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Protein

Peptidyl-prolyl cis-trans isomerase FKBP1A

Gene

FKBP1A

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.

Catalytic activityi

Peptidylproline (omega=180) = peptidylproline (omega=0).

Enzyme regulationi

Inhibited by both FK506 and rapamycin.

GO - Molecular functioni

  1. calcium channel inhibitor activity Source: GO_Central
  2. FK506 binding Source: GO_Central
  3. peptidyl-prolyl cis-trans isomerase activity Source: BHF-UCL

GO - Biological processi

  1. chaperone-mediated protein folding Source: GO_Central
  2. negative regulation of release of sequestered calcium ion into cytosol Source: GO_Central
  3. protein peptidyl-prolyl isomerization Source: GOC
  4. T cell activation Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Isomerase, Rotamase

Enzyme and pathway databases

ReactomeiREACT_285501. TGF-beta receptor signaling activates SMADs.
REACT_296870. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
REACT_312373. TGFBR1 LBD Mutants in Cancer.
REACT_334503. TGFBR1 KD Mutants in Cancer.
REACT_354623. TGFBR2 Kinase Domain Mutants in Cancer.

Names & Taxonomyi

Protein namesi
Recommended name:
Peptidyl-prolyl cis-trans isomerase FKBP1A (EC:5.2.1.8)
Short name:
PPIase FKBP1A
Alternative name(s):
12 kDa FK506-binding protein
Short name:
12 kDa FKBP
Short name:
FKBP-12
Calstabin-1
FK506-binding protein 1A
Short name:
FKBP-1A
Immunophilin FKBP12
Rotamase
Gene namesi
Name:FKBP1A
Synonyms:FKBP1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
ProteomesiUP000009136 Componenti: Chromosome 13

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: BHF-UCL
  2. endoplasmic reticulum membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed4 Publications
Chaini2 – 108107Peptidyl-prolyl cis-trans isomerase FKBP1APRO_0000075288Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei53 – 531N6-acetyllysine; alternateBy similarity
Modified residuei53 – 531N6-succinyllysine; alternateBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiP18203.
PRIDEiP18203.

Expressioni

Gene expression databases

ExpressionAtlasiP18203. baseline.

Interactioni

Subunit structurei

Interacts with TGFBR1; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation. Interacts with ACVR1B and SMAD7. Interacts directly with RYR1, RYR2 and RYR3. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (By similarity).By similarity

Structurei

Secondary structure

1
108
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi3 – 97Combined sources
Beta strandi22 – 3110Combined sources
Beta strandi36 – 405Combined sources
Turni41 – 444Combined sources
Beta strandi47 – 504Combined sources
Beta strandi53 – 564Combined sources
Helixi58 – 658Combined sources
Beta strandi72 – 776Combined sources
Helixi79 – 813Combined sources
Turni82 – 865Combined sources
Turni89 – 913Combined sources
Beta strandi98 – 10811Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1FKKX-ray2.20A2-108[»]
1FKLX-ray1.70A2-108[»]
1TCOX-ray2.50C2-108[»]
SMRiP18203. Positions 2-108.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP18203.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 10889PPIase FKBP-typePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 PPIase FKBP-type domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0545.
GeneTreeiENSGT00760000119159.
HOVERGENiHBG051623.
InParanoidiP18203.
KOiK09568.
OMAiYIPANAK.
OrthoDBiEOG7ZGX5T.
TreeFamiTF105291.

Family and domain databases

InterProiIPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
[Graphical view]
PANTHERiPTHR10516. PTHR10516. 1 hit.
PfamiPF00254. FKBP_C. 1 hit.
[Graphical view]
PROSITEiPS50059. FKBP_PPIASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P18203-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGVQVETISP GDGRTFPKRG QTCVVHYTGM LEDGKKFDSS RDRNKPFKFV
60 70 80 90 100
LGKQEVIRGW EEGVAQMSVG QRAKLTISPD YAYGATGHPG IIPPNATLIF

DVELLKLE
Length:108
Mass (Da):11,910
Last modified:January 23, 2007 - v2
Checksum:i9CD0F1278039C5B4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT021075 mRNA. Translation: AAX09092.1.
PIRiA61431.
RefSeqiNP_001030533.1. NM_001035456.1.
UniGeneiBt.63982.

Genome annotation databases

EnsembliENSBTAT00000010928; ENSBTAP00000010928; ENSBTAG00000008303.
GeneIDi614795.
KEGGibta:614795.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT021075 mRNA. Translation: AAX09092.1.
PIRiA61431.
RefSeqiNP_001030533.1. NM_001035456.1.
UniGeneiBt.63982.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1FKKX-ray2.20A2-108[»]
1FKLX-ray1.70A2-108[»]
1TCOX-ray2.50C2-108[»]
SMRiP18203. Positions 2-108.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

BindingDBiP18203.

Proteomic databases

PaxDbiP18203.
PRIDEiP18203.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000010928; ENSBTAP00000010928; ENSBTAG00000008303.
GeneIDi614795.
KEGGibta:614795.

Organism-specific databases

CTDi2280.

Phylogenomic databases

eggNOGiCOG0545.
GeneTreeiENSGT00760000119159.
HOVERGENiHBG051623.
InParanoidiP18203.
KOiK09568.
OMAiYIPANAK.
OrthoDBiEOG7ZGX5T.
TreeFamiTF105291.

Enzyme and pathway databases

ReactomeiREACT_285501. TGF-beta receptor signaling activates SMADs.
REACT_296870. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
REACT_312373. TGFBR1 LBD Mutants in Cancer.
REACT_334503. TGFBR1 KD Mutants in Cancer.
REACT_354623. TGFBR2 Kinase Domain Mutants in Cancer.

Miscellaneous databases

EvolutionaryTraceiP18203.
NextBioi20899293.

Gene expression databases

ExpressionAtlasiP18203. baseline.

Family and domain databases

InterProiIPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
[Graphical view]
PANTHERiPTHR10516. PTHR10516. 1 hit.
PfamiPF00254. FKBP_C. 1 hit.
[Graphical view]
PROSITEiPS50059. FKBP_PPIASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  2. Cited for: PROTEIN SEQUENCE OF 2-108.
    Tissue: Brain.
  3. "Complete amino acid sequence of the FK506 and rapamycin binding protein, FKBP, isolated from calf thymus."
    Lane W.S., Galat A., Harding M.W., Schreiber S.L.
    J. Protein Chem. 10:151-160(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-108.
    Tissue: Thymus.
  4. "The cytosolic-binding protein for the immunosuppressant FK-506 is both a ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase."
    Siekierka J.J., Widerrecht G., Greulich H., Boulton D., Hung S.H.Y., Cryan J., Hodges P.J., Sigal N.H.
    J. Biol. Chem. 265:21011-21015(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-87.
  5. "A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase."
    Harding M.W., Galat A., Uehling D.E., Schreiber S.L.
    Nature 341:758-760(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-41.
  6. "The peptidyl-prolyl isomerase, FK506-binding protein, is most likely the 12 kd endogenous inhibitor 2 of protein kinase C."
    Goebl M.G.
    Cell 64:1051-1052(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTITY OF FKBP AND PKCI-2.
  7. Cited for: IDENTITY OF FKBP AND PKCI-2.
  8. "The peptidyl-prolyl isomerase, FK506-binding protein, is not identical to protein kinase C inhibitor 2."
    Goebl M.
    Cell 66:423-423(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: SHOWS THAT THE PROTEIN IS NOT AN INHIBITOR OF PROTEIN KINASE C.
  9. "Retraction concerning amino acid sequence of a 12-kDa inhibitor of protein kinase C. Mistaken identity of a protein kinase C inhibitor."
    Walsh M.P.
    Eur. J. Biochem. 200:811-811(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: SHOWS THAT THE PROTEIN IS NOT AN INHIBITOR OF PROTEIN KINASE C.
  10. Cited for: SHOWS THAT THE PROTEIN IS NOT AN INHIBITOR OF PROTEIN KINASE C.
  11. "Solution structure of the major binding protein for the immunosuppressant FK506."
    Moore J.M., Peattie D.A., Fitzgibbon M.J., Thomson J.A.
    Nature 351:248-250(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.
  12. "X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex."
    Griffith J.P., Kim J.L., Kim E.E., Sintchak M.D., Thomson J.A., Fitzgibbon M.J., Fleming M.A., Caron P.R., Hsiao K., Navia M.A.
    Cell 82:507-522(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH CALCINEURIN B.

Entry informationi

Entry nameiFKB1A_BOVIN
AccessioniPrimary (citable) accession number: P18203
Secondary accession number(s): Q5E945
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: January 23, 2007
Last modified: April 1, 2015
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Was originally thought to be protein kinase C inhibitor 2 (PKCI-2 or 12 kDa inhibitor of protein kinase C), but has since been experimentally shown not to inhibit protein kinase C (PubMed:1868545 and PubMed:1710782).1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.