Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

CAD protein

Gene

CAD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).1 Publication

Catalytic activityi

2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate.1 Publication
Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate.1 Publication
(S)-dihydroorotate + H2O = N-carbamoyl-L-aspartate.1 Publication

Cofactori

Zn2+2 PublicationsNote: Binds 3 Zn2+ ions per subunit (for dihydroorotase activity).2 Publications

Enzyme regulationi

Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate (PRPP) is an activator while UMP and UTP are inhibitors of the CPSase reaction.1 Publication

Kineticsi

  1. KM=28 µM for dihydroorotate1 Publication
  2. KM=241 µM for N-carbamoyl-L-aspartate1 Publication

    Pathwayi: UMP biosynthesis via de novo pathway

    This protein is involved in step 1, 2 and 3 of the subpathway that synthesizes (S)-dihydroorotate from bicarbonate.
    Proteins known to be involved in the 3 steps of the subpathway in this organism are:
    1. CAD protein (CAD)
    2. CAD protein (CAD)
    3. CAD protein (CAD)
    This subpathway is part of the pathway UMP biosynthesis via de novo pathway, which is itself part of Pyrimidine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes (S)-dihydroorotate from bicarbonate, the pathway UMP biosynthesis via de novo pathway and in Pyrimidine metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei252For GATase activityBy similarity1
    Active sitei336For GATase activityBy similarity1
    Active sitei338For GATase activityBy similarity1
    Metal bindingi1471Zinc 1; via tele nitrogen1 Publication1
    Metal bindingi1471Zinc 2; via pros nitrogen1 Publication1
    Metal bindingi1473Zinc 1; via tele nitrogen1 Publication1
    Binding sitei1475N-carbamoyl-L-aspartate1
    Binding sitei1505N-carbamoyl-L-aspartate1
    Metal bindingi1556Zinc 1; via carbamate group1 Publication1
    Metal bindingi1556Zinc 3; via carbamate group1 Publication1
    Metal bindingi1590Zinc 3; via pros nitrogen1 Publication1
    Metal bindingi1613Zinc 21 Publication1
    Metal bindingi1614Zinc 3; via tele nitrogen1 Publication1
    Metal bindingi1637Zinc 21 Publication1
    Binding sitei1661N-carbamoyl-L-aspartate; via amide nitrogen and carbonyl oxygen1
    Metal bindingi1686Zinc 11 Publication1
    Binding sitei1686N-carbamoyl-L-aspartate1
    Binding sitei1690N-carbamoyl-L-aspartate1

    GO - Molecular functioni

    GO - Biological processi

    Keywords - Molecular functioni

    Hydrolase, Ligase, Transferase

    Keywords - Biological processi

    Pyrimidine biosynthesis

    Keywords - Ligandi

    ATP-binding, Metal-binding, Nucleotide-binding, Zinc

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000084774-MONOMER.
    ZFISH:ENSG00000084774-MONOMER.
    BRENDAi3.5.2.3. 2681.
    ReactomeiR-HSA-500753. Pyrimidine biosynthesis.
    SIGNORiP27708.
    UniPathwayiUPA00070; UER00115.
    UPA00070; UER00116.
    UPA00070; UER00117.

    Protein family/group databases

    MEROPSiM38.972.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    CAD protein
    Including the following 3 domains:
    Glutamine-dependent carbamoyl-phosphate synthase (EC:6.3.5.5)
    Aspartate carbamoyltransferase (EC:2.1.3.2)
    Dihydroorotase (EC:3.5.2.3)
    Gene namesi
    Name:CAD
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:1424. CAD.

    Subcellular locationi

    GO - Cellular componenti

    • cell projection Source: BHF-UCL
    • cytosol Source: BHF-UCL
    • extracellular exosome Source: UniProtKB
    • membrane Source: UniProtKB
    • neuronal cell body Source: BHF-UCL
    • nuclear matrix Source: BHF-UCL
    • nucleoplasm Source: HPA
    • nucleus Source: BHF-UCL
    • protein complex Source: Ensembl
    • terminal bouton Source: BHF-UCL

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Congenital disorder of glycosylation 1Z (CDG1Z)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1Z patients show abnormal glycosylation of red blood cell proteins, but glycosylation of serum transferrin is normal.
    See also OMIM:616457
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_0739552024R → Q in CDG1Z. 1 PublicationCorresponds to variant rs763410987dbSNPEnsembl.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi1471H → A: No zinc-binding and no catalytic activity. 2 Publications1
    Mutagenesisi1471H → N: Abolishes dihydroorotase activity. 2 Publications1
    Mutagenesisi1473H → A: No zinc-binding and no catalytic activity. 1 Publication1
    Mutagenesisi1512D → N: No change in catalytic activity. 1 Publication1
    Mutagenesisi1562T → A: Abolishes dihydroorotase activity. 1 Publication1
    Mutagenesisi1563F → A: Abolishes dihydroorotase activity. 1 Publication1
    Mutagenesisi1590H → A: Abolishes dihydroorotase activity. 2 Publications1
    Mutagenesisi1590H → N: No catalytic activity. 2 Publications1
    Mutagenesisi1613C → S: Reduces dihydroorotase activity. 1 Publication1
    Mutagenesisi1614H → A: Abolishes dihydroorotase activity. 1 Publication1
    Mutagenesisi1637E → T: Abolishes dihydroorotase activity. 1 Publication1
    Mutagenesisi1642H → N: 11.5% of wild-type catalytic activity. 1 Publication1
    Mutagenesisi1686D → N: Abolishes dihydroorotase activity. 1 Publication1
    Mutagenesisi1690H → N: 3% of wild-type catalytic activity. 1 Publication1
    Mutagenesisi1873S → A: Abolishes PMA-induced Thr-456 phosphorylation. 1 Publication1

    Keywords - Diseasei

    Congenital disorder of glycosylation, Disease mutation

    Organism-specific databases

    DisGeNETi790.
    MIMi616457. phenotype.
    OpenTargetsiENSG00000084774.
    PharmGKBiPA26023.

    Chemistry databases

    ChEMBLiCHEMBL3093.
    DrugBankiDB00128. L-Aspartic Acid.
    DB00130. L-Glutamine.

    Polymorphism and mutation databases

    BioMutaiCAD.
    DMDMi50403731.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedCombined sources1 Publication
    ChainiPRO_00001995062 – 2225CAD proteinAdd BLAST2224

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylalanineCombined sources1 Publication1
    Modified residuei456Phosphothreonine; by MAPK11 Publication1
    Modified residuei747N6-acetyllysineCombined sources1
    Modified residuei1038PhosphoserineCombined sources1
    Modified residuei1406Phosphoserine; by PKACombined sources1 Publication1
    Modified residuei1411N6-acetyllysineCombined sources1
    Modified residuei1556N6-carboxylysine1 Publication1
    Modified residuei1859Phosphoserine; by RPS6KB1 and PKACombined sources3 Publications1
    Modified residuei1873Phosphoserine; by PKC; in vitro1 Publication1
    Modified residuei1884PhosphothreonineCombined sources1
    Modified residuei1900PhosphoserineCombined sources1 Publication1
    Modified residuei1938PhosphoserineCombined sources1

    Post-translational modificationi

    Activated by MAP kinase (Erk1/2) phosphorylation just prior to the S phase of the cell cycle, when the demand for pyrimidine nucleotides is greatest, and down-regulated as the cells emerge from S phase by protein kinase A (PKA) phosphorylation. Phosphorylation at Ser-1859 by RPS6KB1 downstream of MTOR promotes oligomerization and stimulates dihydroorotase activity. Phosphorylation at Ser-1406 reduces sensitivy to feedback inhibition by UTP.3 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiP27708.
    MaxQBiP27708.
    PaxDbiP27708.
    PeptideAtlasiP27708.
    PRIDEiP27708.

    PTM databases

    iPTMnetiP27708.
    PhosphoSitePlusiP27708.
    SwissPalmiP27708.

    Miscellaneous databases

    PMAP-CutDBP27708.

    Expressioni

    Inductioni

    Transcriptionally repressed following hypoxia by HIF1A.1 Publication

    Gene expression databases

    BgeeiENSG00000084774.
    CleanExiHS_CAD.
    ExpressionAtlasiP27708. baseline and differential.
    GenevisibleiP27708. HS.

    Organism-specific databases

    HPAiCAB007781.
    HPA057266.

    Interactioni

    Subunit structurei

    Homohexamer (PubMed:24332717). Interacts with CIPC (PubMed:26657846).2 Publications

    GO - Molecular functioni

    • enzyme binding Source: UniProtKB
    • identical protein binding Source: BHF-UCL

    Protein-protein interaction databases

    BioGridi107243. 105 interactors.
    DIPiDIP-39484N.
    IntActiP27708. 44 interactors.
    MINTiMINT-5000537.
    STRINGi9606.ENSP00000264705.

    Chemistry databases

    BindingDBiP27708.

    Structurei

    Secondary structure

    12225
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi1462 – 1465Combined sources4
    Beta strandi1467 – 1472Combined sources6
    Turni1476 – 1478Combined sources3
    Turni1480 – 1482Combined sources3
    Helixi1485 – 1494Combined sources10
    Beta strandi1497 – 1502Combined sources6
    Beta strandi1506 – 1508Combined sources3
    Helixi1513 – 1526Combined sources14
    Beta strandi1528 – 1533Combined sources6
    Turni1546 – 1548Combined sources3
    Helixi1549 – 1551Combined sources3
    Beta strandi1555 – 1558Combined sources4
    Beta strandi1560 – 1563Combined sources4
    Turni1564 – 1566Combined sources3
    Helixi1571 – 1580Combined sources10
    Beta strandi1587 – 1590Combined sources4
    Helixi1594 – 1605Combined sources12
    Beta strandi1610 – 1612Combined sources3
    Helixi1618 – 1629Combined sources12
    Beta strandi1634 – 1638Combined sources5
    Helixi1640 – 1644Combined sources5
    Helixi1647 – 1649Combined sources3
    Helixi1650 – 1657Combined sources8
    Helixi1667 – 1675Combined sources9
    Helixi1677 – 1679Combined sources3
    Helixi1692 – 1695Combined sources4
    Beta strandi1697 – 1699Combined sources3
    Helixi1707 – 1719Combined sources13
    Helixi1725 – 1732Combined sources8
    Helixi1734 – 1740Combined sources7
    Beta strandi1749 – 1759Combined sources11
    Turni1773 – 1776Combined sources4
    Beta strandi1778 – 1788Combined sources11
    Beta strandi1791 – 1795Combined sources5
    Helixi1809 – 1811Combined sources3
    Helixi1813 – 1815Combined sources3
    Helixi1929 – 1931Combined sources3
    Helixi1934 – 1952Combined sources19
    Turni1959 – 1962Combined sources4
    Beta strandi1964 – 1971Combined sources8
    Helixi1975 – 1986Combined sources12
    Beta strandi1990 – 1995Combined sources6
    Helixi1996 – 1998Combined sources3
    Helixi2000 – 2003Combined sources4
    Helixi2007 – 2014Combined sources8
    Turni2015 – 2017Combined sources3
    Beta strandi2019 – 2027Combined sources9
    Helixi2030 – 2035Combined sources6
    Beta strandi2042 – 2047Combined sources6
    Helixi2053 – 2067Combined sources15
    Beta strandi2074 – 2079Combined sources6
    Turni2081 – 2083Combined sources3
    Helixi2085 – 2094Combined sources10
    Beta strandi2100 – 2104Combined sources5
    Beta strandi2107 – 2109Combined sources3
    Helixi2113 – 2121Combined sources9
    Beta strandi2126 – 2131Combined sources6
    Helixi2132 – 2135Combined sources4
    Helixi2136 – 2138Combined sources3
    Beta strandi2140 – 2144Combined sources5
    Helixi2149 – 2151Combined sources3
    Helixi2155 – 2160Combined sources6
    Helixi2169 – 2172Combined sources4
    Beta strandi2180 – 2182Combined sources3
    Beta strandi2188 – 2191Combined sources4
    Helixi2193 – 2195Combined sources3
    Helixi2203 – 2221Combined sources19

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4BY3X-ray1.73A1456-1846[»]
    4C6BX-ray1.66A1456-1846[»]
    4C6CX-ray1.45A1456-1846[»]
    4C6DX-ray1.30A1456-1846[»]
    4C6EX-ray1.26A1456-1846[»]
    4C6FX-ray1.26A1456-1846[»]
    4C6IX-ray1.35A1456-1846[»]
    4C6JX-ray1.30A1456-1846[»]
    4C6KX-ray1.48A1456-1846[»]
    4C6LX-ray1.55A1456-1846[»]
    4C6MX-ray1.62A1456-1846[»]
    4C6NX-ray1.90A1456-1846[»]
    4C6OX-ray1.65A1456-1846[»]
    4C6PX-ray1.52A1456-1846[»]
    4C6QX-ray1.66A1456-1846[»]
    5G1NX-ray2.10A/B/C/D/E/F1915-2225[»]
    5G1OX-ray2.10A/B/C/D/E/F1915-2225[»]
    5G1PX-ray3.19A/B/C/D/E/F1915-2225[»]
    ProteinModelPortaliP27708.
    SMRiP27708.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini177 – 363Glutamine amidotransferase type-1Add BLAST187
    Domaini519 – 711ATP-grasp 1Add BLAST193
    Domaini1052 – 1243ATP-grasp 2Add BLAST192

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni2 – 365GATase (Glutamine amidotransferase)Add BLAST364
    Regioni366 – 394LinkerAdd BLAST29
    Regioni395 – 1455CPSase (Carbamoyl-phosphate synthase)Add BLAST1061
    Regioni395 – 933CPSase AAdd BLAST539
    Regioni934 – 1455CPSase BAdd BLAST522
    Regioni1456 – 1788DHOase (dihydroorotase)Add BLAST333
    Regioni1789 – 1917LinkerAdd BLAST129
    Regioni1918 – 2225ATCase (Aspartate transcarbamylase)Add BLAST308

    Sequence similaritiesi

    In the central section; belongs to the DHOase family.Curated
    Contains 2 ATP-grasp domains.Curated

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiKOG0370. Eukaryota.
    COG0458. LUCA.
    COG0505. LUCA.
    COG0540. LUCA.
    GeneTreeiENSGT00390000015604.
    HOGENOMiHOG000234584.
    HOVERGENiHBG000279.
    InParanoidiP27708.
    KOiK11540.
    OrthoDBiEOG091G00DC.
    PhylomeDBiP27708.
    TreeFamiTF105604.

    Family and domain databases

    Gene3Di1.10.1030.10. 1 hit.
    3.30.1490.20. 1 hit.
    3.30.470.20. 2 hits.
    3.40.50.1370. 2 hits.
    3.40.50.1380. 1 hit.
    3.40.50.20. 2 hits.
    3.40.50.880. 1 hit.
    3.50.30.20. 1 hit.
    HAMAPiMF_00001. Asp_carb_tr. 1 hit.
    MF_01209. CPSase_S_chain. 1 hit.
    InterProiIPR006680. Amidohydro-rel.
    IPR006132. Asp/Orn_carbamoyltranf_P-bd.
    IPR006130. Asp/Orn_carbamoylTrfase.
    IPR002082. Asp_carbamoyltransf.
    IPR006131. Asp_carbamoyltransf_Asp/Orn-bd.
    IPR011761. ATP-grasp.
    IPR013815. ATP_grasp_subdomain_1.
    IPR013816. ATP_grasp_subdomain_2.
    IPR006275. CarbamoylP_synth_lsu.
    IPR005480. CarbamoylP_synth_lsu_oligo.
    IPR006274. CarbamoylP_synth_ssu.
    IPR002474. CarbamoylP_synth_ssu_N.
    IPR005479. CbamoylP_synth_lsu-like_ATP-bd.
    IPR005483. CbamoylP_synth_lsu_CPSase_dom.
    IPR029062. Class_I_gatase-like.
    IPR002195. Dihydroorotase_CS.
    IPR017926. GATASE.
    IPR011059. Metal-dep_hydrolase_composite.
    IPR032466. Metal_Hydrolase.
    IPR011607. MGS-like_dom.
    IPR016185. PreATP-grasp_dom.
    [Graphical view]
    PfamiPF01979. Amidohydro_1. 1 hit.
    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]
    PRINTSiPR00100. AOTCASE.
    PR00101. ATCASE.
    PR00098. CPSASE.
    SMARTiSM01096. CPSase_L_D3. 1 hit.
    SM01097. CPSase_sm_chain. 1 hit.
    SM00851. MGS. 1 hit.
    [Graphical view]
    SUPFAMiSSF48108. SSF48108. 1 hit.
    SSF51338. SSF51338. 1 hit.
    SSF51556. SSF51556. 1 hit.
    SSF52021. SSF52021. 1 hit.
    SSF52317. SSF52317. 1 hit.
    SSF52335. SSF52335. 1 hit.
    SSF52440. SSF52440. 2 hits.
    SSF53671. SSF53671. 1 hit.
    TIGRFAMsiTIGR00670. asp_carb_tr. 1 hit.
    TIGR01369. CPSaseII_lrg. 1 hit.
    TIGR01368. CPSaseIIsmall. 1 hit.
    PROSITEiPS50975. 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]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P27708-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAALVLEDGS VLRGQPFGAA VSTAGEVVFQ TGMVGYPEAL TDPSYKAQIL
    60 70 80 90 100
    VLTYPLIGNY GIPPDEMDEF GLCKWFESSG IHVAALVVGE CCPTPSHWSA
    110 120 130 140 150
    TRTLHEWLQQ HGIPGLQGVD TRELTKKLRE QGSLLGKLVQ NGTEPSSLPF
    160 170 180 190 200
    LDPNARPLVP EVSIKTPRVF NTGGAPRILA LDCGLKYNQI RCLCQRGAEV
    210 220 230 240 250
    TVVPWDHALD SQEYEGLFLS NGPGDPASYP SVVSTLSRVL SEPNPRPVFG
    260 270 280 290 300
    ICLGHQLLAL AIGAKTYKMR YGNRGHNQPC LLVGSGRCFL TSQNHGFAVE
    310 320 330 340 350
    TDSLPADWAP LFTNANDGSN EGIVHNSLPF FSVQFHPEHQ AGPSDMELLF
    360 370 380 390 400
    DIFLETVKEA TAGNPGGQTV RERLTERLCP PGIPTPGSGL PPPRKVLILG
    410 420 430 440 450
    SGGLSIGQAG EFDYSGSQAI KALKEENIQT LLINPNIATV QTSQGLADKV
    460 470 480 490 500
    YFLPITPHYV TQVIRNERPD GVLLTFGGQT ALNCGVELTK AGVLARYGVR
    510 520 530 540 550
    VLGTPVETIE LTEDRRAFAA RMAEIGEHVA PSEAANSLEQ AQAAAERLGY
    560 570 580 590 600
    PVLVRAAFAL GGLGSGFASN REELSALVAP AFAHTSQVLV DKSLKGWKEI
    610 620 630 640 650
    EYEVVRDAYG NCVTVCNMEN LDPLGIHTGE SIVVAPSQTL NDREYQLLRQ
    660 670 680 690 700
    TAIKVTQHLG IVGECNVQYA LNPESEQYYI IEVNARLSRS SALASKATGY
    710 720 730 740 750
    PLAYVAAKLA LGIPLPELRN SVTGGTAAFE PSVDYCVVKI PRWDLSKFLR
    760 770 780 790 800
    VSTKIGSCMK SVGEVMGIGR SFEEAFQKAL RMVDENCVGF DHTVKPVSDM
    810 820 830 840 850
    ELETPTDKRI FVVAAALWAG YSVDRLYELT RIDRWFLHRM KRIIAHAQLL
    860 870 880 890 900
    EQHRGQPLPP DLLQQAKCLG FSDKQIALAV LSTELAVRKL RQELGICPAV
    910 920 930 940 950
    KQIDTVAAEW PAQTNYLYLT YWGTTHDLTF RTPHVLVLGS GVYRIGSSVE
    960 970 980 990 1000
    FDWCAVGCIQ QLRKMGYKTI MVNYNPETVS TDYDMCDRLY FDEISFEVVM
    1010 1020 1030 1040 1050
    DIYELENPEG VILSMGGQLP NNMAMALHRQ QCRVLGTSPE AIDSAENRFK
    1060 1070 1080 1090 1100
    FSRLLDTIGI SQPQWRELSD LESARQFCQT VGYPCVVRPS YVLSGAAMNV
    1110 1120 1130 1140 1150
    AYTDGDLERF LSSAAAVSKE HPVVISKFIQ EAKEIDVDAV ASDGVVAAIA
    1160 1170 1180 1190 1200
    ISEHVENAGV HSGDATLVTP PQDITAKTLE RIKAIVHAVG QELQVTGPFN
    1210 1220 1230 1240 1250
    LQLIAKDDQL KVIECNVRVS RSFPFVSKTL GVDLVALATR VIMGEEVEPV
    1260 1270 1280 1290 1300
    GLMTGSGVVG VKVPQFSFSR LAGADVVLGV EMTSTGEVAG FGESRCEAYL
    1310 1320 1330 1340 1350
    KAMLSTGFKI PKKNILLTIG SYKNKSELLP TVRLLESLGY SLYASLGTAD
    1360 1370 1380 1390 1400
    FYTEHGVKVT AVDWHFEEAV DGECPPQRSI LEQLAEKNFE LVINLSMRGA
    1410 1420 1430 1440 1450
    GGRRLSSFVT KGYRTRRLAA DFSVPLIIDI KCTKLFVEAL GQIGPAPPLK
    1460 1470 1480 1490 1500
    VHVDCMTSQK LVRLPGLIDV HVHLREPGGT HKEDFASGTA AALAGGITMV
    1510 1520 1530 1540 1550
    CAMPNTRPPI IDAPALALAQ KLAEAGARCD FALFLGASSE NAGTLGTVAG
    1560 1570 1580 1590 1600
    SAAGLKLYLN ETFSELRLDS VVQWMEHFET WPSHLPIVAH AEQQTVAAVL
    1610 1620 1630 1640 1650
    MVAQLTQRSV HICHVARKEE ILLIKAAKAR GLPVTCEVAP HHLFLSHDDL
    1660 1670 1680 1690 1700
    ERLGPGKGEV RPELGSRQDV EALWENMAVI DCFASDHAPH TLEEKCGSRP
    1710 1720 1730 1740 1750
    PPGFPGLETM LPLLLTAVSE GRLSLDDLLQ RLHHNPRRIF HLPPQEDTYV
    1760 1770 1780 1790 1800
    EVDLEHEWTI PSHMPFSKAH WTPFEGQKVK GTVRRVVLRG EVAYIDGQVL
    1810 1820 1830 1840 1850
    VPPGYGQDVR KWPQGAVPQL PPSAPATSEM TTTPERPRRG IPGLPDGRFH
    1860 1870 1880 1890 1900
    LPPRIHRASD PGLPAEEPKE KSSRKVAEPE LMGTPDGTCY PPPPVPRQAS
    1910 1920 1930 1940 1950
    PQNLGTPGLL HPQTSPLLHS LVGQHILSVQ QFTKDQMSHL FNVAHTLRMM
    1960 1970 1980 1990 2000
    VQKERSLDIL KGKVMASMFY EVSTRTSSSF AAAMARLGGA VLSFSEATSS
    2010 2020 2030 2040 2050
    VQKGESLADS VQTMSCYADV VVLRHPQPGA VELAAKHCRR PVINAGDGVG
    2060 2070 2080 2090 2100
    EHPTQALLDI FTIREELGTV NGMTITMVGD LKHGRTVHSL ACLLTQYRVS
    2110 2120 2130 2140 2150
    LRYVAPPSLR MPPTVRAFVA SRGTKQEEFE SIEEALPDTD VLYMTRIQKE
    2160 2170 2180 2190 2200
    RFGSTQEYEA CFGQFILTPH IMTRAKKKMV VMHPMPRVNE ISVEVDSDPR
    2210 2220
    AAYFRQAENG MYIRMALLAT VLGRF
    Length:2,225
    Mass (Da):242,984
    Last modified:July 19, 2004 - v3
    Checksum:i2AB8E8413E825A8F
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti505P → T in BAA11423 (PubMed:8619816).Curated1
    Sequence conflicti535A → G in BAA11423 (PubMed:8619816).Curated1
    Sequence conflicti560L → V in BAA11423 (PubMed:8619816).Curated1
    Sequence conflicti1103T → A in BAA11423 (PubMed:8619816).Curated1
    Sequence conflicti1513A → G in BAA11423 (PubMed:8619816).Curated1
    Sequence conflicti1676N → D in BAA11423 (PubMed:8619816).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_035897177R → Q in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs374122292dbSNPEnsembl.1
    Natural variantiVAR_035898735Y → C in a colorectal cancer sample; somatic mutation. 1 Publication1
    Natural variantiVAR_0739552024R → Q in CDG1Z. 1 PublicationCorresponds to variant rs763410987dbSNPEnsembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D78586 mRNA. Translation: BAA11423.1.
    CH471053 Genomic DNA. Translation: EAX00612.1.
    CH471053 Genomic DNA. Translation: EAX00613.1.
    CH471053 Genomic DNA. Translation: EAX00614.1.
    BC014178 mRNA. Translation: AAH14178.2.
    BC065510 mRNA. Translation: AAH65510.1.
    M38561 Genomic DNA. Translation: AAA51907.1.
    CCDSiCCDS1742.1.
    PIRiA36240.
    RefSeqiNP_001293008.1. NM_001306079.1.
    NP_004332.2. NM_004341.4.
    UniGeneiHs.377010.

    Genome annotation databases

    EnsembliENST00000264705; ENSP00000264705; ENSG00000084774.
    GeneIDi790.
    KEGGihsa:790.
    UCSCiuc002rji.4. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Aspartate carbamoyltransferase entry

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D78586 mRNA. Translation: BAA11423.1.
    CH471053 Genomic DNA. Translation: EAX00612.1.
    CH471053 Genomic DNA. Translation: EAX00613.1.
    CH471053 Genomic DNA. Translation: EAX00614.1.
    BC014178 mRNA. Translation: AAH14178.2.
    BC065510 mRNA. Translation: AAH65510.1.
    M38561 Genomic DNA. Translation: AAA51907.1.
    CCDSiCCDS1742.1.
    PIRiA36240.
    RefSeqiNP_001293008.1. NM_001306079.1.
    NP_004332.2. NM_004341.4.
    UniGeneiHs.377010.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4BY3X-ray1.73A1456-1846[»]
    4C6BX-ray1.66A1456-1846[»]
    4C6CX-ray1.45A1456-1846[»]
    4C6DX-ray1.30A1456-1846[»]
    4C6EX-ray1.26A1456-1846[»]
    4C6FX-ray1.26A1456-1846[»]
    4C6IX-ray1.35A1456-1846[»]
    4C6JX-ray1.30A1456-1846[»]
    4C6KX-ray1.48A1456-1846[»]
    4C6LX-ray1.55A1456-1846[»]
    4C6MX-ray1.62A1456-1846[»]
    4C6NX-ray1.90A1456-1846[»]
    4C6OX-ray1.65A1456-1846[»]
    4C6PX-ray1.52A1456-1846[»]
    4C6QX-ray1.66A1456-1846[»]
    5G1NX-ray2.10A/B/C/D/E/F1915-2225[»]
    5G1OX-ray2.10A/B/C/D/E/F1915-2225[»]
    5G1PX-ray3.19A/B/C/D/E/F1915-2225[»]
    ProteinModelPortaliP27708.
    SMRiP27708.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi107243. 105 interactors.
    DIPiDIP-39484N.
    IntActiP27708. 44 interactors.
    MINTiMINT-5000537.
    STRINGi9606.ENSP00000264705.

    Chemistry databases

    BindingDBiP27708.
    ChEMBLiCHEMBL3093.
    DrugBankiDB00128. L-Aspartic Acid.
    DB00130. L-Glutamine.

    Protein family/group databases

    MEROPSiM38.972.

    PTM databases

    iPTMnetiP27708.
    PhosphoSitePlusiP27708.
    SwissPalmiP27708.

    Polymorphism and mutation databases

    BioMutaiCAD.
    DMDMi50403731.

    Proteomic databases

    EPDiP27708.
    MaxQBiP27708.
    PaxDbiP27708.
    PeptideAtlasiP27708.
    PRIDEiP27708.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000264705; ENSP00000264705; ENSG00000084774.
    GeneIDi790.
    KEGGihsa:790.
    UCSCiuc002rji.4. human.

    Organism-specific databases

    CTDi790.
    DisGeNETi790.
    GeneCardsiCAD.
    HGNCiHGNC:1424. CAD.
    HPAiCAB007781.
    HPA057266.
    MIMi114010. gene.
    616457. phenotype.
    neXtProtiNX_P27708.
    OpenTargetsiENSG00000084774.
    PharmGKBiPA26023.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0370. Eukaryota.
    COG0458. LUCA.
    COG0505. LUCA.
    COG0540. LUCA.
    GeneTreeiENSGT00390000015604.
    HOGENOMiHOG000234584.
    HOVERGENiHBG000279.
    InParanoidiP27708.
    KOiK11540.
    OrthoDBiEOG091G00DC.
    PhylomeDBiP27708.
    TreeFamiTF105604.

    Enzyme and pathway databases

    UniPathwayiUPA00070; UER00115.
    UPA00070; UER00116.
    UPA00070; UER00117.
    BioCyciMetaCyc:ENSG00000084774-MONOMER.
    ZFISH:ENSG00000084774-MONOMER.
    BRENDAi3.5.2.3. 2681.
    ReactomeiR-HSA-500753. Pyrimidine biosynthesis.
    SIGNORiP27708.

    Miscellaneous databases

    ChiTaRSiCAD. human.
    GenomeRNAii790.
    PMAP-CutDBP27708.
    PROiP27708.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000084774.
    CleanExiHS_CAD.
    ExpressionAtlasiP27708. baseline and differential.
    GenevisibleiP27708. HS.

    Family and domain databases

    Gene3Di1.10.1030.10. 1 hit.
    3.30.1490.20. 1 hit.
    3.30.470.20. 2 hits.
    3.40.50.1370. 2 hits.
    3.40.50.1380. 1 hit.
    3.40.50.20. 2 hits.
    3.40.50.880. 1 hit.
    3.50.30.20. 1 hit.
    HAMAPiMF_00001. Asp_carb_tr. 1 hit.
    MF_01209. CPSase_S_chain. 1 hit.
    InterProiIPR006680. Amidohydro-rel.
    IPR006132. Asp/Orn_carbamoyltranf_P-bd.
    IPR006130. Asp/Orn_carbamoylTrfase.
    IPR002082. Asp_carbamoyltransf.
    IPR006131. Asp_carbamoyltransf_Asp/Orn-bd.
    IPR011761. ATP-grasp.
    IPR013815. ATP_grasp_subdomain_1.
    IPR013816. ATP_grasp_subdomain_2.
    IPR006275. CarbamoylP_synth_lsu.
    IPR005480. CarbamoylP_synth_lsu_oligo.
    IPR006274. CarbamoylP_synth_ssu.
    IPR002474. CarbamoylP_synth_ssu_N.
    IPR005479. CbamoylP_synth_lsu-like_ATP-bd.
    IPR005483. CbamoylP_synth_lsu_CPSase_dom.
    IPR029062. Class_I_gatase-like.
    IPR002195. Dihydroorotase_CS.
    IPR017926. GATASE.
    IPR011059. Metal-dep_hydrolase_composite.
    IPR032466. Metal_Hydrolase.
    IPR011607. MGS-like_dom.
    IPR016185. PreATP-grasp_dom.
    [Graphical view]
    PfamiPF01979. Amidohydro_1. 1 hit.
    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]
    PRINTSiPR00100. AOTCASE.
    PR00101. ATCASE.
    PR00098. CPSASE.
    SMARTiSM01096. CPSase_L_D3. 1 hit.
    SM01097. CPSase_sm_chain. 1 hit.
    SM00851. MGS. 1 hit.
    [Graphical view]
    SUPFAMiSSF48108. SSF48108. 1 hit.
    SSF51338. SSF51338. 1 hit.
    SSF51556. SSF51556. 1 hit.
    SSF52021. SSF52021. 1 hit.
    SSF52317. SSF52317. 1 hit.
    SSF52335. SSF52335. 1 hit.
    SSF52440. SSF52440. 2 hits.
    SSF53671. SSF53671. 1 hit.
    TIGRFAMsiTIGR00670. asp_carb_tr. 1 hit.
    TIGR01369. CPSaseII_lrg. 1 hit.
    TIGR01368. CPSaseIIsmall. 1 hit.
    PROSITEiPS50975. 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]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiPYR1_HUMAN
    AccessioniPrimary (citable) accession number: P27708
    Secondary accession number(s): D6W552, Q6P0Q0, Q96CK3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: July 19, 2004
    Last modified: November 30, 2016
    This is version 195 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    GATase (glutamine amidotransferase) and CPSase (carbamoyl phosphate synthase) form together the glutamine-dependent CPSase (GD-CPSase) (EC 6.3.5.5).

    Keywords - Technical termi

    3D-structure, Allosteric enzyme, Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.