ID FKBP8_HUMAN Reviewed; 412 AA. AC Q14318; C8C9T5; Q53GU3; Q7Z349; Q86YK6; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-2008, sequence version 2. DT 28-JAN-2026, entry version 233. DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP8; DE Short=PPIase FKBP8; DE EC=5.2.1.8; DE AltName: Full=38 kDa FK506-binding protein; DE Short=38 kDa FKBP; DE Short=FKBP-38; DE Short=hFKBP38; DE AltName: Full=FK506-binding protein 8; DE Short=FKBP-8; DE AltName: Full=FKBPR38; DE AltName: Full=Rotamase; GN Name=FKBP8; Synonyms=FKBP38; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH BCL2 AND RP BCL2L1/BCLXL, AND SUBCELLULAR LOCATION. RX PubMed=12510191; DOI=10.1038/ncb894; RA Shirane M., Nakayama K.I.; RT "Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and RT inhibits apoptosis."; RL Nat. Cell Biol. 5:28-37(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=15105374; DOI=10.1242/dev.01122; RA Bulgakov O.V., Eggenschwiler J.T., Hong D.-H., Anderson K.V., Li T.; RT "FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural RT tissues."; RL Development 131:2149-2159(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION, INTERACTION RP WITH BCL2L1, AND TISSUE SPECIFICITY. RC TISSUE=Retinal pigment epithelium; RX PubMed=18385096; DOI=10.1167/iovs.07-1121; RA Chen Y., Sternberg P., Cai J.; RT "Characterization of a Bcl-XL-interacting protein FKBP8 and its splice RT variant in human RPE cells."; RL Invest. Ophthalmol. Vis. Sci. 49:1721-1727(2008). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Colon endothelium; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 35-412 (ISOFORM 1). RX PubMed=7543869; DOI=10.1016/0378-1119(95)00216-s; RA Lam E., Martin M., Wiederrecht G.; RT "Isolation of a cDNA encoding a novel human FK506-binding protein homolog RT containing leucine zipper and tetratricopeptide repeat motifs."; RL Gene 160:297-302(1995). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 42-412 (ISOFORM 2). RC TISSUE=Liver; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 54-412 (ISOFORM 1). RC TISSUE=Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=16176796; DOI=10.1016/j.bbrc.2005.09.023; RA Kang C.B., Feng L., Chia J., Yoon H.S.; RT "Molecular characterization of FK-506 binding protein 38 and its potential RT regulatory role on the anti-apoptotic protein Bcl-2."; RL Biochem. Biophys. Res. Commun. 337:30-38(2005). RN [11] RP CATALYTIC ACTIVITY, AND COFACTOR. RX PubMed=15990872; DOI=10.1038/sj.emboj.7600739; RA Edlich F., Weiwad M., Erdmann F., Fanghaenel J., Jarczowski F., RA Rahfeld J.-U., Fischer G.; RT "Bcl-2 regulator FKBP38 is activated by Ca2+/calmodulin."; RL EMBO J. 24:2688-2699(2005). RN [12] RP FUNCTION, AND ABSENCE OF DIRECT INTERACTION WITH CALCINEURIN. RX PubMed=15757646; DOI=10.1016/j.febslet.2004.12.098; RA Weiwad M., Edlich F., Erdmann F., Jarczowski F., Kilka S., Dorn M., RA Pechstein A., Fischer G.; RT "A reassessment of the inhibitory capacity of human FKBP38 on RT calcineurin."; RL FEBS Lett. 579:1591-1596(2005). RN [13] RP INTERACTION WITH BCL2. RX PubMed=15733859; DOI=10.1016/j.febslet.2005.01.053; RA Kang C.B., Tai J., Chia J., Yoon H.S.; RT "The flexible loop of Bcl-2 is required for molecular interaction with RT immunosuppressant FK-506 binding protein 38 (FKBP38)."; RL FEBS Lett. 579:1469-1476(2005). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [15] RP INTERACTION WITH BCL2. RX PubMed=17090549; DOI=10.1074/jbc.m606181200; RA Portier B.P., Taglialatela G.; RT "Bcl-2 localized at the nuclear compartment induces apoptosis after RT transient overexpression."; RL J. Biol. Chem. 281:40493-40502(2006). RN [16] RP INTERACTION WITH HCV NS5A (MICROBIAL INFECTION). RX PubMed=16844119; DOI=10.1016/j.febslet.2006.07.002; RA Wang J., Tong W., Zhang X., Chen L., Yi Z., Pan T., Hu Y., Xiang L., RA Yuan Z.; RT "Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and RT inhibits apoptosis in Huh7 hepatoma cells."; RL FEBS Lett. 580:4392-4400(2006). RN [17] RP INTERACTION WITH ZFYVE27. RX PubMed=18459960; DOI=10.1111/j.1365-2443.2008.01194.x; RA Shirane M., Ogawa M., Motoyama J., Nakayama K.I.; RT "Regulation of apoptosis and neurite extension by FKBP38 is required for RT neural tube formation in the mouse."; RL Genes Cells 13:635-651(2008). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-296, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [20] RP UBIQUITINATION AT LYS-249; LYS-271; LYS-273; LYS-284; LYS-307; LYS-314; RP LYS-334; LYS-340; LYS-348; LYS-351 AND LYS-352. RX PubMed=25621951; DOI=10.1038/ncb3097; RA Cunningham C.N., Baughman J.M., Phu L., Tea J.S., Yu C., Coons M., RA Kirkpatrick D.S., Bingol B., Corn J.E.; RT "USP30 and parkin homeostatically regulate atypical ubiquitin chains on RT mitochondria."; RL Nat. Cell Biol. 17:160-169(2015). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [22] RP FUNCTION. RX PubMed=28169297; DOI=10.1038/ncomms13876; RA Wang L., Fu B., Li W., Patil G., Liu L., Dorf M.E., Li S.; RT "Comparative influenza protein interactomes identify the role of RT plakophilin 2 in virus restriction."; RL Nat. Commun. 8:13876-13876(2017). RN [23] RP STRUCTURE BY NMR OF 92-210. RX PubMed=16604427; DOI=10.1007/s10858-006-0018-6; RA Maestre-Martinez M., Edlich F., Jarczowski F., Weiwad M., Fischer G., RA Luecke C.; RT "Solution structure of the FK506-binding domain of human FKBP38."; RL J. Biomol. NMR 34:197-202(2006). RN [24] RP STRUCTURE BY NMR OF 91-205. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of RSGI RUH-047, an FKBP domain from human cDNA."; RL Submitted (JUN-2006) to the PDB data bank. RN [25] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 90-205. RG Structural genomics consortium (SGC); RT "Structure of the human FK-506 binding protein 8."; RL Submitted (OCT-2006) to the PDB data bank. RN [26] RP X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) OF 92-210, METAL-BINDING SITES, AND RP MUTAGENESIS OF ASP-149 AND ASP-151. RX PubMed=20140889; DOI=10.1002/jmr.1020; RA Maestre-Martinez M., Haupt K., Edlich F., Neumann P., Parthier C., RA Stubbs M.T., Fischer G., Lucke C.; RT "A charge-sensitive loop in the FKBP38 catalytic domain modulates Bcl-2 RT binding."; RL J. Mol. Recognit. 24:23-34(2011). CC -!- FUNCTION: Constitutively inactive PPiase, which becomes active when CC bound to calmodulin and calcium. Seems to act as a chaperone for BCL2, CC targets it to the mitochondria and modulates its phosphorylation state. CC The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the CC binding of BCL2 to its targets. The active form of FKBP8 may therefore CC play a role in the regulation of apoptosis. Involved in the inhibition CC of viral infection by influenza A viruses (IAV) (PubMed:28169297). CC {ECO:0000269|PubMed:12510191, ECO:0000269|PubMed:15757646, CC ECO:0000269|PubMed:16176796, ECO:0000269|PubMed:28169297}. CC -!- CATALYTIC ACTIVITY: CC Reaction=[protein]-peptidylproline (omega=180) = [protein]- CC peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA- CC COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833, CC ChEBI:CHEBI:83834; EC=5.2.1.8; CC Evidence={ECO:0000269|PubMed:15990872}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:15990872}; CC -!- SUBUNIT: Homomultimers or heteromultimers (Potential). Forms CC heterodimer with calmodulin. When activated by calmodulin and calcium, CC interacts with the BH4 domain of BCL2 and weakly with BCL2L1/BCLX CC isoform Bcl-X(L). Does not bind and inhibit calcineurin. Interacts with CC ZFYVE27; may negatively regulate ZFYVE27 phosphorylation. CC {ECO:0000269|PubMed:12510191, ECO:0000269|PubMed:15733859, CC ECO:0000269|PubMed:17090549, ECO:0000269|PubMed:18385096, CC ECO:0000269|PubMed:18459960, ECO:0000305}. CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis C/HCV protein CC NS5A. {ECO:0000269|PubMed:16844119}. CC -!- INTERACTION: CC Q14318; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-724839, EBI-11343438; CC Q14318; P10415: BCL2; NbExp=4; IntAct=EBI-724839, EBI-77694; CC Q14318; P62158: CALM3; NbExp=2; IntAct=EBI-724839, EBI-397435; CC Q14318; P11912: CD79A; NbExp=3; IntAct=EBI-724839, EBI-7797864; CC Q14318; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-724839, EBI-7062247; CC Q14318; P25025: CXCR2; NbExp=3; IntAct=EBI-724839, EBI-2835281; CC Q14318; P49447: CYB561; NbExp=3; IntAct=EBI-724839, EBI-8646596; CC Q14318; Q53TN4: CYBRD1; NbExp=3; IntAct=EBI-724839, EBI-8637742; CC Q14318; Q15125: EBP; NbExp=3; IntAct=EBI-724839, EBI-3915253; CC Q14318; P00533: EGFR; NbExp=4; IntAct=EBI-724839, EBI-297353; CC Q14318; Q9GZT9: EGLN1; NbExp=6; IntAct=EBI-724839, EBI-1174818; CC Q14318; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-724839, EBI-18535450; CC Q14318; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-724839, EBI-781551; CC Q14318; Q8TBP5: FAM174A; NbExp=3; IntAct=EBI-724839, EBI-18636064; CC Q14318; Q92915-2: FGF14; NbExp=3; IntAct=EBI-724839, EBI-12836320; CC Q14318; O75344: FKBP6; NbExp=2; IntAct=EBI-724839, EBI-744771; CC Q14318; Q14318: FKBP8; NbExp=3; IntAct=EBI-724839, EBI-724839; CC Q14318; P07900: HSP90AA1; NbExp=8; IntAct=EBI-724839, EBI-296047; CC Q14318; P08238: HSP90AB1; NbExp=2; IntAct=EBI-724839, EBI-352572; CC Q14318; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-724839, EBI-10266796; CC Q14318; Q5SR56: MFSD14B; NbExp=3; IntAct=EBI-724839, EBI-373355; CC Q14318; O00623: PEX12; NbExp=3; IntAct=EBI-724839, EBI-594836; CC Q14318; P26678: PLN; NbExp=3; IntAct=EBI-724839, EBI-692836; CC Q14318; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-724839, EBI-10192441; CC Q14318; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-724839, EBI-17589229; CC Q14318; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-724839, EBI-17247926; CC Q14318; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-724839, EBI-18159983; CC Q14318; Q9BS91: SLC35A5; NbExp=3; IntAct=EBI-724839, EBI-18915901; CC Q14318; P78383: SLC35B1; NbExp=3; IntAct=EBI-724839, EBI-12147661; CC Q14318; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-724839, EBI-8638294; CC Q14318; Q8TBM7: TMEM254; NbExp=3; IntAct=EBI-724839, EBI-11956809; CC Q14318; Q9BTV4: TMEM43; NbExp=3; IntAct=EBI-724839, EBI-721293; CC Q14318; Q96B21: TMEM45B; NbExp=3; IntAct=EBI-724839, EBI-3923061; CC Q14318; Q96HE8: TMEM80; NbExp=3; IntAct=EBI-724839, EBI-11742770; CC Q14318; Q9H3N1: TMX1; NbExp=3; IntAct=EBI-724839, EBI-1051115; CC Q14318; O95159: ZFPL1; NbExp=3; IntAct=EBI-724839, EBI-718439; CC Q14318; Q5T4F4: ZFYVE27; NbExp=4; IntAct=EBI-724839, EBI-3892947; CC Q14318; O39474: NS5A; Xeno; NbExp=16; IntAct=EBI-724839, EBI-7016711; CC Q14318; C5E526: PB1; Xeno; NbExp=5; IntAct=EBI-724839, EBI-12577179; CC Q14318; P03431: PB1; Xeno; NbExp=5; IntAct=EBI-724839, EBI-2547514; CC Q14318; Q1K9H5: PB1; Xeno; NbExp=5; IntAct=EBI-724839, EBI-6050669; CC Q14318; Q5EP37: PB1; Xeno; NbExp=3; IntAct=EBI-724839, EBI-12577201; CC Q14318; PRO_0000037551 [Q9WMX2]; Xeno; NbExp=11; IntAct=EBI-724839, EBI-6863748; CC Q14318-2; Q15746-1: MYLK; NbExp=5; IntAct=EBI-10968017, EBI-55022150; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16176796}. CC Mitochondrion membrane {ECO:0000305}; Single-pass membrane protein; CC Cytoplasmic side {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion membrane CC {ECO:0000269|PubMed:12510191, ECO:0000269|PubMed:18385096}; Single-pass CC membrane protein; Cytoplasmic side {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Mitochondrion membrane CC {ECO:0000269|PubMed:18385096}; Single-pass membrane protein; CC Cytoplasmic side {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q14318-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14318-2; Sequence=VSP_034486; CC Name=3; CC IsoId=Q14318-3; Sequence=VSP_047717; CC -!- TISSUE SPECIFICITY: Widely expressed. Highest levels seen in the brain. CC Highly abundant in the retina. {ECO:0000269|PubMed:18385096}. CC -!- PTM: Ubiquitinated by PRKN during mitophagy, leading to its degradation CC and enhancement of mitophagy. Deubiquitinated by USP30. CC {ECO:0000269|PubMed:25621951}. CC -!- MISCELLANEOUS: Binds the immunosuppressant FK506 only in its CC calmodulin/calcium activated form. CC -!- MISCELLANEOUS: [Isoform 3]: Interacts with BCL2L1/BCLX. {ECO:0000305}. CC -!- CAUTION: It is uncertain whether Met-1 or Met-58 is the initiator. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB00102.1; Type=Miscellaneous discrepancy; Note=The first part of the cDNA maps to the same locus, but in opposite orientation.; Evidence={ECO:0000305}; CC Sequence=AAH09966.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAD98028.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40579/FKBP8"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY225339; AAO39020.1; -; mRNA. DR EMBL; AY278607; AAQ84561.1; -; mRNA. DR EMBL; GQ372970; ACU65096.1; -; mRNA. DR EMBL; BX538124; CAD98028.1; ALT_INIT; mRNA. DR EMBL; BX647405; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AC005387; AAC28753.1; -; Genomic_DNA. DR EMBL; CH471106; EAW84709.1; -; Genomic_DNA. DR EMBL; L37033; AAB00102.1; ALT_SEQ; mRNA. DR EMBL; AK222838; BAD96558.1; -; mRNA. DR EMBL; BC009966; AAH09966.1; ALT_INIT; mRNA. DR CCDS; CCDS32961.1; -. [Q14318-2] DR CCDS; CCDS77266.1; -. [Q14318-1] DR RefSeq; NP_001295302.1; NM_001308373.2. [Q14318-1] DR RefSeq; NP_036313.3; NM_012181.4. [Q14318-2] DR PDB; 2AWG; X-ray; 1.60 A; A=90-205. DR PDB; 2D9F; NMR; -; A=91-211. DR PDB; 2F2D; NMR; -; A=92-210. DR PDB; 2MF9; NMR; -; A=58-205. DR PDB; 3EY6; X-ray; 1.05 A; A=92-210. DR PDB; 5MGX; X-ray; 2.18 A; E/F/G/H=91-380. DR PDBsum; 2AWG; -. DR PDBsum; 2D9F; -. DR PDBsum; 2F2D; -. DR PDBsum; 2MF9; -. DR PDBsum; 3EY6; -. DR PDBsum; 5MGX; -. DR AlphaFoldDB; Q14318; -. DR BMRB; Q14318; -. DR SMR; Q14318; -. DR BioGRID; 117270; 624. DR CORUM; Q14318; -. DR DIP; DIP-42200N; -. DR ELM; Q14318; -. DR FunCoup; Q14318; 1373. DR IntAct; Q14318; 226. DR MINT; Q14318; -. DR STRING; 9606.ENSP00000471700; -. DR GuidetoPHARMACOLOGY; 3177; -. DR TCDB; 8.A.11.1.4; the immunophilin-like prolyl:peptidyl isomerase regulator (i-ppi) family. DR GlyGen; Q14318; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q14318; -. DR MetOSite; Q14318; -. DR PhosphoSitePlus; Q14318; -. DR SwissPalm; Q14318; -. DR BioMuta; FKBP8; -. DR DMDM; 193806337; -. DR jPOST; Q14318; -. DR MassIVE; Q14318; -. DR PaxDb; 9606-ENSP00000476767; -. DR PeptideAtlas; Q14318; -. DR ProteomicsDB; 59962; -. [Q14318-1] DR ProteomicsDB; 59963; -. [Q14318-2] DR ProteomicsDB; 7612; -. DR Pumba; Q14318; -. DR Antibodypedia; 28073; 402 antibodies from 35 providers. DR DNASU; 23770; -. DR Ensembl; ENST00000222308.8; ENSP00000222308.4; ENSG00000105701.17. [Q14318-1] DR Ensembl; ENST00000596558.6; ENSP00000472302.1; ENSG00000105701.17. [Q14318-1] DR Ensembl; ENST00000597960.7; ENSP00000471700.1; ENSG00000105701.17. [Q14318-2] DR Ensembl; ENST00000608443.6; ENSP00000476767.1; ENSG00000105701.17. [Q14318-2] DR GeneID; 23770; -. DR KEGG; hsa:23770; -. DR MANE-Select; ENST00000608443.6; ENSP00000476767.1; NM_012181.5; NP_036313.3. [Q14318-2] DR UCSC; uc002njj.2; human. [Q14318-1] DR AGR; HGNC:3724; -. DR ClinPGx; PA28165; -. DR CTD; 23770; -. DR DisGeNET; 23770; -. DR GeneCards; FKBP8; -. DR HGNC; HGNC:3724; FKBP8. DR HPA; ENSG00000105701; Low tissue specificity. DR MIM; 604840; gene. DR OpenTargets; ENSG00000105701; -. DR VEuPathDB; HostDB:ENSG00000105701; -. DR eggNOG; KOG0543; Eukaryota. DR GeneTree; ENSGT00940000156705; -. DR HOGENOM; CLU_013615_1_3_1; -. DR InParanoid; Q14318; -. DR OMA; IDAWEMV; -. DR OrthoDB; 532682at2759; -. DR PAN-GO; Q14318; 7 GO annotations based on evolutionary models. DR PhylomeDB; Q14318; -. DR BRENDA; 5.2.1.8; 2681. DR PathwayCommons; Q14318; -. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR SABIO-RK; Q14318; -. DR SignaLink; Q14318; -. DR SIGNOR; Q14318; -. DR Agora; ENSG00000105701; -. DR BioGRID-ORCS; 23770; 28 hits in 1155 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; FKBP8; human. DR EvolutionaryTrace; Q14318; -. DR GeneWiki; FKBP8; -. DR GenomeRNAi; 23770; -. DR Pharos; Q14318; Tbio. DR PRO; PR:Q14318; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q14318; protein. DR Bgee; ENSG00000105701; Expressed in right frontal lobe and 176 other cell types or tissues. DR ExpressionAtlas; Q14318; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:Ensembl. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005740; C:mitochondrial envelope; IBA:GO_Central. DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0032991; C:protein-containing complex; IMP:CAFA. DR GO; GO:0005516; F:calmodulin binding; IPI:DisProt. DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IEA:UniProtKB-KW. DR GO; GO:0044183; F:protein folding chaperone; IMP:MGI. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl. DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl. DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; IEA:Ensembl. DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:CAFA. DR GO; GO:0048665; P:neuron fate specification; IEA:Ensembl. DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IEA:Ensembl. DR GO; GO:0006457; P:protein folding; IMP:MGI. DR GO; GO:0070585; P:protein localization to mitochondrion; IPI:DisProt. DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl. DR GO; GO:1901524; P:regulation of mitophagy; IDA:DisProt. DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl. DR DisProt; DP03659; -. DR FunFam; 1.25.40.10:FF:000113; Peptidylprolyl isomerase; 1. DR FunFam; 3.10.50.40:FF:000027; Peptidylprolyl isomerase; 1. DR Gene3D; 3.10.50.40; -; 1. DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1. DR InterPro; IPR050754; FKBP4/5/8-like. DR InterPro; IPR046357; PPIase_dom_sf. DR InterPro; IPR001179; PPIase_FKBP_dom. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR019734; TPR_rpt. DR PANTHER; PTHR46512:SF3; PEPTIDYL-PROLYL CIS-TRANS ISOMERASE FKBP8; 1. DR PANTHER; PTHR46512; PEPTIDYLPROLYL ISOMERASE; 1. DR Pfam; PF00254; FKBP_C; 1. DR Pfam; PF13432; TPR_16; 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; PS50005; TPR; 2. DR PROSITE; PS50293; TPR_REGION; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Calcium; KW Host-virus interaction; Isomerase; Isopeptide bond; Membrane; KW Metal-binding; Mitochondrion; Phosphoprotein; Proteomics identification; KW Reference proteome; Repeat; Rotamase; TPR repeat; Transmembrane; KW Transmembrane helix; Ubl conjugation. FT CHAIN 1..412 FT /note="Peptidyl-prolyl cis-trans isomerase FKBP8" FT /id="PRO_0000075331" FT TRANSMEM 390..410 FT /note="Helical" FT /evidence="ECO:0000255" FT DOMAIN 120..204 FT /note="PPIase FKBP-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00277" FT REPEAT 221..254 FT /note="TPR 1" FT REPEAT 272..305 FT /note="TPR 2" FT REPEAT 306..339 FT /note="TPR 3" FT REGION 1..68 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 22..50 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 149 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT BINDING 151 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT MOD_RES 296 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 249 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:25621951" FT CROSSLNK 271 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:25621951" FT CROSSLNK 273 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:25621951" FT CROSSLNK 284 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:25621951" FT CROSSLNK 307 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:25621951" FT CROSSLNK 314 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:25621951" FT CROSSLNK 334 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:25621951" FT CROSSLNK 340 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:25621951" FT CROSSLNK 348 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:25621951" FT CROSSLNK 351 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:25621951" FT CROSSLNK 352 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:25621951" FT VAR_SEQ 98..256 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:18385096" FT /id="VSP_047717" FT VAR_SEQ 183 FT /note="G -> GS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005, ECO:0000303|Ref.8" FT /id="VSP_034486" FT VARIANT 87 FT /note="A -> V (in dbSNP:rs11574806)" FT /id="VAR_044225" FT MUTAGEN 149 FT /note="D->N: Abolishes calcium-binding and reduces affinity FT for BCL2; when associated with Asn-151." FT /evidence="ECO:0000269|PubMed:20140889" FT MUTAGEN 151 FT /note="D->N: Abolishes calcium-binding and reduces affinity FT for BCL2; when associated with Asn-149." FT /evidence="ECO:0000269|PubMed:20140889" FT CONFLICT 144 FT /note="V -> A (in Ref. 4; CAD98028)" FT /evidence="ECO:0000305" FT CONFLICT 191 FT /note="H -> R (in Ref. 4; CAD98028)" FT /evidence="ECO:0000305" FT CONFLICT 206 FT /note="G -> R (in Ref. 8; BAD96558)" FT /evidence="ECO:0000305" FT STRAND 94..108 FT /evidence="ECO:0007829|PDB:3EY6" FT STRAND 111..113 FT /evidence="ECO:0007829|PDB:2MF9" FT STRAND 121..131 FT /evidence="ECO:0007829|PDB:3EY6" FT STRAND 136..146 FT /evidence="ECO:0007829|PDB:3EY6" FT TURN 147..150 FT /evidence="ECO:0007829|PDB:2MF9" FT HELIX 154..157 FT /evidence="ECO:0007829|PDB:3EY6" FT HELIX 160..162 FT /evidence="ECO:0007829|PDB:3EY6" FT STRAND 168..173 FT /evidence="ECO:0007829|PDB:3EY6" FT HELIX 175..177 FT /evidence="ECO:0007829|PDB:3EY6" FT HELIX 180..182 FT /evidence="ECO:0007829|PDB:3EY6" FT TURN 185..187 FT /evidence="ECO:0007829|PDB:3EY6" FT STRAND 190..192 FT /evidence="ECO:0007829|PDB:2F2D" FT STRAND 194..204 FT /evidence="ECO:0007829|PDB:3EY6" FT HELIX 209..211 FT /evidence="ECO:0007829|PDB:5MGX" FT HELIX 214..233 FT /evidence="ECO:0007829|PDB:5MGX" FT HELIX 237..252 FT /evidence="ECO:0007829|PDB:5MGX" FT HELIX 261..284 FT /evidence="ECO:0007829|PDB:5MGX" FT HELIX 288..301 FT /evidence="ECO:0007829|PDB:5MGX" FT HELIX 306..319 FT /evidence="ECO:0007829|PDB:5MGX" FT HELIX 322..335 FT /evidence="ECO:0007829|PDB:5MGX" FT HELIX 340..354 FT /evidence="ECO:0007829|PDB:5MGX" SQ SEQUENCE 412 AA; 44562 MW; 887C25ADE71EBA8D CRC64; MASCAEPSEP SAPLPAGVPP LEDFEVLDGV EDAEGEEEEE EEEEEEDDLS ELPPLEDMGQ PPAEEAEQPG ALAREFLAAM EPEPAPAPAP EEWLDILGNG LLRKKTLVPG PPGSSRPVKG QVVTVHLQTS LENGTRVQEE PELVFTLGDC DVIQALDLSV PLMDVGETAM VTADSKYCYG PQGRSPYIPP HAALCLEVTL KTAVDGPDLE MLTGQERVAL ANRKRECGNA HYQRADFVLA ANSYDLAIKA ITSSAKVDMT FEEEAQLLQL KVKCLNNLAA SQLKLDHYRA ALRSCSLVLE HQPDNIKALF RKGKVLAQQG EYSEAIPILR AALKLEPSNK TIHAELSKLV KKHAAQRSTE TALYRKMLGN PSRLPAKCPG KGAWSIPWKW LFGATAVALG GVALSVVIAA RN //