P5CS_MOUSE
ID P5CS_MOUSE Reviewed; 795 AA.
AC Q9Z110; Q8BGM2; Q9R1P6;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Delta-1-pyrroline-5-carboxylate synthase;
DE Short=P5CS;
DE AltName: Full=Aldehyde dehydrogenase family 18 member A1;
DE Includes:
DE RecName: Full=Glutamate 5-kinase;
DE Short=GK;
DE EC=2.7.2.11 {ECO:0000250|UniProtKB:P54886};
DE AltName: Full=Gamma-glutamyl kinase;
DE Includes:
DE RecName: Full=Gamma-glutamyl phosphate reductase;
DE Short=GPR;
DE EC=1.2.1.41 {ECO:0000250|UniProtKB:P54886};
DE AltName: Full=Glutamate-5-semialdehyde dehydrogenase;
DE AltName: Full=Glutamyl-gamma-semialdehyde dehydrogenase;
GN Name=Aldh18a1; Synonyms=P5cs, Pycs;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND ACTIVITY REGULATION.
RX PubMed=10037775; DOI=10.1074/jbc.274.10.6754;
RA Hu C.A., Lin W.-W., Obie C., Valle D.;
RT "Molecular enzymology of mammalian delta1-pyrroline-5-carboxylate synthase.
RT Alternative splice donor utilization generates isoforms with different
RT sensitivity to ornithine inhibition.";
RL J. Biol. Chem. 274:6754-6762(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, Kidney, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N, and FVB/N-3; TISSUE=Mammary tumor, and Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-311; LYS-347 AND LYS-550, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Bifunctional enzyme that converts glutamate to glutamate 5-
CC semialdehyde, an intermediate in the biosynthesis of proline, ornithine
CC and arginine. {ECO:0000250|UniProtKB:P54886}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-glutamate = ADP + L-glutamyl 5-phosphate;
CC Xref=Rhea:RHEA:14877, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:58274, ChEBI:CHEBI:456216; EC=2.7.2.11;
CC Evidence={ECO:0000250|UniProtKB:P54886};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-glutamate 5-semialdehyde + NADP(+) + phosphate = H(+) + L-
CC glutamyl 5-phosphate + NADPH; Xref=Rhea:RHEA:19541,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58066, ChEBI:CHEBI:58274, ChEBI:CHEBI:58349; EC=1.2.1.41;
CC Evidence={ECO:0000250|UniProtKB:P54886};
CC -!- ACTIVITY REGULATION: Isoform Short: Inhibited by L-ornithine with a Ki
CC of approximately 0.25 mm. Isoform Long: Insensitive to ornithine
CC inhibition. Thus, the two amino acid insert in the long isoform
CC abolishes feedback inhibition of P5CS activity by L-ornithine.
CC {ECO:0000269|PubMed:10037775}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-proline biosynthesis; L-glutamate
CC 5-semialdehyde from L-glutamate: step 1/2.
CC {ECO:0000250|UniProtKB:P54886}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-proline biosynthesis; L-glutamate
CC 5-semialdehyde from L-glutamate: step 2/2.
CC {ECO:0000250|UniProtKB:P54886}.
CC -!- SUBUNIT: Homohexamer or homotetramer. {ECO:0000250|UniProtKB:P54886}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P54886}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=Q9Z110-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q9Z110-2; Sequence=VSP_005216;
CC -!- SIMILARITY: In the N-terminal section; belongs to the glutamate 5-
CC kinase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the gamma-glutamyl
CC phosphate reductase family. {ECO:0000305}.
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DR EMBL; AF056573; AAD17517.1; -; mRNA.
DR EMBL; AF056574; AAD17518.1; -; mRNA.
DR EMBL; AK151072; BAE30088.1; -; mRNA.
DR EMBL; AK153946; BAE32270.1; -; mRNA.
DR EMBL; AK168905; BAE40719.1; -; mRNA.
DR EMBL; CH466534; EDL41837.1; -; Genomic_DNA.
DR EMBL; BC033427; AAH33427.1; -; mRNA.
DR EMBL; BC037699; AAH37699.1; -; mRNA.
DR CCDS; CCDS29803.1; -. [Q9Z110-1]
DR CCDS; CCDS57144.1; -. [Q9Z110-2]
DR RefSeq; NP_062672.2; NM_019698.2. [Q9Z110-1]
DR RefSeq; NP_705782.2; NM_153554.2. [Q9Z110-2]
DR AlphaFoldDB; Q9Z110; -.
DR SMR; Q9Z110; -.
DR BioGRID; 207993; 7.
DR IntAct; Q9Z110; 6.
DR STRING; 10090.ENSMUSP00000025979; -.
DR iPTMnet; Q9Z110; -.
DR PhosphoSitePlus; Q9Z110; -.
DR SwissPalm; Q9Z110; -.
DR EPD; Q9Z110; -.
DR MaxQB; Q9Z110; -.
DR PaxDb; Q9Z110; -.
DR PeptideAtlas; Q9Z110; -.
DR PRIDE; Q9Z110; -.
DR ProteomicsDB; 294234; -. [Q9Z110-1]
DR ProteomicsDB; 294235; -. [Q9Z110-2]
DR TopDownProteomics; Q9Z110-1; -. [Q9Z110-1]
DR Antibodypedia; 2043; 215 antibodies from 32 providers.
DR DNASU; 56454; -.
DR Ensembl; ENSMUST00000025979; ENSMUSP00000025979; ENSMUSG00000025007. [Q9Z110-1]
DR Ensembl; ENSMUST00000176939; ENSMUSP00000135426; ENSMUSG00000025007. [Q9Z110-2]
DR GeneID; 56454; -.
DR KEGG; mmu:56454; -.
DR UCSC; uc008hkw.2; mouse. [Q9Z110-2]
DR UCSC; uc008hkx.2; mouse. [Q9Z110-1]
DR CTD; 5832; -.
DR MGI; MGI:1888908; Aldh18a1.
DR VEuPathDB; HostDB:ENSMUSG00000025007; -.
DR eggNOG; KOG1154; Eukaryota.
DR eggNOG; KOG4165; Eukaryota.
DR GeneTree; ENSGT00500000044903; -.
DR HOGENOM; CLU_016144_0_0_1; -.
DR InParanoid; Q9Z110; -.
DR OMA; EGRECIM; -.
DR OrthoDB; 832430at2759; -.
DR PhylomeDB; Q9Z110; -.
DR TreeFam; TF314372; -.
DR BRENDA; 1.2.1.41; 3474.
DR Reactome; R-MMU-8964539; Glutamate and glutamine metabolism.
DR UniPathway; UPA00098; UER00359.
DR UniPathway; UPA00098; UER00360.
DR BioGRID-ORCS; 56454; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Aldh18a1; mouse.
DR PRO; PR:Q9Z110; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9Z110; protein.
DR Bgee; ENSMUSG00000025007; Expressed in lacrimal gland and 263 other tissues.
DR ExpressionAtlas; Q9Z110; baseline and differential.
DR Genevisible; Q9Z110; MM.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004349; F:glutamate 5-kinase activity; IDA:MGI.
DR GO; GO:0004350; F:glutamate-5-semialdehyde dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008652; P:cellular amino acid biosynthetic process; TAS:MGI.
DR GO; GO:0019240; P:citrulline biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006536; P:glutamate metabolic process; ISS:UniProtKB.
DR GO; GO:0055129; P:L-proline biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006592; P:ornithine biosynthetic process; ISO:MGI.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0006561; P:proline biosynthetic process; ISS:UniProtKB.
DR GO; GO:0009266; P:response to temperature stimulus; ISO:MGI.
DR CDD; cd04256; AAK_P5CS_ProBA; 1.
DR CDD; cd07079; ALDH_F18-19_ProA-GPR; 1.
DR Gene3D; 3.40.1160.10; -; 1.
DR Gene3D; 3.40.309.10; -; 1.
DR Gene3D; 3.40.605.10; -; 1.
DR HAMAP; MF_00412; ProA; 1.
DR HAMAP; MF_00456; ProB; 1.
DR InterPro; IPR036393; AceGlu_kinase-like_sf.
DR InterPro; IPR016161; Ald_DH/histidinol_DH.
DR InterPro; IPR016163; Ald_DH_C.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR InterPro; IPR001048; Asp/Glu/Uridylate_kinase.
DR InterPro; IPR020593; G-glutamylP_reductase_CS.
DR InterPro; IPR041744; G5K_ProBA.
DR InterPro; IPR001057; Glu/AcGlu_kinase.
DR InterPro; IPR005715; Glu_5kinase/COase_Synthase.
DR InterPro; IPR019797; Glutamate_5-kinase_CS.
DR InterPro; IPR000965; GPR_dom.
DR InterPro; IPR005766; P5_carboxy_syn.
DR Pfam; PF00696; AA_kinase; 1.
DR Pfam; PF00171; Aldedh; 1.
DR PIRSF; PIRSF036429; P5C_syn; 1.
DR PRINTS; PR00474; GLU5KINASE.
DR SUPFAM; SSF53633; SSF53633; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR TIGRFAMs; TIGR01092; P5CS; 1.
DR TIGRFAMs; TIGR00407; proA; 1.
DR PROSITE; PS00902; GLUTAMATE_5_KINASE; 1.
DR PROSITE; PS01223; PROA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Amino-acid biosynthesis; ATP-binding; Kinase;
KW Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Multifunctional enzyme; NADP; Nucleotide-binding; Oxidoreductase;
KW Proline biosynthesis; Reference proteome; Transferase.
FT CHAIN 1..795
FT /note="Delta-1-pyrroline-5-carboxylate synthase"
FT /id="PRO_0000109770"
FT REGION 1..361
FT /note="Glutamate 5-kinase"
FT REGION 362..795
FT /note="Gamma-glutamyl phosphate reductase"
FT BINDING 117
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 223
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 246
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 266..267
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 305..311
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 311
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 347
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 550
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT VAR_SEQ 239..240
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_005216"
FT CONFLICT 582
FT /note="G -> S (in Ref. 1; AAD17517/AAD17518)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 795 AA; 87266 MW; 877DF1A7B5F84247 CRC64;
MLRHMHRSGV QPFRQRLLPW VQSIAVPRSN RVQPSAIRHV RSWSNIPFIT VPLSRAHGKP
FAHRSELKHA KRIVVKLGSA VVTRGDECGL ALGRLASIVE QVSVLQNQGR EMMLVTSGAV
AFGKQRLRHE ILLSQSVRQA LHSGQNHLKE MAIPVLEARA CAAAGQSGLM ALYEAMFTQY
SICAAQILVT NLDFHDEQKR RNLNGTLHEL LRMNIVPIVN TNDAVVPPAE PNSDLQGVNV
ISVKDNDSLA ARLAVEMKTD LLIVLSDVEG LFDSPPGSDD AKLIDIFYPG DQQSVTFGTK
SRVGLGGMEA KVKAALWALQ GGTSVVIANG THPKVSGHVI TDIVEGKKVG TFFSEVKPAG
PTVEQQGEMA RSGGRMLATL EPEQRAEIIN HLADLLTDQR EEILLANKKD LEEAEGRLAS
PLLKRLSLST SKLNSLAIGL RQIAASSQES VGRVLRRTRI AKNLELEQVT VPIGVLLVIF
ESRPDCLPQV AALAIASGNG LLLKGGKEAA HSNRILHLLT QEALSIHGVK EAIQLVNTRE
EVEDLCRLDK IIDLIIPRGS SQLVRDIQKA AKGIPVMGHS EGICHMYVDS EASVDKVTRL
VRDSKCEYPA ACNALETLLI HRDLLRTPLF DQIIDMLRVE QVKIHAGPKF ASYLTFSPSE
VKSLRTEYGD LEVCIEVVDS VQEAIDHIHK YGSSHTDVIV TENEKTAEFF LQHVDSACVF
WNASTRFSDG YRFGLGAEVG ISTSRIHARG PVGLEGLLTT KWLLRGQDHV VSDFSEHGSL
KYLHENLPVP QRNFS
