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Protein

Peptidyl-prolyl cis-trans isomerase FKBP8

Gene

FKBP8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Constitutively inactive PPiase, which becomes active when bound to calmodulin and calcium. Seems to act as a chaperone for BCL2, targets it to the mitochondria and modulates its phosphorylation state. The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the binding of BCL2 to its targets. The active form of FKBP8 may therefore play a role in the regulation of apoptosis.3 Publications

Catalytic activityi

Peptidylproline (omega=180) = peptidylproline (omega=0).1 Publication

Cofactori

Ca2+1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi149Calcium1
Metal bindingi151Calcium1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Isomerase, Rotamase

Keywords - Biological processi

Apoptosis, Host-virus interaction

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS02799-MONOMER.
BRENDAi5.2.1.8. 2681.
ReactomeiR-HSA-5689880. Ub-specific processing proteases.
SIGNORiQ14318.

Names & Taxonomyi

Protein namesi
Recommended name:
Peptidyl-prolyl cis-trans isomerase FKBP8 (EC:5.2.1.8)
Short name:
PPIase FKBP8
Alternative name(s):
38 kDa FK506-binding protein
Short name:
38 kDa FKBP
Short name:
FKBP-38
Short name:
hFKBP38
FK506-binding protein 8
Short name:
FKBP-8
FKBPR38
Rotamase
Gene namesi
Name:FKBP8
Synonyms:FKBP38
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:3724. FKBP8.

Subcellular locationi

Isoform 1 :
Isoform 3 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei390 – 410HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi149D → N: Abolishes calcium-binding and reduces affinity for BCL2; when associated with Asn-151. 1 Publication1
Mutagenesisi151D → N: Abolishes calcium-binding and reduces affinity for BCL2; when associated with Asn-149. 1 Publication1

Organism-specific databases

DisGeNETi23770.
OpenTargetsiENSG00000105701.
PharmGKBiPA28165.

Polymorphism and mutation databases

BioMutaiFKBP8.
DMDMi193806337.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000753311 – 412Peptidyl-prolyl cis-trans isomerase FKBP8Add BLAST412

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki249Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki271Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki273Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki284Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei296PhosphoserineCombined sources1
Cross-linki307Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki314Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki334Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki340Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki348Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki351Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki352Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Ubiquitinated by PARK2 during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ14318.
MaxQBiQ14318.
PaxDbiQ14318.
PeptideAtlasiQ14318.
PRIDEiQ14318.

PTM databases

iPTMnetiQ14318.
PhosphoSitePlusiQ14318.
SwissPalmiQ14318.

Expressioni

Tissue specificityi

Widely expressed. Highest levels seen in the brain. Highly abundant in the retina.1 Publication

Gene expression databases

BgeeiENSG00000105701.
CleanExiHS_FKBP8.
ExpressionAtlasiQ14318. baseline and differential.
GenevisibleiQ14318. HS.

Organism-specific databases

HPAiCAB025346.
HPA045177.

Interactioni

Subunit structurei

Homomultimers or heteromultimers (Potential). Forms heterodimer with calmodulin. When activated by calmodulin and calcium, interacts with the BH4 domain of BCL2 and weakly with BCL2L1/BCLX isoform Bcl-X(L). Does not bind and inhibit calcineurin. Interacts with HCV NS5A. Interacts with ZFYVE27; may negatively regulate ZFYVE27 phosphorylation.Curated6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-724839,EBI-724839
Q9WMX211EBI-724839,EBI-6863748From a different organism.
EGFRP005333EBI-724839,EBI-297353
EGLN1Q9GZT96EBI-724839,EBI-1174818
FKBP6O753442EBI-724839,EBI-744771
HSP90AA1P079007EBI-724839,EBI-296047
NS5AO3947416EBI-724839,EBI-7016711From a different organism.
ZFYVE27Q5T4F44EBI-724839,EBI-3892947

Protein-protein interaction databases

BioGridi117270. 93 interactors.
DIPiDIP-42200N.
IntActiQ14318. 53 interactors.
MINTiMINT-1338555.
STRINGi9606.ENSP00000222308.

Structurei

Secondary structure

1412
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi94 – 108Combined sources15
Beta strandi111 – 113Combined sources3
Beta strandi121 – 131Combined sources11
Beta strandi136 – 146Combined sources11
Turni147 – 150Combined sources4
Helixi154 – 157Combined sources4
Helixi160 – 162Combined sources3
Beta strandi168 – 173Combined sources6
Helixi175 – 177Combined sources3
Helixi180 – 182Combined sources3
Turni185 – 187Combined sources3
Beta strandi190 – 192Combined sources3
Beta strandi194 – 204Combined sources11
Beta strandi208 – 211Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AWGX-ray1.60A90-205[»]
2D9FNMR-A91-211[»]
2F2DNMR-A92-210[»]
2MF9NMR-A58-205[»]
3EY6X-ray1.05A92-210[»]
ProteinModelPortaliQ14318.
SMRiQ14318.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14318.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini120 – 204PPIase FKBP-typePROSITE-ProRule annotationAdd BLAST85
Repeati221 – 254TPR 1Add BLAST34
Repeati272 – 305TPR 2Add BLAST34
Repeati306 – 339TPR 3Add BLAST34

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi22 – 92Glu-richAdd BLAST71

Sequence similaritiesi

Contains 1 PPIase FKBP-type domain.PROSITE-ProRule annotation
Contains 3 TPR repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, TPR repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0543. Eukaryota.
COG0545. LUCA.
GeneTreeiENSGT00860000133851.
HOVERGENiHBG051626.
InParanoidiQ14318.
KOiK09574.
OMAiAMYKKML.
OrthoDBiEOG091G0AS2.
PhylomeDBiQ14318.
TreeFamiTF105295.

Family and domain databases

Gene3Di1.10.150.160. 1 hit.
1.25.40.10. 1 hit.
InterProiIPR023114. Elongated_TPR_rpt_dom.
IPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR013105. TPR_2.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10516. PTHR10516. 1 hit.
PfamiPF00254. FKBP_C. 1 hit.
PF07719. TPR_2. 1 hit.
[Graphical view]
SMARTiSM00028. TPR. 3 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
PROSITEiPS50059. FKBP_PPIASE. 1 hit.
PS50005. TPR. 2 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14318-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MASCAEPSEP SAPLPAGVPP LEDFEVLDGV EDAEGEEEEE EEEEEEDDLS
60 70 80 90 100
ELPPLEDMGQ PPAEEAEQPG ALAREFLAAM EPEPAPAPAP EEWLDILGNG
110 120 130 140 150
LLRKKTLVPG PPGSSRPVKG QVVTVHLQTS LENGTRVQEE PELVFTLGDC
160 170 180 190 200
DVIQALDLSV PLMDVGETAM VTADSKYCYG PQGRSPYIPP HAALCLEVTL
210 220 230 240 250
KTAVDGPDLE MLTGQERVAL ANRKRECGNA HYQRADFVLA ANSYDLAIKA
260 270 280 290 300
ITSSAKVDMT FEEEAQLLQL KVKCLNNLAA SQLKLDHYRA ALRSCSLVLE
310 320 330 340 350
HQPDNIKALF RKGKVLAQQG EYSEAIPILR AALKLEPSNK TIHAELSKLV
360 370 380 390 400
KKHAAQRSTE TALYRKMLGN PSRLPAKCPG KGAWSIPWKW LFGATAVALG
410
GVALSVVIAA RN
Length:412
Mass (Da):44,562
Last modified:July 1, 2008 - v2
Checksum:i887C25ADE71EBA8D
GO
Isoform 2 (identifier: Q14318-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     183-183: G → GS

Show »
Length:413
Mass (Da):44,649
Checksum:i0C32331CCBE5E4D9
GO
Isoform 3 (identifier: Q14318-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     98-256: Missing.

Note: Interacts with BCL2L1/BCLX.
Show »
Length:253
Mass (Da):27,545
Checksum:iF899112DC6BF5118
GO

Sequence cautioni

The sequence AAB00102 differs from that shown. The first part of the cDNA maps to the same locus, but in opposite orientation.Curated
The sequence AAH09966 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAD98028 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti144V → A in CAD98028 (PubMed:17974005).Curated1
Sequence conflicti191H → R in CAD98028 (PubMed:17974005).Curated1
Sequence conflicti206G → R in BAD96558 (Ref. 8) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04422587A → V.Corresponds to variant rs11574806dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04771798 – 256Missing in isoform 3. 1 PublicationAdd BLAST159
Alternative sequenceiVSP_034486183G → GS in isoform 2. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY225339 mRNA. Translation: AAO39020.1.
AY278607 mRNA. Translation: AAQ84561.1.
GQ372970 mRNA. Translation: ACU65096.1.
BX538124 mRNA. Translation: CAD98028.1. Different initiation.
BX647405 mRNA. No translation available.
AC005387 Genomic DNA. Translation: AAC28753.1.
CH471106 Genomic DNA. Translation: EAW84709.1.
L37033 mRNA. Translation: AAB00102.1. Sequence problems.
AK222838 mRNA. Translation: BAD96558.1.
BC009966 mRNA. Translation: AAH09966.1. Different initiation.
CCDSiCCDS32961.1. [Q14318-2]
CCDS77266.1. [Q14318-1]
RefSeqiNP_001295302.1. NM_001308373.1. [Q14318-1]
NP_036313.3. NM_012181.4. [Q14318-2]
XP_011526165.1. XM_011527863.1. [Q14318-2]
UniGeneiHs.173464.

Genome annotation databases

EnsembliENST00000222308; ENSP00000222308; ENSG00000105701. [Q14318-1]
ENST00000596558; ENSP00000472302; ENSG00000105701. [Q14318-1]
ENST00000597960; ENSP00000471700; ENSG00000105701. [Q14318-2]
ENST00000608443; ENSP00000476767; ENSG00000105701. [Q14318-2]
GeneIDi23770.
KEGGihsa:23770.
UCSCiuc002njj.2. human. [Q14318-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY225339 mRNA. Translation: AAO39020.1.
AY278607 mRNA. Translation: AAQ84561.1.
GQ372970 mRNA. Translation: ACU65096.1.
BX538124 mRNA. Translation: CAD98028.1. Different initiation.
BX647405 mRNA. No translation available.
AC005387 Genomic DNA. Translation: AAC28753.1.
CH471106 Genomic DNA. Translation: EAW84709.1.
L37033 mRNA. Translation: AAB00102.1. Sequence problems.
AK222838 mRNA. Translation: BAD96558.1.
BC009966 mRNA. Translation: AAH09966.1. Different initiation.
CCDSiCCDS32961.1. [Q14318-2]
CCDS77266.1. [Q14318-1]
RefSeqiNP_001295302.1. NM_001308373.1. [Q14318-1]
NP_036313.3. NM_012181.4. [Q14318-2]
XP_011526165.1. XM_011527863.1. [Q14318-2]
UniGeneiHs.173464.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AWGX-ray1.60A90-205[»]
2D9FNMR-A91-211[»]
2F2DNMR-A92-210[»]
2MF9NMR-A58-205[»]
3EY6X-ray1.05A92-210[»]
ProteinModelPortaliQ14318.
SMRiQ14318.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117270. 93 interactors.
DIPiDIP-42200N.
IntActiQ14318. 53 interactors.
MINTiMINT-1338555.
STRINGi9606.ENSP00000222308.

PTM databases

iPTMnetiQ14318.
PhosphoSitePlusiQ14318.
SwissPalmiQ14318.

Polymorphism and mutation databases

BioMutaiFKBP8.
DMDMi193806337.

Proteomic databases

EPDiQ14318.
MaxQBiQ14318.
PaxDbiQ14318.
PeptideAtlasiQ14318.
PRIDEiQ14318.

Protocols and materials databases

DNASUi23770.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000222308; ENSP00000222308; ENSG00000105701. [Q14318-1]
ENST00000596558; ENSP00000472302; ENSG00000105701. [Q14318-1]
ENST00000597960; ENSP00000471700; ENSG00000105701. [Q14318-2]
ENST00000608443; ENSP00000476767; ENSG00000105701. [Q14318-2]
GeneIDi23770.
KEGGihsa:23770.
UCSCiuc002njj.2. human. [Q14318-1]

Organism-specific databases

CTDi23770.
DisGeNETi23770.
GeneCardsiFKBP8.
HGNCiHGNC:3724. FKBP8.
HPAiCAB025346.
HPA045177.
MIMi604840. gene.
neXtProtiNX_Q14318.
OpenTargetsiENSG00000105701.
PharmGKBiPA28165.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0543. Eukaryota.
COG0545. LUCA.
GeneTreeiENSGT00860000133851.
HOVERGENiHBG051626.
InParanoidiQ14318.
KOiK09574.
OMAiAMYKKML.
OrthoDBiEOG091G0AS2.
PhylomeDBiQ14318.
TreeFamiTF105295.

Enzyme and pathway databases

BioCyciZFISH:HS02799-MONOMER.
BRENDAi5.2.1.8. 2681.
ReactomeiR-HSA-5689880. Ub-specific processing proteases.
SIGNORiQ14318.

Miscellaneous databases

ChiTaRSiFKBP8. human.
EvolutionaryTraceiQ14318.
GeneWikiiFKBP8.
GenomeRNAii23770.
PROiQ14318.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105701.
CleanExiHS_FKBP8.
ExpressionAtlasiQ14318. baseline and differential.
GenevisibleiQ14318. HS.

Family and domain databases

Gene3Di1.10.150.160. 1 hit.
1.25.40.10. 1 hit.
InterProiIPR023114. Elongated_TPR_rpt_dom.
IPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR013105. TPR_2.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10516. PTHR10516. 1 hit.
PfamiPF00254. FKBP_C. 1 hit.
PF07719. TPR_2. 1 hit.
[Graphical view]
SMARTiSM00028. TPR. 3 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
PROSITEiPS50059. FKBP_PPIASE. 1 hit.
PS50005. TPR. 2 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFKBP8_HUMAN
AccessioniPrimary (citable) accession number: Q14318
Secondary accession number(s): C8C9T5
, Q53GU3, Q7Z349, Q86YK6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 1, 2008
Last modified: November 30, 2016
This is version 174 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

Miscellaneous

Binds the immunosuppressant FK506 only in its calmodulin/calcium activated form.

Caution

It is uncertain whether Met-1 or Met-58 is the initiator.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.