Q9Z110 (P5CS_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Delta-1-pyrroline-5-carboxylate synthase
Short name=P5CS

Alternative name(s):
Aldehyde dehydrogenase family 18 member A1

Including the following 2 domains:

1. Glutamate 5-kinase
   Short name=GK
   EC=2.7.2.11
   Alternative name(s):
   Gamma-glutamyl kinase
2. Gamma-glutamyl phosphate reductase
   Short name=GPR
   EC=1.2.1.41
   Alternative name(s):
   Glutamate-5-semialdehyde dehydrogenase
   Glutamyl-gamma-semialdehyde dehydrogenase

Gene names

Name:	Aldh18a1
Synonyms:	P5cs, Pycs

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	795 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Bifunctional enzyme that converts glutamate to glutamate 5-semialdehyde, an intermediate in the biosynthesis of proline, ornithine and arginine By similarity.
Catalytic activity	ATP + L-glutamate = ADP + L-glutamate 5-phosphate. L-glutamate 5-semialdehyde + phosphate + NADP+ = L-glutamyl 5-phosphate + NADPH.
Enzyme regulation	The short isoform is inhibited by L-ornithine with a Ki of approximately 0.25 mm. The long isoform is insensitive to ornithine inhibition. Thus, the two amino acid insert in the long isoform abolishes feedback inhibition of P5CS activity by L-ornithine. Ref.1
Pathway	Amino-acid biosynthesis; L-proline biosynthesis; L-glutamate 5-semialdehyde from L-glutamate: step 1/2. Amino-acid biosynthesis; L-proline biosynthesis; L-glutamate 5-semialdehyde from L-glutamate: step 2/2.
Subcellular location	Mitochondrion inner membrane.
Sequence similarities	In the N-terminal section; belongs to the glutamate 5-kinase family. In the C-terminal section; belongs to the gamma-glutamyl phosphate reductase family.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Proline biosynthesis
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding NADP Nucleotide-binding
Molecular function	Kinase Oxidoreductase Transferase
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	L-proline biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway citrulline biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB glutamate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB ornithine biosynthetic process Inferred from electronic annotation. Source: Compara proline biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	mitochondrial inner membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay PubMed 14651853PubMed 18614015. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW glutamate 5-kinase activity Inferred from direct assay Ref.1. Source: MGI glutamate-5-semialdehyde dehydrogenase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: Q9Z110-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: Q9Z110-2)

The sequence of this isoform differs from the canonical sequence as follows:
     239-240: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 795	795	Delta-1-pyrroline-5-carboxylate synthase		PRO_0000109770
Regions
	Nucleotide binding	266 – 267	2	ATP By similarity
	Nucleotide binding	305 – 311	7	ATP By similarity
	Region	1 – 361	361	Glutamate 5-kinase
	Region	362 – 795	434	Gamma-glutamyl phosphate reductase
Sites
	Binding site	117	1	Substrate By similarity
	Binding site	223	1	Substrate By similarity
	Binding site	246	1	Substrate; via amide nitrogen By similarity
Natural variations
	Alternative sequence	239 – 240	2	Missing in isoform Short.		VSP_005216
Experimental info
	Sequence conflict	582	1	G → S in AAD17517. Ref.1
	Sequence conflict	582	1	G → S in AAD17518. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 877DF1A7B5F84247	FASTA	795	87,266
	10 20 30 40 50 60 MLRHMHRSGV QPFRQRLLPW VQSIAVPRSN RVQPSAIRHV RSWSNIPFIT VPLSRAHGKP 70 80 90 100 110 120 FAHRSELKHA KRIVVKLGSA VVTRGDECGL ALGRLASIVE QVSVLQNQGR EMMLVTSGAV 130 140 150 160 170 180 AFGKQRLRHE ILLSQSVRQA LHSGQNHLKE MAIPVLEARA CAAAGQSGLM ALYEAMFTQY 190 200 210 220 230 240 SICAAQILVT NLDFHDEQKR RNLNGTLHEL LRMNIVPIVN TNDAVVPPAE PNSDLQGVNV 250 260 270 280 290 300 ISVKDNDSLA ARLAVEMKTD LLIVLSDVEG LFDSPPGSDD AKLIDIFYPG DQQSVTFGTK 310 320 330 340 350 360 SRVGLGGMEA KVKAALWALQ GGTSVVIANG THPKVSGHVI TDIVEGKKVG TFFSEVKPAG 370 380 390 400 410 420 PTVEQQGEMA RSGGRMLATL EPEQRAEIIN HLADLLTDQR EEILLANKKD LEEAEGRLAS 430 440 450 460 470 480 PLLKRLSLST SKLNSLAIGL RQIAASSQES VGRVLRRTRI AKNLELEQVT VPIGVLLVIF 490 500 510 520 530 540 ESRPDCLPQV AALAIASGNG LLLKGGKEAA HSNRILHLLT QEALSIHGVK EAIQLVNTRE 550 560 570 580 590 600 EVEDLCRLDK IIDLIIPRGS SQLVRDIQKA AKGIPVMGHS EGICHMYVDS EASVDKVTRL 610 620 630 640 650 660 VRDSKCEYPA ACNALETLLI HRDLLRTPLF DQIIDMLRVE QVKIHAGPKF ASYLTFSPSE 670 680 690 700 710 720 VKSLRTEYGD LEVCIEVVDS VQEAIDHIHK YGSSHTDVIV TENEKTAEFF LQHVDSACVF 730 740 750 760 770 780 WNASTRFSDG YRFGLGAEVG ISTSRIHARG PVGLEGLLTT KWLLRGQDHV VSDFSEHGSL 790 KYLHENLPVP QRNFS
	Isoform Short [UniParc]. Checksum: F0076527C19FCDCD	FASTA	793	87,053
	10 20 30 40 50 60 MLRHMHRSGV QPFRQRLLPW VQSIAVPRSN RVQPSAIRHV RSWSNIPFIT VPLSRAHGKP 70 80 90 100 110 120 FAHRSELKHA KRIVVKLGSA VVTRGDECGL ALGRLASIVE QVSVLQNQGR EMMLVTSGAV 130 140 150 160 170 180 AFGKQRLRHE ILLSQSVRQA LHSGQNHLKE MAIPVLEARA CAAAGQSGLM ALYEAMFTQY 190 200 210 220 230 240 SICAAQILVT NLDFHDEQKR RNLNGTLHEL LRMNIVPIVN TNDAVVPPAE PNSDLQGVIS 250 260 270 280 290 300 VKDNDSLAAR LAVEMKTDLL IVLSDVEGLF DSPPGSDDAK LIDIFYPGDQ QSVTFGTKSR 310 320 330 340 350 360 VGLGGMEAKV KAALWALQGG TSVVIANGTH PKVSGHVITD IVEGKKVGTF FSEVKPAGPT 370 380 390 400 410 420 VEQQGEMARS GGRMLATLEP EQRAEIINHL ADLLTDQREE ILLANKKDLE EAEGRLASPL 430 440 450 460 470 480 LKRLSLSTSK LNSLAIGLRQ IAASSQESVG RVLRRTRIAK NLELEQVTVP IGVLLVIFES 490 500 510 520 530 540 RPDCLPQVAA LAIASGNGLL LKGGKEAAHS NRILHLLTQE ALSIHGVKEA IQLVNTREEV 550 560 570 580 590 600 EDLCRLDKII DLIIPRGSSQ LVRDIQKAAK GIPVMGHSEG ICHMYVDSEA SVDKVTRLVR 610 620 630 640 650 660 DSKCEYPAAC NALETLLIHR DLLRTPLFDQ IIDMLRVEQV KIHAGPKFAS YLTFSPSEVK 670 680 690 700 710 720 SLRTEYGDLE VCIEVVDSVQ EAIDHIHKYG SSHTDVIVTE NEKTAEFFLQ HVDSACVFWN 730 740 750 760 770 780 ASTRFSDGYR FGLGAEVGIS TSRIHARGPV GLEGLLTTKW LLRGQDHVVS DFSEHGSLKY 790 LHENLPVPQR NFS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular enzymology of mammalian delta1-pyrroline-5-carboxylate synthase. Alternative splice donor utilization generates isoforms with different sensitivity to ornithine inhibition." Hu C.A., Lin W.-W., Obie C., Valle D. J. Biol. Chem. 274:6754-6762(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, ENZYME REGULATION.
[2]	"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]. Strain: C57BL/6J and NOD. Tissue: Bone marrow, Kidney and Thymus.
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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 and FVB/N-3. Tissue: Mammary tumor and Salivary gland.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF056573 mRNA. Translation: AAD17517.1. AF056574 mRNA. Translation: AAD17518.1. AK151072 mRNA. Translation: BAE30088.1. AK153946 mRNA. Translation: BAE32270.1. AK168905 mRNA. Translation: BAE40719.1. CH466534 Genomic DNA. Translation: EDL41837.1. BC033427 mRNA. Translation: AAH33427.1. BC037699 mRNA. Translation: AAH37699.1.
IPI	IPI00129350. IPI00221398.
RefSeq	NP_062672.2. NM_019698.2. NP_705782.2. NM_153554.2.
UniGene	Mm.233117.
3D structure databases
ProteinModelPortal	Q9Z110.
SMR	Q9Z110. Positions 70-353, 362-793.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4998531.
STRING	10090.ENSMUSP00000025979.
PTM databases
PhosphoSite	Q9Z110.
Proteomic databases
PaxDb	Q9Z110.
PRIDE	Q9Z110.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000025979; ENSMUSP00000025979; ENSMUSG00000025007. ENSMUST00000176939; ENSMUSP00000135426; ENSMUSG00000025007.
GeneID	56454.
KEGG	mmu:56454.
UCSC	uc008hkw.2. mouse. uc008hkx.2. mouse.
Organism-specific databases
CTD	5832.
MGI	MGI:1888908. Aldh18a1.
Phylogenomic databases
eggNOG	COG0014.
GeneTree	ENSGT00500000044903.
HOGENOM	HOG000246357.
HOVERGEN	HBG007911.
InParanoid	Q8BGM2.
KO	K12657.
OMA	LLPWVQS.
OrthoDB	EOG4ZKJKN.
Enzyme and pathway databases
UniPathway	UPA00098; UER00359. UPA00098; UER00360.
Gene expression databases
ArrayExpress	Q9Z110.
Bgee	Q9Z110.
CleanEx	MM_ALDH18A1.
Genevestigator	Q9Z110.
GermOnline	ENSMUSG00000025007. Mus musculus.
Family and domain databases
Gene3D	3.40.1160.10. 1 hit. 3.40.309.10. 1 hit. 3.40.605.10. 2 hits.
InterPro	IPR016161. Ald_DH/histidinol_DH. IPR016163. Ald_DH_C. IPR016162. Ald_DH_N. IPR015590. Aldehyde_DH_dom. IPR001048. Asp/Glu/Uridylate_kinase. IPR000965. G-glutamylP_reductase. IPR020593. G-glutamylP_reductase_CS. IPR001057. Glu/AcGlu_kinase. IPR019797. Glutamate_5-kinase_CS. IPR005766. P5_carboxy_syn. [Graphical view]
Pfam	PF00696. AA_kinase. 1 hit. PF00171. Aldedh. 1 hit. [Graphical view]
PIRSF	PIRSF036429. P5C_syn. 1 hit.
PRINTS	PR00474. GLU5KINASE.
SUPFAM	SSF53633. Aa_kinase. 1 hit. SSF53720. Aldehyde_DH/Histidinol_DH. 1 hit.
TIGRFAMs	TIGR01092. P5CS. 1 hit. TIGR00407. proA. 1 hit.
PROSITE	PS00902. GLUTAMATE_5_KINASE. 1 hit. PS01223. PROA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ALDH18A1. mouse.
NextBio	312680.
SOURCE	Search...

Entry information

Entry name

P5CS_MOUSE

Accession

Primary (citable) accession number: Q9Z110
Secondary accession number(s): Q8BGM2, Q9R1P6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	July 27, 2011
Last modified:	May 29, 2013
This is version 123 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program