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Protein

Peptidyl-prolyl cis-trans isomerase FKBP8

Gene

FKBP8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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

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

Keywordsi

Molecular functionIsomerase, Rotamase
Biological processApoptosis, Host-virus interaction
LigandCalcium, Metal-binding

Enzyme and pathway databases

BRENDAi5.2.1.8 2681
ReactomeiR-HSA-5689880 Ub-specific processing proteases
SABIO-RKiQ14318
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

EuPathDBiHostDB:ENSG00000105701.15
HGNCiHGNC:3724 FKBP8
MIMi604840 gene
neXtProtiNX_Q14318

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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 PRKN 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
ProteomicsDBi59962
59963 [Q14318-2]

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 Expressed in 211 organ(s), highest expression level in anterior cingulate cortex
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 ZFYVE27; may negatively regulate ZFYVE27 phosphorylation.Curated5 Publications
(Microbial infection) Interacts with hepatitis C/HCV protein NS5A.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi117270, 100 interactors
CORUMiQ14318
DIPiDIP-42200N
ELMiQ14318
IntActiQ14318, 92 interactors
MINTiQ14318
STRINGi9606.ENSP00000222308

Structurei

Secondary structure

1412
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Repeat, TPR repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0543 Eukaryota
COG0545 LUCA
GeneTreeiENSGT00760000119159
HOVERGENiHBG051626
InParanoidiQ14318
KOiK09574
OMAiAIYRYKY
OrthoDBiEOG091G0AS2
PhylomeDBiQ14318
TreeFamiTF105295

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR023566 PPIase_FKBP
IPR001179 PPIase_FKBP_dom
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR013105 TPR_2
IPR019734 TPR_repeat
PANTHERiPTHR10516 PTHR10516, 1 hit
PfamiView protein in Pfam
PF00254 FKBP_C, 1 hit
PF07719 TPR_2, 1 hit
SMARTiView protein in SMART
SM00028 TPR, 3 hits
SUPFAMiSSF48452 SSF48452, 1 hit
PROSITEiView protein in PROSITE
PS50059 FKBP_PPIASE, 1 hit
PS50005 TPR, 2 hits
PS50293 TPR_REGION, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MTJ1A0A0A0MTJ1_HUMAN
Peptidyl-prolyl cis-trans isomerase...
FKBP8
249Annotation score:
U3KQ64U3KQ64_HUMAN
Peptidyl-prolyl cis-trans isomerase...
FKBP8
182Annotation score:
M0R2K9M0R2K9_HUMAN
Peptidylprolyl isomerase
FKBP8
257Annotation score:
M0R1Q0M0R1Q0_HUMAN
Peptidylprolyl isomerase
FKBP8
163Annotation score:
M0R2Q6M0R2Q6_HUMAN
Peptidylprolyl isomerase
FKBP8
204Annotation score:
M0R1S6M0R1S6_HUMAN
Peptidylprolyl isomerase
FKBP8
167Annotation score:
U3KQI1U3KQI1_HUMAN
Peptidyl-prolyl cis-trans isomerase...
FKBP8
103Annotation score:
M0R304M0R304_HUMAN
Peptidyl-prolyl cis-trans isomerase...
FKBP8
116Annotation score:
V9GZ05V9GZ05_HUMAN
Peptidyl-prolyl cis-trans isomerase...
FKBP8
23Annotation score:

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 dbSNP:rs11574806Ensembl.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

Similar proteinsi

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[»]
5MGXX-ray2.18E/F/G/H91-380[»]
ProteinModelPortaliQ14318
SMRiQ14318
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117270, 100 interactors
CORUMiQ14318
DIPiDIP-42200N
ELMiQ14318
IntActiQ14318, 92 interactors
MINTiQ14318
STRINGi9606.ENSP00000222308

PTM databases

iPTMnetiQ14318
PhosphoSitePlusiQ14318
SwissPalmiQ14318

Polymorphism and mutation databases

BioMutaiFKBP8
DMDMi193806337

Proteomic databases

EPDiQ14318
MaxQBiQ14318
PaxDbiQ14318
PeptideAtlasiQ14318
PRIDEiQ14318
ProteomicsDBi59962
59963 [Q14318-2]

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
EuPathDBiHostDB:ENSG00000105701.15
GeneCardsiFKBP8
HGNCiHGNC:3724 FKBP8
HPAiCAB025346
HPA045177
MIMi604840 gene
neXtProtiNX_Q14318
OpenTargetsiENSG00000105701
PharmGKBiPA28165
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0543 Eukaryota
COG0545 LUCA
GeneTreeiENSGT00760000119159
HOVERGENiHBG051626
InParanoidiQ14318
KOiK09574
OMAiAIYRYKY
OrthoDBiEOG091G0AS2
PhylomeDBiQ14318
TreeFamiTF105295

Enzyme and pathway databases

BRENDAi5.2.1.8 2681
ReactomeiR-HSA-5689880 Ub-specific processing proteases
SABIO-RKiQ14318
SIGNORiQ14318

Miscellaneous databases

ChiTaRSiFKBP8 human
EvolutionaryTraceiQ14318
GeneWikiiFKBP8
GenomeRNAii23770
PROiPR:Q14318
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105701 Expressed in 211 organ(s), highest expression level in anterior cingulate cortex
CleanExiHS_FKBP8
ExpressionAtlasiQ14318 baseline and differential
GenevisibleiQ14318 HS

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR023566 PPIase_FKBP
IPR001179 PPIase_FKBP_dom
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR013105 TPR_2
IPR019734 TPR_repeat
PANTHERiPTHR10516 PTHR10516, 1 hit
PfamiView protein in Pfam
PF00254 FKBP_C, 1 hit
PF07719 TPR_2, 1 hit
SMARTiView protein in SMART
SM00028 TPR, 3 hits
SUPFAMiSSF48452 SSF48452, 1 hit
PROSITEiView protein in PROSITE
PS50059 FKBP_PPIASE, 1 hit
PS50005 TPR, 2 hits
PS50293 TPR_REGION, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFKBP8_HUMAN
AccessioniPrimary (citable) accession number: Q14318
Secondary accession number(s): C8C9T5
, Q53GU3, Q7Z349, Q86YK6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 1, 2008
Last modified: November 7, 2018
This is version 194 of the entry and version 2 of the sequence. See 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, Reference proteome

Documents

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