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Protein

Inactive peptidyl-prolyl cis-trans isomerase FKBP6

Gene

Fkbp6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Co-chaperone required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Acts as a co-chaperone via its interaction with HSP90 and is required for the piRNA amplification process, the secondary piRNA biogenesis. May be required together with HSP90 in removal of 16 nucleotide ping-pong by-products from Piwi complexes, possibly facilitating turnover of Piwi complexes.3 Publications

Caution

Although it contains a PPIase FKBP-type domain, does not show peptidyl-prolyl cis-trans isomerase activity.1 Publication

GO - Molecular functioni

  • FK506 binding Source: MGI
  • Hsp90 protein binding Source: UniProtKB
  • identical protein binding Source: MGI
  • peptidyl-prolyl cis-trans isomerase activity Source: MGI

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • chaperone-mediated protein folding Source: GO_Central
  • DNA methylation involved in gamete generation Source: UniProtKB
  • gene silencing by RNA Source: UniProtKB
  • meiotic cell cycle Source: UniProtKB
  • peptidyl-proline modification Source: MGI
  • piRNA metabolic process Source: UniProtKB
  • positive regulation of viral genome replication Source: MGI
  • protein folding Source: UniProtKB
  • spermatogenesis Source: UniProtKB

Keywordsi

Biological processDifferentiation, Meiosis, RNA-mediated gene silencing, Spermatogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Inactive peptidyl-prolyl cis-trans isomerase FKBP6
Short name:
Inactive PPIase FKBP6
Alternative name(s):
36 kDa FK506-binding protein
Short name:
36 kDa FKBP
Short name:
FKBP-36
FK506-binding protein 6
Short name:
FKBP-6
Immunophilin FKBP36
Gene namesi
Name:Fkbp6
Synonyms:Fkbp36
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:2137612 Fkbp6

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

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Males mice are sterile and aspermic due to abnormal pachytene spermatocytes, characterized by the appearance of unusual inclusion bodies and dense compacted nuclei. Spermatocytes fail to proceed beyond the pachytene stage due to abnormal pairing and misalignments between homologous chromosomes, non-homologous partner switches and autosynapsis of X chromosome cores in meiotic spermatocytes. No other abnormalities are detected in any tissues of males. Females mice are fertile (PubMed:12764197). Spermatocytes show derepressed LINE-1 retrotransposon and reduced DNA methylation due to deficient nuclear accumulation of Miwi2 (PubMed:22902560).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi254K → A: Abolishes interaction with HSP90. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000753301 – 327Inactive peptidyl-prolyl cis-trans isomerase FKBP6Add BLAST327

Proteomic databases

PaxDbiQ91XW8
PRIDEiQ91XW8

PTM databases

iPTMnetiQ91XW8
PhosphoSitePlusiQ91XW8

Expressioni

Tissue specificityi

Testis-specific.1 Publication

Developmental stagei

Present in spermatocytes. Expression is lost as cells exit prophase I. Not detected in spermatids (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000040013
CleanExiMM_FKBP6
GenevisibleiQ91XW8 MM

Interactioni

Subunit structurei

Interacts with HSP72/HSPA2 and CLTC. Interacts with GAPDH; leading to inhibit GAPDH catalytic activity (By similarity). Interacts (via TPR repeats) with HSP90.By similarity1 Publication

GO - Molecular functioni

  • Hsp90 protein binding Source: UniProtKB
  • identical protein binding Source: MGI

Protein-protein interaction databases

BioGridi220490, 1 interactor
STRINGi10090.ENSMUSP00000043193

Structurei

3D structure databases

ProteinModelPortaliQ91XW8
SMRiQ91XW8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 143PPIase FKBP-typePROSITE-ProRule annotationAdd BLAST90
Repeati171 – 204TPR 1Add BLAST34
Repeati219 – 252TPR 2Add BLAST34
Repeati253 – 286TPR 3Add BLAST34

Sequence similaritiesi

Belongs to the FKBP6 family.Curated

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0543 Eukaryota
COG0545 LUCA
GeneTreeiENSGT00760000119159
HOGENOMiHOG000251594
HOVERGENiHBG051625
InParanoidiQ91XW8
KOiK09572
OMAiCPPRIKP
OrthoDBiEOG091G0FWD
PhylomeDBiQ91XW8

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
PS50293 TPR_REGION, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q91XW8-1) [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
MGGSTRDPGA LEGAGILGQS PYERLSQRML DISGDRGVLK DIIREGTGDT
60 70 80 90 100
VTPDASVLVK YSGYLEHMDK PFDSNCFRKT PRLMKLGEDI TLWGMELGLL
110 120 130 140 150
SMRKGELARF LFKPAYAYGT LGCPPLIPPN ATVLFEIELI DFLDSAESDK
160 170 180 190 200
FCALSAEQQE QFPLQKVLKV AATEREFGNY LFRQNRFCDA KVRYKRALLL
210 220 230 240 250
LHRRLATCEE QHLVEPAVLL VLLNLSFVYL KLDRPAMALR YGEQALLIDK
260 270 280 290 300
RNAKALFRCG QACLLLTEYE RARDFLVRAQ KEQPCNHDIN NELKKLSSHY
310 320
RDYVDREREM CHRMFAPCGS RSSVGGN
Length:327
Mass (Da):37,125
Last modified:December 1, 2001 - v1
Checksum:i9A2AE310DDC064CD
GO
Isoform 2 (identifier: Q91XW8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: MGGSTRDPGALEGAGILG → MSVFSRLRNGIPPSRDDC
     157-196: Missing.

Show »
Length:287
Mass (Da):32,599
Checksum:iD2F13117FF2DAF0A
GO
Isoform 3 (identifier: Q91XW8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: MGGSTRDPGALEGAGILG → MSVFSRLRNGIPPSRDDC

Show »
Length:327
Mass (Da):37,516
Checksum:i30B43484430A0187
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti19Q → H in BAC41058 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0051851 – 18MGGST…AGILG → MSVFSRLRNGIPPSRDDC in isoform 2 and isoform 3. 3 PublicationsAdd BLAST18
Alternative sequenceiVSP_005186157 – 196Missing in isoform 2. 1 PublicationAdd BLAST40

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY029192 mRNA Translation: AAK39645.1
AF367709 mRNA Translation: AAK53411.1
AF367710 mRNA Translation: AAK53412.1
AF367711 mRNA Translation: AAK53413.1
AK090036 mRNA Translation: BAC41058.1
AC074359 Genomic DNA No translation available.
CH466529 Genomic DNA Translation: EDL19373.1
CH466529 Genomic DNA Translation: EDL19374.1
BC139092 mRNA Translation: AAI39093.1
BC139097 mRNA Translation: AAI39098.1
CCDSiCCDS19738.1 [Q91XW8-3]
CCDS80425.1 [Q91XW8-1]
CCDS80426.1 [Q91XW8-2]
RefSeqiNP_001264820.1, NM_001277891.1 [Q91XW8-3]
NP_001264821.1, NM_001277892.1 [Q91XW8-1]
NP_001264822.1, NM_001277893.1 [Q91XW8-2]
NP_291049.1, NM_033571.3 [Q91XW8-3]
XP_011239215.1, XM_011240913.1 [Q91XW8-3]
XP_011239217.1, XM_011240915.1 [Q91XW8-2]
XP_017176679.1, XM_017321190.1 [Q91XW8-3]
UniGeneiMm.26037

Genome annotation databases

EnsembliENSMUST00000044972; ENSMUSP00000043193; ENSMUSG00000040013 [Q91XW8-3]
ENSMUST00000201534; ENSMUSP00000144471; ENSMUSG00000040013 [Q91XW8-3]
ENSMUST00000201784; ENSMUSP00000144381; ENSMUSG00000040013 [Q91XW8-1]
ENSMUST00000201791; ENSMUSP00000144460; ENSMUSG00000040013 [Q91XW8-2]
GeneIDi94244
KEGGimmu:94244
UCSCiuc008zyb.2 mouse [Q91XW8-3]
uc008zyc.2 mouse [Q91XW8-2]
uc008zyd.1 mouse [Q91XW8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiFKBP6_MOUSE
AccessioniPrimary (citable) accession number: Q91XW8
Secondary accession number(s): Q8C1Y1, Q91VB7, Q91Y30
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: December 1, 2001
Last modified: May 23, 2018
This is version 129 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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