Gene/Proteome Database (LMPD)
LMPD ID
LMP000324
Gene ID
Species
Homo sapiens (Human)
Gene Name
hydroxysteroid (17-beta) dehydrogenase 10
Gene Symbol
Synonyms
17b-HSD10; ABAD; CAMR; DUPXp11.22; ERAB; HADH2; HCD2; MHBD; MRPP2; MRX17; MRX31; MRXS10; SCHAD; SDR5C1
Alternate Names
3-hydroxyacyl-CoA dehydrogenase type-2; mitochondrial RNase P subunit 2; AB-binding alcohol dehydrogenase; mitochondrial ribonuclease P protein 2; 3-hydroxy-2-methylbutyryl-CoA dehydrogenase; short chain type dehydrogenase/reductase XH98G2; amyloid-beta peptide binding alcohol dehydrogenase; short chain L-3-hydroxyacyl-CoA dehydrogenase type 2; short chain dehydrogenase/reductase family 5C, member 1; endoplasmic reticulum-associated amyloid beta-peptide-binding protein
Chromosome
X
Map Location
Xp11.2
EC Number
1.1.1.35
Summary
This gene encodes 3-hydroxyacyl-CoA dehydrogenase type II, a member of the short-chain dehydrogenase/reductase superfamily. The gene product is a mitochondrial protein that catalyzes the oxidation of a wide variety of fatty acids and steroids, and is a subunit of mitochondrial ribonuclease P, which is involved in tRNA maturation. The protein has been implicated in the development of Alzheimer disease, and mutations in the gene are the cause of 17beta-hydroxysteroid dehydrogenase type 10 (HSD10) deficiency. Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Aug 2014]
Orthologs
Proteins
| 3-hydroxyacyl-CoA dehydrogenase type-2 isoform 1 | |
|---|---|
| Refseq ID | NP_004484 |
| Protein GI | 4758504 |
| UniProt ID | Q99714 |
| mRNA ID | NM_004493 |
| Length | 261 |
| RefSeq Status | REVIEWED |
| MAAACRSVKGLVAVITGGASGLGLATAERLVGQGASAVLLDLPNSGGEAQAKKLGNNCVFAPADVTSEKDVQTALALAKGKFGRVDVAVNCAGIAVASKTYNLKKGQTHTLEDFQRVLDVNLMGTFNVIRLVAGEMGQNEPDQGGQRGVIINTASVAAFEGQVGQAAYSASKGGIVGMTLPIARDLAPIGIRVMTIAPGLFGTPLLTSLPEKVCNFLASQVPFPSRLGDPAEYAHLVQAIIENPFLNGEVIRLDGAIRMQP | |
| transit_peptide: 1..11 calculated_mol_wt: 1106 peptide sequence: MAAACRSVKGL transit_peptide: 1..11 calculated_mol_wt: 1106 peptide sequence: MAAACRSVKGL | |
| 3-hydroxyacyl-CoA dehydrogenase type-2 isoform 2 | |
|---|---|
| Refseq ID | NP_001032900 |
| Protein GI | 83715985 |
| UniProt ID | Q99714 |
| mRNA ID | NM_001037811 |
| Length | 252 |
| RefSeq Status | REVIEWED |
| MAAACRSVKGLVAVITGGASGLGLATAERLVGQGASAVLLDLPNSGGEAQAKKLGNNCVFAPADVTSEKDVQTALALAKGKFGRVDVAVNCAGIAVASKTYNLKKGQTHTLEDFQRVLDVNLMGTFNVIRLVAGEMGQNEPDQGGQRGVIINTASVAAFEGQVGQAAYSASKGGIVGMTLPIARDLAPIGLFGTPLLTSLPEKVCNFLASQVPFPSRLGDPAEYAHLVQAIIENPFLNGEVIRLDGAIRMQP | |
Gene Information
Entrez Gene ID
Gene Name
hydroxysteroid (17-beta) dehydrogenase 10
Gene Symbol
Species
Homo sapiens
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005737 | TAS:ProtInc | C | cytoplasm |
| GO:0005783 | IEA:Ensembl | C | endoplasmic reticulum |
| GO:0005743 | IEA:Ensembl | C | mitochondrial inner membrane |
| GO:0005759 | TAS:Reactome | C | mitochondrial matrix |
| GO:0005739 | ISS:UniProtKB | C | mitochondrion |
| GO:0005886 | TAS:ProtInc | C | plasma membrane |
| GO:0047015 | IEA:UniProtKB-EC | F | 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity |
| GO:0003857 | EXP:Reactome | F | 3-hydroxyacyl-CoA dehydrogenase activity |
| GO:0008709 | TAS:ProtInc | F | cholate 7-alpha-dehydrogenase activity |
| GO:0044822 | IDA:UniProtKB | F | poly(A) RNA binding |
| GO:0030283 | IEA:UniProtKB-EC | F | testosterone dehydrogenase [NAD(P)] activity |
| GO:0009083 | TAS:Reactome | P | branched-chain amino acid catabolic process |
| GO:0034641 | TAS:Reactome | P | cellular nitrogen compound metabolic process |
| GO:0006629 | TAS:ProtInc | P | lipid metabolic process |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
| GO:0008033 | IEA:UniProtKB-KW | P | tRNA processing |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| hsa05010 | Alzheimer's disease |
BIOCYC Pathway Links
| BIOCYC Pathway ID | Description |
|---|---|
| FAO-PWY | fatty acid beta-oxidation I |
| ILEUDEG-PWY | isoleucine degradation I |
Domain Information
UniProt Annotations
Entry Information
Gene Name
hydroxysteroid (17-beta) dehydrogenase 10
Protein Entry
HCD2_HUMAN
UniProt ID
Species
Human
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q99714-1; Sequence=Displayed; Name=2; IsoId=Q99714-2; Sequence=VSP_007830; Note=No experimental confirmation available.; |
| Biophysicochemical Properties | Kinetic parameters: KM=25.7 uM for acetoacetyl-CoA (in the presence of 0.2 mM NADH, at pH 7.0 and 25 degrees Celsius) ; KM=85.2 uM for beta-hydroxybutyryl-CoA (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) ; KM=41 uM for androsterone (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) ; KM=5 uM for 5-alpha-pregnan-20-beta-ol-3-one (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) ; KM=219 uM for isoursodeoxycholic acid (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) ; KM=36.4 uM for chenodeoxycholic acid (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) ; KM=1.7 uM for dehydrocorticosterone (in the presence of 1 mM NAD, at pH 9.3 and 25 degrees Celsius) ; KM=30.6 uM for NADH (in the presence of acetoacetyl-CoA, at pH 7.0 and 25 degrees Celsius) ; KM=42.3 uM for NAD (in the presence of beta-hydroxybutyryl-CoA, at pH 9.3 and 25 degrees Celsius) ; pH dependence: Optimum pH is 9.3 for the dehydrogenase reaction at 25 degrees Celsius, and 7.0 for the reductase reaction at 25 degrees Celsius. ; |
| Catalytic Activity | (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA + NAD(+) = 2-methylacetoacetyl-CoA + NADH. |
| Catalytic Activity | (S)-3-hydroxyacyl-CoA + NAD(+) = 3-oxoacyl-CoA + NADH. |
| Catalytic Activity | Testosterone + NAD(P)(+) = androst-4-ene-3,17- dione + NAD(P)H. |
| Disease | 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (MHBD deficiency) [MIM |
| Disease | Mental retardation, X-linked 17 (MRX17) [MIM |
| Disease | Mental retardation, X-linked, syndromic, 10 (MRXS10) [MIM |
| Function | Functions in mitochondrial tRNA maturation. Part of mitochondrial ribonuclease P, an enzyme composed of MRPP1/TRMT10C, MRPP2/HSD17B10 and MRPP3/KIAA0391, which cleaves tRNA molecules in their 5'-ends. Catalyzes the beta-oxidation at position 17 of androgens and estrogens and has 3-alpha-hydroxysteroid dehydrogenase activity with androsterone. Catalyzes the third step in the beta-oxidation of fatty acids. Carries out oxidative conversions of 7-alpha-OH and 7-beta-OH bile acids. Also exhibits 20-beta-OH and 21-OH dehydrogenase activities with C21 steroids. By interacting with intracellular amyloid-beta, it may contribute to the neuronal dysfunction associated with Alzheimer disease (AD). {ECO |
| Interaction | P05067:APP; NbExp=4; IntAct=EBI-79964, EBI-77613; Q7L0Y3:TRMT10C; NbExp=4; IntAct=EBI-79964, EBI-2107046; |
| Similarity | Belongs to the short-chain dehydrogenases/reductases (SDR) family. |
| Subcellular Location | Mitochondrion {ECO |
| Subunit | Homotetramer (By similarity). Interacts with MRPP1/TRMT10C and MRPP3/KIAA0391. {ECO |
| Tissue Specificity | Ubiquitously expressed in normal tissues but is overexpressed in neurons affected in AD. |
Identical and Related Proteins
Unique RefSeq proteins for LMP000324 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 4758504 | RefSeq | NP_004484 | 261 | 3-hydroxyacyl-CoA dehydrogenase type-2 isoform 1 |
| 83715985 | RefSeq | NP_001032900 | 252 | 3-hydroxyacyl-CoA dehydrogenase type-2 isoform 2 |
Identical Sequences to LMP000324 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:83715985 | GenBank | EAW93158.1 | 252 | hydroxyacyl-Coenzyme A dehydrogenase, type II, isoform CRA_b [Homo sapiens] |
| GI:4758504 | GenBank | ACH32233.1 | 261 | Sequence 6713 from patent US 7411051 |
| GI:83715985 | GenBank | ADZ15690.1 | 252 | hydroxysteroid (17-beta) dehydrogenase 10, partial [synthetic construct] |
| GI:83715985 | GenBank | JAA03543.1 | 252 | hydroxysteroid (17-beta) dehydrogenase 10 [Pan troglodytes] |
| GI:4758504 | GenBank | JAA03544.1 | 261 | hydroxysteroid (17-beta) dehydrogenase 10 [Pan troglodytes] |
| GI:83715985 | GenBank | JAA20430.1 | 252 | hydroxysteroid (17-beta) dehydrogenase 10 [Pan troglodytes] |
| GI:4758504 | GenBank | JAA20431.1 | 261 | hydroxysteroid (17-beta) dehydrogenase 10 [Pan troglodytes] |
| GI:83715985 | GenBank | AIC48915.1 | 252 | HSD17B10, partial [synthetic construct] |
| GI:4758504 | GenBank | AIC48916.1 | 261 | HSD17B10, partial [synthetic construct] |
| GI:83715985 | RefSeq | XP_001146501.1 | 252 | PREDICTED: 3-hydroxyacyl-CoA dehydrogenase type-2 isoform X2 [Pan troglodytes] |
| GI:4758504 | RefSeq | XP_003317521.1 | 261 | PREDICTED: 3-hydroxyacyl-CoA dehydrogenase type-2 isoform X1 [Pan troglodytes] |
| GI:4758504 | RefSeq | XP_003805947.1 | 261 | PREDICTED: 3-hydroxyacyl-CoA dehydrogenase type-2 [Pan paniscus] |
Related Sequences to LMP000324 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:83715985 | GenBank | AAC15902.1 | 261 | 17beta-hydroxysteroid dehydrogenase type 10/short chain L-3-hydroxyacyl-CoA dehydrogenase [Homo sapiens] |
| GI:83715985 | GenBank | AAC16419.1 | 261 | 17beta-hydroxysteroid dehydrogenase type 10/short chain L-3-hydroxyacyl-CoA dehydrogenase [Homo sapiens] |
| GI:83715985 | GenBank | AAC39900.1 | 261 | putative short-chain type dehydrogenase/reductase [Homo sapiens] |
| GI:4758504 | PDB | 1U7T | 261 | Chain A, Crystal Structure Of AbadHSD10 WITH A BOUND INHIBITOR |
| GI:4758504 | PDB | 1U7T | 261 | Chain B, Crystal Structure Of AbadHSD10 WITH A BOUND INHIBITOR |
| GI:4758504 | PDB | 1U7T | 261 | Chain C, Crystal Structure Of AbadHSD10 WITH A BOUND INHIBITOR |
| GI:4758504 | PDB | 1U7T | 261 | Chain D, Crystal Structure Of AbadHSD10 WITH A BOUND INHIBITOR |
| GI:4758504 | PDB | 2O23 | 265 | Chain A, The Structure Of Wild-Type Human Hadh2 (17beta-Hydroxysteroid Dehydrogenase Type 10) Bound To Nad+ At 1.2 A |
| GI:4758504 | PDB | 2O23 | 265 | Chain B, The Structure Of Wild-Type Human Hadh2 (17beta-Hydroxysteroid Dehydrogenase Type 10) Bound To Nad+ At 1.2 A |
| GI:83715985 | RefSeq | NP_004484.1 | 261 | 3-hydroxyacyl-CoA dehydrogenase type-2 isoform 1 [Homo sapiens] |
| GI:83715985 | RefSeq | XP_004064260.1 | 252 | PREDICTED: 3-hydroxyacyl-CoA dehydrogenase type-2-like isoform 2 [Gorilla gorilla gorilla] |
| GI:83715985 | RefSeq | XP_004064262.1 | 252 | PREDICTED: 3-hydroxyacyl-CoA dehydrogenase type-2-like isoform 2 [Gorilla gorilla gorilla] |