ID A0A3P8NFU8_ASTCA Unreviewed; 2234 AA.
AC A0A3P8NFU8;
DT 13-FEB-2019, integrated into UniProtKB/TrEMBL.
DT 13-FEB-2019, sequence version 1.
DT 24-JAN-2024, entry version 23.
DE RecName: Full=CAD protein {ECO:0000256|ARBA:ARBA00017075};
DE EC=2.1.3.2 {ECO:0000256|ARBA:ARBA00013008};
DE EC=3.5.2.3 {ECO:0000256|ARBA:ARBA00012860};
DE EC=6.3.5.5 {ECO:0000256|ARBA:ARBA00012738};
OS Astatotilapia calliptera (Eastern happy) (Chromis callipterus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC Ovalentaria; Cichlomorphae; Cichliformes; Cichlidae; African cichlids;
OC Pseudocrenilabrinae; Haplochromini; Astatotilapia.
OX NCBI_TaxID=8154 {ECO:0000313|Ensembl:ENSACLP00000003644.1, ECO:0000313|Proteomes:UP000265100};
RN [1] {ECO:0000313|Ensembl:ENSACLP00000003644.1, ECO:0000313|Proteomes:UP000265100}
RP NUCLEOTIDE SEQUENCE.
RA Datahose.;
RL Submitted (MAY-2018) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSACLP00000003644.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-2023) to UniProtKB.
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 Evidence={ECO:0000256|ARBA:ARBA00000462};
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 Evidence={ECO:0000256|ARBA:ARBA00001777};
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 Evidence={ECO:0000256|ARBA:ARBA00001363};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000256|ARBA:ARBA00001947};
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC (S)-dihydroorotate from bicarbonate: step 1/3.
CC {ECO:0000256|ARBA:ARBA00004812}.
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC (S)-dihydroorotate from bicarbonate: step 2/3.
CC {ECO:0000256|ARBA:ARBA00004852}.
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC (S)-dihydroorotate from bicarbonate: step 3/3.
CC {ECO:0000256|ARBA:ARBA00004880}.
CC -!- SIMILARITY: In the central section; belongs to the metallo-dependent
CC hydrolases superfamily. DHOase family. CAD subfamily.
CC {ECO:0000256|ARBA:ARBA00008454}.
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DR STRING; 8154.ENSACLP00000003644; -.
DR Ensembl; ENSACLT00000003724.1; ENSACLP00000003644.1; ENSACLG00000002358.1.
DR GeneTree; ENSGT00940000157241; -.
DR OMA; FTGDLRY; -.
DR OrthoDB; 309at2759; -.
DR UniPathway; UPA00070; UER00115.
DR Proteomes; UP000265100; Chromosome 15.
DR Bgee; ENSACLG00000002358; Expressed in liver and 7 other cell types or tissues.
DR GO; GO:0016597; F:amino acid binding; IEA:InterPro.
DR GO; GO:0004070; F:aspartate carbamoyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004088; F:carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity; IEA:UniProtKB-EC.
DR GO; GO:0004151; F:dihydroorotase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IEA:InterPro.
DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-UniRule.
DR CDD; cd01316; CAD_DHOase; 1.
DR CDD; cd01744; GATase1_CPSase; 1.
DR CDD; cd01423; MGS_CPS_I_III; 1.
DR Gene3D; 3.40.50.20; -; 2.
DR Gene3D; 3.40.50.880; -; 1.
DR Gene3D; 3.40.50.1370; Aspartate/ornithine carbamoyltransferase; 2.
DR Gene3D; 3.30.1490.20; ATP-grasp fold, A domain; 1.
DR Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 2.
DR Gene3D; 3.50.30.20; Carbamoyl-phosphate synthase small subunit, N-terminal domain; 1.
DR Gene3D; 1.10.1030.10; Carbamoyl-phosphate synthetase, large subunit oligomerisation domain; 1.
DR Gene3D; 3.20.20.140; Metal-dependent hydrolases; 1.
DR Gene3D; 3.40.50.1380; Methylglyoxal synthase-like domain; 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 NCBIfam; TIGR00670; asp_carb_tr; 1.
DR NCBIfam; TIGR01369; CPSaseII_lrg; 1.
DR NCBIfam; TIGR01368; CPSaseIIsmall; 1.
DR NCBIfam; TIGR00857; pyrC_multi; 1.
DR PANTHER; PTHR11405:SF5; CAD PROTEIN; 1.
DR PANTHER; PTHR11405; CARBAMOYLTRANSFERASE FAMILY MEMBER; 1.
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; PR00101; ATCASE.
DR PRINTS; PR00098; CPSASE.
DR PRINTS; PR00099; CPSGATASE.
DR SMART; SM01096; CPSase_L_D3; 1.
DR SMART; SM01097; CPSase_sm_chain; 1.
DR SMART; SM00851; MGS; 1.
DR SUPFAM; SSF53671; Aspartate/ornithine carbamoyltransferase; 1.
DR SUPFAM; SSF48108; Carbamoyl phosphate synthetase, large subunit connection domain; 1.
DR SUPFAM; SSF52021; Carbamoyl phosphate synthetase, small subunit N-terminal domain; 1.
DR SUPFAM; SSF52317; Class I glutamine amidotransferase-like; 1.
DR SUPFAM; SSF51338; Composite domain of metallo-dependent hydrolases; 1.
DR SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 2.
DR SUPFAM; SSF51556; Metallo-dependent hydrolases; 1.
DR SUPFAM; SSF52335; Methylglyoxal synthase-like; 1.
DR SUPFAM; SSF52440; PreATP-grasp domain; 2.
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 3: Inferred from homology;
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PROSITE-
KW ProRule:PRU00409};
KW Glutamine amidotransferase {ECO:0000256|PROSITE-ProRule:PRU00605};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801};
KW Ligase {ECO:0000256|ARBA:ARBA00022598};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW Multifunctional enzyme {ECO:0000256|ARBA:ARBA00023268};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|PROSITE-
KW ProRule:PRU00409}; Pyrimidine biosynthesis {ECO:0000256|ARBA:ARBA00022975};
KW Repeat {ECO:0000256|ARBA:ARBA00022737};
KW Transferase {ECO:0000256|ARBA:ARBA00022679}.
FT DOMAIN 520..712
FT /note="ATP-grasp"
FT /evidence="ECO:0000259|PROSITE:PS50975"
FT DOMAIN 1056..1247
FT /note="ATP-grasp"
FT /evidence="ECO:0000259|PROSITE:PS50975"
FT DOMAIN 1312..1469
FT /note="MGS-like"
FT /evidence="ECO:0000259|PROSITE:PS51855"
FT REGION 1817..1863
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1832..1853
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 255
FT /note="Nucleophile"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00605"
FT ACT_SITE 339
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00605"
FT ACT_SITE 341
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00605"
SQ SEQUENCE 2234 AA; 247228 MW; 5DB7B372C3ED6999 CRC64;
MANMATLILE DGTTFKGRQF GASVSVSGEV VFQTGMVGYP EALTDPSYRC QLLTLTYPLV
GNYGVPMDEE GEFGLSKWFE SYKIHAAALI IGELSESPSH WSSAKSLDQW LKEQGIPGLQ
GVDTRCLTKK IREKGTMLGK LIVDGTPEES IPFDNPDKRN LVREVSMKEP KVFNHSGSFR
ITVVDCGIKY NQIRCLAQRG ARVTVVPWDH PLDTADFDGL FVSNGPGDPQ LCQATINNVR
KVISVDQPKP VFGICLGHQL LSLVIGAKTY KMKYGNRGHN QPCIHNGTER CFITSQNHGF
AVDPDTLPKD WDVLFTNAND HTNEGIVHNT KPLFSVQFHP EHMAGPTDLV GLFDVFIETV
KDHKEGNTGK SVKQRLMDHL TFTGSPKAEG HVRSKKVLIL GSGGLSIGQA GEFDYSGSQA
IKALKEENIQ TVLINPNIAT VQTSKDLADK VYFLPITAEY VTQVIKNERP DGVLLTFGGQ
TALNCGVELT KLGVLEKYKV QVLGTPVSSI EMTEDRKIFV EKMEEINEHV APSEAALSVE
QAVAAAERLG YPVLVRSAFA LGGLGSGFAN NREELTSLVT AAFAHTSQVL VDKSLKGWKE
IEYEVVRDAY DNCVTVCNME NIDPLGIHTG ESIVVAPSQT LNDREYNMLR NTAIKVIRHL
GIVGECNIQY ALNPESEQYY IIEVNARLSR SSALASKATG YPLAYVAAKL GLGIPLPQLK
NSVTNSTTAN FEPSLDYCVV KVPRWDLSKF LRVSTKIGSS MKSVGEVMAI GRSFEEAFQK
ALRMVDENCV GFDHTIKPVS EKELQTPTDK RIFVLAAAFK AGYTVEKLYE LTKIDRWFLH
KMKNIADHEL LLETYNQDES SMPPEVMLKA KQLGFSDKQI ALAVQSTELA VRKLRHDWSI
LPVVKQIDTV AAEWPAYTNY LYLTYHGTED DLSFNDQHVM VIGSGVYRIG SSVEFDWCAV
GCITELRKMG YKTIMVNYNP ETVSTDYDMC DRLYFDEISF EVVMDIYERE NPEGVILSMG
GQLPNNIAMS LHRQQCHILG TSPEFIDSAE NRFKFSRMLD TIGISQPQWK ELSDTESAVK
FCETVGYPCL VRPSYVLSGA AMNVAYSDSD LEKYLSNAVA VSKEHPVVIS KFIQEAKEID
VDAVACDGVV MGIAISEHVE NAGVHSGDAT LVTPPQDLNQ KTIERIMQIV HAIGQELQVT
GPFNLQLIAK DDQLKVIECN VRVSRSFPFV SKTLGVDLVA LATQYIMGED VEPVGLMKGK
GIVGVKVPQF SFSRLAGADV VLGVEMTSTG EVACFGENRY EAYLKAMLST GFKIPKKNIL
LSIGSYKNKS ELLPTVQALE SLGYDLYASM GTADFYTEHG VKVTAIDWPF EEYDSDECAT
KEKQRSIMNY LEENHFDLVI NLSMRNSGGR RLSSFVTKGY RTRRMAIDYS VPLIIDIKCT
KLFVQALRQI GRTPPVKTHV DSMASQTLVR LPGLIDVHVH LREPGATHKE DFSSGTAAAL
AGGVTLVCAM PNTSPAITDA NNLALVQKLA KAGSRCDYAL YVGAATDNAA VLPPIASQTA
GLKMYLNDTY STLKMDNVSL WMEHFEKWPK QMPIVAHAEK QTVAAILMVA QLYQRPVHIC
HVAKKEEILI IRAAKQKGIQ VTCEVAPHHL FLCEDNVAQI GDGRAQVRPM LGTREDMETL
WENLDIIDCF ATDHAPHSVD EKNSERPPPG YPGLETMLPL LLTSVSDGRL TLDDITRRLY
DNPRRIFNLP VQENTYVEVD LEQEWVIPQA MQFTKSKWTP FEGMKVKGKV RRVVLRGEVA
YIDGQVLVPP GYGEDVKTWP TSSTHPPEPV KETPMTPERR RPTPPRDGVR TRAASPRRIG
GESRYLLPPR IHRASDPGLP PEMVMLPPAA AVDGYSHPPP LSRLLSPQSG SGQVPPGQVS
HLQMSPLLHP LVGQHILSVR QFSKEQISHL FNVAHTLRLM VQKERSLEIL KGKVMASIFY
EVSTRTSSSF AAAMQRLGGS VVHSSEATSS SLKGESLADS VQIMSGYADV LVLRHPTPGA
VESASRQCRK PLINAGDGVG EHPTQALLDV FTIREELGTV NGMTITMVGD LKHGRTVHSL
AKLLTQYRIT LRYVAPKNLH MPAEIVSYVA SKGIKQEEFD SIEEALPDTD VLYMTRIQKE
RFASEEEYKA CFGQFVLTPH IMTGAKQKMV VMHPLPRVNE ISVEVDTDPR AAYFRQAENG
MYIRMALLAT VLGR
//