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FKBP12-rapamycin-binding domain of FKBP-rapamycin-associated protein (FRAP) superfamily

SCOP classification
Root:   SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:   All alpha proteins [ 46456] (284)
Fold:   Four-helical up-and-down bundle [ 47161] (28)
Superfamily:   FKBP12-rapamycin-binding domain of FKBP-rapamycin-associated protein (FRAP) [ 47212]
Families:   FKBP12-rapamycin-binding domain of FKBP-rapamycin-associated protein (FRAP) [ 47213]


Superfamily statistics
Genomes (450) Uniprot 2014_06 PDB chains (SCOP 1.75)
Domains 603 728 3
Proteins 601 726 3


Functional annotation
General category General
Detailed category Small molecule binding

Document:
Function annotation of SCOP domain superfamilies

Gene Ontology (high-coverage)

(show details)
GO term FDR (all) SDFO level Annotation (direct or inherited)
Biological Process (BP) regulation of cellular process 0.000008576 Least Informative Direct
Biological Process (BP) response to stimulus 0.00002445 Least Informative Direct
Biological Process (BP) cellular component organization or biogenesis 0.0001676 Least Informative Direct
Biological Process (BP) single-organism cellular process 0.009453 Least Informative Inherited
Biological Process (BP) regulation of metabolic process 0.05227 Least Informative Inherited
Biological Process (BP) protein metabolic process 0.1245 Least Informative Inherited
Biological Process (BP) cellular macromolecule metabolic process 0.08809 Least Informative Inherited
Biological Process (BP) cellular protein modification process 0.00001845 Moderately Informative Direct
Biological Process (BP) phosphate-containing compound metabolic process 0.0000000009426 Moderately Informative Direct
Biological Process (BP) negative regulation of metabolic process 0.0001581 Moderately Informative Direct
Biological Process (BP) signal transduction 0.008781 Moderately Informative Inherited
Biological Process (BP) negative regulation of cellular process 0.04068 Moderately Informative Inherited
Biological Process (BP) regulation of cellular catabolic process 0.0000004228 Informative Direct
Biological Process (BP) response to nutrient levels 0.00000002395 Informative Direct
Biological Process (BP) intracellular signal transduction 0.000000001201 Informative Direct
Biological Process (BP) phosphorylation 0.01491 Informative Inherited
Biological Process (BP) protein phosphorylation 0.0003429 Highly Informative Direct
Biological Process (BP) regulation of autophagy 0 Highly Informative Direct
Biological Process (BP) negative regulation of cellular catabolic process 0 Highly Informative Direct
Molecular Function (MF) transferase activity 0.000000001129 Least Informative Direct
Molecular Function (MF) binding 0.007879 Least Informative Inherited
Molecular Function (MF) transferase activity, transferring phosphorus-containing groups 0.000000000001367 Moderately Informative Direct
Molecular Function (MF) kinase activity 0.00000000000021 Informative Direct
Molecular Function (MF) phosphotransferase activity, alcohol group as acceptor 0.00000000000006076 Informative Direct
Cellular Component (CC) protein complex 0.000005704 Least Informative Direct
Cellular Component (CC) intracellular organelle part 0.09105 Least Informative Inherited
Cellular Component (CC) intracellular membrane-bounded organelle 0.005218 Least Informative Inherited
Cellular Component (CC) cytoplasmic part 0.03961 Least Informative Inherited
Cellular Component (CC) membrane 0.09747 Least Informative Inherited
Cellular Component (CC) organelle membrane 0.0002978 Moderately Informative Direct
Cellular Component (CC) lytic vacuole 0.00000000001093 Informative Direct
Cellular Component (CC) vacuolar part 0.0000006431 Informative Direct

Document: GO annotation of SCOP domains

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEO levelAnnotation (direct or inherited)
Enzyme Commission (EC)Protein-serine/threonine kinases0.00000007787Moderately InformativeDirect

Document: EC annotation of SCOP domains

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEC levelAnnotation (direct or inherited)
Enzyme Commission (EC)Transferring phosphorous-containing groups0Least InformativeDirect
Enzyme Commission (EC)Protein-serine/threonine kinases0.00000007333Moderately InformativeDirect
Enzyme Commission (EC)Non-specific serine/threonine protein kinase2.432e-16InformativeDirect

Document: EC annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processCell cycle0.000000005192Moderately InformativeDirect
Cellular componentNucleus0.0001971Least InformativeDirect
DomainRepeat0Least InformativeDirect
DomainTPR repeat0.000000003564Highly InformativeDirect
Molecular functionNucleotide-binding0Least InformativeDirect
Molecular functionATP-binding0Moderately InformativeDirect
Post-translational modificationTransferase0Least InformativeDirect
Post-translational modificationKinase0Moderately InformativeDirect
Post-translational modificationSerine/threonine-protein kinase0.00001468InformativeDirect
Post-translational modificationPhosphoprotein0.00001735Least InformativeDirect

Document: KW annotation of SCOP domains

InterPro annotation
Cross references IPR009076 SSF47212 Protein matches
Abstract

Rapamycin and FK506 are potent immunosuppressive agents that bind to the FK506-binding protein (FKBP12), inhibiting its peptidyl-prolyl isomerase activity. The rapamycin-FKBP12 complex can then bind to and inhibit the FKBP12-rapamycin-associated protein (FRAP) in humans and RAFT1 in rats, causing cell-cycle arrest [PubMed10089303]. The FK506-FKBP12 complex cannot bind FRAP, but can bind to and inhibit calcineurin. Rapamycin is able to bind to two proteins, FKBP12 and FRAP, by simultaneously occupying two hydrophobic binding pockets, thereby linking these two proteins together to form a dimer [PubMed8662507]. The structure of the FKBP12-rapamycin-binding domain of FRAP consists of a core bundle of four helices arranged up-and-down in a left-handed twist.

FRAP has been shown to interact in vitro with CLIP-170, a protein involved in microtubule organisation and function [PubMed12231510]. FRAP is thought to act as a kinase to phosphorylate CLIP-170, thereby regulating its binding to microtubules. FRAP is also thought to cooperate with p85/p110 phosphatidylinositol 3-kinase (PI3K) to induce the activation of the serine/threonine kinase p70 S6 kinase (p70S6K), which in turn phosphorylates the 40S ribosomal protein S6, thereby altering the translation of ribosomal proteins and translation elongation factors [PubMed11684675].


InterPro database


PDBeMotif information about ligands, sequence and structure motifs
Cross references PDB entries
Ligand binding statistics
Nucleic-acid binding statistics
Occurrence of secondary structure elements
Occurrence of small 3D structural motifs

PDBeMotif resource

Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Gene Ontology (high-coverage) · Enzyme Commission (EC) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) ]

Internal database links

Browse genome assignments for this superfamily. The SUPERFAMILY hidden Markov model library has been used to carry out SCOP domain assignments to all genomes at the superfamily level.


Alignments of sequences to 1 models in this superfamily are available by clicking on the 'Alignments' icon above. PDB sequences less than 40% identical are shown by default, but any other sequence(s) may be aligned. Select PDB sequences, genome sequences, or paste in or upload your own sequences.


Browse and view proteins in genomes which have different domain combinations including a FKBP12-rapamycin-binding domain of FKBP-rapamycin-associated protein (FRAP) domain.


Examine the distribution of domain superfamilies, or families, across the major taxonomic kingdoms or genomes within a kingdom. This gives an immediate impression of how superfamilies, or families, are restricted to certain kingdoms of life.


Explore domain occurrence network where nodes represent genomes and edges are domain architectures (shared between genomes) containing the superfamily of interest.

There are 1 hidden Markov models representing the FKBP12-rapamycin-binding domain of FKBP-rapamycin-associated protein (FRAP) superfamily. Information on how the models are built, and plots showing hydrophobicity, match emmission probabilities and insertion/deletion probabilities can be inspected.


Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Gene Ontology (high-coverage) · Enzyme Commission (EC) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) · Internal database links ]