Q8C196 (CPSM_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carbamoyl-phosphate synthase [ammonia], mitochondrial
EC=6.3.4.16

Alternative name(s):
Carbamoyl-phosphate synthetase I
Short name=CPSase I

Gene names

Name:

Cps1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1500 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.
Catalytic activity	2 ATP + NH3 + CO2 + H2O = 2 ADP + phosphate + carbamoyl phosphate.
Enzyme regulation	Requires N-acetyl-L-glutamate (NAG) as an allosteric activator By similarity.
Subcellular location	Mitochondrion By similarity. Nucleus › nucleolus By similarity.
Domain	The type-1 glutamine amidotransferase domain is defective By similarity.
Post-translational modification	Acetylation of Lys-287, Lys-603, Lys-841 and Lys-1291 is observed in liver mitochondria from fasted mice but not from fed mice. Succinylated at Lys-44, Lys-287 and Lys-1291. Desuccinylated at Lys-1291 by SIRT5, leading to activation. Ref.8
Sequence similarities	Contains 2 ATP-grasp domains. Contains 1 glutamine amidotransferase type-1 domain.
Caution	Was initially reported to be deacetylated by Sirt5 (Ref.7). However, it was later shown that Sirt5 has poor deacetylase activity and mediates desuccinylation of Cps1 instead (Ref.8).

Ontologies

Keywords
Biological process	Urea cycle
Cellular component	Mitochondrion Nucleus
Domain	Repeat Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	Allosteric enzyme Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	anion homeostasis Inferred from electronic annotation. Source: Compara carbamoyl phosphate biosynthetic process Inferred from electronic annotation. Source: InterPro cellular response to cAMP Inferred from electronic annotation. Source: Compara cellular response to fibroblast growth factor stimulus Inferred from electronic annotation. Source: Compara cellular response to glucagon stimulus Inferred from electronic annotation. Source: Compara cellular response to oleic acid Inferred from electronic annotation. Source: Compara glutamine catabolic process Inferred from electronic annotation. Source: InterPro glycogen catabolic process Inferred from electronic annotation. Source: Compara hepatocyte differentiation Inferred from electronic annotation. Source: Compara homocysteine metabolic process Inferred from electronic annotation. Source: Compara midgut development Inferred from electronic annotation. Source: Compara nitric oxide metabolic process Inferred from electronic annotation. Source: Compara positive regulation of vasodilation Inferred from electronic annotation. Source: Compara response to amine stimulus Inferred from electronic annotation. Source: Compara response to amino acid stimulus Inferred from electronic annotation. Source: Compara response to dexamethasone stimulus Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to food Inferred from electronic annotation. Source: Compara response to growth hormone stimulus Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to starvation Inferred from electronic annotation. Source: Compara response to toxin Inferred from electronic annotation. Source: Compara response to zinc ion Inferred from electronic annotation. Source: Compara triglyceride catabolic process Inferred from electronic annotation. Source: Compara urea cycle Inferred by curator PubMed 9862865. Source: MGI
Cellular_component	mitochondrial inner membrane Inferred from electronic annotation. Source: Compara mitochondrial nucleoid Inferred from electronic annotation. Source: Compara mitochondrion Inferred from direct assay PubMed 22402285PubMed 6200105. Source: MGI nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell protein complex Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: Compara carbamoyl-phosphate synthase (ammonia) activity Inferred from mutant phenotype PubMed 9862865. Source: MGI endopeptidase activity Inferred from electronic annotation. Source: Compara glutamate binding Inferred from electronic annotation. Source: Compara modified amino acid binding Inferred from electronic annotation. Source: Compara phospholipid binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Sirt5	Q8K2C6	2	EBI-2348828,EBI-2348809

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 38	38	Mitochondrion By similarity
	Chain	39 – 1500	1462	Carbamoyl-phosphate synthase [ammonia], mitochondrial By similarity		PRO_0000029898
Regions
	Domain	219 – 404	186	Glutamine amidotransferase type-1
	Domain	551 – 743	193	ATP-grasp 1
	Domain	1093 – 1284	192	ATP-grasp 2
	Region	39 – 218	180	Anthranilate phosphoribosyltransferase homolog
Sites
	Binding site	1391	1	Allosteric activator By similarity
	Binding site	1394	1	Allosteric activator By similarity
	Binding site	1410	1	Allosteric activator By similarity
	Binding site	1437	1	Allosteric activator By similarity
	Binding site	1440	1	Allosteric activator By similarity
	Binding site	1449	1	Allosteric activator By similarity
Amino acid modifications
	Modified residue	44	1	N6-acetyllysine; alternate Ref.8
	Modified residue	44	1	N6-succinyllysine; alternate Ref.8
	Modified residue	55	1	N6-acetyllysine Ref.5
	Modified residue	119	1	N6-acetyllysine Ref.5
	Modified residue	287	1	N6-acetyllysine; alternate Ref.5 Ref.8
	Modified residue	287	1	N6-succinyllysine; alternate Ref.8
	Modified residue	527	1	N6-acetyllysine Ref.5
	Modified residue	603	1	N6-acetyllysine Ref.5
	Modified residue	840	1	N6-acetyllysine Ref.5
	Modified residue	841	1	N6-acetyllysine Ref.5
	Modified residue	892	1	N6-acetyllysine Ref.5
	Modified residue	898	1	Phosphoserine Ref.6
	Modified residue	1291	1	N6-acetyllysine; alternate Ref.5 Ref.7 Ref.8
	Modified residue	1291	1	N6-succinyllysine; alternate Ref.8
Experimental info
	Sequence conflict	931 – 934	4	LRLK → HASE in AAH67211. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8C196 [UniParc]. Last modified August 30, 2005. Version 2. Checksum: 84A7268C1D7E8101	FASTA	1,500	164,618
	10 20 30 40 50 60 MTRILTACKV VKTLKSGFGF ANVTTKRQWD FSRPGIRLLS VKAKTAHIVL EDGTKMKGYS 70 80 90 100 110 120 FGHPSSVAGE VVFNTGLGGY PEALTDPAYK GQILTMANPI IGNGGAPDTT ARDELGLNKY 130 140 150 160 170 180 MESDGIKVAG LLVLNYSNDY NHWLATKSLG QWLQEEKVPA IYGVDTRMLT KIIRDKGTML 190 200 210 220 230 240 GKIEFEGQSV DFVDPNKQNL IAEVSTKDVK VFGKGNPTKV VAVDCGIKNN VIRLLVKRGA 250 260 270 280 290 300 EVHLVPWNHD FTQMEYDGLL IAGGPGNPAL AQPLIQNVKK ILESDRKEPL FGISTGNIIT 310 320 330 340 350 360 GLAAGAKSYK MSMANRGQNQ PVLNITNRQA FITAQNHGYA LDNTLPAGWK PLFVNVNDQT 370 380 390 400 410 420 NEGIMHESKP FFAVQFHPEV SPGPTDTEYL FDSFFSLIKK GKGTTITSVL PKPALVASRV 430 440 450 460 470 480 EVSKVLILGS GGLSIGQAGE FDYSGSQAVK AMKEENVKTV LMNPNIASVQ TNEVGLKQAD 490 500 510 520 530 540 AVYFLPITPQ FVTEVIKAER PDGLILGMGG QTALNCGVEL FKRGVLKEYG VKVLGTSVES 550 560 570 580 590 600 IMATEDRQLF SDKLNEINEK IAPSFAVESM EDALKAADTI GYPVMIRSAY ALGGLGSGIC 610 620 630 640 650 660 PNKETLIDLG TKAFAMTNQI LVERSVTGWK EIEYEVVRDA DDNCVTVCNM ENVDAMGVHT 670 680 690 700 710 720 GDSVVVAPAQ TLSNAEFQML RRTSVNVVRH LGIVGECNIQ FALHPTSMEY CIIEVNARLS 730 740 750 760 770 780 RSSALASKAT GYPLAFIAAK IALGIPLPEI KNVVSGKTSA CFEPSLDYMV TKIPRWDLDR 790 800 810 820 830 840 FHGTSSRIGS SMKSVGEVMA IGRTFEESFQ KALRMCHPSV DGFTPRLPMN KEWPANLDLK 850 860 870 880 890 900 KELSEPSSTR IYAIAKALEN NMSLDEIVRL TSIDKWFLYK MRDILNMDKT LKGLNSDSVT 910 920 930 940 950 960 EETLRKAKEI GFSDKQISKC LGLTEAQTRE LRLKKNIHPW VKQIDTLAAE YPSVTNYLYV 970 980 990 1000 1010 1020 TYNGQEHDIK FDEHGIMVLG CGPYHIGSSV EFDWCAVSSI RTLRQLGKKT VVVNCNPETV 1030 1040 1050 1060 1070 1080 STDFDECDKL YFEELSLERI LDIYHQEACN GCIISVGGQI PNNLAVPLYK NGVKIMGTSP 1090 1100 1110 1120 1130 1140 LQIDRAEDRS IFSAVLDELK VAQAPWKAVN TLNEALEFAN SVGYPCLLRP SYVLSGSAMN 1150 1160 1170 1180 1190 1200 VVFSEDEMKR FLEEATRVSQ EHPVVLTKFV EGAREVEMDA VGKEGRVISH AISEHVEDAG 1210 1220 1230 1240 1250 1260 VHSGDATLML PTQTISQGAI EKVKDATRKI AKAFAISGPF NVQFLVKGND VLVIECNLRA 1270 1280 1290 1300 1310 1320 SRSFPFVSKT LGVDFIDVAT KVMIGESIDE KRLPTLEQPI IPSDYVAIKA PMFSWPRLRD 1330 1340 1350 1360 1370 1380 ADPILRCEMA STGEVACFGE GIHTAFLKAM LSTGFKIPQK GILIGIQQSF RPRFLGVAEQ 1390 1400 1410 1420 1430 1440 LHNEGFKLFA TEATSDWLNA NNVPATPVAW PSQEGQNPSL SSIRKLIRDG SIDLVINLPN 1450 1460 1470 1480 1490 1500 NNTKFVHDNY VIRRTAVDSG IALLTNFQVT KLFAEAVQKS RTVDSKSLFH YRQYSAGKAA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[2]	"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]. Strain: FVB/N. Tissue: Liver.
[3]	Bienvenut W.V. Submitted (JUL-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 113-167; 183-207; 287-307; 317-328; 403-419; 459-522; 533-624; 631-638; 683-689; 729-740; 794-811; 815-826; 842-850; 857-880; 883-889; 893-905; 1030-1039; 1075-1085; 1090-1100; 1158-1168; 1175-1183; 1233-1259; 1270-1317; 1320-1326; 1349-1356; 1361-1387; 1429-1444 AND 1455-1479, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Liver.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 753-1500. Strain: C57BL/6J. Tissue: Skin.
[5]	"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey." Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y. Mol. Cell 23:607-618(2006) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-55; LYS-119; LYS-287; LYS-527; LYS-603; LYS-840; LYS-841; LYS-892 AND LYS-1291, MASS SPECTROMETRY. Tissue: Liver.
[6]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-898, MASS SPECTROMETRY. Tissue: Liver.
[7]	"SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle." Nakagawa T., Lomb D.J., Haigis M.C., Guarente L. Cell 137:560-570(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT LYS-1291, DEACETYLATION.
[8]	"Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase." Du J., Zhou Y., Su X., Yu J.J., Khan S., Jiang H., Kim J., Woo J., Kim J.H., Choi B.H., He B., Chen W., Zhang S., Cerione R.A., Auwerx J., Hao Q., Lin H. Science 334:806-809(2011) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT LYS-44; LYS-287 AND LYS-1291, SUCCINYLATION AT LYS-44; LYS-287 AND LYS-1291, DESUCCINYLATION BY SIRT5.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AC101854 Genomic DNA. No translation available. AC133187 Genomic DNA. No translation available. BC067211 mRNA. Translation: AAH67211.1. BC126969 mRNA. Translation: AAI26970.1. AK028683 mRNA. Translation: BAC26064.1.
IPI	IPI00111908.
RefSeq	NP_001074278.1. NM_001080809.1.
UniGene	Mm.343942.
3D structure databases
ProteinModelPortal	Q8C196.
SMR	Q8C196. Positions 44-404, 535-812, 996-1338, 1343-1478.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8C196. 2 interactions.
PTM databases
PhosphoSite	Q8C196.
Proteomic databases
PaxDb	Q8C196.
PRIDE	Q8C196.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000027144; ENSMUSP00000027144; ENSMUSG00000025991.
GeneID	227231.
KEGG	mmu:227231.
UCSC	uc007biy.1. mouse.
Organism-specific databases
CTD	1373.
MGI	MGI:891996. Cps1.
Phylogenomic databases
eggNOG	COG0458.
GeneTree	ENSGT00390000015604.
HOGENOM	HOG000234583.
HOVERGEN	HBG000279.
InParanoid	A0JNU4.
KO	K01948.
OMA	SEFFEIV.
OrthoDB	EOG45MN4G.
Enzyme and pathway databases
SABIO-RK	Q8C196.
Gene expression databases
ArrayExpress	Q8C196.
Bgee	Q8C196.
CleanEx	MM_CPS1.
Genevestigator	Q8C196.
GermOnline	ENSMUSG00000025991. Mus musculus.
Family and domain databases
Gene3D	1.10.1030.10. 1 hit. 3.30.1490.20. 2 hits. 3.30.470.20. 2 hits. 3.40.50.1380. 1 hit. 3.40.50.20. 2 hits. 3.50.30.20. 1 hit.
InterPro	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. IPR017926. GATASE_1. IPR011607. MGS-like_dom. IPR016185. PreATP-grasp_dom. [Graphical view]
Pfam	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. [Graphical view]
PRINTS	PR00098. CPSASE.
SMART	SM01096. CPSase_L_D3. 1 hit. SM01097. CPSase_sm_chain. 1 hit. SM00851. MGS. 1 hit. [Graphical view]
SUPFAM	SSF48108. CarbamoylP_synth_lsu_oligo. 1 hit. SSF52021. CP_synthsmall. 1 hit. SSF52335. MGS-like_dom. 1 hit. SSF52440. PreATP-grasp-like. 2 hits.
TIGRFAMs	TIGR01369. CPSaseII_lrg. 1 hit. TIGR01368. CPSaseIIsmall. 1 hit.
PROSITE	PS50975. ATP_GRASP. 2 hits. PS00866. CPSASE_1. 2 hits. PS00867. CPSASE_2. 2 hits. PS51273. GATASE_TYPE_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	378522.
SOURCE	Search...

Entry information

Entry name

CPSM_MOUSE

Accession

Primary (citable) accession number: Q8C196
Secondary accession number(s): A0JNU4, Q6NX75

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	August 30, 2005
Last modified:	May 1, 2013
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program