PYR1_DICDI
ID PYR1_DICDI Reviewed; 2225 AA.
AC P20054; Q551R5; Q86AD0;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 3.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Protein PYR1-3;
DE Includes:
DE RecName: Full=Glutamine-dependent carbamoyl-phosphate synthase;
DE EC=6.3.5.5;
DE Includes:
DE RecName: Full=Aspartate carbamoyltransferase;
DE EC=2.1.3.2;
DE Includes:
DE RecName: Full=Dihydroorotase;
DE EC=3.5.2.3;
GN Name=pyr1-3; ORFNames=DDB_G0276335;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [3]
RP PROTEIN SEQUENCE OF 1-6; 262-269; 461-473; 559-566; 720-730; 773-782;
RP 823-831; 893-902; 948-958; 1013-1019; 1051-1065; 1279-1286; 1427-1440 AND
RP 1732-1740, ACETYLATION AT MET-1, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=AX2;
RA Bienvenut W.V., Ura S., Insall R.H.;
RL Submitted (JUL-2009) to UniProtKB.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 40-506 AND 1214-2224.
RC STRAIN=AX3;
RX PubMed=2917570; DOI=10.1111/j.1432-1033.1989.tb14560.x;
RA Faure M., Camonis J.H., Jacquet M.;
RT "Molecular characterization of a Dictyostelium discoideum gene encoding a
RT multifunctional enzyme of the pyrimidine pathway.";
RL Eur. J. Biochem. 179:345-358(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 406-1447.
RC STRAIN=AX2;
RX PubMed=1627825; DOI=10.3109/10425179209020806;
RA Elgar G., Schofield J.P.;
RT "Carbamoyl phosphate synthetase (CPSase) in the PYR1-3 multigene of
RT Dictyostelium discoideum.";
RL DNA Seq. 2:219-226(1992).
CC -!- FUNCTION: This protein is a 'fusion' protein encoding four enzymatic
CC activities of the pyrimidine pathway (GATase, CPSase, ATCase and
CC DHOase).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 ATP + H2O + hydrogencarbonate + L-glutamine = 2 ADP +
CC carbamoyl phosphate + 2 H(+) + L-glutamate + phosphate;
CC Xref=Rhea:RHEA:18633, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58228, ChEBI:CHEBI:58359,
CC ChEBI:CHEBI:456216; EC=6.3.5.5;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=carbamoyl phosphate + L-aspartate = H(+) + N-carbamoyl-L-
CC aspartate + phosphate; Xref=Rhea:RHEA:20013, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29991, ChEBI:CHEBI:32814, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58228; EC=2.1.3.2;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-dihydroorotate + H2O = H(+) + N-carbamoyl-L-aspartate;
CC Xref=Rhea:RHEA:24296, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30864, ChEBI:CHEBI:32814; EC=3.5.2.3;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000305};
CC Note=Binds 1 zinc ion per subunit (for dihydroorotase activity).
CC {ECO:0000305};
CC -!- ACTIVITY REGULATION: Allosterically regulated and controlled by
CC phosphorylation. 5-phosphoribose 1-diphosphate is an activator while
CC UMP is an inhibitor of the CPSase reaction.
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC (S)-dihydroorotate from bicarbonate: step 1/3.
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC (S)-dihydroorotate from bicarbonate: step 2/3.
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC (S)-dihydroorotate from bicarbonate: step 3/3.
CC -!- SUBUNIT: Homohexamer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- DEVELOPMENTAL STAGE: Seen during growth but not during development.
CC -!- MISCELLANEOUS: GATase (glutamine amidotransferase) and CPSase
CC (carbamoyl phosphate synthase) form together the glutamine-dependent
CC CPSase (GD-CPSase) (EC 6.3.5.5).
CC -!- SIMILARITY: In the central section; belongs to the metallo-dependent
CC hydrolases superfamily. DHOase family. CAD subfamily. {ECO:0000305}.
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DR EMBL; AAFI02000014; EAL69248.1; -; Genomic_DNA.
DR EMBL; X14633; CAA32781.1; -; Genomic_DNA.
DR EMBL; X14634; CAA32782.1; -; Genomic_DNA.
DR EMBL; X55433; CAA39077.1; -; Genomic_DNA.
DR PIR; S02800; QZDOP3.
DR PIR; S23738; S23738.
DR RefSeq; XP_643196.1; XM_638104.1.
DR AlphaFoldDB; P20054; -.
DR SMR; P20054; -.
DR STRING; 44689.DDB0201646; -.
DR PaxDb; P20054; -.
DR PRIDE; P20054; -.
DR EnsemblProtists; EAL69248; EAL69248; DDB_G0276335.
DR GeneID; 8620470; -.
DR KEGG; ddi:DDB_G0276335; -.
DR dictyBase; DDB_G0276335; pyr1-3.
DR eggNOG; KOG0370; Eukaryota.
DR HOGENOM; CLU_000513_2_1_1; -.
DR InParanoid; P20054; -.
DR OMA; IPCTSML; -.
DR PhylomeDB; P20054; -.
DR Reactome; R-DDI-500753; Pyrimidine biosynthesis.
DR Reactome; R-DDI-70635; Urea cycle.
DR UniPathway; UPA00070; UER00115.
DR UniPathway; UPA00070; UER00116.
DR UniPathway; UPA00070; UER00117.
DR PRO; PR:P20054; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016597; F:amino acid binding; IEA:InterPro.
DR GO; GO:0004070; F:aspartate carbamoyltransferase activity; IDA:dictyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004088; F:carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity; IDA:dictyBase.
DR GO; GO:0004151; F:dihydroorotase activity; IDA:dictyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; ISS:dictyBase.
DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006541; P:glutamine metabolic process; IDA:dictyBase.
DR GO; GO:0006807; P:nitrogen compound metabolic process; IBA:GO_Central.
DR CDD; cd01744; GATase1_CPSase; 1.
DR Gene3D; 1.10.1030.10; -; 1.
DR Gene3D; 3.30.1490.20; -; 1.
DR Gene3D; 3.40.50.1370; -; 2.
DR Gene3D; 3.40.50.1380; -; 1.
DR Gene3D; 3.40.50.880; -; 1.
DR Gene3D; 3.50.30.20; -; 1.
DR HAMAP; MF_00001; Asp_carb_tr; 1.
DR HAMAP; MF_01209; CPSase_S_chain; 1.
DR InterPro; IPR006680; Amidohydro-rel.
DR InterPro; IPR006132; Asp/Orn_carbamoyltranf_P-bd.
DR InterPro; IPR006130; Asp/Orn_carbamoylTrfase.
DR InterPro; IPR036901; Asp/Orn_carbamoylTrfase_sf.
DR InterPro; IPR002082; Asp_carbamoyltransf.
DR InterPro; IPR006131; Asp_carbamoyltransf_Asp/Orn-bd.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR013815; ATP_grasp_subdomain_1.
DR InterPro; IPR006275; CarbamoylP_synth_lsu.
DR InterPro; IPR005480; CarbamoylP_synth_lsu_oligo.
DR InterPro; IPR036897; CarbamoylP_synth_lsu_oligo_sf.
DR InterPro; IPR006274; CarbamoylP_synth_ssu.
DR InterPro; IPR002474; CarbamoylP_synth_ssu_N.
DR InterPro; IPR036480; CarbP_synth_ssu_N_sf.
DR InterPro; IPR005479; CbamoylP_synth_lsu-like_ATP-bd.
DR InterPro; IPR005483; CbamoylP_synth_lsu_CPSase_dom.
DR InterPro; IPR029062; Class_I_gatase-like.
DR InterPro; IPR035686; CPSase_GATase1.
DR InterPro; IPR002195; Dihydroorotase_CS.
DR InterPro; IPR017926; GATASE.
DR InterPro; IPR011059; Metal-dep_hydrolase_composite.
DR InterPro; IPR032466; Metal_Hydrolase.
DR InterPro; IPR011607; MGS-like_dom.
DR InterPro; IPR036914; MGS-like_dom_sf.
DR InterPro; IPR016185; PreATP-grasp_dom_sf.
DR Pfam; PF01979; Amidohydro_1; 1.
DR Pfam; PF02786; CPSase_L_D2; 2.
DR Pfam; PF02787; CPSase_L_D3; 1.
DR Pfam; PF00988; CPSase_sm_chain; 1.
DR Pfam; PF00117; GATase; 1.
DR Pfam; PF02142; MGS; 1.
DR Pfam; PF00185; OTCace; 1.
DR Pfam; PF02729; OTCace_N; 1.
DR PRINTS; PR00100; AOTCASE.
DR PRINTS; PR00098; CPSASE.
DR SMART; SM01096; CPSase_L_D3; 1.
DR SMART; SM01097; CPSase_sm_chain; 1.
DR SMART; SM00851; MGS; 1.
DR SUPFAM; SSF48108; SSF48108; 1.
DR SUPFAM; SSF51338; SSF51338; 1.
DR SUPFAM; SSF51556; SSF51556; 1.
DR SUPFAM; SSF52021; SSF52021; 1.
DR SUPFAM; SSF52317; SSF52317; 1.
DR SUPFAM; SSF52335; SSF52335; 1.
DR SUPFAM; SSF52440; SSF52440; 2.
DR SUPFAM; SSF53671; SSF53671; 1.
DR TIGRFAMs; TIGR00670; asp_carb_tr; 1.
DR TIGRFAMs; TIGR01369; CPSaseII_lrg; 1.
DR TIGRFAMs; TIGR01368; CPSaseIIsmall; 1.
DR PROSITE; PS50975; ATP_GRASP; 2.
DR PROSITE; PS00097; CARBAMOYLTRANSFERASE; 1.
DR PROSITE; PS00866; CPSASE_1; 2.
DR PROSITE; PS00867; CPSASE_2; 2.
DR PROSITE; PS00482; DIHYDROOROTASE_1; 1.
DR PROSITE; PS00483; DIHYDROOROTASE_2; 1.
DR PROSITE; PS51273; GATASE_TYPE_1; 1.
DR PROSITE; PS51855; MGS; 1.
PE 1: Evidence at protein level;
KW Acetylation; Allosteric enzyme; ATP-binding; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Ligase; Metal-binding;
KW Multifunctional enzyme; Nucleotide-binding; Pyrimidine biosynthesis;
KW Reference proteome; Repeat; Transferase; Zinc.
FT CHAIN 1..2225
FT /note="Protein PYR1-3"
FT /id="PRO_0000199504"
FT DOMAIN 196..388
FT /note="Glutamine amidotransferase type-1"
FT DOMAIN 530..722
FT /note="ATP-grasp 1"
FT DOMAIN 1069..1260
FT /note="ATP-grasp 2"
FT DOMAIN 1324..1470
FT /note="MGS-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01202"
FT REGION 40..390
FT /note="GATase (Glutamine amidotransferase)"
FT REGION 391..405
FT /note="Linker"
FT REGION 406..1461
FT /note="CPSase (Carbamoyl-phosphate synthase)"
FT REGION 406..948
FT /note="CPSase A"
FT REGION 949..1461
FT /note="CPSase B"
FT REGION 1463..1797
FT /note="DHOase (dihydroorotase)"
FT REGION 1798..1916
FT /note="Linker"
FT REGION 1917..2225
FT /note="ATCase (Aspartate transcarbamylase)"
FT ACT_SITE 275
FT /note="For GATase activity"
FT /evidence="ECO:0000250"
FT ACT_SITE 361
FT /note="For GATase activity"
FT /evidence="ECO:0000250"
FT ACT_SITE 363
FT /note="For GATase activity"
FT /evidence="ECO:0000250"
FT BINDING 1479
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255"
FT BINDING 1481
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|Ref.3"
FT CONFLICT 1224..1231
FT /note="NNEIKVIE -> TMKSKLSN (in Ref. 4; CAA32782)"
FT /evidence="ECO:0000305"
FT CONFLICT 1402
FT /note="Missing (in Ref. 5; CAA39077)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2225 AA; 246027 MW; FAE746B19F772AE2 CRC64;
MDILNRKKGC LVLEDGTKLS GYSFGSERSV AGECVFSTGM VGYNESISDP SYTGQILVFS
FPLIGNYGVP SFRERDPESG LAVNFESDKA HVQAIICSEY CDEYSHWAAE KSLSEWLKES
NIPGLYGIDT RALITKIREK GSLKGKVIIG DFDESKLEFE DINLRNLVAE VSTKEIKEYK
AAENNKKTGE KRKNKKVIVL DCGIKNNQIR CLLNRGVDLK VVPWDYDVVA NESINDYDGV
FISNGPGDPS LCGKAIENIR KVLALPVAKA VFGVCMGNQL LGLAAGAQTH KMAFGNRGLN
QPCVDQISGR CHITSQNHGF VIDSNSLPAG SGWKTYFINA NDASNEGIYH ESKPWFSVQF
HPEAMAGPTD TEYLFDNFVD NVCGEQQHKS PMNKSKIIDC PKGINKVLIL GSGGLSIGQA
GEFDYSGSQA IKALKEEGIK TILINPNIAT VQTSPGLADK VYFLPVNASS VQKVIENENP
DGILVTFGGQ TALNCGIELY KSGILEKYNC KVLGTPIETI IATEDRGIFA EKLSEINERI
APSMACNSLE ESLIEAEKIG YPVIVRAAYC LGGLGSGFAD NKEQLTALVT EAMATSSQVL
VEKSLKGWKE IEYEVLRDSK DNCITVCNME NFDPLGIHTG ESIVVAPSQT LSDREYQMLR
ETAIKTVRHL GVIGECNIQY SLNPYSEEYC IIEVNARLSR SSALASKATG YPLAFISAKV
ALGYDLAALR NTITKKTTAC FEPSLDYLVV KMPRWDLKKF TRVSNKISSS MKSVGEVMSI
GRKFEEAIQK AIRMVMDGAV EGFQAGVFPT SDEELEHPTN NRILVLASAF KDGYSIDRVH
QLTKIDKWFL TKLKAIIDLE NHLSTYKEPS QIPSEILKFS KQQGFSDKQI ARAVGTTELN
VRDYRKKMGI IPCTKHIDTV AAEFPAQNNY LYMTYNGETN DVNINEKSYI TLGSGSYRIG
SSVEFDWCAV SCIRTLRSLG LKSIMINFNP ETVSTDYDEC DYLYFEELSL ERVLDIYERG
GPNSNHGVIL SVGGQIPNNL AIPLSRCNVK VLGTHPDMID SAENRYKFSR LLDTIGIDQP
LWKELTSVSD TKDFCESVGF PCLVRPSYVL SGAAMNVVHS SQDLETFLTE AAAVSRDHPV
VISKFIQEAK EIEIDAVADN GRIVLFAISE HVENAGVHSG DATIVCPAQD LDDATILKVE
ETARKIAEAL NVSGPFNIQF IAKNNEIKVI ECNLRCSRSF PFVSKTLNIN FIELATKIII
KHQYDLPVVN PINYVGVKVP QFSFIRLKGA DPVLGVEMAS TGEVACFGNT REEAYVKGLI
STGFKAPEKN VLLSIGSFKE KHEFLPSAHK LIKLGYTLFG TQGTADFYSE NGVPVTQLNW
DEEDLGENVI QKKMTENTIH LFINLPSKNK YRRPSSFMSR GYSLRRVAID FQVPLITNIK
CAKLFVDSLS YMKGPMPIEN VDWRTSNKII RLPGLVDVHV HLREPGATHK EDWDSGTATA
LAGGFTMVGA MPNTNPAIMD DASFELCKSL AASKARCDYG IFIGATFTNT TTAGKFASDA
MGMKMYLEET FAPLPLKDDI NVWRDHIMNW PGTTPICVHA DGRNLAAILL LGWMYDKHMH
VCHVSHKEEI DIIRDAKKRG MKLSCEVSPH HLTLCDKDIP RIGAGQSEVR PKLGTEEDLN
ALWDNIDYID MIATDHAPHT WEEKCSAKPP PGFPGLETSL PLMLTAVHNG RITIEDLVMK
MHTNPIRIFN LPEQPDTYIE VDMEQEWTIP KKPLYSRCGW TPFEGLQVRG KVVKVVLRGQ
IAFIDGKIIA QKGFGLNLRS KEYQVEKERL LNTTKPIYDK IPTVQSTKNQ TTNITSPSLI
SDSPNKAINK IKSTSTSTTP NTQEQSTQHL PLVGSNLASA VLNKKEDTLQ TAFNISDNSL
AGKHIFSVKQ FNRKQLHALF GIAHEMRILV KRSGGSDLLK GKVLATLFYE PSTRTQCSFT
AAMQRLGGSV VTVDNVSSSV AKGESIADTI QTLESYCDAV CMRHPAVGSV ESAIQVAKKP
IINAGDGVGE HPTQALLDVF TIREELGTVN GLTITVVGDL KHGRTVHSLV RLLANYQVKI
NYVSPSSLSM PTEIIKELNE KGIEQKEYTN IESILPTTNV LYVTRVQKER FQSIEEYEKV
KDSFIITPHT LTKASDNMIV MHPLPRINEI SPEVDSDPRA AYFRQMENGL YVRMSLLALV
FGAGV
