Glutamine-dependent carbamoyl-phosphate synthase
     (EC 6.3.5.5)
Aspartate carbamoyltransferase
     (EC 2.1.3.2)
Dihydroorotase
     (EC 3.5.2.3)

Gene name

	Name:	pyr1-3
	ORFNames:	DDB_0201646

From

Dictyostelium discoideum (Slime mold)

[TaxID: 44689]

Taxonomy

Eukaryota; Amoebozoa; Mycetozoa; Dictyosteliida; Dictyostelium.

Protein existence

2: Evidence at transcript level;

References

[1]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. STRAIN=AX4; DOI=10.1038/nature00847; PubMed=12097910 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Sequence and analysis of chromosome 2 of Dictyostelium discoideum."; Nature 418:79-85(2002).
[2]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. STRAIN=AX4; DOI=10.1038/nature03481; PubMed=15875012 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "The genome of the social amoeba Dictyostelium discoideum."; Nature 435:43-57(2005).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 40-506 AND 1214-2224. STRAIN=AX3; PubMed=2917570 [NCBI, ExPASy, EBI, Israel, Japan] Faure M., Camonis J.H., Jacquet M.; "Molecular characterization of a Dictyostelium discoideum gene encoding a multifunctional enzyme of the pyrimidine pathway."; Eur. J. Biochem. 179:345-358(1989).
[4]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 406-1447. STRAIN=AX2; PubMed=1627825 [NCBI, ExPASy, EBI, Israel, Japan] Elgar G., Schofield J.P.; "Carbamoyl phosphate synthetase (CPSase) in the PYR1-3 multigene of Dictyostelium discoideum."; DNA Seq. 2:219-226(1992).

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.
CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate.
CATALYTIC ACTIVITY: (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. PRPP is an activator while UMP is an inhibitor of the CPSase reaction.
PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; UMP from HCO(3)(-): step 1/6 .
PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; UMP from HCO(3)(-): step 2/6 .
PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; UMP from HCO(3)(-): step 3/6 .
SUBUNIT: 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).
SIMILARITY: In the central section; belongs to the DHOase family.
SIMILARITY: Contains 2 ATP-grasp domains.
SIMILARITY: Contains 1 glutamine amidotransferase type-1 domain.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AC115592; AAO51647.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AAFI02000014; EAL69248.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X14633; CAA32781.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X14634; CAA32782.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X55433; CAA39077.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

S02800; QZDOP3.
S23738; S23738.

RefSeq

XP_643196.1; -.

3D structure databases

HSSP

P77918; 1ML4. [HSSP ENTRY / PDB]

ModBase

P20054.

Organism-specific databases

dictyBase

DDB0201646; pyr1-3.

Ontologies

GO:0004088;	Molecular function: carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity (inferred from electronic annotation from EC).
QuickGo view.

Family and domain databases

InterPro

IPR006680; Amidohydro_1.
IPR006130; Asp/Orn_carbamoyltranf.
IPR006132; Asp/Orn_carbamoyltranf_P_bd.
IPR006131; Asp_carbamoyltransf_Asp/Orn_bd.
IPR002082; Aspartate_carbamoyltransf_euk.
IPR011761; ATP-grasp.
IPR013816; ATP_grasp_subdomain_2.
IPR001317; CarbamoylP_synth_GATase.
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.
IPR012998; GATase_1_AS.
IPR000991; GATase_class1_C.
IPR011607; MGS.
IPR013817; Pre-ATP_grasp.
Graphical view of domain structure.

Gene3D

G3DSA:3.30.470.20; ATP_grasp_subdomain_2; 2.
G3DSA:3.40.50.20; Pre-ATP_grasp; 4.

Pfam

PF01979; Amidohydro_1; 2.
PF00289; CPSase_L_chain; 4.
PF02786; CPSase_L_D2; 4.
PF02787; CPSase_L_D3; 2.
PF00988; CPSase_sm_chain; 2.
PF00117; GATase; 2.
PF02142; MGS; 2.
PF00185; OTCace; 2.
PF02729; OTCace_N; 2.
Pfam graphical view of domain structure.

PRINTS

PR00100; AOTCASE.
PR00101; ATCASE.
PR00098; CPSASE.
PR00099; CPSGATASE.
PR00096; GATASE.

TIGRFAMs

TIGR00670; asp_carb_tr; 1.
TIGR01369; CPSaseII_lrg; 1.
TIGR01368; CPSaseIIsmall; 1.
TIGR00857; pyrC_multi; 1.

PROSITE

PS50975; ATP_GRASP; 2.
PS00097; CARBAMOYLTRANSFERASE; 1.
PS00866; CPSASE_1; 2.
PS00867; CPSASE_2; 2.
PS00482; DIHYDROOROTASE_1; 1.
PS00483; DIHYDROOROTASE_2; 1.
PS51273; GATASE_TYPE_1; 1.
PROSITE graphical view of domain structure (profiles).

BLOCKS

P20054.

Genome annotation databases

GeneID

3394344; -.

KEGG

ddi:DDB_0201646; -.

Other

ProtoNet

P20054.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Allosteric enzyme; Complete proteome; Cytoplasm; Hydrolase; Ligase; Metal-binding; Multifunctional enzyme; Pyrimidine biosynthesis; Repeat; Transferase; Zinc.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 2225`	`2225`	`Protein PYR1-3.`	`PRO_0000199504`
`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).`
`ACT_SITE`	`275 275`		`For GATase activity (By similarity).`
`ACT_SITE`	`361 361`		`For GATase activity (By similarity).`
`ACT_SITE`	`363 363`		`For GATase activity (By similarity).`
`METAL`	`1479 1479`		`Zinc (Potential).`
`METAL`	`1481 1481`		`Zinc (Potential).`
`CONFLICT`	`1224 1231`		`NNEIKVIE -> TMKSKLSN (in Ref. 3; CAA32782).`
`CONFLICT`	`1402 1402`		`Missing (in Ref. 4; CAA39077).`

Sequence information

Length: 2225 AA [This is the length of the unprocessed precursor]

Molecular weight: 246027 Da [This is the MW of the unprocessed precursor]

CRC64: FAE746B19F772AE2 [This is a checksum on the sequence]

        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

P20054 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools