AL4A1_HUMAN
ID AL4A1_HUMAN Reviewed; 563 AA.
AC P30038; A8K1Q7; B4DGE4; D2D4A3; Q16882; Q53HU4; Q5JNV6; Q8IZ38; Q96IF0;
AC Q9UDI6;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 3.
DT 03-AUG-2022, entry version 214.
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; Synonyms=ALDH4, P5CDH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Kidney, and Retina;
RX PubMed=8621661; DOI=10.1074/jbc.271.16.9795;
RA Hu C.-A., Lin W.-W., Valle D.;
RT "Cloning, characterization, and expression of cDNAs encoding human delta 1-
RT pyrroline-5-carboxylate dehydrogenase.";
RL J. Biol. Chem. 271:9795-9800(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Stagos D., Vasiliou V.;
RT "A novel transcript variant of human ALDH4A1 gene.";
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ILE-470.
RC TISSUE=Amygdala, and Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Adipose tissue;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-470.
RC TISSUE=Lung, and Placenta;
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 [8]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=1395511; DOI=10.1016/0305-0491(92)90081-2;
RA Hempel J., Eckey R., Berie D., Romovacek H., Agarwal D.P., Goedde H.W.;
RT "Human liver glutamic gamma-semialdehyde dehydrogenase: structural
RT relationship to the yeast enzyme.";
RL Comp. Biochem. Physiol. 102B:791-793(1992).
RN [9]
RP PROTEIN SEQUENCE OF 25-35.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [10]
RP PROTEIN SEQUENCE OF 94-99; 105-113; 125-139; 176-191; 251-273; 339-347;
RP 354-365 AND 510-526.
RC TISSUE=Liver;
RX PubMed=8493898; DOI=10.1007/978-1-4615-2904-0_21;
RA Agarwal D.P., Eckey R., Hempel J., Goedde H.W.;
RT "Human liver high Km aldehyde dehydrogenase (ALDH4): properties and
RT structural relationship to the glutamic gamma-semialdehyde dehydrogenase.";
RL Adv. Exp. Med. Biol. 328:191-197(1993).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 18-563 OF WILD-TYPE; MUTANT
RP ALA-352 AND VARIANT HYRPRO2 LEU-352, CATALYTIC ACTIVITY, FUNCTION, PATHWAY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ACTIVE SITE, CHARACTERIZATION OF
RP VARIANT HYRPRO2 LEU-352, AND MUTAGENESIS OF SER-352.
RX PubMed=22516612; DOI=10.1016/j.jmb.2012.04.010;
RA Srivastava D., Singh R.K., Moxley M.A., Henzl M.T., Becker D.F.,
RA Tanner J.J.;
RT "The three-dimensional structural basis of type II hyperprolinemia.";
RL J. Mol. Biol. 420:176-189(2012).
RN [16]
RP VARIANT HYRPRO2 LEU-352, AND VARIANT LEU-16.
RX PubMed=9700195; DOI=10.1093/hmg/7.9.1411;
RA Geraghty M.T., Vaughn D., Nicholson A.J., Lin W.-W., Jimenez-Sanchez G.,
RA Obie C., Flynn M.P., Valle D., Hu C.-A.A.;
RT "Mutations in the Delta1-pyrroline 5-carboxylate dehydrogenase gene cause
RT type II hyperprolinemia.";
RL Hum. Mol. Genet. 7:1411-1415(1998).
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. {ECO:0000269|PubMed:22516612}.
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 Evidence={ECO:0000269|PubMed:22516612};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=100 uM for NAD {ECO:0000269|PubMed:22516612};
CC KM=32 uM for L-pyrroline-5-carboxylate {ECO:0000269|PubMed:22516612};
CC -!- PATHWAY: Amino-acid degradation; L-proline degradation into L-
CC glutamate; L-glutamate from L-proline: step 2/2.
CC {ECO:0000269|PubMed:22516612}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:22516612}.
CC -!- INTERACTION:
CC P30038; P30038: ALDH4A1; NbExp=2; IntAct=EBI-3926971, EBI-3926971;
CC P30038; Q09028: RBBP4; NbExp=3; IntAct=EBI-3926971, EBI-620823;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P30038-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P30038-2; Sequence=VSP_043785;
CC Name=3;
CC IsoId=P30038-3; Sequence=VSP_047732;
CC -!- TISSUE SPECIFICITY: Highest expression is found in liver followed by
CC skeletal muscle, kidney, heart, brain, placenta, lung and pancreas.
CC -!- DISEASE: Hyperprolinemia 2 (HYRPRO2) [MIM:239510]: An inborn error of
CC proline metabolism resulting in elevated plasma levels of proline and
CC delta-1-pyrroline-5-carboxylate (P5C). The condition is considered to
CC be benign, but affected individuals can exhibit neurological
CC manifestations that vary in severity. Clinical signs include seizures,
CC intellectual deficit and mild developmental delay.
CC {ECO:0000269|PubMed:22516612, ECO:0000269|PubMed:9700195}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; U24267; AAC50501.1; -; mRNA.
DR EMBL; U24266; AAC50500.1; -; mRNA.
DR EMBL; FJ462711; ACN89883.1; -; mRNA.
DR EMBL; AK289972; BAF82661.1; -; mRNA.
DR EMBL; AK294552; BAG57755.1; -; mRNA.
DR EMBL; AK222486; BAD96206.1; -; mRNA.
DR EMBL; AL080251; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL954340; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX537160; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471134; EAW94858.1; -; Genomic_DNA.
DR EMBL; BC007581; AAH07581.1; -; mRNA.
DR EMBL; BC023600; AAH23600.1; -; mRNA.
DR CCDS; CCDS188.1; -. [P30038-1]
DR CCDS; CCDS53272.1; -. [P30038-2]
DR CCDS; CCDS81273.1; -. [P30038-3]
DR RefSeq; NP_001154976.1; NM_001161504.1. [P30038-2]
DR RefSeq; NP_001306147.1; NM_001319218.1. [P30038-3]
DR RefSeq; NP_003739.2; NM_003748.3. [P30038-1]
DR RefSeq; NP_733844.1; NM_170726.2. [P30038-1]
DR PDB; 3V9G; X-ray; 2.50 A; A/B/C/D=18-563.
DR PDB; 3V9H; X-ray; 2.40 A; A/B/C/D=18-563.
DR PDB; 3V9I; X-ray; 2.85 A; A/B/C/D=18-563.
DR PDB; 4OE5; X-ray; 1.95 A; A/B/C/D=18-563.
DR PDBsum; 3V9G; -.
DR PDBsum; 3V9H; -.
DR PDBsum; 3V9I; -.
DR PDBsum; 4OE5; -.
DR AlphaFoldDB; P30038; -.
DR SMR; P30038; -.
DR BioGRID; 114208; 92.
DR IntAct; P30038; 8.
DR STRING; 9606.ENSP00000364490; -.
DR ChEMBL; CHEMBL3414418; -.
DR DrugBank; DB00157; NADH.
DR CarbonylDB; P30038; -.
DR GlyGen; P30038; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P30038; -.
DR PhosphoSitePlus; P30038; -.
DR BioMuta; ALDH4A1; -.
DR DMDM; 62511241; -.
DR OGP; P30038; -.
DR SWISS-2DPAGE; P30038; -.
DR CPTAC; CPTAC-165; -.
DR CPTAC; CPTAC-166; -.
DR EPD; P30038; -.
DR jPOST; P30038; -.
DR MassIVE; P30038; -.
DR MaxQB; P30038; -.
DR PaxDb; P30038; -.
DR PeptideAtlas; P30038; -.
DR PRIDE; P30038; -.
DR ProteomicsDB; 12731; -.
DR ProteomicsDB; 54616; -. [P30038-1]
DR ProteomicsDB; 54617; -. [P30038-2]
DR Antibodypedia; 1590; 318 antibodies from 31 providers.
DR DNASU; 8659; -.
DR Ensembl; ENST00000290597.9; ENSP00000290597.5; ENSG00000159423.17. [P30038-1]
DR Ensembl; ENST00000375341.8; ENSP00000364490.3; ENSG00000159423.17. [P30038-1]
DR Ensembl; ENST00000538309.5; ENSP00000442988.1; ENSG00000159423.17. [P30038-2]
DR Ensembl; ENST00000538839.5; ENSP00000446071.1; ENSG00000159423.17. [P30038-3]
DR GeneID; 8659; -.
DR KEGG; hsa:8659; -.
DR MANE-Select; ENST00000375341.8; ENSP00000364490.3; NM_003748.4; NP_003739.2.
DR UCSC; uc001bbb.4; human. [P30038-1]
DR CTD; 8659; -.
DR DisGeNET; 8659; -.
DR GeneCards; ALDH4A1; -.
DR HGNC; HGNC:406; ALDH4A1.
DR HPA; ENSG00000159423; Tissue enhanced (kidney, liver).
DR MalaCards; ALDH4A1; -.
DR MIM; 239510; phenotype.
DR MIM; 606811; gene.
DR neXtProt; NX_P30038; -.
DR OpenTargets; ENSG00000159423; -.
DR Orphanet; 79101; Hyperprolinemia type 2.
DR PharmGKB; PA24701; -.
DR VEuPathDB; HostDB:ENSG00000159423; -.
DR eggNOG; KOG2455; Eukaryota.
DR GeneTree; ENSGT00560000077335; -.
DR HOGENOM; CLU_005391_4_1_1; -.
DR InParanoid; P30038; -.
DR OMA; FAGIHFT; -.
DR PhylomeDB; P30038; -.
DR TreeFam; TF300481; -.
DR BioCyc; MetaCyc:HS14757-MON; -.
DR BRENDA; 1.2.1.88; 2681.
DR PathwayCommons; P30038; -.
DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-HSA-70688; Proline catabolism.
DR SABIO-RK; P30038; -.
DR SignaLink; P30038; -.
DR UniPathway; UPA00261; UER00374.
DR BioGRID-ORCS; 8659; 8 hits in 1079 CRISPR screens.
DR ChiTaRS; ALDH4A1; human.
DR GeneWiki; Aldehyde_dehydrogenase_4_family,_member_A1; -.
DR GenomeRNAi; 8659; -.
DR Pharos; P30038; Tbio.
DR PRO; PR:P30038; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P30038; protein.
DR Bgee; ENSG00000159423; Expressed in right lobe of liver and 166 other tissues.
DR ExpressionAtlas; P30038; baseline and differential.
DR Genevisible; P30038; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0003842; F:1-pyrroline-5-carboxylate dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IDA:CACAO.
DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019470; P:4-hydroxyproline catabolic process; TAS:BHF-UCL.
DR GO; GO:0006562; P:proline catabolic process; TAS:ProtInc.
DR GO; GO:0010133; P:proline catabolic process to glutamate; IEA:UniProtKB-UniPathway.
DR GO; GO:0006560; P:proline metabolic process; TAS:ProtInc.
DR CDD; cd07123; ALDH_F4-17_P5CDH; 1.
DR Gene3D; 3.40.309.10; -; 1.
DR Gene3D; 3.40.605.10; -; 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 Pfam; PF00171; Aldedh; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR TIGRFAMs; TIGR01236; D1pyr5carbox1; 1.
DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing;
KW Disease variant; Mitochondrion; NAD; Oxidoreductase; Phosphoprotein;
KW Proline metabolism; Reference proteome; Transit peptide.
FT TRANSIT 1..24
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1286669"
FT CHAIN 25..563
FT /note="Delta-1-pyrroline-5-carboxylate dehydrogenase,
FT mitochondrial"
FT /id="PRO_0000007173"
FT ACT_SITE 314
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT ACT_SITE 348
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008,
FT ECO:0000269|PubMed:22516612"
FT BINDING 208
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 233
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 286..290
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 447
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 513
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 211
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT MOD_RES 31
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 52
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 93
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 93
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 99
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 99
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 114
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 114
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 130
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 130
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 175
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 175
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 318
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 347
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 365
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 376
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 395
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 462
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 509
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 509
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 531
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT MOD_RES 552
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHT0"
FT VAR_SEQ 1..60
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043785"
FT VAR_SEQ 396..446
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_047732"
FT VARIANT 16
FT /note="P -> L (in allele ALDH4A1*4; dbSNP:rs146450609)"
FT /evidence="ECO:0000269|PubMed:9700195"
FT /id="VAR_002259"
FT VARIANT 352
FT /note="S -> L (in HYRPRO2; allele ALDH4A1*3; loss of enzyme
FT activity; dbSNP:rs137852937)"
FT /evidence="ECO:0000269|PubMed:22516612,
FT ECO:0000269|PubMed:9700195"
FT /id="VAR_002260"
FT VARIANT 470
FT /note="V -> I (in dbSNP:rs2230709)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_029337"
FT VARIANT 473
FT /note="T -> A (in dbSNP:rs6695033)"
FT /id="VAR_048903"
FT MUTAGEN 352
FT /note="S->A: Reduced affinity for NAD. No effect on enzyme
FT activity."
FT /evidence="ECO:0000269|PubMed:22516612"
FT CONFLICT 68
FT /note="V -> M (in Ref. 1; AAC50501/AAC50500)"
FT /evidence="ECO:0000305"
FT CONFLICT 189..191
FT /note="PPS -> LPY (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="P -> L (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="M -> I (in Ref. 4; BAD96206)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="D -> E (in Ref. 8; AA sequence and 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="L -> K (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="K -> R (in Ref. 4; BAD96206)"
FT /evidence="ECO:0000305"
FT CONFLICT 524..526
FT /note="RAS -> GSA (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 24..30
FT /evidence="ECO:0007829|PDB:3V9H"
FT HELIX 45..57
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 86..95
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 99..118
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 121..136
FT /evidence="ECO:0007829|PDB:4OE5"
FT TURN 137..139
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 140..151
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 155..165
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 167..180
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 192..199
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 201..207
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 217..225
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 229..233
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 239..251
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 258..261
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 266..274
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 279..286
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 288..300
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 301..304
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 310..315
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 319..323
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 329..341
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 342..345
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 351..357
FT /evidence="ECO:0007829|PDB:4OE5"
FT TURN 358..360
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 361..372
FT /evidence="ECO:0007829|PDB:4OE5"
FT TURN 380..382
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 394..409
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 413..417
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 424..426
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 432..437
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 442..445
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 450..458
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 460..462
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 463..472
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 475..477
FT /evidence="ECO:0007829|PDB:3V9I"
FT STRAND 479..483
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 487..496
FT /evidence="ECO:0007829|PDB:4OE5"
FT TURN 497..500
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 502..508
FT /evidence="ECO:0007829|PDB:4OE5"
FT TURN 515..517
FT /evidence="ECO:0007829|PDB:3V9H"
FT HELIX 528..530
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 534..536
FT /evidence="ECO:0007829|PDB:3V9H"
FT HELIX 537..541
FT /evidence="ECO:0007829|PDB:4OE5"
FT STRAND 542..549
FT /evidence="ECO:0007829|PDB:4OE5"
FT HELIX 560..562
FT /evidence="ECO:0007829|PDB:3V9H"
SQ SEQUENCE 563 AA; 61719 MW; 4D964771B7DB5FFD CRC64;
MLLPAPALRR ALLSRPWTGA GLRWKHTSSL KVANEPVLAF TQGSPERDAL QKALKDLKGR
MEAIPCVVGD EEVWTSDVQY QVSPFNHGHK VAKFCYADKS LLNKAIEAAL AARKEWDLKP
IADRAQIFLK AADMLSGPRR AEILAKTMVG QGKTVIQAEI DAAAELIDFF RFNAKYAVEL
EGQQPISVPP STNSTVYRGL EGFVAAISPF NFTAIGGNLA GAPALMGNVV LWKPSDTAML
ASYAVYRILR EAGLPPNIIQ FVPADGPLFG DTVTSSEHLC GINFTGSVPT FKHLWKQVAQ
NLDRFHTFPR LAGECGGKNF HFVHRSADVE SVVSGTLRSA FEYGGQKCSA CSRLYVPHSL
WPQIKGRLLE EHSRIKVGDP AEDFGTFFSA VIDAKSFARI KKWLEHARSS PSLTILAGGK
CDDSVGYFVE PCIVESKDPQ EPIMKEEIFG PVLSVYVYPD DKYKETLQLV DSTTSYGLTG
AVFSQDKDVV QEATKVLRNA AGNFYINDKS TGSIVGQQPF GGARASGTND KPGGPHYILR
WTSPQVIKET HKPLGDWSYA YMQ
