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Protein

Peptidyl-prolyl cis-trans isomerase FKBP1A

Gene

FKBP1A

Organism
Homo sapiens (Human)
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. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. 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.2 Publications

Catalytic activityi

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

Enzyme regulationi

Inhibited by both FK506 and rapamycin.

GO - Molecular functioni

  • activin binding Source: BHF-UCL
  • FK506 binding Source: BHF-UCL
  • ion channel binding Source: BHF-UCL
  • macrolide binding Source: BHF-UCL
  • peptidyl-prolyl cis-trans isomerase activity Source: BHF-UCL
  • signal transducer activity Source: UniProtKB
  • SMAD binding Source: BHF-UCL
  • transforming growth factor beta receptor binding Source: BHF-UCL
  • type I transforming growth factor beta receptor binding Source: BHF-UCL

GO - Biological processi

  • 'de novo' protein folding Source: BHF-UCL
  • amyloid fibril formation Source: BHF-UCL
  • calcium ion transmembrane transport Source: BHF-UCL
  • chaperone-mediated protein folding Source: GO_Central
  • extracellular fibril organization Source: BHF-UCL
  • heart morphogenesis Source: BHF-UCL
  • heart trabecula formation Source: BHF-UCL
  • negative regulation of protein phosphatase type 2B activity Source: BHF-UCL
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of protein binding Source: BHF-UCL
  • positive regulation of protein ubiquitination Source: BHF-UCL
  • protein folding Source: UniProtKB
  • protein maturation by protein folding Source: BHF-UCL
  • protein peptidyl-prolyl isomerization Source: BHF-UCL
  • protein refolding Source: BHF-UCL
  • regulation of activin receptor signaling pathway Source: BHF-UCL
  • regulation of amyloid precursor protein catabolic process Source: ParkinsonsUK-UCL
  • regulation of immune response Source: BHF-UCL
  • regulation of protein localization Source: ParkinsonsUK-UCL
  • regulation of ryanodine-sensitive calcium-release channel activity Source: BHF-UCL
  • SMAD protein complex assembly Source: BHF-UCL
  • T cell activation Source: BHF-UCL
  • transforming growth factor beta receptor signaling pathway Source: Reactome
  • ventricular cardiac muscle tissue morphogenesis Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Isomerase, Rotamase

Enzyme and pathway databases

BRENDAi5.2.1.8. 2681.
ReactomeiR-HSA-2173789. TGF-beta receptor signaling activates SMADs.
R-HSA-2173791. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
R-HSA-3645790. TGFBR2 Kinase Domain Mutants in Cancer.
R-HSA-3656532. TGFBR1 KD Mutants in Cancer.
R-HSA-3656535. TGFBR1 LBD Mutants in Cancer.
SignaLinkiP62942.
SIGNORiP62942.

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, FKBP12
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:3711. FKBP1A.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • cytosol Source: BHF-UCL
  • endoplasmic reticulum membrane Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • extracellular matrix Source: GOC
  • membrane Source: BHF-UCL
  • terminal cisterna Source: BHF-UCL
  • Z disc Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28153.

Chemistry

ChEMBLiCHEMBL2221341.
DrugBankiDB00337. Pimecrolimus.
DB00877. Sirolimus.
DB00864. Tacrolimus.
GuidetoPHARMACOLOGYi2609.

Polymorphism and mutation databases

BioMutaiFKBP1A.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved3 Publications
Chaini2 – 108107Peptidyl-prolyl cis-trans isomerase FKBP1APRO_0000075289Add
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

EPDiP62942.
MaxQBiP62942.
PaxDbiP62942.
PeptideAtlasiP62942.
PRIDEiP62942.
TopDownProteomicsiP62942.

PTM databases

iPTMnetiP62942.
PhosphoSiteiP62942.

Miscellaneous databases

PMAP-CutDBP62942.

Expressioni

Gene expression databases

BgeeiENSG00000088832.
CleanExiHS_FKBP1A.
ExpressionAtlasiP62942. baseline and differential.
GenevisibleiP62942. HS.

Organism-specific databases

HPAiCAB004639.
HPA051798.

Interactioni

Subunit structurei

Interacts directly with RYR1, RYR2 and RYR3. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (By similarity). Interacts with TGFBR1; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation. Interacts with ACVR1B and SMAD7.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ACVR1BP368962EBI-1027571,EBI-1384128
AHSPQ9NZD43EBI-1027571,EBI-720250
MTORP423452EBI-1027571,EBI-359260
RYR2Q927362EBI-1027571,EBI-1170425
SMAD7O151053EBI-1027571,EBI-3861591
TGFBR1P368972EBI-1027571,EBI-1027557

GO - Molecular functioni

  • activin binding Source: BHF-UCL
  • ion channel binding Source: BHF-UCL
  • SMAD binding Source: BHF-UCL
  • transforming growth factor beta receptor binding Source: BHF-UCL
  • type I transforming growth factor beta receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi108570. 60 interactions.
DIPiDIP-29710N.
IntActiP62942. 15 interactions.
MINTiMINT-87893.
STRINGi9606.ENSP00000371138.

Chemistry

BindingDBiP62942.

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 – 394Combined sources
Helixi40 – 434Combined sources
Beta strandi47 – 504Combined sources
Turni51 – 544Combined sources
Helixi58 – 647Combined 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
1A7XX-ray2.00A/B2-108[»]
1B6CX-ray2.60A/C/E/G2-108[»]
1BKFX-ray1.60A2-108[»]
1BL4X-ray1.90A/B2-108[»]
1D6OX-ray1.85A/B2-108[»]
1D7HX-ray1.90A/B2-108[»]
1D7IX-ray1.90A/B2-108[»]
1D7JX-ray1.85A/B2-108[»]
1EYMX-ray2.00A/B2-108[»]
1F40NMR-A2-108[»]
1FAPX-ray2.70A2-108[»]
1FKBX-ray1.70A2-108[»]
1FKDX-ray1.72A2-108[»]
1FKFX-ray1.70A2-108[»]
1FKGX-ray2.00A2-108[»]
1FKHX-ray1.95A2-108[»]
1FKIX-ray2.20A/B2-108[»]
1FKJX-ray1.70A2-108[»]
1FKRNMR-A2-108[»]
1FKSNMR-A2-108[»]
1FKTNMR-A2-108[»]
1J4HX-ray1.80A2-108[»]
1J4IX-ray1.80A2-108[»]
1J4RX-ray1.80A/B/D2-108[»]
1NSGX-ray2.20A2-108[»]
1QPFX-ray2.50A/D2-108[»]
1QPLX-ray2.90A/C2-108[»]
2DG3X-ray1.70A2-108[»]
2DG4X-ray1.70A2-108[»]
2DG9X-ray1.70A2-108[»]
2FAPX-ray2.20A2-108[»]
2FKEX-ray1.72A2-108[»]
2PPNX-ray0.92A2-108[»]
2PPOX-ray1.29A2-108[»]
2PPPX-ray0.94A2-108[»]
2RSENMR-A2-108[»]
3FAPX-ray1.85A2-108[»]
3H9RX-ray2.35B1-108[»]
3MDYX-ray2.05B/D1-108[»]
4DH0X-ray2.10A2-108[»]
4FAPX-ray2.80A2-108[»]
4IPXX-ray1.70A2-108[»]
4N19X-ray1.20A2-108[»]
4ODPX-ray1.75A85-97[»]
4ODQX-ray2.00A85-97[»]
4ODRX-ray1.93A/B85-97[»]
ProteinModelPortaliP62942.
SMRiP62942. Positions 2-108.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP62942.

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

eggNOGiKOG0544. Eukaryota.
COG0545. LUCA.
GeneTreeiENSGT00760000119159.
HOVERGENiHBG051623.
InParanoidiP62942.
KOiK09568.
OMAiCRSTPPV.
PhylomeDBiP62942.
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.

P62942-1 [UniParc]FASTAAdd to basket

« Hide

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

DVELLKLE
Length:108
Mass (Da):11,951
Last modified:January 23, 2007 - v2
Checksum:i9CC8493C802540B4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti60 – 601W → R in CAG28541 (Ref. 6) Curated
Sequence conflicti91 – 911I → V in CAG28541 (Ref. 6) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34539 mRNA. Translation: AAA35844.1.
M92423, M92422 Genomic DNA. Translation: AAA58476.1.
M93060 Genomic DNA. No translation available.
X55741 Genomic DNA. Translation: CAA39272.1.
M80199 Genomic DNA. Translation: AAA58472.1.
X52220 mRNA. Translation: CAA36462.1.
BT007066 mRNA. Translation: AAP35729.1.
CR407613 mRNA. Translation: CAG28541.1.
CR542168 mRNA. Translation: CAG46965.1.
AL136531, AL109658 Genomic DNA. Translation: CAH72382.1.
AL109658, AL136531 Genomic DNA. Translation: CAI22728.1.
CH471133 Genomic DNA. Translation: EAX10633.1.
CH471133 Genomic DNA. Translation: EAX10634.1.
CH471133 Genomic DNA. Translation: EAX10635.1.
BC001925 mRNA. Translation: AAH01925.3.
BC005147 mRNA. Translation: AAH05147.1.
CCDSiCCDS13014.1.
PIRiI65284. A35780.
RefSeqiNP_000792.1. NM_000801.4.
NP_463460.1. NM_054014.3.
UniGeneiHs.471933.
Hs.700839.

Genome annotation databases

EnsembliENST00000381719; ENSP00000371138; ENSG00000088832.
ENST00000400137; ENSP00000383003; ENSG00000088832.
GeneIDi2280.
KEGGihsa:2280.
UCSCiuc002wey.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34539 mRNA. Translation: AAA35844.1.
M92423, M92422 Genomic DNA. Translation: AAA58476.1.
M93060 Genomic DNA. No translation available.
X55741 Genomic DNA. Translation: CAA39272.1.
M80199 Genomic DNA. Translation: AAA58472.1.
X52220 mRNA. Translation: CAA36462.1.
BT007066 mRNA. Translation: AAP35729.1.
CR407613 mRNA. Translation: CAG28541.1.
CR542168 mRNA. Translation: CAG46965.1.
AL136531, AL109658 Genomic DNA. Translation: CAH72382.1.
AL109658, AL136531 Genomic DNA. Translation: CAI22728.1.
CH471133 Genomic DNA. Translation: EAX10633.1.
CH471133 Genomic DNA. Translation: EAX10634.1.
CH471133 Genomic DNA. Translation: EAX10635.1.
BC001925 mRNA. Translation: AAH01925.3.
BC005147 mRNA. Translation: AAH05147.1.
CCDSiCCDS13014.1.
PIRiI65284. A35780.
RefSeqiNP_000792.1. NM_000801.4.
NP_463460.1. NM_054014.3.
UniGeneiHs.471933.
Hs.700839.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1A7XX-ray2.00A/B2-108[»]
1B6CX-ray2.60A/C/E/G2-108[»]
1BKFX-ray1.60A2-108[»]
1BL4X-ray1.90A/B2-108[»]
1D6OX-ray1.85A/B2-108[»]
1D7HX-ray1.90A/B2-108[»]
1D7IX-ray1.90A/B2-108[»]
1D7JX-ray1.85A/B2-108[»]
1EYMX-ray2.00A/B2-108[»]
1F40NMR-A2-108[»]
1FAPX-ray2.70A2-108[»]
1FKBX-ray1.70A2-108[»]
1FKDX-ray1.72A2-108[»]
1FKFX-ray1.70A2-108[»]
1FKGX-ray2.00A2-108[»]
1FKHX-ray1.95A2-108[»]
1FKIX-ray2.20A/B2-108[»]
1FKJX-ray1.70A2-108[»]
1FKRNMR-A2-108[»]
1FKSNMR-A2-108[»]
1FKTNMR-A2-108[»]
1J4HX-ray1.80A2-108[»]
1J4IX-ray1.80A2-108[»]
1J4RX-ray1.80A/B/D2-108[»]
1NSGX-ray2.20A2-108[»]
1QPFX-ray2.50A/D2-108[»]
1QPLX-ray2.90A/C2-108[»]
2DG3X-ray1.70A2-108[»]
2DG4X-ray1.70A2-108[»]
2DG9X-ray1.70A2-108[»]
2FAPX-ray2.20A2-108[»]
2FKEX-ray1.72A2-108[»]
2PPNX-ray0.92A2-108[»]
2PPOX-ray1.29A2-108[»]
2PPPX-ray0.94A2-108[»]
2RSENMR-A2-108[»]
3FAPX-ray1.85A2-108[»]
3H9RX-ray2.35B1-108[»]
3MDYX-ray2.05B/D1-108[»]
4DH0X-ray2.10A2-108[»]
4FAPX-ray2.80A2-108[»]
4IPXX-ray1.70A2-108[»]
4N19X-ray1.20A2-108[»]
4ODPX-ray1.75A85-97[»]
4ODQX-ray2.00A85-97[»]
4ODRX-ray1.93A/B85-97[»]
ProteinModelPortaliP62942.
SMRiP62942. Positions 2-108.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108570. 60 interactions.
DIPiDIP-29710N.
IntActiP62942. 15 interactions.
MINTiMINT-87893.
STRINGi9606.ENSP00000371138.

Chemistry

BindingDBiP62942.
ChEMBLiCHEMBL2221341.
DrugBankiDB00337. Pimecrolimus.
DB00877. Sirolimus.
DB00864. Tacrolimus.
GuidetoPHARMACOLOGYi2609.

PTM databases

iPTMnetiP62942.
PhosphoSiteiP62942.

Polymorphism and mutation databases

BioMutaiFKBP1A.

Proteomic databases

EPDiP62942.
MaxQBiP62942.
PaxDbiP62942.
PeptideAtlasiP62942.
PRIDEiP62942.
TopDownProteomicsiP62942.

Protocols and materials databases

DNASUi2280.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000381719; ENSP00000371138; ENSG00000088832.
ENST00000400137; ENSP00000383003; ENSG00000088832.
GeneIDi2280.
KEGGihsa:2280.
UCSCiuc002wey.4. human.

Organism-specific databases

CTDi2280.
GeneCardsiFKBP1A.
HGNCiHGNC:3711. FKBP1A.
HPAiCAB004639.
HPA051798.
MIMi186945. gene.
neXtProtiNX_P62942.
PharmGKBiPA28153.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0544. Eukaryota.
COG0545. LUCA.
GeneTreeiENSGT00760000119159.
HOVERGENiHBG051623.
InParanoidiP62942.
KOiK09568.
OMAiCRSTPPV.
PhylomeDBiP62942.
TreeFamiTF105291.

Enzyme and pathway databases

BRENDAi5.2.1.8. 2681.
ReactomeiR-HSA-2173789. TGF-beta receptor signaling activates SMADs.
R-HSA-2173791. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
R-HSA-3645790. TGFBR2 Kinase Domain Mutants in Cancer.
R-HSA-3656532. TGFBR1 KD Mutants in Cancer.
R-HSA-3656535. TGFBR1 LBD Mutants in Cancer.
SignaLinkiP62942.
SIGNORiP62942.

Miscellaneous databases

EvolutionaryTraceiP62942.
GeneWikiiFKBP1A.
GenomeRNAii2280.
PMAP-CutDBP62942.
PROiP62942.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000088832.
CleanExiHS_FKBP1A.
ExpressionAtlasiP62942. baseline and differential.
GenevisibleiP62942. HS.

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...

Entry informationi

Entry nameiFKB1A_HUMAN
AccessioniPrimary (citable) accession number: P62942
Secondary accession number(s): D3DVW6
, P20071, Q4VC47, Q6FGD9, Q6LEU3, Q9H103, Q9H566
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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 one 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.