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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei252 – 2521For GATase activityBy similarity
Active sitei336 – 3361For GATase activityBy similarity
Active sitei338 – 3381For GATase activityBy similarity
Metal bindingi1471 – 14711Zinc 1; via tele nitrogen1 Publication
Metal bindingi1471 – 14711Zinc 2; via pros nitrogen1 Publication
Metal bindingi1473 – 14731Zinc 1; via tele nitrogen1 Publication
Binding sitei1475 – 14751N-carbamoyl-L-aspartate
Binding sitei1505 – 15051N-carbamoyl-L-aspartate
Metal bindingi1556 – 15561Zinc 1; via carbamate group1 Publication
Metal bindingi1556 – 15561Zinc 3; via carbamate group1 Publication
Metal bindingi1590 – 15901Zinc 3; via pros nitrogen1 Publication
Metal bindingi1613 – 16131Zinc 21 Publication
Metal bindingi1614 – 16141Zinc 3; via tele nitrogen1 Publication
Metal bindingi1637 – 16371Zinc 21 Publication
Binding sitei1661 – 16611N-carbamoyl-L-aspartate; via amide nitrogen and carbonyl oxygen
Metal bindingi1686 – 16861Zinc 11 Publication
Binding sitei1686 – 16861N-carbamoyl-L-aspartate
Binding sitei1690 – 16901N-carbamoyl-L-aspartate

GO - Molecular functioni

  1. aspartate binding Source: BHF-UCL
  2. aspartate carbamoyltransferase activity Source: BHF-UCL
  3. ATP binding Source: BHF-UCL
  4. carbamoyl-phosphate synthase (ammonia) activity Source: GO_Central
  5. carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity Source: BHF-UCL
  6. dihydroorotase activity Source: UniProtKB
  7. enzyme binding Source: UniProtKB
  8. identical protein binding Source: BHF-UCL
  9. protein kinase activity Source: BHF-UCL
  10. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. 'de novo' pyrimidine nucleobase biosynthetic process Source: UniProtKB
  2. 'de novo' UMP biosynthetic process Source: UniProtKB-UniPathway
  3. arginine biosynthetic process Source: GO_Central
  4. carbamoyl phosphate biosynthetic process Source: InterPro
  5. cellular response to drug Source: Ensembl
  6. cellular response to epidermal growth factor stimulus Source: Ensembl
  7. drug metabolic process Source: BHF-UCL
  8. female pregnancy Source: Ensembl
  9. glutamine catabolic process Source: InterPro
  10. glutamine metabolic process Source: BHF-UCL
  11. heart development Source: Ensembl
  12. lactation Source: Ensembl
  13. liver development Source: Ensembl
  14. nucleobase-containing small molecule metabolic process Source: Reactome
  15. organ regeneration Source: Ensembl
  16. peptidyl-threonine phosphorylation Source: BHF-UCL
  17. protein autophosphorylation Source: BHF-UCL
  18. pyrimidine nucleobase metabolic process Source: Reactome
  19. pyrimidine nucleoside biosynthetic process Source: Reactome
  20. response to amine Source: Ensembl
  21. response to caffeine Source: Ensembl
  22. response to cortisol Source: Ensembl
  23. response to testosterone Source: Ensembl
  24. small molecule metabolic process Source: Reactome
  25. urea cycle Source: GO_Central
  26. UTP biosynthetic process Source: Ensembl
Complete GO annotation...

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.
BRENDAi3.5.2.3. 2681.
ReactomeiREACT_21376. Pyrimidine biosynthesis.
UniPathwayiUPA00070; UER00115.
UPA00070; UER00116.
UPA00070; UER00117.

Protein family/group databases

MEROPSiC26.952.

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
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:1424. CAD.

Subcellular locationi

Cytoplasm 1 Publication. Nucleus 1 Publication
Note: Cytosolic and unphosphorylated in resting cells, translocates to the nucleus in response to EGF stimulation, nuclear import promotes optimal cell growth.

GO - Cellular componenti

  1. cell projection Source: BHF-UCL
  2. cytosol Source: BHF-UCL
  3. extracellular vesicular exosome Source: UniProtKB
  4. membrane Source: UniProtKB
  5. neuronal cell body Source: BHF-UCL
  6. nuclear matrix Source: BHF-UCL
  7. nucleoplasm Source: HPA
  8. nucleus Source: BHF-UCL
  9. plasma membrane Source: HPA
  10. protein complex Source: Ensembl
  11. terminal bouton Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1471 – 14711H → A: No zinc-binding and no catalytic activity. 2 Publications
Mutagenesisi1471 – 14711H → N: Abolishes dihydroorotase activity. 2 Publications
Mutagenesisi1473 – 14731H → A: No zinc-binding and no catalytic activity. 1 Publication
Mutagenesisi1512 – 15121D → N: No change in catalytic activity. 1 Publication
Mutagenesisi1562 – 15621T → A: Abolishes dihydroorotase activity. 1 Publication
Mutagenesisi1563 – 15631F → A: Abolishes dihydroorotase activity. 1 Publication
Mutagenesisi1590 – 15901H → A: Abolishes dihydroorotase activity. 2 Publications
Mutagenesisi1590 – 15901H → N: No catalytic activity. 2 Publications
Mutagenesisi1613 – 16131C → S: Reduces dihydroorotase activity. 1 Publication
Mutagenesisi1614 – 16141H → A: Abolishes dihydroorotase activity. 1 Publication
Mutagenesisi1637 – 16371E → T: Abolishes dihydroorotase activity. 1 Publication
Mutagenesisi1642 – 16421H → N: 11.5% of wild-type catalytic activity. 1 Publication
Mutagenesisi1686 – 16861D → N: Abolishes dihydroorotase activity. 1 Publication
Mutagenesisi1690 – 16901H → N: 3% of wild-type catalytic activity. 1 Publication
Mutagenesisi1873 – 18731S → A: Abolishes PMA-induced Thr-456 phosphorylation. 1 Publication

Organism-specific databases

PharmGKBiPA26023.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed4 Publications
Chaini2 – 22252224CAD proteinPRO_0000199506Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine4 Publications
Modified residuei456 – 4561Phosphothreonine; by MAPK11 Publication
Modified residuei747 – 7471N6-acetyllysine1 Publication
Modified residuei1406 – 14061Phosphoserine; by PKA2 Publications
Modified residuei1411 – 14111N6-acetyllysine1 Publication
Modified residuei1556 – 15561N6-carboxylysine1 Publication
Modified residuei1859 – 18591Phosphoserine; by RPS6KB1 and PKA8 Publications
Modified residuei1873 – 18731Phosphoserine; by PKC; in vitro1 Publication
Modified residuei1884 – 18841Phosphothreonine2 Publications
Modified residuei1900 – 19001Phosphoserine2 Publications
Modified residuei1906 – 19061Phosphothreonine1 Publication

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.9 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP27708.
PaxDbiP27708.
PeptideAtlasiP27708.
PRIDEiP27708.

PTM databases

PhosphoSiteiP27708.

Miscellaneous databases

PMAP-CutDBP27708.

Expressioni

Inductioni

Transcriptionally repressed following hypoxia by HIF1A.1 Publication

Gene expression databases

BgeeiP27708.
CleanExiHS_CAD.
ExpressionAtlasiP27708. baseline and differential.
GenevestigatoriP27708.

Organism-specific databases

HPAiCAB007781.

Interactioni

Subunit structurei

Homohexamer.1 Publication

Protein-protein interaction databases

BioGridi107243. 45 interactions.
DIPiDIP-39484N.
IntActiP27708. 23 interactions.
MINTiMINT-5000537.
STRINGi9606.ENSP00000264705.

Structurei

Secondary structure

1
2225
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi1462 – 14654Combined sources
Beta strandi1467 – 14726Combined sources
Turni1476 – 14783Combined sources
Turni1480 – 14823Combined sources
Helixi1485 – 149410Combined sources
Beta strandi1497 – 15026Combined sources
Beta strandi1506 – 15083Combined sources
Helixi1513 – 152614Combined sources
Beta strandi1528 – 15336Combined sources
Turni1546 – 15483Combined sources
Helixi1549 – 15513Combined sources
Beta strandi1555 – 15584Combined sources
Beta strandi1560 – 15634Combined sources
Turni1564 – 15663Combined sources
Helixi1571 – 158010Combined sources
Beta strandi1587 – 15904Combined sources
Helixi1594 – 160512Combined sources
Beta strandi1610 – 16123Combined sources
Helixi1618 – 162912Combined sources
Beta strandi1634 – 16385Combined sources
Helixi1640 – 16445Combined sources
Helixi1647 – 16493Combined sources
Helixi1650 – 16578Combined sources
Helixi1667 – 16759Combined sources
Helixi1677 – 16793Combined sources
Helixi1692 – 16954Combined sources
Beta strandi1697 – 16993Combined sources
Helixi1707 – 171913Combined sources
Helixi1725 – 17328Combined sources
Helixi1734 – 17407Combined sources
Beta strandi1749 – 175911Combined sources
Turni1773 – 17764Combined sources
Beta strandi1778 – 178811Combined sources
Beta strandi1791 – 17955Combined sources
Helixi1809 – 18113Combined sources
Helixi1813 – 18153Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP27708.
SMRiP27708. Positions 2-359, 394-1823, 1923-2223.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini177 – 363187Glutamine amidotransferase type-1Add
BLAST
Domaini519 – 711193ATP-grasp 1Add
BLAST
Domaini1052 – 1243192ATP-grasp 2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 365364GATase (Glutamine amidotransferase)Add
BLAST
Regioni366 – 39429LinkerAdd
BLAST
Regioni395 – 14551061CPSase (Carbamoyl-phosphate synthase)Add
BLAST
Regioni395 – 933539CPSase AAdd
BLAST
Regioni934 – 1455522CPSase BAdd
BLAST
Regioni1456 – 1788333DHOase (dihydroorotase)Add
BLAST
Regioni1789 – 1917129LinkerAdd
BLAST
Regioni1918 – 2225308ATCase (Aspartate transcarbamylase)Add
BLAST

Sequence similaritiesi

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiCOG0458.
GeneTreeiENSGT00390000015604.
HOGENOMiHOG000234584.
HOVERGENiHBG000279.
InParanoidiP27708.
KOiK11540.
OrthoDBiEOG7M6D6F.
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.
MF_01209. CPSase_S_chain.
InterProiIPR006132. 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.
IPR005481. CarbamoylP_synth_lsu_N.
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.
IPR011607. MGS-like_dom.
IPR016185. PreATP-grasp_dom.
[Graphical view]
PfamiPF00289. 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]
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.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti505 – 5051P → T in BAA11423. (PubMed:8619816)Curated
Sequence conflicti535 – 5351A → G in BAA11423. (PubMed:8619816)Curated
Sequence conflicti560 – 5601L → V in BAA11423. (PubMed:8619816)Curated
Sequence conflicti1103 – 11031T → A in BAA11423. (PubMed:8619816)Curated
Sequence conflicti1513 – 15131A → G in BAA11423. (PubMed:8619816)Curated
Sequence conflicti1676 – 16761N → D in BAA11423. (PubMed:8619816)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti177 – 1771R → Q in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_035897
Natural varianti735 – 7351Y → C in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_035898

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_004332.2. NM_004341.3.
UniGeneiHs.377010.

Genome annotation databases

EnsembliENST00000264705; ENSP00000264705; ENSG00000084774.
GeneIDi790.
KEGGihsa:790.
UCSCiuc002rji.3. human.

Polymorphism databases

DMDMi50403731.

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_004332.2. NM_004341.3.
UniGeneiHs.377010.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP27708.
SMRiP27708. Positions 2-359, 394-1823, 1923-2223.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107243. 45 interactions.
DIPiDIP-39484N.
IntActiP27708. 23 interactions.
MINTiMINT-5000537.
STRINGi9606.ENSP00000264705.

Chemistry

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

Protein family/group databases

MEROPSiC26.952.

PTM databases

PhosphoSiteiP27708.

Polymorphism databases

DMDMi50403731.

Proteomic databases

MaxQBiP27708.
PaxDbiP27708.
PeptideAtlasiP27708.
PRIDEiP27708.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264705; ENSP00000264705; ENSG00000084774.
GeneIDi790.
KEGGihsa:790.
UCSCiuc002rji.3. human.

Organism-specific databases

CTDi790.
GeneCardsiGC02P027440.
HGNCiHGNC:1424. CAD.
HPAiCAB007781.
MIMi114010. gene.
neXtProtiNX_P27708.
PharmGKBiPA26023.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0458.
GeneTreeiENSGT00390000015604.
HOGENOMiHOG000234584.
HOVERGENiHBG000279.
InParanoidiP27708.
KOiK11540.
OrthoDBiEOG7M6D6F.
PhylomeDBiP27708.
TreeFamiTF105604.

Enzyme and pathway databases

UniPathwayiUPA00070; UER00115.
UPA00070; UER00116.
UPA00070; UER00117.
BioCyciMetaCyc:ENSG00000084774-MONOMER.
BRENDAi3.5.2.3. 2681.
ReactomeiREACT_21376. Pyrimidine biosynthesis.

Miscellaneous databases

ChiTaRSiCAD. human.
GenomeRNAii790.
NextBioi3214.
PMAP-CutDBP27708.
PROiP27708.
SOURCEiSearch...

Gene expression databases

BgeeiP27708.
CleanExiHS_CAD.
ExpressionAtlasiP27708. baseline and differential.
GenevestigatoriP27708.

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.
MF_01209. CPSase_S_chain.
InterProiIPR006132. 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.
IPR005481. CarbamoylP_synth_lsu_N.
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.
IPR011607. MGS-like_dom.
IPR016185. PreATP-grasp_dom.
[Graphical view]
PfamiPF00289. 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]
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.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of a human cDNA encoding a trifunctional enzyme of carbamoyl-phosphate synthetase-aspartate transcarbamoylase-dihydroorotase in de Novo pyrimidine synthesis."
    Iwahana H., Fujimura M., Ii S., Kondo M., Moritani M., Takahashi Y., Yamaoka T., Yoshimoto K., Itakura M.
    Biochem. Biophys. Res. Commun. 219:249-255(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Fetal lung fibroblast.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Eye.
  4. Cited for: PROTEIN SEQUENCE OF 2-13; 157-165; 169-177; 359-371; 501-516; 548-555; 599-606; 697-719; 761-778; 843-854; 932-944; 1034-1048; 1067-1075; 1110-1127; 1229-1240; 1263-1270; 1313-1323; 1326-1333; 1658-1667; 1723-1731; 1840-1848; 1976-1986; 2025-2036; 2103-2110; 2179-2187 AND 2215-2225, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Colon adenocarcinoma and Hepatoma.
  5. "Organization and nucleotide sequence of the 3' end of the human CAD gene."
    Davidson J.N., Rao G.N., Niswander L., Andreano C., Tamer C., Chen K.C.
    DNA Cell Biol. 9:667-676(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1752-2225.
  6. "Function of conserved histidine residues in mammalian dihydroorotase."
    Zimmermann B.H., Kemling N.M., Evans D.R.
    Biochemistry 34:7038-7046(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF HIS-1471; HIS-1473; ASP-1512; HIS-1590; HIS-1642 AND HIS-1690, COFACTOR, ZINC-BINDING SITES.
  7. "Growth-dependent regulation of mammalian pyrimidine biosynthesis by the protein kinase A and MAPK signaling cascades."
    Sigoillot F.D., Evans D.R., Guy H.I.
    J. Biol. Chem. 277:15745-15751(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION.
  8. "Nuclear localization and mitogen-activated protein kinase phosphorylation of the multifunctional protein CAD."
    Sigoillot F.D., Kotsis D.H., Serre V., Sigoillot S.M., Evans D.R., Guy H.I.
    J. Biol. Chem. 280:25611-25620(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  9. "Transcriptional repression of human cad gene by hypoxia inducible factor-1alpha."
    Chen K.F., Lai Y.Y., Sun H.S., Tsai S.J.
    Nucleic Acids Res. 33:5190-5198(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  10. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
    Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
    Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1859, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  11. "A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
    Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
    Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1859, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  12. "Protein kinase C modulates the up-regulation of the pyrimidine biosynthetic complex, CAD, by MAP kinase."
    Sigoillot F.D., Kotsis D.H., Masko E.M., Bame M., Evans D.R., Evans H.I.
    Front. Biosci. 12:3892-3898(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-456; SER-1406; SER-1859 AND SER-1873, MUTAGENESIS OF SER-1873.
  13. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1859 AND THR-1884, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  14. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1884, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  15. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  16. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  17. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-747 AND LYS-1411, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  18. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1859; SER-1900 AND THR-1906, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  19. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  20. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1406 AND SER-1859, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  21. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
    Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
    Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  22. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  23. "Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis."
    Robitaille A.M., Christen S., Shimobayashi M., Cornu M., Fava L.L., Moes S., Prescianotto-Baschong C., Sauer U., Jenoe P., Hall M.N.
    Science 339:1320-1323(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-1859.
  24. "Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1."
    Ben-Sahra I., Howell J.J., Asara J.M., Manning B.D.
    Science 339:1323-1328(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-1859 AND SER-1900.
  25. "Structure, functional characterization, and evolution of the dihydroorotase domain of human CAD."
    Grande-Garcia A., Lallous N., Diaz-Tejada C., Ramon-Maiques S.
    Structure 22:185-198(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1456-1846 IN COMPLEX WITH DIHYDROOROTATE; N-CARBAMOYL-L-ASPARTIC ACID AND ZINC, COFACTOR, CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-1471; THR-1562; PHE-1563; HIS-1590; CYS-1613; HIS-1614; GLU-1637 AND ASP-1686, CARBAMYLATION AT LYS-1556.
  26. Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-177 AND CYS-735.

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: February 4, 2015
This is version 175 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

External Data

Dasty 3

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 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.