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Protein

Succinate-semialdehyde dehydrogenase, mitochondrial

Gene

ALDH5A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).1 Publication

Catalytic activityi

Succinate semialdehyde + NAD+ + H2O = succinate + NADH.

Enzyme regulationi

Redox-regulated. Inhibited under oxydizing conditions. Inhibited by hydrogen peroxide H2O2.1 Publication

Pathwayi: 4-aminobutanoate degradation

This protein is involved in the pathway 4-aminobutanoate degradation, which is part of Amino-acid degradation.
View all proteins of this organism that are known to be involved in the pathway 4-aminobutanoate degradation and in Amino-acid degradation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei205Transition state stabilizerBy similarity1
Binding sitei213NAD1
Binding sitei213Substrate1
Active sitei306Proton acceptorPROSITE-ProRule annotation1
Binding sitei334Substrate1
Active sitei340NucleophilePROSITE-ProRule annotation1
Binding sitei498Substrate1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi228 – 231NAD4
Nucleotide bindingi284 – 289NAD6

GO - Molecular functioni

  • NAD binding Source: GO_Central
  • protein homodimerization activity Source: UniProtKB
  • succinate-semialdehyde dehydrogenase (NAD+) activity Source: UniProtKB
  • succinate-semialdehyde dehydrogenase [NAD(P)+] activity Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
LigandNAD

Enzyme and pathway databases

BioCyciMetaCyc:HS03550-MONOMER
BRENDAi1.2.1.24 2681
ReactomeiR-HSA-916853 Degradation of GABA
SABIO-RKiP51649
UniPathwayiUPA00733

Names & Taxonomyi

Protein namesi
Recommended name:
Succinate-semialdehyde dehydrogenase, mitochondrial (EC:1.2.1.24)
Alternative name(s):
Aldehyde dehydrogenase family 5 member A1
NAD(+)-dependent succinic semialdehyde dehydrogenase
Gene namesi
Name:ALDH5A1
Synonyms:SSADH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000112294.12
HGNCiHGNC:408 ALDH5A1
MIMi610045 gene
neXtProtiNX_P51649

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Succinic semialdehyde dehydrogenase deficiency (SSADHD)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare inborn error of 4-aminobutyric acid (GABA) metabolism, which leads to accumulation of 4-hydroxybutyric acid in physiologic fluids of patients. The disease is clinically characterized by developmental delay, hypotonia, mental retardation, ataxia, seizures, hyperkinetic behavior, aggression, and sleep disturbances.
See also OMIM:271980
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02619993C → F in SSADHD; 3% of activity. 1 PublicationCorresponds to variant dbSNP:rs765561257EnsemblClinVar.1
Natural variantiVAR_026200176G → R in SSADHD; <1% of activity. 1 PublicationCorresponds to variant dbSNP:rs72552281EnsemblClinVar.1
Natural variantiVAR_026201223C → Y in SSADHD; 5% of activity. 1 PublicationCorresponds to variant dbSNP:rs72552282EnsemblClinVar.1
Natural variantiVAR_026202233T → M in SSADHD; 4% of activity. 1 Publication1
Natural variantiVAR_026203255N → S in SSADHD; 17% of activity. 1 PublicationCorresponds to variant dbSNP:rs145087265Ensembl.1
Natural variantiVAR_026204268G → E in SSADHD; <1% of activity. 2 PublicationsCorresponds to variant dbSNP:rs375628463EnsemblClinVar.1
Natural variantiVAR_026205335N → K in SSADHD; 1% of activity. 1 PublicationCorresponds to variant dbSNP:rs72552283Ensembl.1
Natural variantiVAR_026206382P → L in SSADHD; 2% of activity. 1 Publication1
Natural variantiVAR_026207382P → Q in SSADHD. 1 Publication1
Natural variantiVAR_026208409G → D in SSADHD; <1% of activity. 2 PublicationsCorresponds to variant dbSNP:rs118203984EnsemblClinVar.1
Natural variantiVAR_026209487V → E in SSADHD. 1 Publication1
Natural variantiVAR_026210533G → R in SSADHD; <1% of activity. 1 PublicationCorresponds to variant dbSNP:rs72552284EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi213R → A: Reduces catalytic activity to less than 15% of wild-type. 1 Publication1
Mutagenesisi334R → A: Reduces catalytic activity to less than 15% of wild-type. 1 Publication1
Mutagenesisi342C → A: Loss of regulation by redox state. 1 Publication1
Mutagenesisi498S → A: Reduces catalytic activity to less than 15% of wild-type. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi7915
GeneReviewsiALDH5A1
MalaCardsiALDH5A1
MIMi271980 phenotype
OpenTargetsiENSG00000112294
Orphaneti22 4-hydroxybutyric aciduria
PharmGKBiPA24702

Chemistry databases

ChEMBLiCHEMBL1911
DrugBankiDB00534 Chlormerodrin
DB00157 NADH
DB00139 Succinic acid
DB00313 Valproic Acid
GuidetoPHARMACOLOGYi2466

Polymorphism and mutation databases

BioMutaiALDH5A1
DMDMi7531278

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 47MitochondrionSequence analysisAdd BLAST47
ChainiPRO_000000718448 – 535Succinate-semialdehyde dehydrogenase, mitochondrialAdd BLAST488

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei126N6-acetyllysine; alternateCombined sources1
Modified residuei126N6-succinyllysine; alternateBy similarity1
Modified residuei135N6-succinyllysineBy similarity1
Modified residuei184N6-succinyllysineBy similarity1
Modified residuei265N6-acetyllysine; alternateBy similarity1
Modified residuei265N6-succinyllysine; alternateBy similarity1
Disulfide bondi340 ↔ 342In inhibited form1 Publication
Modified residuei365N6-acetyllysineBy similarity1
Modified residuei402N6-succinyllysineBy similarity1
Modified residuei411N6-acetyllysineBy similarity1
Modified residuei499PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

EPDiP51649
PaxDbiP51649
PeptideAtlasiP51649
PRIDEiP51649
ProteomicsDBi56358

PTM databases

iPTMnetiP51649
PhosphoSitePlusiP51649
SwissPalmiP51649

Expressioni

Tissue specificityi

Brain, pancreas, heart, liver, skeletal muscle and kidney. Lower in placenta.

Gene expression databases

BgeeiENSG00000112294
CleanExiHS_ALDH5A1
ExpressionAtlasiP51649 baseline and differential
GenevisibleiP51649 HS

Organism-specific databases

HPAiHPA029715
HPA029716

Interactioni

Subunit structurei

Homotetramer.2 Publications

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi113645, 24 interactors
IntActiP51649, 4 interactors
MINTiP51649
STRINGi9606.ENSP00000314649

Chemistry databases

BindingDBiP51649

Structurei

Secondary structure

1535
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni56 – 58Combined sources3
Beta strandi62 – 65Combined sources4
Beta strandi68 – 70Combined sources3
Beta strandi75 – 79Combined sources5
Turni81 – 83Combined sources3
Beta strandi86 – 91Combined sources6
Helixi95 – 112Combined sources18
Helixi117 – 133Combined sources17
Helixi135 – 146Combined sources12
Helixi150 – 170Combined sources21
Helixi171 – 173Combined sources3
Beta strandi177 – 179Combined sources3
Beta strandi187 – 194Combined sources8
Beta strandi197 – 201Combined sources5
Beta strandi204 – 206Combined sources3
Helixi209 – 221Combined sources13
Beta strandi224 – 228Combined sources5
Helixi235 – 247Combined sources13
Beta strandi253 – 256Combined sources4
Helixi261 – 271Combined sources11
Beta strandi277 – 284Combined sources8
Helixi286 – 297Combined sources12
Turni298 – 300Combined sources3
Beta strandi302 – 307Combined sources6
Beta strandi309 – 315Combined sources7
Beta strandi317 – 319Combined sources3
Helixi321 – 332Combined sources12
Helixi334 – 337Combined sources4
Beta strandi341 – 349Combined sources9
Helixi350 – 367Combined sources18
Beta strandi373 – 375Combined sources3
Helixi386 – 400Combined sources15
Turni401 – 403Combined sources3
Beta strandi405 – 408Combined sources4
Beta strandi423 – 428Combined sources6
Helixi430 – 433Combined sources4
Beta strandi441 – 450Combined sources10
Helixi452 – 459Combined sources8
Beta strandi466 – 471Combined sources6
Helixi475 – 484Combined sources10
Beta strandi487 – 493Combined sources7
Helixi508 – 510Combined sources3
Beta strandi511 – 513Combined sources3
Turni517 – 519Combined sources3
Helixi520 – 524Combined sources5
Beta strandi525 – 532Combined sources8

3D structure databases

ProteinModelPortaliP51649
SMRiP51649
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51649

Family & Domainsi

Sequence similaritiesi

Belongs to the aldehyde dehydrogenase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2451 Eukaryota
COG1012 LUCA
GeneTreeiENSGT00910000144187
HOGENOMiHOG000271509
HOVERGENiHBG108515
InParanoidiP51649
KOiK00139
OMAiYNVIPCS
PhylomeDBiP51649
TreeFamiTF352906

Family and domain databases

Gene3Di3.40.309.10, 1 hit
3.40.605.10, 2 hits
InterProiView protein in InterPro
IPR016161 Ald_DH/histidinol_DH
IPR016163 Ald_DH_C
IPR016160 Ald_DH_CS_CYS
IPR029510 Ald_DH_CS_GLU
IPR016162 Ald_DH_N
IPR015590 Aldehyde_DH_dom
IPR010102 Succ_semiAld_DH
PfamiView protein in Pfam
PF00171 Aldedh, 1 hit
SUPFAMiSSF53720 SSF53720, 1 hit
TIGRFAMsiTIGR01780 SSADH, 1 hit
PROSITEiView protein in PROSITE
PS00070 ALDEHYDE_DEHYDR_CYS, 1 hit
PS00687 ALDEHYDE_DEHYDR_GLU, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P51649-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MATCIWLRSC GARRLGSTFP GCRLRPRAGG LVPASGPAPG PAQLRCYAGR
60 70 80 90 100
LAGLSAALLR TDSFVGGRWL PAAATFPVQD PASGAALGMV ADCGVREARA
110 120 130 140 150
AVRAAYEAFC RWREVSAKER SSLLRKWYNL MIQNKDDLAR IITAESGKPL
160 170 180 190 200
KEAHGEILYS AFFLEWFSEE ARRVYGDIIH TPAKDRRALV LKQPIGVAAV
210 220 230 240 250
ITPWNFPSAM ITRKVGAALA AGCTVVVKPA EDTPFSALAL AELASQAGIP
260 270 280 290 300
SGVYNVIPCS RKNAKEVGEA ICTDPLVSKI SFTGSTTTGK ILLHHAANSV
310 320 330 340 350
KRVSMELGGL APFIVFDSAN VDQAVAGAMA SKFRNTGQTC VCSNQFLVQR
360 370 380 390 400
GIHDAFVKAF AEAMKKNLRV GNGFEEGTTQ GPLINEKAVE KVEKQVNDAV
410 420 430 440 450
SKGATVVTGG KRHQLGKNFF EPTLLCNVTQ DMLCTHEETF GPLAPVIKFD
460 470 480 490 500
TEEEAIAIAN AADVGLAGYF YSQDPAQIWR VAEQLEVGMV GVNEGLISSV
510 520 530
ECPFGGVKQS GLGREGSKYG IDEYLELKYV CYGGL
Length:535
Mass (Da):57,215
Last modified:May 30, 2000 - v2
Checksum:iC63A9431D3FA16C7
GO
Isoform 2 (identifier: P51649-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     242-242: E → EVNQGFLLDLDPLL

Show »
Length:548
Mass (Da):58,653
Checksum:i98C7673CBBF74FC8
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02622736G → R1 PublicationCorresponds to variant dbSNP:rs4646832EnsemblClinVar.1
Natural variantiVAR_02619993C → F in SSADHD; 3% of activity. 1 PublicationCorresponds to variant dbSNP:rs765561257EnsemblClinVar.1
Natural variantiVAR_026200176G → R in SSADHD; <1% of activity. 1 PublicationCorresponds to variant dbSNP:rs72552281EnsemblClinVar.1
Natural variantiVAR_016758180H → Y 83% of activity. 2 PublicationsCorresponds to variant dbSNP:rs2760118EnsemblClinVar.1
Natural variantiVAR_016759182P → L 48% of activity. 1 PublicationCorresponds to variant dbSNP:rs3765310EnsemblClinVar.1
Natural variantiVAR_026201223C → Y in SSADHD; 5% of activity. 1 PublicationCorresponds to variant dbSNP:rs72552282EnsemblClinVar.1
Natural variantiVAR_026202233T → M in SSADHD; 4% of activity. 1 Publication1
Natural variantiVAR_026228237A → S 65% of activity. 1 PublicationCorresponds to variant dbSNP:rs62621664EnsemblClinVar.1
Natural variantiVAR_026203255N → S in SSADHD; 17% of activity. 1 PublicationCorresponds to variant dbSNP:rs145087265Ensembl.1
Natural variantiVAR_026204268G → E in SSADHD; <1% of activity. 2 PublicationsCorresponds to variant dbSNP:rs375628463EnsemblClinVar.1
Natural variantiVAR_026205335N → K in SSADHD; 1% of activity. 1 PublicationCorresponds to variant dbSNP:rs72552283Ensembl.1
Natural variantiVAR_069047372N → S1 Publication1
Natural variantiVAR_026206382P → L in SSADHD; 2% of activity. 1 Publication1
Natural variantiVAR_026207382P → Q in SSADHD. 1 Publication1
Natural variantiVAR_026229406V → I1 PublicationCorresponds to variant dbSNP:rs143741652Ensembl.1
Natural variantiVAR_026208409G → D in SSADHD; <1% of activity. 2 PublicationsCorresponds to variant dbSNP:rs118203984EnsemblClinVar.1
Natural variantiVAR_026209487V → E in SSADHD. 1 Publication1
Natural variantiVAR_026210533G → R in SSADHD; <1% of activity. 1 PublicationCorresponds to variant dbSNP:rs72552284EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045231242E → EVNQGFLLDLDPLL in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y11192 mRNA Translation: CAA72076.1
AJ427354 mRNA Translation: CAD20883.2
AJ427355 mRNA Translation: CAD20884.1
AK315380 mRNA Translation: BAG37773.1
AL031230 Genomic DNA No translation available.
CH471087 Genomic DNA Translation: EAW55452.1
CH471087 Genomic DNA Translation: EAW55453.1
BC034321 mRNA Translation: AAH34321.1
L34820 mRNA Translation: AAA67057.1
CCDSiCCDS4555.1 [P51649-1]
CCDS4556.1 [P51649-2]
PIRiA55773
RefSeqiNP_001071.1, NM_001080.3 [P51649-1]
NP_733936.1, NM_170740.1 [P51649-2]
UniGeneiHs.371723

Genome annotation databases

EnsembliENST00000348925; ENSP00000314649; ENSG00000112294 [P51649-2]
ENST00000357578; ENSP00000350191; ENSG00000112294 [P51649-1]
GeneIDi7915
KEGGihsa:7915

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSSDH_HUMAN
AccessioniPrimary (citable) accession number: P51649
Secondary accession number(s): B2RD26
, G5E949, Q546H9, Q8N3W6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 30, 2000
Last modified: June 20, 2018
This is version 176 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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