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2097  structures 314  species 8  interactions 14256  sequences 172  architectures

Family: Hormone_recep (PF00104)

Summary: Ligand-binding domain of nuclear hormone receptor

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This is the Wikipedia entry entitled "Nuclear receptor". More...

Nuclear receptor Edit Wikipedia article

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Ligand-binding domain of nuclear hormone receptor Provide feedback

This all helical domain is involved in binding the hormone in these receptors.

Literature references

  1. Tanenbaum DM, Wang Y, Williams SP, Sigler PB; , Proc Natl Acad Sci U S A 1998;95:5998-6003.: Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains. PUBMED:9600906 EPMC:9600906


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000536

Nuclear receptors (NRs), such as the receptors for steroids and thyroid hormones, retinoids and vitamin D3, are one of the most abundant classes of transcriptional regulators in animals (metazoans). They regulate diverse functions, such as homeostasis, reproduction, development and metabolism. The most prominent feature differentiating them from other transcription factors is their capacity to bind small hydrophobic molecules specifically. These ligands constitute regulatory signals, which modify the NR transcriptional activity through conformational changes. Prototypical NRs share a common structural organization with a variable amino-terminal (Nter) domain that contains a constitutively active activation function (AF)-1, a conserved DNA- binding domain (DBD) consisting of two zinc fingers, a linker region, and a C-terminal (Cter) ligand-binding domain (LBD), also called HOLI domain [PUBMED:12538758, PUBMED:15105832, PUBMED:24844133].

The NR LBD plays a crucial role in ligand-mediated NR activity. In addition to its role is ligand recognition, the LBD also contains a ligand-dependent AF-2. Conformational changes in AF-2 induced by various ligands can modulate interactions with conserved motifs of coregulatory proteins. Specifically, the binding of ligands to the LBD determines the recruiting of transcriptional coregulators which triggers induction or repression of target genes. The coregulators include coactivators like the p160 factors also referred to as the steroid receptor coactivators (SRC) family, and corepressors such as SMART (silencing mediator for retinoid and thyroid hormone receptors) and N-CoR (nuclear corepressor) [PUBMED:24361687, PUBMED:11050318, PUBMED:9640540, PUBMED:20723571].

The overall structure of NR LBD is composed of about 11-13 alpha-helices that are arranged into a three-layer antiparallel alpha-helical sandwich with the three long helices (helices 3, 7, and 10) forming the two outer layers. The middle layer of helices (helices 4, 5, 8 and 9) is present only in the top half of the domain but is missing from the bottom half, thereby creating a cavity, so called ligand-binding pocket, for ligand binding in most receptors. The bound ligands stabilize the NR conformation through direct contacts with multiple structural elements including helices H3, H5, H6, H7, H10, and the loop preceeding the AF-2 helix. The C-terminal activation region also forms an alpha-helix (AF-2), which can adopt multiple conformation depending on the nature of the bound ligand. Helices 3,4 and 12 enclose a shallow hydrophobic groove which is the site for coregulator binding. Despite the conserved fold of NR LBDs, the ligand-binding pocket is the least conserved region among different NR LBDs [PUBMED:11050318, PUBMED:9640540, PUBMED:20723571].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(337)
Full
(14256)
Representative proteomes UniProt
(23898)
NCBI
(38717)
Meta
(1)
RP15
(3184)
RP35
(6406)
RP55
(10525)
RP75
(12032)
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PP/heatmap 1                

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

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  Seed
(337)
Full
(14256)
Representative proteomes UniProt
(23898)
NCBI
(38717)
Meta
(1)
RP15
(3184)
RP35
(6406)
RP55
(10525)
RP75
(12032)
Alignment:
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Order:
Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(337)
Full
(14256)
Representative proteomes UniProt
(23898)
NCBI
(38717)
Meta
(1)
RP15
(3184)
RP35
(6406)
RP55
(10525)
RP75
(12032)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: hormone_rec;
Type: Domain
Sequence Ontology: SO:0000417
Author: Sonnhammer ELL , Griffiths-Jones SR , Bateman A
Number in seed: 337
Number in full: 14256
Average length of the domain: 179.80 aa
Average identity of full alignment: 18 %
Average coverage of the sequence by the domain: 38.66 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.5 23.5
Trusted cut-off 23.5 23.5
Noise cut-off 23.4 23.4
Model length: 207
Family (HMM) version: 30
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 8 interactions for this family. More...

fn3 Androgen_recep Hormone_recep SRC-1 Arm zf-C4 ARA70 FTZ

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Hormone_recep domain has been found. There are 2097 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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