SUPERFAMILY 1.75 HMM library and genome assignments server


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 (400) Uniprot 2013_05 PDB chains (SCOP 1.75)
Domains 566 497 3
Proteins 564 495 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 7.144e-06 Least Informative Direct
Biological Process (BP) cellular component organization or biogenesis 0.0002698 Least Informative Direct
Biological Process (BP) single-organism cellular process 0.006018 Least Informative Inherited
Biological Process (BP) regulation of cellular process 0.3628 Least Informative Inherited
Biological Process (BP) regulation of metabolic process 0.1154 Least Informative Inherited
Biological Process (BP) protein metabolic process 0.1221 Least Informative Inherited
Biological Process (BP) cellular macromolecule metabolic process 0.08978 Least Informative Inherited
Biological Process (BP) cellular protein modification process 3.063e-05 Moderately Informative Direct
Biological Process (BP) phosphate-containing compound metabolic process 2.262e-09 Moderately Informative Direct
Biological Process (BP) negative regulation of metabolic process 0.00013 Moderately Informative Direct
Biological Process (BP) signal transduction 0.01958 Moderately Informative Inherited
Biological Process (BP) positive regulation of metabolic process 0.01866 Moderately Informative Inherited
Biological Process (BP) negative regulation of cellular process 0.0368 Moderately Informative Inherited
Biological Process (BP) response to nutrient levels 7.439e-10 Informative Direct
Biological Process (BP) intracellular signal transduction 2.787e-09 Informative Direct
Biological Process (BP) phosphorylation 0.01625 Informative Inherited
Biological Process (BP) protein phosphorylation 0.0003534 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, transferring phosphorus-containing groups 3.351e-12 Moderately Informative Direct
Molecular Function (MF) kinase activity 5.405e-13 Informative Direct
Molecular Function (MF) phosphotransferase activity, alcohol group as acceptor 1.619e-13 Informative Direct
Cellular Component (CC) protein complex 1.004e-05 Least Informative Direct
Cellular Component (CC) intracellular organelle part 0.07654 Least Informative Inherited
Cellular Component (CC) intracellular membrane-bounded organelle 0.006296 Least Informative Inherited
Cellular Component (CC) cytoplasmic part 0.0455 Least Informative Inherited
Cellular Component (CC) membrane 0.07944 Least Informative Inherited
Cellular Component (CC) organelle membrane 0.0003416 Moderately Informative Direct
Cellular Component (CC) lytic vacuole 1.659e-11 Informative Direct
Cellular Component (CC) vacuolar part 8.437e-07 Informative Direct
Cellular Component (CC) vacuolar membrane 1.22e-08 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 kinases7.787e-08Moderately 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 kinases7.345e-08Moderately InformativeDirect
Enzyme Commission (EC)Non-specific serine/threonine protein kinase2.419e-16InformativeDirect

Document: EC annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processCell cycle5.689e-09Moderately InformativeDirect
Cellular componentNucleus0.0001874Least InformativeDirect
DomainRepeat0Least InformativeDirect
DomainTPR repeat3.443e-09Highly InformativeDirect
Molecular functionNucleotide-binding0Least InformativeDirect
Post-translational modificationTransferase0Least InformativeDirect
Post-translational modificationKinase0Moderately InformativeDirect
Post-translational modificationSerine/threonine-protein kinase1.49e-05InformativeDirect
Post-translational modificationPhosphoprotein0.0002282Least 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 ]