ID   AL4A1_RAT               Reviewed;         563 AA.
AC   P0C2X9;
DT   15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   15-MAY-2007, sequence version 1.
DT   24-JAN-2024, entry version 96.
DE   RecName: Full=Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial;
DE            Short=P5C dehydrogenase;
DE            EC=1.2.1.88;
DE   AltName: Full=Aldehyde dehydrogenase family 4 member A1;
DE   AltName: Full=L-glutamate gamma-semialdehyde dehydrogenase;
DE   Flags: Precursor;
GN   Name=Aldh4a1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2]
RP   PROTEIN SEQUENCE OF 79-89 AND 318-337, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA   Lubec G., Chen W.-Q.;
RL   Submitted (APR-2007) to UniProtKB.
CC   -!- FUNCTION: Irreversible conversion of delta-1-pyrroline-5-carboxylate
CC       (P5C), derived either from proline or ornithine, to glutamate. This is
CC       a necessary step in the pathway interconnecting the urea and
CC       tricarboxylic acid cycles. The preferred substrate is glutamic gamma-
CC       semialdehyde, other substrates include succinic, glutaric and adipic
CC       semialdehydes (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + L-glutamate 5-semialdehyde + NAD(+) = 2 H(+) + L-
CC         glutamate + NADH; Xref=Rhea:RHEA:30235, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945, ChEBI:CHEBI:58066; EC=1.2.1.88;
CC   -!- PATHWAY: Amino-acid degradation; L-proline degradation into L-
CC       glutamate; L-glutamate from L-proline: step 2/2.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC       {ECO:0000305}.
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DR   EMBL; AABR03107656; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   AlphaFoldDB; P0C2X9; -.
DR   SMR; P0C2X9; -.
DR   STRING; 10116.ENSRNOP00000069221; -.
DR   iPTMnet; P0C2X9; -.
DR   PhosphoSitePlus; P0C2X9; -.
DR   SwissPalm; P0C2X9; -.
DR   jPOST; P0C2X9; -.
DR   PaxDb; 10116-ENSRNOP00000062857; -.
DR   UCSC; RGD:1624206; rat.
DR   AGR; RGD:1624206; -.
DR   RGD; 1624206; Aldh4a1.
DR   eggNOG; KOG1056; Eukaryota.
DR   eggNOG; KOG2455; Eukaryota.
DR   InParanoid; P0C2X9; -.
DR   PhylomeDB; P0C2X9; -.
DR   Reactome; R-RNO-389661; Glyoxylate metabolism and glycine degradation.
DR   Reactome; R-RNO-70688; Proline catabolism.
DR   SABIO-RK; P0C2X9; -.
DR   UniPathway; UPA00261; UER00374.
DR   PRO; PR:P0C2X9; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR   GO; GO:0003842; F:1-pyrroline-5-carboxylate dehydrogenase activity; ISO:RGD.
DR   GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; ISO:RGD.
DR   GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR   GO; GO:0010133; P:proline catabolic process to glutamate; IEA:UniProtKB-UniPathway.
DR   CDD; cd07123; ALDH_F4-17_P5CDH; 1.
DR   InterPro; IPR016161; Ald_DH/histidinol_DH.
DR   InterPro; IPR016163; Ald_DH_C.
DR   InterPro; IPR016160; Ald_DH_CS_CYS.
DR   InterPro; IPR029510; Ald_DH_CS_GLU.
DR   InterPro; IPR016162; Ald_DH_N.
DR   InterPro; IPR015590; Aldehyde_DH_dom.
DR   InterPro; IPR005931; P5CDH/ALDH4A1.
DR   NCBIfam; TIGR01236; D1pyr5carbox1; 1.
DR   PANTHER; PTHR14516; 1-PYRROLINE-5-CARBOXYLATE DEHYDROGENASE FAMILY MEMBER; 1.
DR   PANTHER; PTHR14516:SF3; DELTA-1-PYRROLINE-5-CARBOXYLATE DEHYDROGENASE, MITOCHONDRIAL; 1.
DR   Pfam; PF00171; Aldedh; 1.
DR   SUPFAM; SSF53720; ALDH-like; 1.
DR   PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR   PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Direct protein sequencing; Mitochondrion; NAD; Oxidoreductase;
KW   Phosphoprotein; Proline metabolism; Reference proteome; Transit peptide.
FT   TRANSIT         1..23
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250"
FT   CHAIN           24..563
FT                   /note="Delta-1-pyrroline-5-carboxylate dehydrogenase,
FT                   mitochondrial"
FT                   /id="PRO_0000287827"
FT   ACT_SITE        313
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT                   ECO:0000255|PROSITE-ProRule:PRU10008"
FT   ACT_SITE        347
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT                   ECO:0000255|PROSITE-ProRule:PRU10008"
FT   BINDING         207
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         232
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         285..289
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         446
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         512
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   SITE            210
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         30
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         43
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P30038"
FT   MOD_RES         51
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         92
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         92
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         98
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         98
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         113
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         113
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         129
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         129
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         174
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         174
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         317
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         346
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         364
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         375
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         394
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         461
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         508
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT   MOD_RES         508
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CHT0"
SQ   SEQUENCE   563 AA;  61869 MW;  AF19417D93825EA5 CRC64;
     MLPPALLRRS LLSYAWRGSG LRWKHASSLK VANEPILAFT QGSPERDALQ KALNDLKDQT
     EAIPCVVGDE EVWTSDVRYQ LSPFNHGHKV AKFCYADKAL LNKAIEAAVL ARKEWDLKPV
     ADRAQIFLKA ADMLSGPRRA EILAKTMVGQ GKTVIQAEID AAAELIDFFR FNAKFAVELE
     GEQPISVPPS TNHVVYRGLE GFVAAISPFN FTAIGGNLAG APALMGNVVL WKPSDTAMLA
     SYAVYRILRE AGLPPNVIQF VPADGPTFGD TVTSSEHLCG INFTGSVPTF KHLWKQVAQN
     LDRFRTFPRL AGECGGKNFH FVHSSADVDS VVSGTLRSAF EYGGQKCSAC SRLYVPQSLW
     PQIKGRLLEE HSRIKVGNPA EDFGTFFSAV IDAKAFARIK KWLEHARSSP SLSILAGGQC
     NESVGYFVEP CIIESKDPQE PIMKEEIFGP VLTVYVYPDE KYRETLQLVD STTSYGLTGA
     VFAQDKTIVQ EATRMLRNAA GNFYINDKST GSVVGQQPFG GARASGERDI PGQPRLVQLW
     TEPPFTPLAV SPPLGDWRYS YMQ
//