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Protein

Inactive peptidyl-prolyl cis-trans isomerase FKBP6

Gene

Fkbp6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Molecular functioni

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

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • DNA methylation involved in gamete generation Source: UniProtKB
  • gene silencing by RNA Source: UniProtKB
  • meiotic nuclear division Source: UniProtKB
  • peptidyl-proline modification Source: MGI
  • piRNA metabolic process Source: UniProtKB
  • protein folding Source: UniProtKB
  • protein peptidyl-prolyl isomerization Source: GOC
  • spermatogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Differentiation, Meiosis, RNA-mediated gene silencing, Spermatogenesis

Enzyme and pathway databases

ReactomeiR-MMU-1221633. Meiotic Synapsis.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:2137612. Fkbp6.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • membrane Source: MGI
  • nucleoplasm Source: Reactome
  • synaptonemal complex Source: UniProtKB
Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi254 – 2541K → A: Abolishes interaction with HSP90. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 327327Inactive peptidyl-prolyl cis-trans isomerase FKBP6PRO_0000075330Add
BLAST

Proteomic databases

PaxDbiQ91XW8.
PRIDEiQ91XW8.

PTM databases

iPTMnetiQ91XW8.
PhosphoSiteiQ91XW8.

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

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

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000043193.

Structurei

3D structure databases

ProteinModelPortaliQ91XW8.
SMRiQ91XW8. Positions 19-315.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini54 – 14390PPIase FKBP-typePROSITE-ProRule annotationAdd
BLAST
Repeati171 – 20434TPR 1Add
BLAST
Repeati219 – 25234TPR 2Add
BLAST
Repeati253 – 28634TPR 3Add
BLAST

Sequence similaritiesi

Belongs to the FKBP6 family.Curated
Contains 1 PPIase FKBP-type domain.PROSITE-ProRule annotation
Contains 3 TPR repeats.Curated

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0543. Eukaryota.
COG0545. LUCA.
GeneTreeiENSGT00760000119159.
HOGENOMiHOG000251594.
HOVERGENiHBG051625.
InParanoidiQ91XW8.
KOiK09572.
OMAiNRFCDAK.
OrthoDBiEOG7GTT49.
PhylomeDBiQ91XW8.

Family and domain databases

Gene3Di1.25.40.10. 1 hit.
InterProiIPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10516. PTHR10516. 1 hit.
PfamiPF00254. FKBP_C. 1 hit.
[Graphical view]
SMARTiSM00028. TPR. 3 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
PROSITEiPS50059. FKBP_PPIASE. 1 hit.
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: 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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti19 – 191Q → H in BAC41058 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1818MGGST…AGILG → MSVFSRLRNGIPPSRDDC in isoform 2 and isoform 3. 3 PublicationsVSP_005185Add
BLAST
Alternative sequencei157 – 19640Missing in isoform 2. 1 PublicationVSP_005186Add
BLAST

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_006504598.1. XM_006504535.2. [Q91XW8-3]
XP_011239214.1. XM_011240912.1. [Q91XW8-3]
XP_011239215.1. XM_011240913.1. [Q91XW8-3]
XP_011239216.1. XM_011240914.1. [Q91XW8-2]
XP_011239217.1. XM_011240915.1. [Q91XW8-2]
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

Cross-referencesi

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_006504598.1. XM_006504535.2. [Q91XW8-3]
XP_011239214.1. XM_011240912.1. [Q91XW8-3]
XP_011239215.1. XM_011240913.1. [Q91XW8-3]
XP_011239216.1. XM_011240914.1. [Q91XW8-2]
XP_011239217.1. XM_011240915.1. [Q91XW8-2]
UniGeneiMm.26037.

3D structure databases

ProteinModelPortaliQ91XW8.
SMRiQ91XW8. Positions 19-315.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000043193.

PTM databases

iPTMnetiQ91XW8.
PhosphoSiteiQ91XW8.

Proteomic databases

PaxDbiQ91XW8.
PRIDEiQ91XW8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi8468.
MGIiMGI:2137612. Fkbp6.

Phylogenomic databases

eggNOGiKOG0543. Eukaryota.
COG0545. LUCA.
GeneTreeiENSGT00760000119159.
HOGENOMiHOG000251594.
HOVERGENiHBG051625.
InParanoidiQ91XW8.
KOiK09572.
OMAiNRFCDAK.
OrthoDBiEOG7GTT49.
PhylomeDBiQ91XW8.

Enzyme and pathway databases

ReactomeiR-MMU-1221633. Meiotic Synapsis.

Miscellaneous databases

NextBioi352251.
PROiQ91XW8.
SOURCEiSearch...

Gene expression databases

CleanExiMM_FKBP6.
GenevisibleiQ91XW8. MM.

Family and domain databases

Gene3Di1.25.40.10. 1 hit.
InterProiIPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10516. PTHR10516. 1 hit.
PfamiPF00254. FKBP_C. 1 hit.
[Graphical view]
SMARTiSM00028. TPR. 3 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
PROSITEiPS50059. FKBP_PPIASE. 1 hit.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A murine homolog of the human FKBP6 gene, deleted in Williams-Beuren syndrome, is expressed in the embryonic structures involved in sensory cognition."
    Guimiot F., Mas C., Levacher B., Bourgeois F., Simonneau M.
    Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
    Tissue: Telencephalon and Testis.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Testis.
  6. Cited for: FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  7. "Affected homologous chromosome pairing and phosphorylation of testis specific histone, H2AX, in male meiosis under FKBP6 deficiency."
    Noguchi J., Ozawa M., Nakai M., Somfai T., Kikuchi K., Kaneko H., Kunieda T.
    J. Reprod. Dev. 54:203-207(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Testis.
  9. Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HSP90, DISRUPTION PHENOTYPE, MUTAGENESIS OF LYS-254.

Entry informationi

Entry nameiFKBP6_MOUSE
AccessioniPrimary (citable) accession number: Q91XW8
Secondary accession number(s): Q8C1Y1, Q91VB7, Q91Y30
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: December 1, 2001
Last modified: May 11, 2016
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.