Reviewed, UniProtKB/Swiss-Prot P20054 (PYR1_DICDI)

Names and origin

Protein names

Recommended name:
    Protein PYR1-3
Including the following 3 domains:
    1- Recommended name:
            Glutamine-dependent carbamoyl-phosphate synthase
              EC=6.3.5.5
    2- Recommended name:
            Aspartate carbamoyltransferase
              EC=2.1.3.2
    3- Recommended name:
            Dihydroorotase
              EC=3.5.2.3

Gene names

Name:	pyr1-3
ORF Names:	DDB_G0276335

Organism

Dictyostelium discoideum (Slime mold) [Complete proteome]

Taxonomic identifier

44689 [NCBI]

Taxonomic lineage

Eukaryota › Amoebozoa › Mycetozoa › Dictyosteliida › Dictyostelium

Protein attributes

Sequence length	2225 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).
Catalytic activity	2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate. Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate. (S)-dihydroorotate + H2O = N-carbamoyl-L-aspartate.
Cofactor	Binds 1 zinc ion per subunit (for dihydroorotase activity) Potential.
Enzyme regulation	Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate is an activator while UMP is an inhibitor of the CPSase reaction.
Pathway	Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 1/3. Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 2/3. Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 3/3.
Subunit structure	Homohexamer.
Subcellular location	Cytoplasm.
Developmental stage	Seen during growth but not during development.
Miscellaneous	GATase (glutamine amidotransferase) and CPSase (carbamoyl phosphate synthase) form together the glutamine-dependent CPSase (GD-CPSase) (EC 6.3.5.5).
Sequence similarities	In the central section; belongs to the DHOase family. Contains 2 ATP-grasp domains. Contains 1 glutamine amidotransferase type-1 domain.

Ontologies

Keywords
Biological process	Pyrimidine biosynthesis
Cellular component	Cytoplasm
Domain	Repeat
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Hydrolase Ligase Transferase
PTM	Acetylation
Technical term	Allosteric enzyme Complete proteome Direct protein sequencing Multifunctional enzyme
Gene Ontology (GO)
Biological process	'de novo' pyrimidine base biosynthetic process Inferred from electronic annotation. Source: InterPro glutamine metabolic process Inferred from direct assay. Source: dictyBase pyrimidine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW amino acid binding Inferred from electronic annotation. Source: InterPro aspartate carbamoyltransferase activity Inferred from direct assay. Source: dictyBase carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity Inferred from direct assay. Source: dictyBase dihydroorotase activity Inferred from direct assay. Source: dictyBase zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 2225	2225	Protein PYR1-3		PRO_0000199504
Regions
	Domain	196 – 388	193	Glutamine amidotransferase type-1
	Domain	530 – 722	193	ATP-grasp 1
	Domain	1069 – 1260	192	ATP-grasp 2
	Region	40 – 390	351	GATase (Glutamine amidotransferase)
	Region	391 – 405	15	Linker
	Region	406 – 1461	1056	CPSase (Carbamoyl-phosphate synthase)
	Region	406 – 948	543	CPSase A
	Region	949 – 1461	513	CPSase B
	Region	1463 – 1797	335	DHOase (dihydroorotase)
	Region	1798 – 1916	119	Linker
	Region	1917 – 2225	309	ATCase (Aspartate transcarbamylase)
Sites
	Active site	275	1	For GATase activity By similarity
	Active site	361	1	For GATase activity By similarity
	Active site	363	1	For GATase activity By similarity
	Metal binding	1479	1	Zinc Potential
	Metal binding	1481	1	Zinc Potential
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.3
Experimental info
	Sequence conflict	1224 – 1231	8	NNEIKVIE → TMKSKLSN in CAA32782. Ref.4
	Sequence conflict	1402	1	Missing in CAA39077. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P20054-1 [UniParc]. Last modified December 4, 2007. Version 3. Checksum: FAE746B19F772AE2	FASTA	2,225	246,027
	10 20 30 40 50 60 MDILNRKKGC LVLEDGTKLS GYSFGSERSV AGECVFSTGM VGYNESISDP SYTGQILVFS 70 80 90 100 110 120 FPLIGNYGVP SFRERDPESG LAVNFESDKA HVQAIICSEY CDEYSHWAAE KSLSEWLKES 130 140 150 160 170 180 NIPGLYGIDT RALITKIREK GSLKGKVIIG DFDESKLEFE DINLRNLVAE VSTKEIKEYK 190 200 210 220 230 240 AAENNKKTGE KRKNKKVIVL DCGIKNNQIR CLLNRGVDLK VVPWDYDVVA NESINDYDGV 250 260 270 280 290 300 FISNGPGDPS LCGKAIENIR KVLALPVAKA VFGVCMGNQL LGLAAGAQTH KMAFGNRGLN 310 320 330 340 350 360 QPCVDQISGR CHITSQNHGF VIDSNSLPAG SGWKTYFINA NDASNEGIYH ESKPWFSVQF 370 380 390 400 410 420 HPEAMAGPTD TEYLFDNFVD NVCGEQQHKS PMNKSKIIDC PKGINKVLIL GSGGLSIGQA 430 440 450 460 470 480 GEFDYSGSQA IKALKEEGIK TILINPNIAT VQTSPGLADK VYFLPVNASS VQKVIENENP 490 500 510 520 530 540 DGILVTFGGQ TALNCGIELY KSGILEKYNC KVLGTPIETI IATEDRGIFA EKLSEINERI 550 560 570 580 590 600 APSMACNSLE ESLIEAEKIG YPVIVRAAYC LGGLGSGFAD NKEQLTALVT EAMATSSQVL 610 620 630 640 650 660 VEKSLKGWKE IEYEVLRDSK DNCITVCNME NFDPLGIHTG ESIVVAPSQT LSDREYQMLR 670 680 690 700 710 720 ETAIKTVRHL GVIGECNIQY SLNPYSEEYC IIEVNARLSR SSALASKATG YPLAFISAKV 730 740 750 760 770 780 ALGYDLAALR NTITKKTTAC FEPSLDYLVV KMPRWDLKKF TRVSNKISSS MKSVGEVMSI 790 800 810 820 830 840 GRKFEEAIQK AIRMVMDGAV EGFQAGVFPT SDEELEHPTN NRILVLASAF KDGYSIDRVH 850 860 870 880 890 900 QLTKIDKWFL TKLKAIIDLE NHLSTYKEPS QIPSEILKFS KQQGFSDKQI ARAVGTTELN 910 920 930 940 950 960 VRDYRKKMGI IPCTKHIDTV AAEFPAQNNY LYMTYNGETN DVNINEKSYI TLGSGSYRIG 970 980 990 1000 1010 1020 SSVEFDWCAV SCIRTLRSLG LKSIMINFNP ETVSTDYDEC DYLYFEELSL ERVLDIYERG 1030 1040 1050 1060 1070 1080 GPNSNHGVIL SVGGQIPNNL AIPLSRCNVK VLGTHPDMID SAENRYKFSR LLDTIGIDQP 1090 1100 1110 1120 1130 1140 LWKELTSVSD TKDFCESVGF PCLVRPSYVL SGAAMNVVHS SQDLETFLTE AAAVSRDHPV 1150 1160 1170 1180 1190 1200 VISKFIQEAK EIEIDAVADN GRIVLFAISE HVENAGVHSG DATIVCPAQD LDDATILKVE 1210 1220 1230 1240 1250 1260 ETARKIAEAL NVSGPFNIQF IAKNNEIKVI ECNLRCSRSF PFVSKTLNIN FIELATKIII 1270 1280 1290 1300 1310 1320 KHQYDLPVVN PINYVGVKVP QFSFIRLKGA DPVLGVEMAS TGEVACFGNT REEAYVKGLI 1330 1340 1350 1360 1370 1380 STGFKAPEKN VLLSIGSFKE KHEFLPSAHK LIKLGYTLFG TQGTADFYSE NGVPVTQLNW 1390 1400 1410 1420 1430 1440 DEEDLGENVI QKKMTENTIH LFINLPSKNK YRRPSSFMSR GYSLRRVAID FQVPLITNIK 1450 1460 1470 1480 1490 1500 CAKLFVDSLS YMKGPMPIEN VDWRTSNKII RLPGLVDVHV HLREPGATHK EDWDSGTATA 1510 1520 1530 1540 1550 1560 LAGGFTMVGA MPNTNPAIMD DASFELCKSL AASKARCDYG IFIGATFTNT TTAGKFASDA 1570 1580 1590 1600 1610 1620 MGMKMYLEET FAPLPLKDDI NVWRDHIMNW PGTTPICVHA DGRNLAAILL LGWMYDKHMH 1630 1640 1650 1660 1670 1680 VCHVSHKEEI DIIRDAKKRG MKLSCEVSPH HLTLCDKDIP RIGAGQSEVR PKLGTEEDLN 1690 1700 1710 1720 1730 1740 ALWDNIDYID MIATDHAPHT WEEKCSAKPP PGFPGLETSL PLMLTAVHNG RITIEDLVMK 1750 1760 1770 1780 1790 1800 MHTNPIRIFN LPEQPDTYIE VDMEQEWTIP KKPLYSRCGW TPFEGLQVRG KVVKVVLRGQ 1810 1820 1830 1840 1850 1860 IAFIDGKIIA QKGFGLNLRS KEYQVEKERL LNTTKPIYDK IPTVQSTKNQ TTNITSPSLI 1870 1880 1890 1900 1910 1920 SDSPNKAINK IKSTSTSTTP NTQEQSTQHL PLVGSNLASA VLNKKEDTLQ TAFNISDNSL 1930 1940 1950 1960 1970 1980 AGKHIFSVKQ FNRKQLHALF GIAHEMRILV KRSGGSDLLK GKVLATLFYE PSTRTQCSFT 1990 2000 2010 2020 2030 2040 AAMQRLGGSV VTVDNVSSSV AKGESIADTI QTLESYCDAV CMRHPAVGSV ESAIQVAKKP 2050 2060 2070 2080 2090 2100 IINAGDGVGE HPTQALLDVF TIREELGTVN GLTITVVGDL KHGRTVHSLV RLLANYQVKI 2110 2120 2130 2140 2150 2160 NYVSPSSLSM PTEIIKELNE KGIEQKEYTN IESILPTTNV LYVTRVQKER FQSIEEYEKV 2170 2180 2190 2200 2210 2220 KDSFIITPHT LTKASDNMIV MHPLPRINEI SPEVDSDPRA AYFRQMENGL YVRMSLLALV FGAGV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence and analysis of chromosome 2 of Dictyostelium discoideum." Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T., Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R., Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A., Noegel A.A. Nature 418:79-85(2002) [PubMed: 12097910] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: AX4.
[2]	"The genome of the social amoeba Dictyostelium discoideum." Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R., Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B., Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T., Lehmann R., Hamlin N. , Davies R., Gaudet P., Fey P., Pilcher K., Chen G., Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N., Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E., Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N., Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D., Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T., Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D., Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A., Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M., Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A., Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y., Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C., Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R., Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A. Nature 435:43-57(2005) [PubMed: 15875012] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: AX4.
[3]	Bienvenut W.V., Ura S., Insall R.H. Submitted (JUL-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 1-6; 262-269; 461-473; 559-566; 720-730; 773-782; 823-831; 893-902; 948-958; 1013-1019; 1051-1065; 1279-1286; 1427-1440 AND 1732-1740, ACETYLATION AT MET-1, MASS SPECTROMETRY. Strain: AX2.
[4]	"Molecular characterization of a Dictyostelium discoideum gene encoding a multifunctional enzyme of the pyrimidine pathway." Faure M., Camonis J.H., Jacquet M. Eur. J. Biochem. 179:345-358(1989) [PubMed: 2917570] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 40-506 AND 1214-2224. Strain: AX3.
[5]	"Carbamoyl phosphate synthetase (CPSase) in the PYR1-3 multigene of Dictyostelium discoideum." Elgar G., Schofield J.P. DNA Seq. 2:219-226(1992) [PubMed: 1627825] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 406-1447. Strain: AX2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AAFI02000014 Genomic DNA. Translation: EAL69248.1. X14633 Genomic DNA. Translation: CAA32781.1. X14634 Genomic DNA. Translation: CAA32782.1. X55433 Genomic DNA. Translation: CAA39077.1.
PIR	QZDOP3. S02800. S23738.
RefSeq	XP_643196.1.
3D structure databases
SMR	P20054. Positions 197-584, 1468-1792, 1470-1822, 1920-2223.
ModBase	Search...
Protein-protein interaction databases
STRING	P20054.
Genome annotation databases
GeneID	8620470.
KEGG	ddi:DDB_0201646.
Organism-specific databases
dictyBase	DDB_G0276335. pyr1-3.
Phylogenomic databases
eggNOG	KOG0370.
HOGENOM	HBG405439.
OMA	TIQTSKG.
PhylomeDB	P20054.
Enzyme and pathway databases
BRENDA	2.1.3.2. 424. 3.5.2.3. 424. 6.3.5.5. 424.
Family and domain databases
InterPro	IPR006680. Amidohydro_1. IPR006132. Asp/Orn_carbamoyltranf_P_bd. IPR006130. Asp/Orn_carbamoylTrfase. IPR006131. Asp_carbamoyltransf_Asp/Orn_bd. IPR002082. Asp_carbamoyltransf_euk. IPR011761. ATP-grasp. IPR013816. ATP_grasp_subdomain_2. IPR001317. CarbamoylP_synth_GATase_dom. IPR005483. CarbamoylP_synth_lsu. IPR005479. CarbamoylP_synth_lsu_ATP-bd. IPR006275. CarbamoylP_synth_lsu_Gln-dep. IPR005481. CarbamoylP_synth_lsu_N. IPR005480. CarbamoylP_synth_lsu_oligo. IPR006274. CarbamoylP_synth_ssu. IPR002474. CarbamoylP_synth_ssu_N. IPR004722. DHOmult. IPR002195. Dihydroorotase_CS. IPR011702. GATASE. IPR017926. GATASE_1. IPR000991. GATase_class1_C. IPR011059. Metal-dep_hydrolase_composite. IPR011607. MGS. IPR013817. Pre-ATP_grasp. IPR016185. PreATP-grasp-like. [Graphical view]
Gene3D	G3DSA:3.30.470.20. ATP_grasp_subdomain_2. 2 hits. G3DSA:3.40.50.20. Pre-ATP_grasp. 4 hits.
Pfam	PF01979. Amidohydro_1. 1 hit. PF00289. CPSase_L_chain. 2 hits. PF02786. CPSase_L_D2. 2 hits. PF02787. CPSase_L_D3. 1 hit. PF00988. CPSase_sm_chain. 1 hit. PF00117. GATase. 1 hit. PF02142. MGS. 1 hit. PF00185. OTCace. 1 hit. PF02729. OTCace_N. 1 hit. [Graphical view]
PRINTS	PR00100. AOTCASE. PR00101. ATCASE. PR00098. CPSASE. PR00099. CPSGATASE. PR00096. GATASE.
SMART	SM00851. MGS. 1 hit. [Graphical view]
TIGRFAMs	TIGR00670. asp_carb_tr. 1 hit. TIGR01369. CPSaseII_lrg. 1 hit. TIGR01368. CPSaseIIsmall. 1 hit. TIGR00857. pyrC_multi. 1 hit.
PROSITE	PS50975. ATP_GRASP. 2 hits. PS00097. CARBAMOYLTRANSFERASE. 1 hit. PS00866. CPSASE_1. 2 hits. PS00867. CPSASE_2. 2 hits. PS00482. DIHYDROOROTASE_1. 1 hit. PS00483. DIHYDROOROTASE_2. 1 hit. PS51273. GATASE_TYPE_1. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

PYR1_DICDI

Accession

Primary (citable) accession number: P20054
Secondary accession number(s): Q551R5, Q86AD0

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	December 4, 2007
Last modified:	February 9, 2010
This is version 102 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)