Search Results

Overview

Uniprot ID	Q92506
Protein Name	(3R)-3-hydroxyacyl-CoA dehydrogenase
Gene Name	HSD17B8
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
213	MTQKVPQKVVDKITE
61	LLGGPGSKEGPPRGN

Function

Required for the solubility and assembly of the heterotetramer 3-ketoacyl-[acyl carrier protein] (ACP) reductase functional complex (KAR or KAR1) that forms part of the mitochondrial fatty acid synthase (mtFAS). Alpha-subunit of the KAR complex that acts as a scaffold protein required for the stability of carbonyl reductase type-4 (CBR4, beta-subunit of the KAR complex) and for its 3-ketoacyl-ACP reductase activity, thereby participating in mitochondrial fatty acid biosynthesis. Catalyzes the NAD-dependent conversion of (3R)-3-hydroxyacyl-CoA into 3-ketoacyl-CoA (3-oxoacyl-CoA) with no chain length preference; this enzymatic activity is not needed for the KAR function (PubMed:19571038, PubMed:25203508, PubMed:30508570). Prefers (3R)-3-hydroxyacyl-CoA over (3S)-3-hydroxyacyl-CoA and displays enzymatic activity only in the presence of NAD(+) (PubMed:19571038). Cooperates with enoyl-CoA hydratase 1 in mitochondria, together they constitute an alternative route to the auxiliary enzyme pathways for the breakdown of Z-PUFA (cis polyunsaturated fatty acid) enoyl-esters (Probable) (PubMed:30508570). NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest activity towards estradiol (17beta-estradiol or E2). Has very low activity towards testosterone and dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one). Primarily an oxidative enzyme, it can switch to a reductive mode determined in the appropriate physiologic milieu and catalyze the reduction of estrone (E1) to form biologically active 17beta-estradiol (PubMed:17978863)

Protein Sequence

10 MASQLQNRLR 20 SALALVTGAG 30 SGIGRAVSVR 40 LAGEGATVAA 50 CDLDRAAAQE 60 TVRLLGGPGS 70 KEGPPRGNHA 80 AFQADVSEAR 90 AARCLLEQVQ 100 ACFSRPPSVV 110 VSCAGITQDE 120 FLLHMSEDDW 130 DKVIAVNLKG 140 TFLVTQAAAQ 150 ALVSNGCRGS 160 IINISSIVGK 170 VGNVGQTNYA 180 ASKAGVIGLT 190 QTAARELGRH 200 GIRCNSVLPG 210 FIATPMTQKV 220 PQKVVDKITE 230 MIPMGHLGDP 240 EDVADVVAFL 250 ASEDSGYITG 260 TSVEVTGGLF M

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005783	endoplasmic reticulum
Cellular Component	GO:0005740	mitochondrial envelope
Cellular Component	GO:0005759	mitochondrial matrix
Cellular Component	GO:0005739	mitochondrion
Cellular Component	GO:1990204	oxidoreductase complex
Cellular Component	GO:0005886	plasma membrane
Molecular Function	GO:0106386	(3R)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
Molecular Function	GO:0004303	estradiol 17-beta-dehydrogenase [NAD(P)+] activity
Molecular Function	GO:0070404	NADH binding
Molecular Function	GO:0048038	quinone binding
Molecular Function	GO:0047035	testosterone dehydrogenase (NAD+) activity
Biological Process	GO:0006703	estrogen biosynthetic process
Biological Process	GO:0006633	fatty acid biosynthetic process
Biological Process	GO:0051290	protein heterotetramerization

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.