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P27708

- PYR1_HUMAN

UniProt

P27708 - PYR1_HUMAN

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Protein
CAD protein
Gene
CAD
Organism
Homo sapiens (Human)
Status
Reviewed - 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

Binds 3 zinc 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-aspartate

Pathwayi

Sites

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

GO - Molecular functioni

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

GO - Biological processi

  1. 'de novo' UMP biosynthetic process Source: UniProtKB-UniPathway
  2. 'de novo' pyrimidine nucleobase biosynthetic process Source: UniProtKB
  3. UTP biosynthetic process Source: Ensembl
  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. embryo development Source: Ensembl
  9. female pregnancy Source: Ensembl
  10. glutamine catabolic process Source: InterPro
  11. glutamine metabolic process Source: BHF-UCL
  12. lactation Source: Ensembl
  13. nucleobase-containing small molecule metabolic process Source: Reactome
  14. organ regeneration Source: Ensembl
  15. peptidyl-threonine phosphorylation Source: BHF-UCL
  16. protein autophosphorylation Source: BHF-UCL
  17. pyrimidine nucleobase metabolic process Source: Reactome
  18. pyrimidine nucleoside biosynthetic process Source: Reactome
  19. response to amine Source: Ensembl
  20. response to caffeine Source: Ensembl
  21. response to cortisol Source: Ensembl
  22. response to testosterone Source: Ensembl
  23. small molecule metabolic process Source: Reactome
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. Nucleus
Note: Cytosolic and unphosphorylated in resting cells, translocates to the nucleus in response to EGF stimulation, nuclear import promotes optimal cell growth.1 Publication

GO - Cellular componenti

  1. cell projection Source: BHF-UCL
  2. cytosol Source: BHF-UCL
  3. extracellular vesicular exosome Source: UniProt
  4. neuronal cell body Source: BHF-UCL
  5. nuclear matrix Source: BHF-UCL
  6. nucleus Source: BHF-UCL
  7. protein complex Source: Ensembl
  8. 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 – 11Removed1 Publication
Chaini2 – 22252224CAD proteinUniRule annotation
PRO_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-carboxylysineUniRule annotation
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.UniRule annotation

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.2 Publications

Gene expression databases

ArrayExpressiP27708.
BgeeiP27708.
CleanExiHS_CAD.
GenevestigatoriP27708.

Organism-specific databases

HPAiCAB007781.

Interactioni

Subunit structurei

Homohexamer.

Protein-protein interaction databases

BioGridi107243. 41 interactions.
DIPiDIP-39484N.
IntActiP27708. 23 interactions.
MINTiMINT-5000537.
STRINGi9606.ENSP00000264705.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
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.

Family & Domainsi

Domains and Repeats

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

Region

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

Sequence similaritiesi

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiCOG0458.
HOGENOMiHOG000234584.
HOVERGENiHBG000279.
InParanoidiP27708.
KOiK11540.
OMAiACLQCWI.
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

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MAALVLEDGS VLRGQPFGAA VSTAGEVVFQ TGMVGYPEAL TDPSYKAQIL     50
VLTYPLIGNY GIPPDEMDEF GLCKWFESSG IHVAALVVGE CCPTPSHWSA 100
TRTLHEWLQQ HGIPGLQGVD TRELTKKLRE QGSLLGKLVQ NGTEPSSLPF 150
LDPNARPLVP EVSIKTPRVF NTGGAPRILA LDCGLKYNQI RCLCQRGAEV 200
TVVPWDHALD SQEYEGLFLS NGPGDPASYP SVVSTLSRVL SEPNPRPVFG 250
ICLGHQLLAL AIGAKTYKMR YGNRGHNQPC LLVGSGRCFL TSQNHGFAVE 300
TDSLPADWAP LFTNANDGSN EGIVHNSLPF FSVQFHPEHQ AGPSDMELLF 350
DIFLETVKEA TAGNPGGQTV RERLTERLCP PGIPTPGSGL PPPRKVLILG 400
SGGLSIGQAG EFDYSGSQAI KALKEENIQT LLINPNIATV QTSQGLADKV 450
YFLPITPHYV TQVIRNERPD GVLLTFGGQT ALNCGVELTK AGVLARYGVR 500
VLGTPVETIE LTEDRRAFAA RMAEIGEHVA PSEAANSLEQ AQAAAERLGY 550
PVLVRAAFAL GGLGSGFASN REELSALVAP AFAHTSQVLV DKSLKGWKEI 600
EYEVVRDAYG NCVTVCNMEN LDPLGIHTGE SIVVAPSQTL NDREYQLLRQ 650
TAIKVTQHLG IVGECNVQYA LNPESEQYYI IEVNARLSRS SALASKATGY 700
PLAYVAAKLA LGIPLPELRN SVTGGTAAFE PSVDYCVVKI PRWDLSKFLR 750
VSTKIGSCMK SVGEVMGIGR SFEEAFQKAL RMVDENCVGF DHTVKPVSDM 800
ELETPTDKRI FVVAAALWAG YSVDRLYELT RIDRWFLHRM KRIIAHAQLL 850
EQHRGQPLPP DLLQQAKCLG FSDKQIALAV LSTELAVRKL RQELGICPAV 900
KQIDTVAAEW PAQTNYLYLT YWGTTHDLTF RTPHVLVLGS GVYRIGSSVE 950
FDWCAVGCIQ QLRKMGYKTI MVNYNPETVS TDYDMCDRLY FDEISFEVVM 1000
DIYELENPEG VILSMGGQLP NNMAMALHRQ QCRVLGTSPE AIDSAENRFK 1050
FSRLLDTIGI SQPQWRELSD LESARQFCQT VGYPCVVRPS YVLSGAAMNV 1100
AYTDGDLERF LSSAAAVSKE HPVVISKFIQ EAKEIDVDAV ASDGVVAAIA 1150
ISEHVENAGV HSGDATLVTP PQDITAKTLE RIKAIVHAVG QELQVTGPFN 1200
LQLIAKDDQL KVIECNVRVS RSFPFVSKTL GVDLVALATR VIMGEEVEPV 1250
GLMTGSGVVG VKVPQFSFSR LAGADVVLGV EMTSTGEVAG FGESRCEAYL 1300
KAMLSTGFKI PKKNILLTIG SYKNKSELLP TVRLLESLGY SLYASLGTAD 1350
FYTEHGVKVT AVDWHFEEAV DGECPPQRSI LEQLAEKNFE LVINLSMRGA 1400
GGRRLSSFVT KGYRTRRLAA DFSVPLIIDI KCTKLFVEAL GQIGPAPPLK 1450
VHVDCMTSQK LVRLPGLIDV HVHLREPGGT HKEDFASGTA AALAGGITMV 1500
CAMPNTRPPI IDAPALALAQ KLAEAGARCD FALFLGASSE NAGTLGTVAG 1550
SAAGLKLYLN ETFSELRLDS VVQWMEHFET WPSHLPIVAH AEQQTVAAVL 1600
MVAQLTQRSV HICHVARKEE ILLIKAAKAR GLPVTCEVAP HHLFLSHDDL 1650
ERLGPGKGEV RPELGSRQDV EALWENMAVI DCFASDHAPH TLEEKCGSRP 1700
PPGFPGLETM LPLLLTAVSE GRLSLDDLLQ RLHHNPRRIF HLPPQEDTYV 1750
EVDLEHEWTI PSHMPFSKAH WTPFEGQKVK GTVRRVVLRG EVAYIDGQVL 1800
VPPGYGQDVR KWPQGAVPQL PPSAPATSEM TTTPERPRRG IPGLPDGRFH 1850
LPPRIHRASD PGLPAEEPKE KSSRKVAEPE LMGTPDGTCY PPPPVPRQAS 1900
PQNLGTPGLL HPQTSPLLHS LVGQHILSVQ QFTKDQMSHL FNVAHTLRMM 1950
VQKERSLDIL KGKVMASMFY EVSTRTSSSF AAAMARLGGA VLSFSEATSS 2000
VQKGESLADS VQTMSCYADV VVLRHPQPGA VELAAKHCRR PVINAGDGVG 2050
EHPTQALLDI FTIREELGTV NGMTITMVGD LKHGRTVHSL ACLLTQYRVS 2100
LRYVAPPSLR MPPTVRAFVA SRGTKQEEFE SIEEALPDTD VLYMTRIQKE 2150
RFGSTQEYEA CFGQFILTPH IMTRAKKKMV VMHPMPRVNE ISVEVDSDPR 2200
AAYFRQAENG MYIRMALLAT VLGRF 2225
Length:2,225
Mass (Da):242,984
Last modified:July 19, 2004 - v3
Checksum:i2AB8E8413E825A8F
GO

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 conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti505 – 5051P → T in BAA11423. 1 Publication
Sequence conflicti535 – 5351A → G in BAA11423. 1 Publication
Sequence conflicti560 – 5601L → V in BAA11423. 1 Publication
Sequence conflicti1103 – 11031T → A in BAA11423. 1 Publication
Sequence conflicti1513 – 15131A → G in BAA11423. 1 Publication
Sequence conflicti1676 – 16761N → D in BAA11423. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS1742.1.
PIRi A36240.
RefSeqi NP_004332.2. NM_004341.3.
UniGenei Hs.377010.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4BY3 X-ray 1.73 A 1456-1846 [» ]
4C6B X-ray 1.66 A 1456-1846 [» ]
4C6C X-ray 1.45 A 1456-1846 [» ]
4C6D X-ray 1.30 A 1456-1846 [» ]
4C6E X-ray 1.26 A 1456-1846 [» ]
4C6F X-ray 1.26 A 1456-1846 [» ]
4C6I X-ray 1.35 A 1456-1846 [» ]
4C6J X-ray 1.30 A 1456-1846 [» ]
4C6K X-ray 1.48 A 1456-1846 [» ]
4C6L X-ray 1.55 A 1456-1846 [» ]
4C6M X-ray 1.62 A 1456-1846 [» ]
4C6N X-ray 1.90 A 1456-1846 [» ]
4C6O X-ray 1.65 A 1456-1846 [» ]
4C6P X-ray 1.52 A 1456-1846 [» ]
4C6Q X-ray 1.66 A 1456-1846 [» ]
ProteinModelPortali P27708.
SMRi P27708. Positions 2-359, 394-1823, 1923-2223.
ModBasei Search...

Protein-protein interaction databases

BioGridi 107243. 41 interactions.
DIPi DIP-39484N.
IntActi P27708. 23 interactions.
MINTi MINT-5000537.
STRINGi 9606.ENSP00000264705.

Chemistry

BindingDBi P27708.
ChEMBLi CHEMBL3093.
DrugBanki DB00128. L-Aspartic Acid.
DB00130. L-Glutamine.

Protein family/group databases

MEROPSi C26.952.

PTM databases

PhosphoSitei P27708.

Polymorphism databases

DMDMi 50403731.

Proteomic databases

MaxQBi P27708.
PaxDbi P27708.
PeptideAtlasi P27708.
PRIDEi P27708.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000264705 ; ENSP00000264705 ; ENSG00000084774 .
GeneIDi 790.
KEGGi hsa:790.
UCSCi uc002rji.3. human.

Organism-specific databases

CTDi 790.
GeneCardsi GC02P027440.
HGNCi HGNC:1424. CAD.
HPAi CAB007781.
MIMi 114010. gene.
neXtProti NX_P27708.
PharmGKBi PA26023.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0458.
HOGENOMi HOG000234584.
HOVERGENi HBG000279.
InParanoidi P27708.
KOi K11540.
OMAi ACLQCWI.
OrthoDBi EOG7M6D6F.
PhylomeDBi P27708.
TreeFami TF105604.

Enzyme and pathway databases

UniPathwayi UPA00070 ; UER00115 .
UPA00070 ; UER00116 .
UPA00070 ; UER00117 .
BioCyci MetaCyc:ENSG00000084774-MONOMER.
BRENDAi 3.5.2.3. 2681.
Reactomei REACT_21376. Pyrimidine biosynthesis.

Miscellaneous databases

ChiTaRSi cad. human.
GenomeRNAii 790.
NextBioi 3214.
PMAP-CutDB P27708.
PROi P27708.
SOURCEi Search...

Gene expression databases

ArrayExpressi P27708.
Bgeei P27708.
CleanExi HS_CAD.
Genevestigatori P27708.

Family and domain databases

Gene3Di 1.10.1030.10. 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.
HAMAPi MF_00001. Asp_carb_tr.
MF_01209. CPSase_S_chain.
InterProi 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.
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 ]
Pfami PF00289. 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 ]
PRINTSi PR00100. AOTCASE.
PR00101. ATCASE.
PR00098. CPSASE.
SMARTi SM01096. CPSase_L_D3. 1 hit.
SM01097. CPSase_sm_chain. 1 hit.
SM00851. MGS. 1 hit.
[Graphical view ]
SUPFAMi SSF48108. 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.
TIGRFAMsi TIGR00670. asp_carb_tr. 1 hit.
TIGR01369. CPSaseII_lrg. 1 hit.
TIGR01368. CPSaseIIsmall. 1 hit.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 170 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

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