HSD17B1

Protein identityUniProt · HPA

UniProt accession

P14061

Gene

HSD17B1

Ensembl

ENSG00000108786

Chromosome

17

Canonical length

328 aa

Protein class

Enzymes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the 17beta-hydroxysteroid dehydrogenase family of short-chain dehydrogenases/reductases. It has a dual function in estrogen activation and androgen inactivation and plays a major role in establishing the estrogen E2 concentration gradient between serum and peripheral tissues. The encoded protein catalyzes the last step in estrogen activation, using NADPH to convert estrogens E1 and E2 and androgens like 4-androstenedione, to testosterone. It has an N-terminal short-chain dehydrogenase domain with a cofactor binding site, and a narrow, hydrophobic C-terminal domain with a steroid substrate binding site. This gene is expressed primarily in the placenta and ovarian granulosa cells, and to a lesser extent, in the endometrium, adipose tissue, and prostate. Polymorphisms in this gene have been linked to breast and prostate cancer. A pseudogene of this gene has been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

Canonical amino-acid sequenceUniProt

328 residues, UniProt reviewed canonical sequence.

>P14061|HSD17B1
     1  MARTVVLITG CSSGIGLHLA VRLASDPSQS FKVYATLRDL KTQGRLWEAA RALACPPGSL
    61  ETLQLDVRDS KSVAAARERV TEGRVDVLVC NAGLGLLGPL EALGEDAVAS VLDVNVVGTV
   121  RMLQAFLPDM KRRGSGRVLV TGSVGGLMGL PFNDVYCASK FALEGLCESL AVLLLPFGVH
   181  LSLIECGPVH TAFMEKVLGS PEEVLDRTDI HTFHRFYQYL AHSKQVFREA AQNPEEVAEV
   241  FLTALRAPKP TLRYFTTERF LPLLRMRLDD PSGSNYVTAM HREVFGDVPA KAEAGAEAGG
   301  GAGPGAEDEA GRGAVGDPEL GDPPAAPQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HSD17B1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

78 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.35

gnomAD pLI

0

gnomAD missense Z

-0.35

DepMap mean gene effect

-0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adipose tissue development
• bone development
• cellular response to metal ion
• estrogen biosynthetic process
• gene expression
• lysosome organization
• skeletal muscle tissue development
• testosterone biosynthetic process

Molecular functions

• 17-beta-hydroxysteroid dehydrogenase (NADP+) activity
• estradiol 17-beta-dehydrogenase [NAD(P)+] activity
• estradiol binding
• NADP binding
• NADP+ binding
• protein homodimerization activity
• small molecule binding
• steroid binding
• testosterone dehydrogenase (NAD+) activity
• testosterone dehydrogenase (NADP+) activity

Cellular components

• cytosol

Protein domainsUniProt · Pfam · InterPro

• Short-chain dehydrogenase/reductase SDR
• 17beta-dehydrogenase
• Short-chain dehydrogenase/reductase, conserved site
• NAD(P)-binding domain superfamily
• short chain dehydrogenase

KeywordsUniProt

• Cytoplasm
• Lipid biosynthesis
• Lipid metabolism
• NADP
• Oxidoreductase
• Phosphoprotein
• Steroid biosynthesis