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Protein

CAD protein

Gene

CAD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

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

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

Protein has several cofactor binding sites:
  • Zn2+2 PublicationsNote: Binds 3 Zn2+ ions per subunit (for dihydroorotase activity).2 Publications
  • Mg2+PROSITE-ProRule annotation, Mn2+PROSITE-ProRule annotationNote: Binds 4 magnesium or manganese ions per subunit.PROSITE-ProRule annotation

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.1 Publication
    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 sitei252Nucleophile; for GATase activityPROSITE-ProRule annotation1
    Active sitei336For GATase activityPROSITE-ProRule annotation1
    Active sitei338For GATase activityPROSITE-ProRule annotation1
    Metal bindingi668Magnesium or manganese 1PROSITE-ProRule annotation1
    Metal bindingi682Magnesium or manganese 1PROSITE-ProRule annotation1
    Metal bindingi682Magnesium or manganese 2PROSITE-ProRule annotation1
    Metal bindingi684Magnesium or manganese 2PROSITE-ProRule annotation1
    Metal bindingi1202Magnesium or manganese 3PROSITE-ProRule annotation1
    Metal bindingi1214Magnesium or manganese 3PROSITE-ProRule annotation1
    Metal bindingi1214Magnesium or manganese 4PROSITE-ProRule annotation1
    Metal bindingi1216Magnesium or manganese 4PROSITE-ProRule annotation1
    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 Publication1
    Binding sitei1505N-carbamoyl-L-aspartate1 Publication1
    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 Publication1
    Metal bindingi1686Zinc 11 Publication1
    Binding sitei1686N-carbamoyl-L-aspartate1 Publication1
    Binding sitei1690N-carbamoyl-L-aspartate1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi545 – 600ATPPROSITE-ProRule annotationAdd BLAST56
    Nucleotide bindingi1078 – 1135ATPPROSITE-ProRule annotationAdd BLAST58

    GO - Molecular functioni

    • aspartate binding Source: BHF-UCL
    • aspartate carbamoyltransferase activity Source: BHF-UCL
    • ATP binding Source: BHF-UCL
    • carbamoyl-phosphate synthase (ammonia) activity Source: GO_Central
    • carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity Source: BHF-UCL
    • dihydroorotase activity Source: UniProtKB
    • enzyme binding Source: UniProtKB
    • identical protein binding Source: IntAct
    • protein kinase activity Source: BHF-UCL
    • zinc ion binding Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionAllosteric enzyme, Hydrolase, Ligase, Multifunctional enzyme, Transferase
    Biological processPyrimidine biosynthesis
    LigandATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding, Zinc

    Enzyme and pathway databases

    BioCyciMetaCyc: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:6.3.5.51 Publication)
    Aspartate carbamoyltransferase (EC:2.1.3.21 Publication)
    Dihydroorotase (EC:3.5.2.31 Publication)
    Gene namesi
    Name:CADImported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 2

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000084774.13
    HGNCiHGNC:1424 CAD
    MIMi114010 gene
    neXtProtiNX_P27708

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Epileptic encephalopathy, early infantile, 50 (EIEE50)2 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE50 is an autosomal recessive, progressive disease with onset in infancy and favorable response to treatment with oral uridine.
    See also OMIM:616457
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07828933M → R in EIEE50; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs751610198EnsemblClinVar.1
    Natural variantiVAR_0782901789 – 2225Missing in EIEE50; unknown pathological significance. 1 PublicationAdd BLAST437
    Natural variantiVAR_0739552024R → Q in EIEE50. 1 PublicationCorresponds to variant dbSNP:rs763410987Ensembl.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, Epilepsy

    Organism-specific databases

    DisGeNETi790
    MalaCardsiCAD
    MIMi616457 phenotype
    OpenTargetsiENSG00000084774
    PharmGKBiPA26023

    Chemistry databases

    ChEMBLiCHEMBL3093
    DrugBankiDB00128 L-Aspartic Acid
    DB00130 L-Glutamine
    DB03459 Sparfosic acid

    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
    ProteomicsDBi54409

    PTM databases

    iPTMnetiP27708
    PhosphoSitePlusiP27708
    SwissPalmiP27708

    Miscellaneous databases

    PMAP-CutDBiP27708

    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
    HPA069341

    Interactioni

    Subunit structurei

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

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself3EBI-355504,EBI-355504

    GO - Molecular functioni

    • enzyme binding Source: UniProtKB
    • identical protein binding Source: IntAct

    Protein-protein interaction databases

    BioGridi107243, 117 interactors
    DIPiDIP-39484N
    IntActiP27708, 67 interactors
    MINTiP27708
    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

    DisProtiDP01024
    ProteinModelPortaliP27708
    SMRiP27708
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini177 – 363Glutamine amidotransferase type-1PROSITE-ProRule annotationAdd BLAST187
    Domaini519 – 711ATP-grasp 1PROSITE-ProRule annotationAdd BLAST193
    Domaini1052 – 1243ATP-grasp 2PROSITE-ProRule annotationAdd BLAST192
    Domaini1308 – 1462MGS-likePROSITE-ProRule annotationAdd BLAST155

    Region

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

    Sequence similaritiesi

    In the central section; belongs to the metallo-dependent hydrolases superfamily. DHOase family. CAD subfamily.Curated

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiKOG0370 Eukaryota
    COG0458 LUCA
    COG0505 LUCA
    COG0540 LUCA
    GeneTreeiENSGT00910000144175
    HOGENOMiHOG000234584
    HOVERGENiHBG000279
    InParanoidiP27708
    KOiK11540
    OrthoDBiEOG091G00DC
    PhylomeDBiP27708
    TreeFamiTF105604

    Family and domain databases

    CDDicd01744 GATase1_CPSase, 1 hit
    Gene3Di1.10.1030.10, 1 hit
    3.30.1490.20, 1 hit
    3.40.50.1370, 3 hits
    3.40.50.1380, 1 hit
    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
    InterProiView protein in InterPro
    IPR006680 Amidohydro-rel
    IPR006132 Asp/Orn_carbamoyltranf_P-bd
    IPR006130 Asp/Orn_carbamoylTrfase
    IPR036901 Asp/Orn_carbamoylTrfase_sf
    IPR002082 Asp_carbamoyltransf
    IPR006131 Asp_carbamoyltransf_Asp/Orn-bd
    IPR011761 ATP-grasp
    IPR013815 ATP_grasp_subdomain_1
    IPR006275 CarbamoylP_synth_lsu
    IPR005480 CarbamoylP_synth_lsu_oligo
    IPR036897 CarbamoylP_synth_lsu_oligo_sf
    IPR006274 CarbamoylP_synth_ssu
    IPR002474 CarbamoylP_synth_ssu_N
    IPR036480 CarbP_synth_ssu_N_sf
    IPR005479 CbamoylP_synth_lsu-like_ATP-bd
    IPR005483 CbamoylP_synth_lsu_CPSase_dom
    IPR029062 Class_I_gatase-like
    IPR035686 CPSase_GATase1
    IPR002195 Dihydroorotase_CS
    IPR017926 GATASE
    IPR011059 Metal-dep_hydrolase_composite
    IPR032466 Metal_Hydrolase
    IPR011607 MGS-like_dom
    IPR036914 MGS-like_dom_sf
    IPR016185 PreATP-grasp_dom_sf
    PfamiView protein in Pfam
    PF01979 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
    PRINTSiPR00100 AOTCASE
    PR00101 ATCASE
    PR00098 CPSASE
    SMARTiView protein in SMART
    SM01096 CPSase_L_D3, 1 hit
    SM01097 CPSase_sm_chain, 1 hit
    SM00851 MGS, 1 hit
    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
    PROSITEiView protein in 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
    PS51855 MGS, 1 hit

    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_07828933M → R in EIEE50; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs751610198EnsemblClinVar.1
    Natural variantiVAR_035897177R → Q in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs374122292Ensembl.1
    Natural variantiVAR_035898735Y → C in a colorectal cancer sample; somatic mutation. 1 Publication1
    Natural variantiVAR_0782901789 – 2225Missing in EIEE50; unknown pathological significance. 1 PublicationAdd BLAST437
    Natural variantiVAR_0739552024R → Q in EIEE50. 1 PublicationCorresponds to variant dbSNP:rs763410987Ensembl.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

    Similar proteinsi

    Entry informationi

    Entry nameiPYR1_HUMAN
    AccessioniPrimary (citable) accession number: P27708
    Secondary accession number(s): D6W552, Q6P0Q0, Q96CK3
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: July 19, 2004
    Last modified: July 18, 2018
    This is version 213 of the entry and version 3 of the sequence. See 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

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, 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

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