ID   P5CS_PONAB              Reviewed;         795 AA.
AC   Q5R4M8;
DT   10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   27-MAR-2024, entry version 102.
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;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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   -!- 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   -!- 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; CR861217; CAH93288.1; -; mRNA.
DR   AlphaFoldDB; Q5R4M8; -.
DR   SMR; Q5R4M8; -.
DR   STRING; 9601.ENSPPYP00000002911; -.
DR   Ensembl; ENSPPYT00000003013.3; ENSPPYP00000002911.3; ENSPPYG00000002509.3.
DR   eggNOG; KOG1154; Eukaryota.
DR   eggNOG; KOG4165; Eukaryota.
DR   GeneTree; ENSGT00500000044903; -.
DR   InParanoid; Q5R4M8; -.
DR   OMA; MGHAEGI; -.
DR   OrthoDB; 314297at2759; -.
DR   UniPathway; UPA00098; UER00359.
DR   UniPathway; UPA00098; UER00360.
DR   Proteomes; UP000001595; Chromosome 10.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004349; F:glutamate 5-kinase activity; ISS:UniProtKB.
DR   GO; GO:0004350; F:glutamate-5-semialdehyde dehydrogenase activity; ISS:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
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; IEA:Ensembl.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0006561; P:proline biosynthetic process; ISS:UniProtKB.
DR   CDD; cd04256; AAK_P5CS_ProBA; 1.
DR   CDD; cd07079; ALDH_F18-19_ProA-GPR; 1.
DR   Gene3D; 3.40.1160.10; Acetylglutamate kinase-like; 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   NCBIfam; TIGR01092; P5CS; 1.
DR   NCBIfam; TIGR00407; proA; 1.
DR   PANTHER; PTHR11063:SF8; DELTA-1-PYRROLINE-5-CARBOXYLATE SYNTHASE; 1.
DR   PANTHER; PTHR11063; GLUTAMATE SEMIALDEHYDE DEHYDROGENASE; 1.
DR   Pfam; PF00696; AA_kinase; 1.
DR   Pfam; PF00171; Aldedh; 1.
DR   PIRSF; PIRSF036429; P5C_syn; 1.
DR   PRINTS; PR00474; GLU5KINASE.
DR   SUPFAM; SSF53720; ALDH-like; 1.
DR   SUPFAM; SSF53633; Carbamate kinase-like; 1.
DR   PROSITE; PS00902; GLUTAMATE_5_KINASE; 1.
DR   PROSITE; PS01223; PROA; 1.
PE   2: Evidence at transcript level;
KW   Amino-acid biosynthesis; ATP-binding; Kinase; Membrane; Mitochondrion;
KW   Mitochondrion inner membrane; Multifunctional enzyme; NADP;
KW   Nucleotide-binding; Oxidoreductase; Proline biosynthesis;
KW   Reference proteome; Transferase.
FT   CHAIN           1..795
FT                   /note="Delta-1-pyrroline-5-carboxylate synthase"
FT                   /id="PRO_0000294073"
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:0000250|UniProtKB:Q9Z110"
FT   MOD_RES         347
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Z110"
FT   MOD_RES         550
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Z110"
SQ   SEQUENCE   795 AA;  87341 MW;  3ACAE0F726665CD9 CRC64;
     MLSQVYRYGF QPFNQHLLPW VQCTTISRSH CIQPSVIRHV RSWSNIPFIT VPLSRTHGKS
     FAHRSELKHA KRIVVKLGSA VVTRGDECGL ALGRLASIVE QVSVLQNQGR EMMLVTSGAV
     AFGKQRLRHE ILLSQSVRQA LHSGQNQLKE MAIPVLEARA CAAAGQSGLM ALYEAMFTQY
     SICAAQILVT NLDFHDEQKR RNLNGTLHEL LRMNIVPIVN TNDAVVPPAE PNSDLQGVNV
     ISVKDNDSLA ARLAVEMKTD LLIVLSDVEG LFDSPPGSDD AKLIDIFYPG DQQSVTFGTK
     SRVGMGGMEA KVKAALWALQ GGTSVVIANG THPKVSGHVI TDIVEGKKVG TFFSEVKPAG
     PTVEQQGEMA RSGGRMLATL EPEQRAEIIH HLADLLTDQR DEILLANKKD LEEAEGRLAP
     PLLKRLSLST SKLNSLAIGL RQIAASSQDS VGRVLRRTRI AKNLELEQVT VPIGVLLVIF
     ESRPDCLPQV AALAIASGNG LLLKGGKEAA HSNRILHLLT QEALSIHGVK EAVQLVNTRE
     EVEDLCRLDK MIDLIIPRGS SQLVRDIQKA AKGIPVMGHS EGICHMYVDS EASVDKVTRL
     VRDSKCEYPA ACNALETLLI HRDLLRTPLF DQIIDMLRVE QVKIHAGPKF ASYLTFSPSE
     VKSLRTEYGD LELCIEVVDN VQDAIDHIHK YGSSHTDVIV TENENTAEFF LQHVDSACVF
     WNASTRFSDG YRFGLGAEVG ISTSRIHARG PVGLEGLLTT KWLLRGKDHV VSDFSEHGSL
     KYLHENLPIP QRNTN
//