

PRO_0000165906

Sites

Metal binding

67

1

Zinc 1

Metal binding

69

1

Zinc 1

Metal binding

159

1

Zinc 1; via carbamate group

Metal binding

159

1

Zinc 2; via carbamate group

Metal binding

192

1

Zinc 2

Metal binding

248

1

Zinc 2

Metal binding

326

1

Zinc 1

Binding site

164

1

Substrate By similarity

Binding site

347

1

Substrate; via carbonyl oxygen By similarity

Amino acid modifications

Modified residue

159

1

N6-carboxylysine By similarity

Natural variations

Natural variant

68

1

T → R in DHPD. Ref.2

VAR_002267

Natural variant

334

1

Q → R in DHPD. Ref.2

VAR_002268

Natural variant

360

1

W → R in DHPD. Ref.2

VAR_002269

Natural variant

435

1

G → R in DHPD. Ref.2

VAR_002270

Natural variant

490

1

R → T in DHPD. Ref.2

VAR_002271

Secondary structure

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519

Helix Strand Turn

Details...

Beta strand

6 – 11

6

Beta strand

13 – 15

3

Beta strand

20 – 22

3

Beta strand

24 – 28

5

Beta strand

31 – 36

6

Beta strand

50 – 53

4

Beta strand

57 – 61

5

Beta strand

63 – 68

6

Beta strand

75 – 78

4

Helix

85 – 91

7

Turn

92 – 94

3

Beta strand

95 – 102

8

Helix

110 – 121

12

Turn

122 – 124

3

Beta strand

126 – 135

10

Helix

140 – 151

12

Beta strand

157 – 164

8

Turn

165 – 168

4

Helix

172 – 185

14

Beta strand

188 – 192

5

Helix

196 – 208

13

Helix

215 – 219

5

Helix

223 – 240

18

Beta strand

244 – 249

6

Helix

252 – 263

12

Beta strand

268 – 273

6

Helix

274 – 278

5

Helix

282 – 285

4

Helix

289 – 293

5

Helix

307 – 316

10

Helix

332 – 335

4

Helix

336 – 338

3

Helix

342 – 344

3

Turn

352 – 354

3

Helix

355 – 363

9

Turn

364 – 367

4

Helix

371 – 378

8

Helix

380 – 385

6

Turn

389 – 391

3

Beta strand

403 – 413

11

Turn

416 – 418

3

Beta strand

420 – 422

3

Turn

427 – 430

4

Beta strand

432 – 442

11

Beta strand

445 – 449

5

Helix

470 – 482

13

Sequences

	Sequence		Length	Mass (Da)
	Q14117 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 882E33D7C49D6ECC	FASTA	519	56,630
	10 20 30 40 50 60 MAAPSRLLIR GGRVVNDDFS EVADVLVEDG VVRALGHDLL PPGGAPAGLR VLDAAGKLVL 70 80 90 100 110 120 PGGIDTHTHM QFPFMGSRSI DDFHQGTKAA LSGGTTMIID FAIPQKGGSL IEAFETWRSW 130 140 150 160 170 180 ADPKVCCDYS LHVAVTWWSD QVKEEMKILV QDKGVNSFKM FMAYKDLYMV TDLELYEAFS 190 200 210 220 230 240 RCKEIGAIAQ VHAENGDLIA EGAKKMLALG ITGPEGHELC RPEAVEAEAT LRAITIASAV 250 260 270 280 290 300 NCPLYIVHVM SKSAAKVIAD ARRDGKVVYG EPIAASLGTD GTHYWNKEWH HAAHHVMGPP 310 320 330 340 350 360 LRPDPSTPDF LMNLLANDDL TTTGTDNCTF NTCQKALGKD DFTKIPNGVN GVEDRMSVIW 370 380 390 400 410 420 EKGVHSGKMD ENRFVAVTST NAAKIFNLYP RKGRIAVGSD ADIVIWDPKG TRTISAKTHH 430 440 450 460 470 480 QAVNFNIFEG MVCHGVPLVT ISRGKVVYEA GVFSVTAGDG KFIPRKPFAE YIYKRIKQRD 490 500 510 RTCTPTPVER APYKGEVATL KSRVTKEDAT AGTRKQAHP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel gene family defined by human dihydropyrimidinase and three related proteins with differential tissue distribution." Hamajima N., Matsuda K., Sakata S., Tamaki N., Sasaki M., Nonaka M. Gene 180:157-163(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Dihydropyrimidinase deficiency: structural organization, chromosomal localization, and mutation analysis of the human dihydropyrimidinase gene." Hamajima N., Kouwaki M., Vreken P., Matsuda K., Sumi S., Imaeda M., Ohba S., Kidouchi K., Nonaka M., Sasaki M., Tamaki N., Endo Y., de Abreu R., Rottevell J., van Kuilenburg A., van Gennip A., Togari H., Wada Y. Am. J. Hum. Genet. 63:717-726(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS DHPD ARG-68; ARG-334; ARG-360; ARG-435 AND THR-490.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon, Kidney and Stomach.
[4]	"The crystal structure of human dihydropyrimidinase." Structural genomics consortium (SGC) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH ZINC IONS, COFACTOR.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D78011 mRNA. Translation: BAA11189.1.
AB004678 Genomic DNA. Translation: BAA33067.1.
BC034395 mRNA. Translation: AAH34395.1.

IPI

IPI00028910.

PIR

JC5315.

RefSeq

NP_001376.1. NM_001385.2.

UniGene

Hs.443161.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VR2	X-ray	2.80	A	1-519	[»]

ProteinModelPortal

Q14117.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000276651.

Protein family/group databases

MEROPS

M38.973.

PTM databases

PhosphoSite

Q14117.

Polymorphism databases

DMDM

3122049.

Proteomic databases

PaxDb

Q14117.

PRIDE

Q14117.

Protocols and materials databases

DNASU

1807.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000351513; ENSP00000276651; ENSG00000147647.

GeneID

1807.

KEGG

hsa:1807.

UCSC

uc003yly.4. human.

Organism-specific databases

CTD

1807.

GeneCards

GC08M105391.

HGNC

HGNC:3013. DPYS.

HPA

HPA024785.

MIM

222748. phenotype.
613326. gene.

neXtProt

NX_Q14117.

Orphanet

38874. Dihydropyrimidinuria.

PharmGKB

PA146.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0044.

HOGENOM

HOG000219145.

HOVERGEN

HBG000806.

InParanoid

Q14117.

KO

K01464.

OMA

AITWWSE.

OrthoDB

EOG45HRX7.

PhylomeDB

Q14117.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q14117.

Bgee

Q14117.

CleanEx

HS_DPYS.

Genevestigator

Q14117.

GermOnline

ENSG00000147647. Homo sapiens.

Family and domain databases

InterPro

IPR006680. Amidohydro_1.
IPR011778. Hydantoinase/dihydroPyrase.
IPR011059. Metal-dep_hydrolase_composite.
[Graphical view]

Pfam

PF01979. Amidohydro_1. 1 hit.
[Graphical view]

SUPFAM

SSF51338. Metalo_hydrolase. 2 hits.

TIGRFAMs

TIGR02033. D-hydantoinase. 1 hit.

ProtoNet

Search...

Other

ChEMBL

CHEMBL2465.

EvolutionaryTrace

Q14117.

GenomeRNAi

1807.

NextBio

7365.

SOURCE

Search...

Entry information

Entry name

DPYS_HUMAN

Accession

Primary (citable) accession number: Q14117

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 119 of the entry and version 1 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.