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Overview

Uniprot ID	P27708
Protein Name	Multifunctional protein CAD
Gene Name	CAD
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
1411	RLSSFVTKGYRTRRL
1875	PKEKSSRKVAEPELM
739	SVDYCVVKIPRWDLS

Function

Multifunctional protein that encodes the first 3 enzymatic activities of the de novo pyrimidine pathway: carbamoylphosphate synthetase (CPSase; EC 6.3.5.5), aspartate transcarbamylase (ATCase; EC 2.1.3.2) and dihydroorotase (DHOase; EC 3.5.2.3). The CPSase-function is accomplished in 2 steps, by a glutamine-dependent amidotransferase activity (GATase) that binds and cleaves glutamine to produce ammonia, followed by an ammonium-dependent carbamoyl phosphate synthetase, which reacts with the ammonia, hydrogencarbonate and ATP to form carbamoyl phosphate. The endogenously produced carbamoyl phosphate is sequestered and channeled to the ATCase active site. ATCase then catalyzes the formation of carbamoyl-L-aspartate from L-aspartate and carbamoyl phosphate. In the last step, DHOase catalyzes the cyclization of carbamoyl aspartate to dihydroorotate

Protein Sequence

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

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0042995	cell projection
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0070062	extracellular exosome
Cellular Component	GO:0016020	membrane
Cellular Component	GO:0043025	neuronal cell body
Cellular Component	GO:0016363	nuclear matrix
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0032991	protein-containing complex
Cellular Component	GO:0043195	terminal bouton
Molecular Function	GO:0070335	aspartate binding
Molecular Function	GO:0004070	aspartate carbamoyltransferase activity
Molecular Function	GO:0005524	ATP binding
Molecular Function	GO:0004087	carbamoyl-phosphate synthase (ammonia) activity
Molecular Function	GO:0004088	carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity
Molecular Function	GO:0004151	dihydroorotase activity
Molecular Function	GO:0019899	enzyme binding
Molecular Function	GO:0004359	glutaminase activity
Molecular Function	GO:0042802	identical protein binding
Molecular Function	GO:0004672	protein kinase activity
Molecular Function	GO:0008270	zinc ion binding
Biological Process	GO:0006207	'de novo' pyrimidine nucleobase biosynthetic process
Biological Process	GO:0044205	'de novo' UMP biosynthetic process
Biological Process	GO:0031100	animal organ regeneration
Biological Process	GO:0071364	cellular response to epidermal growth factor stimulus
Biological Process	GO:0019240	citrulline biosynthetic process
Biological Process	GO:0007565	female pregnancy
Biological Process	GO:0006541	glutamine metabolic process
Biological Process	GO:0007507	heart development
Biological Process	GO:0007595	lactation
Biological Process	GO:0001889	liver development
Biological Process	GO:0014075	response to amine
Biological Process	GO:0031000	response to caffeine
Biological Process	GO:0051414	response to cortisol
Biological Process	GO:0032868	response to insulin
Biological Process	GO:0042594	response to starvation
Biological Process	GO:0033574	response to testosterone
Biological Process	GO:0006225	UDP biosynthetic process
Biological Process	GO:0006228	UTP biosynthetic process
Biological Process	GO:0006805	xenobiotic metabolic process

Reference

[1] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.