ID FKBP6_HORSE Reviewed; 316 AA.
AC F6PHZ6;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 2.
DT 27-MAR-2024, entry version 60.
DE RecName: Full=Inactive peptidyl-prolyl cis-trans isomerase FKBP6;
DE Short=Inactive PPIase FKBP6;
DE AltName: Full=36 kDa FK506-binding protein;
DE AltName: Full=FK506-binding protein 6;
DE Short=FKBP-6;
DE AltName: Full=Immunophilin FKBP36;
GN Name=FKBP6; Synonyms=FKBP36;
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thoroughbred;
RX PubMed=19892987; DOI=10.1126/science.1178158;
RA Wade C.M., Giulotto E., Sigurdsson S., Zoli M., Gnerre S., Imsland F.,
RA Lear T.L., Adelson D.L., Bailey E., Bellone R.R., Bloecker H., Distl O.,
RA Edgar R.C., Garber M., Leeb T., Mauceli E., MacLeod J.N., Penedo M.C.T.,
RA Raison J.M., Sharpe T., Vogel J., Andersson L., Antczak D.F., Biagi T.,
RA Binns M.M., Chowdhary B.P., Coleman S.J., Della Valle G., Fryc S.,
RA Guerin G., Hasegawa T., Hill E.W., Jurka J., Kiialainen A., Lindgren G.,
RA Liu J., Magnani E., Mickelson J.R., Murray J., Nergadze S.G., Onofrio R.,
RA Pedroni S., Piras M.F., Raudsepp T., Rocchi M., Roeed K.H., Ryder O.A.,
RA Searle S., Skow L., Swinburne J.E., Syvaenen A.C., Tozaki T., Valberg S.J.,
RA Vaudin M., White J.R., Zody M.C., Lander E.S., Lindblad-Toh K.;
RT "Genome sequence, comparative analysis, and population genetics of the
RT domestic horse.";
RL Science 326:865-867(2009).
RN [2]
RP VARIANTS ASN-174 AND ARG-229, CHARACTERIZATION OF VARIANT ASN-174, AND
RP TISSUE SPECIFICITY.
RX PubMed=23284302; DOI=10.1371/journal.pgen.1003139;
RA Raudsepp T., McCue M.E., Das P.J., Dobson L., Vishnoi M., Fritz K.L.,
RA Schaefer R., Rendahl A.K., Derr J.N., Love C.C., Varner D.D.,
RA Chowdhary B.P.;
RT "Genome-wide association study implicates testis-sperm specific FKBP6 as a
RT susceptibility locus for impaired acrosome reaction in stallions.";
RL PLoS Genet. 8:E1003139-E1003139(2012).
CC -!- FUNCTION: Co-chaperone required during spermatogenesis to repress
CC transposable elements and prevent their mobilization, which is
CC essential for the germline integrity. Acts via the piRNA metabolic
CC process, which mediates the repression of transposable elements during
CC meiosis by forming complexes composed of piRNAs and Piwi proteins and
CC govern the methylation and subsequent repression of transposons. Acts
CC as a co-chaperone via its interaction with HSP90 and is required for
CC the piRNA amplification process, the secondary piRNA biogenesis. May be
CC required together with HSP90 in removal of 16 nucleotide ping-pong by-
CC products from Piwi complexes, possibly facilitating turnover of Piwi
CC complexes (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with HSP72/HSPA2 and CLTC. Interacts with GAPDH;
CC leading to inhibit GAPDH catalytic activity. Interacts (via TPR
CC repeats) with HSP90 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:O75344,
CC ECO:0000250|UniProtKB:Q91XW8}. Nucleus {ECO:0000250|UniProtKB:O75344,
CC ECO:0000250|UniProtKB:Q91XW8}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in testis and sperm.
CC {ECO:0000269|PubMed:23284302}.
CC -!- DISEASE: Note=Defects in FKBP6 may be a cause of stallion sterility due
CC to defects in acrosomal reaction. Disease susceptibility is associated
CC with variants affecting the gene represented in this entry
CC (PubMed:23284302). {ECO:0000269|PubMed:23284302}.
CC -!- SIMILARITY: Belongs to the FKBP6 family. {ECO:0000305}.
CC -!- CAUTION: Although it contains a PPIase FKBP-type domain, does not show
CC peptidyl-prolyl cis-trans isomerase activity. {ECO:0000305}.
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DR EMBL; AAWR02041948; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAWR02041947; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001296390.1; NM_001309461.1.
DR AlphaFoldDB; F6PHZ6; -.
DR SMR; F6PHZ6; -.
DR STRING; 9796.ENSECAP00000015572; -.
DR PaxDb; 9796-ENSECAP00000015572; -.
DR GeneID; 100061393; -.
DR KEGG; ecb:100061393; -.
DR CTD; 8468; -.
DR InParanoid; F6PHZ6; -.
DR OrthoDB; 7173at2759; -.
DR TreeFam; TF354214; -.
DR Proteomes; UP000002281; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0000795; C:synaptonemal complex; ISS:UniProtKB.
DR GO; GO:0051879; F:Hsp90 protein binding; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0051321; P:meiotic cell cycle; ISS:UniProtKB.
DR GO; GO:0034587; P:piRNA processing; ISS:UniProtKB.
DR GO; GO:0006457; P:protein folding; ISS:UniProtKB.
DR GO; GO:0031047; P:regulatory ncRNA-mediated gene silencing; ISS:UniProtKB.
DR GO; GO:0141007; P:siRNA-mediated retrotransposon silencing by heterochromatin formation; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR Gene3D; 3.10.50.40; -; 1.
DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1.
DR InterPro; IPR042282; FKBP6/shu.
DR InterPro; IPR046357; PPIase_dom_sf.
DR InterPro; IPR001179; PPIase_FKBP_dom.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR46674; INACTIVE PEPTIDYL-PROLYL CIS-TRANS ISOMERASE FKBP6; 1.
DR PANTHER; PTHR46674:SF1; INACTIVE PEPTIDYL-PROLYL CIS-TRANS ISOMERASE FKBP6; 1.
DR Pfam; PF00254; FKBP_C; 1.
DR SMART; SM00028; TPR; 3.
DR SUPFAM; SSF54534; FKBP-like; 1.
DR SUPFAM; SSF48452; TPR-like; 1.
DR PROSITE; PS50059; FKBP_PPIASE; 1.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Differentiation; Meiosis; Nucleus; Reference proteome; Repeat;
KW RNA-mediated gene silencing; Spermatogenesis; TPR repeat.
FT CHAIN 1..316
FT /note="Inactive peptidyl-prolyl cis-trans isomerase FKBP6"
FT /id="PRO_0000428727"
FT DOMAIN 43..132
FT /note="PPIase FKBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00277"
FT REPEAT 160..193
FT /note="TPR 1"
FT REPEAT 208..241
FT /note="TPR 2"
FT REPEAT 242..275
FT /note="TPR 3"
FT VARIANT 174
FT /note="H -> N (associated with the impaired acrosomal
FT reaction phenotype)"
FT /evidence="ECO:0000269|PubMed:23284302"
FT VARIANT 229
FT /note="C -> R"
FT /evidence="ECO:0000269|PubMed:23284302"
SQ SEQUENCE 316 AA; 35983 MW; FDD9DB2933A27685 CRC64;
MGGSAPGQSP YQRLSQRMLD ISGDRGVLKD VIREGAGELV TPDASVLVKY SGYLEHMDKP
FDSNCFRKTP RLMKLGEDIT LWGMELGLLS MRRGELARFL FKPTYAYGTL GCPPLIPPNT
TVLFEIELLD FLDSAESDKF CALSAEQQDQ FPLQKVLKVA ATEREFGNYL FRQHRFYDAK
VRYKRALLLL HRRSAPPEEQ HLVEAAKLLV LLNLSFTYLK LERPTTALCY GEQALVIDQK
NAKALFRCGQ ACLLMTEYQK ARDFLVQAQK AQPFNHDINN ELKKLASCYK DYTDKEKEMC
HRMFAPCDDD SAVGEN
//
