Reviewed, UniProtKB/Swiss-Prot Q9Z110 (P5CS_MOUSE)

Names and origin

Protein names

Recommended name:
    Delta-1-pyrroline-5-carboxylate synthetase
      Short name=P5CS
Alternative name(s):
    Aldehyde dehydrogenase family 18 member A1
Including the following 2 domains:
    1- Recommended name:
            Glutamate 5-kinase
                Short name=GK
              EC=2.7.2.11
        Alternative name(s):
            Gamma-glutamyl kinase
    2- Recommended name:
            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)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

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

General annotation (Comments)

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	Multifunctional enzyme
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW proline biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial inner membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW glutamate 5-kinase activity Ref.1 Inferred from direct assay. Source: MGI glutamate-5-semialdehyde dehydrogenase activity Inferred from electronic annotation. Source: EC
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 synthetase		PRO_0000109770
Regions
	Region	1 – 361	361	Glutamate 5-kinase
	Region	362 – 795	434	Gamma-glutamyl phosphate reductase
Natural variations
	Alternative sequence	239 – 240	2	Missing in isoform Short.		VSP_005216

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified May 1, 1999. Version 1. Checksum: E3FCB9B334B69706	FASTA	795	87,296
	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 ESICHMYVDS 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. Checksum: 94862D3340D1188C	FASTA	793	87,083
	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 GIPVMGHSES 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

[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: 10037775] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF056573 mRNA. Translation: AAD17517.1. AF056574 mRNA. Translation: AAD17518.1.
IPI	IPI00129350. IPI00221398.
UniGene	Mm.233117
3D structure databases
SMR	Q9Z110. Positions 69-355, 336-764, 362-793.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9Z110.
PTM databases
PhosphoSite	Q9Z110.
Proteomic databases
PRIDE	Q9Z110.
Genome annotation databases
Ensembl	ENSMUST00000025979; ENSMUSP00000025979; ENSMUSG00000025007; Mus musculus. [Genome view]
UCSC	uc008hkw.1. mouse. uc008hkx.1. mouse.
Organism-specific databases
MGI	MGI:1888908. Aldh18a1.
Phylogenomic databases
HOGENOM	HBG318080.
HOVERGEN	Q9Z110.
InParanoid	Q9Z110.
PhylomeDB	Q9Z110.
Enzyme and pathway databases
BRENDA	1.2.1.41. 244. 2.7.2.11. 244.
Gene expression databases
ArrayExpress	Q9Z110.
Bgee	Q9Z110.
CleanEx	MM_ALDH18A1.
Genevestigator	Q9Z110.
GermOnline	ENSMUSG00000025007. Mus musculus.
Family and domain databases
InterPro	IPR016161. Ald_DH/histidinol_DH. IPR016163. Ald_DH_C. IPR016162. Ald_DH_N. IPR015590. Aldehyde_DH. IPR001048. Asp/Glu/Uridylate_kinase. IPR000965. G-glutamylP_reductase. IPR020593. G-glutamylP_reductase_CS. IPR001057. Glu_5kinase. IPR019797. Glutamate_5-kinase_CS. IPR005766. P5_carboxy_syn. IPR005715. ProB. [Graphical view]
Gene3D	G3DSA:3.40.1160.10. Aa_kinase. 1 hit. G3DSA:3.40.309.10. Aldehyde_dehydrogenase_C. 1 hit. G3DSA:3.40.605.10. Aldehyde_dehydrogenase_N. 1 hit.
Pfam	PF00696. AA_kinase. 1 hit. PF00171. Aldedh. 1 hit. [Graphical view]
PIRSF	PIRSF036429. P5C_syn. 1 hit.
PRINTS	PR00474. GLU5KINASE.
TIGRFAMs	TIGR01092. P5CS. 1 hit. TIGR00407. proA. 1 hit. TIGR01027. proB. 1 hit.
PROSITE	PS00902. GLUTAMATE_5_KINASE. 1 hit. PS01223. PROA. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	312680.
SOURCE	Search...

Entry information

Entry name

P5CS_MOUSE

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 1, 1999
Last modified:	February 9, 2010
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)