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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 (451) Uniprot 2014_06 PDB chains (SCOP 1.75)
Domains 604 728 3
Proteins 602 726 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) response to stimulus 0.0008245 Least Informative Direct
Biological Process (BP) biological regulation 0.00001523 Least Informative Direct
Biological Process (BP) primary metabolic process 0.001441 Least Informative Inherited
Biological Process (BP) single-organism cellular process 0.1224 Least Informative Inherited
Biological Process (BP) macromolecule metabolic process 0.01301 Least Informative Inherited
Biological Process (BP) reproduction 0.0003693 Moderately Informative Direct
Biological Process (BP) cellular protein modification process 0.0000008274 Moderately Informative Direct
Biological Process (BP) cell communication 0.00001427 Moderately Informative Direct
Biological Process (BP) signaling 0.0002004 Moderately Informative Direct
Biological Process (BP) positive regulation of cellular process 0.0002648 Moderately Informative Direct
Biological Process (BP) regulation of response to stimulus 0.0008822 Moderately Informative Direct
Biological Process (BP) system development 0.0004514 Moderately Informative Direct
Biological Process (BP) regulation of biosynthetic process 0.2956 Moderately Informative Inherited
Biological Process (BP) regulation of multicellular organismal process 0.00543 Moderately Informative Inherited
Biological Process (BP) regulation of developmental process 0.002005 Moderately Informative Inherited
Biological Process (BP) negative regulation of cellular process 0.05926 Moderately Informative Inherited
Biological Process (BP) response to external stimulus 0.01995 Moderately Informative Inherited
Biological Process (BP) regulation of cellular component organization 0.01567 Moderately Informative Inherited
Biological Process (BP) regulation of lipid metabolic process 0.000004079 Informative Direct
Biological Process (BP) cell cycle process 0.0001757 Informative Direct
Biological Process (BP) intracellular signal transduction 0.0006112 Informative Direct
Biological Process (BP) growth 0.00004268 Informative Direct
Biological Process (BP) positive regulation of developmental process 0.0003515 Informative Direct
Biological Process (BP) positive regulation of multicellular organismal process 0.001217 Informative Inherited
Biological Process (BP) regulation of system process 0.002005 Informative Inherited
Biological Process (BP) regulation of nervous system development 0.02437 Informative Inherited
Biological Process (BP) phosphorylation 0.00488 Informative Inherited
Biological Process (BP) regulation of growth 0.001518 Informative Inherited
Biological Process (BP) regulation of cell growth 0.0002767 Highly Informative Direct
Biological Process (BP) response to nutrient levels 0.0000001225 Highly Informative Direct
Biological Process (BP) positive regulation of nervous system development 0.0002935 Highly Informative Direct
Biological Process (BP) cellular response to external stimulus 0.0006151 Highly Informative Direct
Molecular Function (MF) transferase activity 0.0000002631 Least Informative Direct
Molecular Function (MF) transferase activity, transferring phosphorus-containing groups 0.00000000007219 Moderately Informative Direct
Molecular Function (MF) kinase activity 0.000000000007401 Informative Direct
Molecular Function (MF) phosphotransferase activity, alcohol group as acceptor 0.000000000001975 Informative Direct
Cellular Component (CC) protein complex 0.007038 Least Informative Inherited
Cellular Component (CC) membrane 0.2118 Least Informative Inherited
Cellular Component (CC) intracellular organelle part 0.1086 Least Informative Inherited
Cellular Component (CC) intracellular membrane-bounded organelle 0.001761 Least Informative Inherited
Cellular Component (CC) cytoplasmic part 0.08573 Least Informative Inherited
Cellular Component (CC) vacuole 0.000000003284 Moderately Informative Direct
Cellular Component (CC) organelle membrane 0.0008434 Moderately Informative Direct
Cellular Component (CC) whole membrane 0.00002069 Moderately Informative Direct
Cellular Component (CC) lytic vacuole 0.000000000001003 Informative Direct
Cellular Component (CC) vacuolar part 0.000001625 Informative Direct
Cellular Component (CC) lytic vacuole membrane 0.000000001206 Highly 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 phosphorus-containing groups0Least InformativeDirect
Enzyme Commission (EC)Protein-serine/threonine kinases0Moderately InformativeDirect
Enzyme Commission (EC)Non-specific serine/threonine protein kinase0InformativeDirect

Document: EC annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processCell cycle0.000000005248Moderately InformativeDirect
Cellular componentNucleus0.0003893Least InformativeDirect
DomainRepeat0Least InformativeDirect
DomainTPR repeat0.000000003669Highly InformativeDirect
Molecular functionNucleotide-binding0Least InformativeDirect
Molecular functionATP-binding0Moderately InformativeDirect
Post-translational modificationTransferase0Least InformativeDirect
Post-translational modificationKinase0Moderately InformativeDirect
Post-translational modificationSerine/threonine-protein kinase0.00000002282InformativeDirect
Post-translational modificationPhosphoprotein0.000005165Least 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 ]