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Protein

Very-long-chain 3-oxoacyl-CoA reductase

Gene

HSD17B12

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

Functioni

Catalyzes the second of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme has a 3-ketoacyl-CoA reductase activity, reducing 3-ketoacyl-CoA to 3-hydroxyacyl-CoA, within each cycle of fatty acid elongation. Thereby, it may participate in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May also catalyze the transformation of estrone (E1) into estradiol (E2) and play a role in estrogen formation.2 Publications

Catalytic activityi

A very-long-chain (3R)-3-hydroxyacyl-CoA + NADP+ = a very-long-chain 3-oxoacyl-CoA + NADPH.1 Publication
17-beta-estradiol + NAD(P)+ = estrone + NAD(P)H.1 Publication

Kineticsi

  1. KM=3.5 µM for estrone1 Publication

    Pathwayi: fatty acid biosynthesis

    This protein is involved in the pathway fatty acid biosynthesis, which is part of Lipid metabolism.1 Publication
    View all proteins of this organism that are known to be involved in the pathway fatty acid biosynthesis and in Lipid metabolism.

    Pathwayi: estrogen biosynthesis

    This protein is involved in the pathway estrogen biosynthesis, which is part of Steroid biosynthesis.1 Publication
    View all proteins of this organism that are known to be involved in the pathway estrogen biosynthesis and in Steroid biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei189SubstrateBy similarity1
    Active sitei202Proton acceptorPROSITE-ProRule annotation1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi50 – 79NADPBy similarityAdd BLAST30

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionOxidoreductase
    Biological processLipid biosynthesis, Lipid metabolism, Steroid biosynthesis
    LigandNADP

    Enzyme and pathway databases

    BRENDAi1.1.1.62 2681
    ReactomeiR-HSA-193048 Androgen biosynthesis
    R-HSA-75876 Synthesis of very long-chain fatty acyl-CoAs
    SABIO-RKQ53GQ0
    UniPathwayiUPA00094
    UPA00769

    Chemistry databases

    SwissLipidsiSLP:000000433

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Very-long-chain 3-oxoacyl-CoA reductaseCurated (EC:1.1.1.3301 Publication)
    Alternative name(s):
    17-beta-hydroxysteroid dehydrogenase 121 Publication
    Short name:
    17-beta-HSD 121 Publication
    3-ketoacyl-CoA reductase1 Publication
    Short name:
    KAR1 Publication
    Estradiol 17-beta-dehydrogenase 121 Publication (EC:1.1.1.621 Publication)
    Short chain dehydrogenase/reductase family 12C member 1
    Gene namesi
    Name:HSD17B12Imported
    Synonyms:SDR12C1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 11

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000149084.11
    HGNCiHGNC:18646 HSD17B12
    MIMi609574 gene
    neXtProtiNX_Q53GQ0

    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

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transmembranei4 – 24HelicalSequence analysisAdd BLAST21
    Transmembranei182 – 202HelicalSequence analysisAdd BLAST21
    Transmembranei271 – 291HelicalSequence analysisAdd BLAST21

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi196V → W: No effect. 1 Publication1
    Mutagenesisi234F → A: Allows the conversion of androstenedione to testosterone. 1 Publication1

    Organism-specific databases

    DisGeNETi51144
    MalaCardsiHSD17B12
    OpenTargetsiENSG00000149084
    PharmGKBiPA38618

    Chemistry databases

    ChEMBLiCHEMBL5998

    Polymorphism and mutation databases

    BioMutaiHSD17B12
    DMDMi158931120

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002483681 – 312Very-long-chain 3-oxoacyl-CoA reductaseAdd BLAST312

    Proteomic databases

    EPDiQ53GQ0
    MaxQBiQ53GQ0
    PaxDbiQ53GQ0
    PeptideAtlasiQ53GQ0
    PRIDEiQ53GQ0

    PTM databases

    iPTMnetiQ53GQ0
    PhosphoSitePlusiQ53GQ0
    SwissPalmiQ53GQ0

    Expressioni

    Tissue specificityi

    Expressed in most tissues tested. Highly expressed in the ovary and mammary. Expressed in platelets.3 Publications

    Gene expression databases

    BgeeiENSG00000149084
    CleanExiHS_HSD17B12
    ExpressionAtlasiQ53GQ0 baseline and differential
    GenevisibleiQ53GQ0 HS

    Organism-specific databases

    HPAiHPA016427

    Interactioni

    Subunit structurei

    Interacts with ELOVL1 and LASS2.1 Publication

    Binary interactionsi

    Show more details

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi119328, 47 interactors
    IntActiQ53GQ0, 20 interactors
    MINTiQ53GQ0
    STRINGi9606.ENSP00000278353

    Structurei

    3D structure databases

    ProteinModelPortaliQ53GQ0
    SMRiQ53GQ0
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi308 – 312Di-lysine motif5

    Domaini

    The di-lysine motif confers endoplasmic reticulum localization for type I membrane proteins.By similarity

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG1014 Eukaryota
    COG0300 LUCA
    GeneTreeiENSGT00390000010069
    HOGENOMiHOG000039237
    HOVERGENiHBG005478
    InParanoidiQ53GQ0
    KOiK10251
    OMAiYLVTSAM
    OrthoDBiEOG091G06T2
    PhylomeDBiQ53GQ0
    TreeFamiTF314591

    Family and domain databases

    InterProiView protein in InterPro
    IPR036291 NAD(P)-bd_dom_sf
    IPR020904 Sc_DH/Rdtase_CS
    IPR002347 SDR_fam
    PfamiView protein in Pfam
    PF00106 adh_short, 1 hit
    PRINTSiPR00081 GDHRDH
    PR00080 SDRFAMILY
    SUPFAMiSSF51735 SSF51735, 1 hit
    PROSITEiView protein in PROSITE
    PS00061 ADH_SHORT, 1 hit

    Sequences (2)i

    Sequence statusi: Complete.

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

    Isoform 1 (identifier: Q53GQ0-1) [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
    MESALPAAGF LYWVGAGTVA YLALRISYSL FTALRVWGVG NEAGVGPGLG
    60 70 80 90 100
    EWAVVTGSTD GIGKSYAEEL AKHGMKVVLI SRSKDKLDQV SSEIKEKFKV
    110 120 130 140 150
    ETRTIAVDFA SEDIYDKIKT GLAGLEIGIL VNNVGMSYEY PEYFLDVPDL
    160 170 180 190 200
    DNVIKKMINI NILSVCKMTQ LVLPGMVERS KGAILNISSG SGMLPVPLLT
    210 220 230 240 250
    IYSATKTFVD FFSQCLHEEY RSKGVFVQSV LPYFVATKLA KIRKPTLDKP
    260 270 280 290 300
    SPETFVKSAI KTVGLQSRTN GYLIHALMGS IISNLPSWIY LKIVMNMNKS
    310
    TRAHYLKKTK KN
    Length:312
    Mass (Da):34,324
    Last modified:October 2, 2007 - v2
    Checksum:i8518336D7F514E50
    GO
    Isoform 2 (identifier: Q53GQ0-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         95-98: KEKF → SNYT
         99-312: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:98
    Mass (Da):10,342
    Checksum:i2EEE844E7FDC97A1
    GO

    Sequence cautioni

    The sequence AK027882 differs from that shown. Reason: Frameshift at position 92.Curated

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_027277280S → L3 PublicationsCorresponds to variant dbSNP:rs11555762Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_05638095 – 98KEKF → SNYT in isoform 2. 1 Publication4
    Alternative sequenceiVSP_05638199 – 312Missing in isoform 2. 1 PublicationAdd BLAST214

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF078850 mRNA Translation: AAD44482.1
    AK027882 mRNA No translation available.
    AK074952 mRNA Translation: BAG52039.1
    AK075216 mRNA Translation: BAG52086.1
    AK222881 mRNA Translation: BAD96601.1
    AK292625 mRNA Translation: BAF85314.1
    AC023085 Genomic DNA No translation available.
    AC068205 Genomic DNA No translation available.
    AC087521 Genomic DNA No translation available.
    CH471064 Genomic DNA Translation: EAW68082.1
    CH471064 Genomic DNA Translation: EAW68087.1
    CH471064 Genomic DNA Translation: EAW68088.1
    BC012043 mRNA Translation: AAH12043.1
    BC012536 mRNA Translation: AAH12536.1
    CCDSiCCDS7905.1 [Q53GQ0-1]
    RefSeqiNP_057226.1, NM_016142.2 [Q53GQ0-1]
    UniGeneiHs.132513

    Genome annotation databases

    EnsembliENST00000278353; ENSP00000278353; ENSG00000149084 [Q53GQ0-1]
    ENST00000395700; ENSP00000379052; ENSG00000149084 [Q53GQ0-2]
    GeneIDi51144
    KEGGihsa:51144
    UCSCiuc001mxq.5 human [Q53GQ0-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiDHB12_HUMAN
    AccessioniPrimary (citable) accession number: Q53GQ0
    Secondary accession number(s): A8K9B0
    , D3DR23, Q96EA9, Q96JU2, Q9Y6G8
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 5, 2006
    Last sequence update: October 2, 2007
    Last modified: May 23, 2018
    This is version 134 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

    Complete proteome, Direct protein sequencing, Reference proteome

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