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49  structures 959  species 2  interactions 1344  sequences 67  architectures

Family: FRB_dom (PF08771)

Summary: FKBP12-rapamycin binding domain

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FKBP12-rapamycin binding domain Provide feedback

The macrolide antibiotic rapamycin and the cytosol protein FKBP12 can form a complex which specifically inhibits the TORC1 complex, leading to growth arrest. The FKBP12-rapamycin complex interferes with TORC1 function by binding to the FKBP12-rapamycin binding domain (FRB) of the TOR proteins. This entry represents the FRB domain [1, 2].

Literature references

  1. Choi J, Chen J, Schreiber SL, Clardy J; , Science. 1996;273:239-242.: Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP. PUBMED:8662507 EPMC:8662507

  2. Hu K, Guo S, Yan G, Yuan W, Zheng Y, Jiang Y;, Mol Microbiol. 2015; [Epub ahead of print]: Ubiquitin regulates TORC1 in yeast Saccharomyces cerevisiae. PUBMED:26700129 EPMC:26700129

  3. Gaubitz C, Oliveira TM, Prouteau M, Leitner A, Karuppasamy M, Konstantinidou G, Rispal D, Eltschinger S, Robinson GC, Thore S, Aebersold R, Schaffitzel C, Loewith R;, Mol Cell. 2015;58:977-988.: Molecular Basis of the Rapamycin Insensitivity of Target Of Rapamycin Complex 2. PUBMED:26028537 EPMC:26028537


This tab holds annotation information from the InterPro database.

InterPro entry IPR009076

The macrolide antibiotic rapamycin and the cytosol protein FKBP12 can form a complex which specifically inhibits the TORC1 complex, leading to growth arrest. The FKBP12-rapamycin complex interferes with TORC1 function by binding to the FKBP12-rapamycin binding domain (FRB) of the Tor proteins.

This entry represents the FRB domain [PUBMED:8662507, PUBMED:26700129]. Proteins containing this domain include Tor proteins which are serine/threonine kinases conserved from fungi to humans. While higher eukaryotes such as humans possess a single Tor protein, yeasts contain two (Tor1 and Tor2) [PUBMED:26028537].

In budding yeast, the Tor2 protein exists in two distinct multi-component complexes, TORC1 and TORC2. TORC1 regulates cell growth by regulating many growth-related processes and is rapamycin sensitive, while TROC2 regulates the cell cytoskeleton and is rapamycin insensitive. Budding yeast TORC1 consists of either Tor1 or Tor2 in complex with Kog1, Lst8 and Tco89, while TORC2 is composed of Avo1, Avo2, Tsc11, Lst8, Bit61, Slm, Slm2 and Tor2 [PUBMED:26700129, PUBMED:15689497]. In both yeast and mammals, FKBP12-rapamycin binds to Tor (Tor1, Tor2, or mTOR) in TORC1, but not to Tor (Tor2 or mTOR) in TORC2. It has been suggested that the architecture of TORC2 or its unique composition might be responsible for the observed rapamycin resistance [PUBMED:26028537].

Gene Ontology

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Domain organisation

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Alignments

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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
(96)
Full
(1344)
Representative proteomes UniProt
(1986)
NCBI
(2446)
Meta
(15)
RP15
(433)
RP35
(777)
RP55
(1035)
RP75
(1246)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

Format an alignment

  Seed
(96)
Full
(1344)
Representative proteomes UniProt
(1986)
NCBI
(2446)
Meta
(15)
RP15
(433)
RP35
(777)
RP55
(1035)
RP75
(1246)
Alignment:
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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
(96)
Full
(1344)
Representative proteomes UniProt
(1986)
NCBI
(2446)
Meta
(15)
RP15
(433)
RP35
(777)
RP55
(1035)
RP75
(1246)
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

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Curation and family details

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Curation View help on the curation process

Seed source: pdb_1aue
Previous IDs: Rapamycin_bind;
Type: Domain
Sequence Ontology: SO:0000417
Author: Mistry J
Number in seed: 96
Number in full: 1344
Average length of the domain: 98.00 aa
Average identity of full alignment: 54 %
Average coverage of the sequence by the domain: 4.34 %

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 24.7 24.7
Trusted cut-off 24.7 24.7
Noise cut-off 24.6 24.6
Model length: 99
Family (HMM) version: 11
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

PI3_PI4_kinase FKBP_C

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 FRB_dom domain has been found. There are 49 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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