ID F7AQA4_HORSE Unreviewed; 1025 AA.
AC F7AQA4;
DT 27-JUL-2011, integrated into UniProtKB/TrEMBL.
DT 10-APR-2019, sequence version 2.
DT 27-MAR-2024, entry version 67.
DE RecName: Full=Dihydropyrimidine dehydrogenase [NADP(+)] {ECO:0000256|ARBA:ARBA00018247, ECO:0000256|RuleBase:RU364041};
DE Short=DHPDHase {ECO:0000256|RuleBase:RU364041};
DE Short=DPD {ECO:0000256|RuleBase:RU364041};
DE EC=1.3.1.2 {ECO:0000256|ARBA:ARBA00013004, ECO:0000256|RuleBase:RU364041};
DE AltName: Full=Dihydrothymine dehydrogenase {ECO:0000256|ARBA:ARBA00032722, ECO:0000256|RuleBase:RU364041};
DE AltName: Full=Dihydrouracil dehydrogenase {ECO:0000256|ARBA:ARBA00030119, ECO:0000256|RuleBase:RU364041};
GN Name=DPYD {ECO:0000313|Ensembl:ENSECAP00000009226.2,
GN ECO:0000313|VGNC:VGNC:17302};
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796 {ECO:0000313|Ensembl:ENSECAP00000009226.2, ECO:0000313|Proteomes:UP000002281};
RN [1] {ECO:0000313|Ensembl:ENSECAP00000009226.2, ECO:0000313|Proteomes:UP000002281}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000009226.2,
RC ECO:0000313|Proteomes:UP000002281};
RX PubMed=19892987; DOI=10.1126/science.1178158;
RG Broad Institute Genome Sequencing Platform;
RG Broad Institute Whole Genome Assembly Team;
RA Wade C.M., Giulotto E., Sigurdsson S., Zoli M., Gnerre S., Imsland F.,
RA Lear T.L., Adelson D.L., Bailey E., Bellone R.R., Bloecker H., Distl O.,
RA Edgar R.C., Garber M., Leeb T., Mauceli E., MacLeod J.N., Penedo M.C.T.,
RA Raison J.M., Sharpe T., Vogel J., Andersson L., Antczak D.F., Biagi T.,
RA Binns M.M., Chowdhary B.P., Coleman S.J., Della Valle G., Fryc S.,
RA Guerin G., Hasegawa T., Hill E.W., Jurka J., Kiialainen A., Lindgren G.,
RA Liu J., Magnani E., Mickelson J.R., Murray J., Nergadze S.G., Onofrio R.,
RA Pedroni S., Piras M.F., Raudsepp T., Rocchi M., Roeed K.H., Ryder O.A.,
RA Searle S., Skow L., Swinburne J.E., Syvaenen A.C., Tozaki T., Valberg S.J.,
RA Vaudin M., White J.R., Zody M.C., Lander E.S., Lindblad-Toh K.;
RT "Genome sequence, comparative analysis, and population genetics of the
RT domestic horse.";
RL Science 326:865-867(2009).
RN [2] {ECO:0000313|Ensembl:ENSECAP00000009226.2}
RP IDENTIFICATION.
RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000009226.2};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: Involved in pyrimidine base degradation. Catalyzes the
CC reduction of uracil and thymine. {ECO:0000256|RuleBase:RU364041}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5,6-dihydrothymine + NADP(+) = H(+) + NADPH + thymine;
CC Xref=Rhea:RHEA:58284, ChEBI:CHEBI:15378, ChEBI:CHEBI:17821,
CC ChEBI:CHEBI:27468, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.2;
CC Evidence={ECO:0000256|ARBA:ARBA00033676};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58286;
CC Evidence={ECO:0000256|ARBA:ARBA00033676};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5,6-dihydrouracil + NADP(+) = H(+) + NADPH + uracil;
CC Xref=Rhea:RHEA:18093, ChEBI:CHEBI:15378, ChEBI:CHEBI:15901,
CC ChEBI:CHEBI:17568, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.2;
CC Evidence={ECO:0000256|ARBA:ARBA00033654};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18095;
CC Evidence={ECO:0000256|ARBA:ARBA00033654};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000256|ARBA:ARBA00001974,
CC ECO:0000256|RuleBase:RU364041};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000256|ARBA:ARBA00001917,
CC ECO:0000256|RuleBase:RU364041};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000256|RuleBase:RU364041};
CC Note=Binds 4 [4Fe-4S] clusters. Contains approximately 16 iron atoms
CC per subunit. {ECO:0000256|RuleBase:RU364041};
CC -!- PATHWAY: Amino-acid biosynthesis; beta-alanine biosynthesis.
CC {ECO:0000256|ARBA:ARBA00004668, ECO:0000256|RuleBase:RU364041}.
CC -!- SIMILARITY: Belongs to the dihydropyrimidine dehydrogenase family.
CC {ECO:0000256|ARBA:ARBA00010804, ECO:0000256|RuleBase:RU364041}.
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DR STRING; 9796.ENSECAP00000028069; -.
DR PaxDb; 9796-ENSECAP00000028069; -.
DR Ensembl; ENSECAT00000011760.4; ENSECAP00000009226.2; ENSECAG00000010881.4.
DR Ensembl; ENSECAT00000050955.3; ENSECAP00000034155.1; ENSECAG00000010881.4.
DR VGNC; VGNC:17302; DPYD.
DR GeneTree; ENSGT00500000044896; -.
DR HOGENOM; CLU_003991_0_0_1; -.
DR OMA; SIHCQLQ; -.
DR OrthoDB; 1211169at2759; -.
DR TreeFam; TF105791; -.
DR UniPathway; UPA00131; -.
DR Proteomes; UP000002281; Chromosome 5.
DR Bgee; ENSECAG00000010881; Expressed in liver and 20 other cell types or tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0017113; F:dihydropyrimidine dehydrogenase (NADP+) activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050661; F:NADP binding; IBA:GO_Central.
DR GO; GO:0002058; F:uracil binding; IBA:GO_Central.
DR GO; GO:0019483; P:beta-alanine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006210; P:thymine catabolic process; IBA:GO_Central.
DR GO; GO:0006212; P:uracil catabolic process; IBA:GO_Central.
DR CDD; cd02940; DHPD_FMN; 1.
DR Gene3D; 3.30.70.20; -; 1.
DR Gene3D; 3.20.20.70; Aldolase class I; 1.
DR Gene3D; 1.10.1060.10; Alpha-helical ferredoxin; 1.
DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 2.
DR InterPro; IPR017896; 4Fe4S_Fe-S-bd.
DR InterPro; IPR017900; 4Fe4S_Fe_S_CS.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR005720; Dihydroorotate_DH_cat.
DR InterPro; IPR028261; DPD_II.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR009051; Helical_ferredxn.
DR PANTHER; PTHR43073; DIHYDROPYRIMIDINE DEHYDROGENASE [NADP(+)]; 1.
DR PANTHER; PTHR43073:SF2; DIHYDROPYRIMIDINE DEHYDROGENASE [NADP(+)]; 1.
DR Pfam; PF01180; DHO_dh; 1.
DR Pfam; PF14691; Fer4_20; 1.
DR Pfam; PF14697; Fer4_21; 1.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR PRINTS; PR00419; ADXRDTASE.
DR SUPFAM; SSF54862; 4Fe-4S ferredoxins; 1.
DR SUPFAM; SSF46548; alpha-helical ferredoxin; 1.
DR SUPFAM; SSF51395; FMN-linked oxidoreductases; 1.
DR SUPFAM; SSF51971; Nucleotide-binding domain; 2.
DR PROSITE; PS00198; 4FE4S_FER_1; 1.
DR PROSITE; PS51379; 4FE4S_FER_2; 2.
PE 1: Evidence at protein level;
KW 4Fe-4S {ECO:0000256|ARBA:ARBA00022485, ECO:0000256|RuleBase:RU364041};
KW FAD {ECO:0000256|ARBA:ARBA00022827, ECO:0000256|RuleBase:RU364041};
KW Flavoprotein {ECO:0000256|RuleBase:RU364041};
KW FMN {ECO:0000256|ARBA:ARBA00022643, ECO:0000256|RuleBase:RU364041};
KW Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|RuleBase:RU364041};
KW Iron-sulfur {ECO:0000256|ARBA:ARBA00023014};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW NADP {ECO:0000256|RuleBase:RU364041};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW ECO:0000256|RuleBase:RU364041};
KW Proteomics identification {ECO:0007829|PeptideAtlas:F7AQA4};
KW Reference proteome {ECO:0000313|Proteomes:UP000002281};
KW Repeat {ECO:0000256|ARBA:ARBA00022737}.
FT DOMAIN 944..976
FT /note="4Fe-4S ferredoxin-type"
FT /evidence="ECO:0000259|PROSITE:PS51379"
FT DOMAIN 978..1007
FT /note="4Fe-4S ferredoxin-type"
FT /evidence="ECO:0000259|PROSITE:PS51379"
SQ SEQUENCE 1025 AA; 111291 MW; B572B68F215E3C29 CRC64;
MAPVLSKDPA DIESILALNP RTQTHAVLRS TSAKKLDKKH WKRNPDKNCF NCEKLENNFD
DIKHTTLGER GALREAMRCL KCADAPCQKS CPTNLDIKSF ITSIANKNYY GSAKTIFSDN
PLGLTCGMVC PTSDLCVGGC NLYATEEGPI NIGGLQQFST EVFKAMNIPQ IRNPSLPPPE
KMPEAYSAKI ALFGAGPASI SCASFLARLG YSDITIFEKQ EYVGGLSTSE IPQFRLPYDV
VNFEIELMKD LGVKIICGKS LSVNEMTLST VKEEGYKAVF IGIGLPEPKK DQIFQGLTQD
QGFYTSKDFL PLVAKGSKPG MCACHSPLPS IRGAVIVLGA GDTAFDCATS ALRCGARRVF
IVFRKGFVNI RAVPEEMELA KEEKCEFLPF LSPRKVVVRG GRIVAMQFVR TEQDEAGNWS
EDEDQIVQLK ADVIISAFGS VLSDPKVKEA LSPIKFNKWG LPEVDPETMQ TSEPWVFAGG
DIVGTANTTV ESVNDGKQAS WFIHKYIQSQ HGASVAAKPE LPLFYTPIDL VDISVEMAGL
KFVNPFGLAS ATPATSASMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI IRGITSGPMY
GPGQSSFLNI ELISEKTAAY WCQSVTELKA DFPDNIVIAS IMCSYNKNDW MELAKQAEAS
GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ AVRVPFFAKL TPNVTDIVSI
ARAAKEGGAD GVTATNTVSG LMELKADGTP WPAVGIGKRT TYGGVSGTAI RPIALRAVTS
IARALPGFPI LATGGIDSAE SGLQFLHSGA SVLQVCSAIQ NQDFTVIEDY CTGLKALLYL
KSIEELQDWD GQSPATVSHQ KGKPVPRIPE LIGKKLPSFG PYLEKRKKII AENKIREKGQ
NAAFPPLERN PFIPKKPIPA IKDVIGKALR YLGAYGELSN TEHVVAVIDE EMCINCGKCY
MTCNDSGYQA IEFDPETHLP TVTDSCTGCT LCFSVCPIID CIKMVSRTTP YEPKRGLPLA
VNPVC
//
