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Protein

Peptidyl-prolyl cis-trans isomerase FKBP8

Gene

Fkbp8

Organism
Mus musculus (Mouse)
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 (By similarity). Required for normal embryonic development.By similarity

Miscellaneous

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

Catalytic activityi

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

Cofactori

Ca2+By similarity

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • camera-type eye development Source: MGI
  • cell fate specification Source: MGI
  • chaperone-mediated protein folding Source: GO_Central
  • dorsal/ventral neural tube patterning Source: MGI
  • dorsal/ventral pattern formation Source: MGI
  • multicellular organism growth Source: MGI
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of protein phosphorylation Source: MGI
  • neural tube development Source: MGI
  • positive regulation of BMP signaling pathway Source: MGI
  • regulation of BMP signaling pathway Source: MGI
  • regulation of gene expression Source: MGI
  • smoothened signaling pathway Source: MGI

Keywordsi

Molecular functionIsomerase, Rotamase
Biological processApoptosis
LigandCalcium

Enzyme and pathway databases

ReactomeiR-MMU-5689880 Ub-specific processing proteases

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:
mFKBP38
FK506-binding protein 8
Short name:
FKBP-8
FKBPR38
Rotamase
Gene namesi
Name:Fkbp8
Synonyms:Fkbp38, Sam11
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1341070 Fkbp8

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
Transmembranei380 – 400HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Membrane, Mitochondrion

Pathology & Biotechi

Disruption phenotypei

Mice die shortly after birth. They display neural tube and skeletal defects. The neuroepithelium is disorganized and the formation of dorsal root ganglia is defective, likely as a result of an increased frequency of apoptosis and aberrant migration of neuronal cells. The extension of nerve fibers in the spinal cord is also abnormal.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000753321 – 402Peptidyl-prolyl cis-trans isomerase FKBP8Add BLAST402

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki239Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki261Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki263Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki274Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei286PhosphoserineBy similarity1
Cross-linki297Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki304Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki324Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki330Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki338Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki341Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki342Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

Post-translational modificationi

Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO35465
PaxDbiO35465
PeptideAtlasiO35465
PRIDEiO35465

PTM databases

iPTMnetiO35465
PhosphoSitePlusiO35465
SwissPalmiO35465

Expressioni

Tissue specificityi

Detected throughout the embryonic body, in caudal neural tube, limbs and head. Detected in adult retina, brain, heart, kidney, liver, pancreas, lung, testis and urinary bladder (at protein level). Detected in adult brain, kidney, liver, testis and trigeminal nerve, and in embryo. Detected at lower levels in lung, spleen, heart and ovary. Widely expressed in forebrain. Detected in the Purkinje cell layer in the cerebellum and in hippocampus neurons.3 Publications

Gene expression databases

BgeeiENSMUSG00000019428
CleanExiMM_FKBP8
ExpressionAtlasiO35465 baseline and differential
GenevisibleiO35465 MM

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 BCLX isoform Bcl-X(L). Does not bind and inhibit calcineurin (By similarity). Interacts with ZFYVE27; may negatively regulate ZFYVE27 phosphorylation (By similarity).By similarityCurated

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199689, 2 interactors
IntActiO35465, 1 interactor
STRINGi10090.ENSMUSP00000074935

Structurei

3D structure databases

ProteinModelPortaliO35465
SMRiO35465
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini110 – 194PPIase FKBP-typePROSITE-ProRule annotationAdd BLAST85
Repeati211 – 244TPR 1Add BLAST34
Repeati262 – 295TPR 2Add BLAST34
Repeati296 – 329TPR 3Add BLAST34

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi252 – 256Poly-Glu5

Keywords - Domaini

Repeat, TPR repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0543 Eukaryota
COG0545 LUCA
GeneTreeiENSGT00910000144255
HOVERGENiHBG051626
InParanoidiO35465
KOiK09574
OMAiAIYRYKY
OrthoDBiEOG091G0AS2
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
IPR019734 TPR_repeat
PANTHERiPTHR10516 PTHR10516, 1 hit
PfamiView protein in Pfam
PF00254 FKBP_C, 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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O35465-1) [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
MASWAEPSEP AALRLPGAPL LEGFEVLDGV DDAEEEDDLS GLPPLEDMGQ
60 70 80 90 100
PTVEEAEQPG ALAREFLAAT EPEPAPAPAP EEWLDILGNG LLRMKTLVPG
110 120 130 140 150
PKGSSRPLKG QVVTVHLQMS LENGTRVQEE PELAFTLGDC DVIQALDLSV
160 170 180 190 200
PLMDVGETAM VTADSKYCYG PQGRSPYIPP HAALCLEVTL KTAEDGPDLE
210 220 230 240 250
MLSGQERVAL ANRKRECGNA HYQRADFVLA ANSYDLAIKA ITSNTKVDMT
260 270 280 290 300
CEEEEELLQL KVKCLNNLAA SQLKLDHYRA ALRSCSQVLE HQPDNIKALF
310 320 330 340 350
RKGKVLAQQG EYSEAIPILR AALKLEPSNK TIHAELSKLV KKRAAQRSTE
360 370 380 390 400
TALYRKMLGN PSRLPAKCPG KGAWSIPWKW LFGATAVALG GVALSVVIAA

RN
Length:402
Mass (Da):43,529
Last modified:July 1, 2008 - v2
Checksum:i609A954FAD3A76F8
GO
Isoform 2 (identifier: O35465-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     173-173: G → GS

Show »
Length:403
Mass (Da):43,616
Checksum:i6273711EEB410AFA
GO

Sequence cautioni

The sequence AAB86422 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAH03739 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAH27808 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAO27795 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence BAC40541 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAE26916 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAE31027 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAE38118 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAE39713 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti100G → C in AAO39021 (PubMed:12510191).Curated1
Sequence conflicti100G → C in AAQ84562 (PubMed:15105374).Curated1
Sequence conflicti100G → C in AAH03739 (PubMed:15489334).Curated1
Sequence conflicti100G → C in AAB86422 (PubMed:10197430).Curated1
Sequence conflicti163A → T in BAE26916 (PubMed:16141072).Curated1
Sequence conflicti170G → A in BAC40541 (PubMed:16141072).Curated1
Sequence conflicti400A → G in AAO39021 (PubMed:12510191).Curated1
Sequence conflicti400A → G in AAQ84562 (PubMed:15105374).Curated1
Sequence conflicti400A → G in AAH03739 (PubMed:15489334).Curated1
Sequence conflicti400A → G in AAB86422 (PubMed:10197430).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_034487173G → GS in isoform 2. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY225340 mRNA Translation: AAO39021.1
AY278608 mRNA Translation: AAQ84562.1
AK088739 mRNA Translation: BAC40541.1 Different initiation.
AK146122 mRNA Translation: BAE26916.1 Different initiation.
AK152198 mRNA Translation: BAE31027.1 Different initiation.
AK165281 mRNA Translation: BAE38118.1 Different initiation.
AK167663 mRNA Translation: BAE39713.1 Different initiation.
BC003739 mRNA Translation: AAH03739.1 Different initiation.
BC027808 mRNA Translation: AAH27808.1 Different initiation.
AF030635 mRNA Translation: AAB86422.1 Different initiation.
AY187231 Genomic DNA Translation: AAO27795.1 Sequence problems.
CCDSiCCDS52575.1 [O35465-2]
CCDS52576.1 [O35465-1]
RefSeqiNP_001104536.1, NM_001111066.1 [O35465-2]
NP_001186560.1, NM_001199631.1 [O35465-2]
NP_034353.2, NM_010223.2 [O35465-1]
XP_006509619.1, XM_006509556.2 [O35465-2]
XP_017168056.1, XM_017312567.1 [O35465-1]
XP_017168057.1, XM_017312568.1 [O35465-1]
UniGeneiMm.141864

Genome annotation databases

EnsembliENSMUST00000075491; ENSMUSP00000074935; ENSMUSG00000019428 [O35465-2]
ENSMUST00000119353; ENSMUSP00000112527; ENSMUSG00000019428 [O35465-1]
ENSMUST00000119698; ENSMUSP00000114069; ENSMUSG00000019428 [O35465-2]
GeneIDi14232
KEGGimmu:14232
UCSCiuc009mao.2 mouse [O35465-2]
uc009map.2 mouse [O35465-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiFKBP8_MOUSE
AccessioniPrimary (citable) accession number: O35465
Secondary accession number(s): Q3UK86
, Q6GTX9, Q811M7, Q811R4, Q8C2F0, Q99L93
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: July 1, 2008
Last modified: May 23, 2018
This is version 164 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

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