ID FKB14_HUMAN Reviewed; 211 AA. AC Q9NWM8; DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 27-MAR-2024, entry version 192. DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP14; DE Short=PPIase FKBP14; DE EC=5.2.1.8 {ECO:0000269|PubMed:24821723}; DE AltName: Full=22 kDa FK506-binding protein; DE Short=22 kDa FKBP; DE Short=FKBP-22; DE AltName: Full=FK506-binding protein 14; DE Short=FKBP-14; DE AltName: Full=Rotamase; DE Flags: Precursor; GN Name=FKBP14; Synonyms=FKBP22; ORFNames=UNQ322/PRO381; 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 [LARGE SCALE MRNA]. RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney; 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 [4] RP PROTEIN SEQUENCE OF 20-34. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [5] RP INVOLVEMENT IN EDSKSCL2, AND SUBCELLULAR LOCATION. RX PubMed=22265013; DOI=10.1016/j.ajhg.2011.12.004; RA Baumann M., Giunta C., Krabichler B., Ruschendorf F., Zoppi N., Colombi M., RA Bittner R.E., Quijano-Roy S., Muntoni F., Cirak S., Schreiber G., Zou Y., RA Hu Y., Romero N.B., Carlier R.Y., Amberger A., Deutschmann A., Straub V., RA Rohrbach M., Steinmann B., Rostasy K., Karall D., Bonnemann C.G., RA Zschocke J., Fauth C.; RT "Mutations in FKBP14 cause a variant of Ehlers-Danlos syndrome with RT progressive kyphoscoliosis, myopathy, and hearing loss."; RL Am. J. Hum. Genet. 90:201-216(2012). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, CALCIUM RP BINDING, AND PRESENCE OF DISULFIDE BOND. RX PubMed=24821723; DOI=10.1074/jbc.m114.561944; RA Ishikawa Y., Baechinger H.P.; RT "A substrate preference for the rough endoplasmic reticulum resident RT protein FKBP22 during collagen biosynthesis."; RL J. Biol. Chem. 289:18189-18201(2014). RN [7] {ECO:0007744|PDB:4DIP} RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 19-138, AND DISULFIDE BOND. RA Krojer T., Kiyani W., Goubin S., Muniz J.R.C., Filippakopoulos P., RA Arrowsmith C.H., Edwards A., Bountra C., von Delft F., Oppermann U., RA Zschocke J., Yue W.W.; RT "Crystal structure of human peptidyl-prolyl cis-trans isomerase FKBP14."; RL Submitted (JAN-2012) to the PDB data bank. RN [8] {ECO:0007744|PDB:4MSP} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 21-211 IN COMPLEX WITH CALCIUM, RP SUBUNIT, AND DISULFIDE BOND. RX PubMed=24272907; DOI=10.1002/pro.2391; RA Boudko S.P., Ishikawa Y., Nix J., Chapman M.S., Bachinger H.P.; RT "Structure of human peptidyl-prolyl cis-trans isomerase FKBP22 containing RT two EF-hand motifs."; RL Protein Sci. 23:67-75(2014). CC -!- FUNCTION: PPIase which accelerates the folding of proteins during CC protein synthesis. Has a preference for substrates containing 4- CC hydroxylproline modifications, including type III collagen. May also CC target type VI and type X collagens. {ECO:0000269|PubMed:24821723}. 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:24821723}; CC -!- ACTIVITY REGULATION: Inhibited by tacrolimus/FK506. CC {ECO:0000269|PubMed:24821723}. CC -!- SUBUNIT: Monomer (PubMed:24821723, PubMed:24272907). Homodimer CC (PubMed:24821723, PubMed:24272907). Interacts with type III, type IV CC and type X collagens (PubMed:24821723). {ECO:0000269|PubMed:24272907, CC ECO:0000269|PubMed:24821723}. CC -!- INTERACTION: CC Q9NWM8; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-2477093, EBI-10982110; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000255|PROSITE- CC ProRule:PRU10138, ECO:0000269|PubMed:22265013}. CC -!- DISEASE: Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (EDSKSCL2) CC [MIM:614557]: A form of Ehlers-Danlos syndrome, a group of connective CC tissue disorders characterized by skin hyperextensibility, articular CC hypermobility, and tissue fragility. EDSKSCL2 is an autosomal recessive CC form characterized by severe generalized hypotonia at birth, myopathy, CC early-onset progressive kyphoscoliosis, joint hypermobility without CC contractures, hyperelastic skin with follicular hyperkeratosis, easy CC bruising, and occasional abnormal scarring, sensorineural hearing CC impairment, and normal pyridinoline excretion in urine. CC {ECO:0000269|PubMed:22265013}. Note=The disease is caused by variants CC affecting the gene represented in this entry. 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; AY358643; AAQ89006.1; -; mRNA. DR EMBL; AK000738; BAA91351.1; -; mRNA. DR EMBL; BC005206; AAH05206.1; -; mRNA. DR CCDS; CCDS5423.1; -. DR RefSeq; NP_060416.1; NM_017946.3. DR PDB; 4DIP; X-ray; 1.82 A; A/B/C/D/E/F/G/H/I/J=19-138. DR PDB; 4MSP; X-ray; 1.90 A; A/B=21-211. DR PDBsum; 4DIP; -. DR PDBsum; 4MSP; -. DR AlphaFoldDB; Q9NWM8; -. DR SMR; Q9NWM8; -. DR BioGRID; 120362; 93. DR IntAct; Q9NWM8; 25. DR MINT; Q9NWM8; -. DR STRING; 9606.ENSP00000222803; -. DR BindingDB; Q9NWM8; -. DR ChEMBL; CHEMBL2342; -. DR GlyCosmos; Q9NWM8; 1 site, No reported glycans. DR GlyGen; Q9NWM8; 1 site. DR iPTMnet; Q9NWM8; -. DR PhosphoSitePlus; Q9NWM8; -. DR BioMuta; FKBP14; -. DR DMDM; 23821568; -. DR EPD; Q9NWM8; -. DR jPOST; Q9NWM8; -. DR MassIVE; Q9NWM8; -. DR MaxQB; Q9NWM8; -. DR PaxDb; 9606-ENSP00000222803; -. DR PeptideAtlas; Q9NWM8; -. DR ProteomicsDB; 82955; -. DR Pumba; Q9NWM8; -. DR Antibodypedia; 2831; 239 antibodies from 26 providers. DR DNASU; 55033; -. DR Ensembl; ENST00000222803.10; ENSP00000222803.5; ENSG00000106080.11. DR GeneID; 55033; -. DR KEGG; hsa:55033; -. DR MANE-Select; ENST00000222803.10; ENSP00000222803.5; NM_017946.4; NP_060416.1. DR UCSC; uc003tal.3; human. DR AGR; HGNC:18625; -. DR CTD; 55033; -. DR DisGeNET; 55033; -. DR GeneCards; FKBP14; -. DR GeneReviews; FKBP14; -. DR HGNC; HGNC:18625; FKBP14. DR HPA; ENSG00000106080; Low tissue specificity. DR MalaCards; FKBP14; -. DR MIM; 614505; gene. DR MIM; 614557; phenotype. DR neXtProt; NX_Q9NWM8; -. DR OpenTargets; ENSG00000106080; -. DR Orphanet; 300179; Kyphoscoliotic Ehlers-Danlos syndrome due to FKBP22 deficiency. DR PharmGKB; PA38608; -. DR VEuPathDB; HostDB:ENSG00000106080; -. DR eggNOG; KOG0549; Eukaryota. DR GeneTree; ENSGT00940000157858; -. DR HOGENOM; CLU_013615_5_0_1; -. DR InParanoid; Q9NWM8; -. DR OMA; LVHYDGF; -. DR OrthoDB; 25281at2759; -. DR PhylomeDB; Q9NWM8; -. DR TreeFam; TF105296; -. DR BRENDA; 5.2.1.8; 2681. DR PathwayCommons; Q9NWM8; -. DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes. DR SignaLink; Q9NWM8; -. DR BioGRID-ORCS; 55033; 11 hits in 1158 CRISPR screens. DR ChiTaRS; FKBP14; human. DR GenomeRNAi; 55033; -. DR Pharos; Q9NWM8; Tbio. DR PRO; PR:Q9NWM8; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q9NWM8; Protein. DR Bgee; ENSG00000106080; Expressed in tibia and 181 other cell types or tissues. DR ExpressionAtlas; Q9NWM8; baseline and differential. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IEA:UniProtKB-KW. DR Gene3D; 3.10.50.40; -; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR InterPro; IPR046357; PPIase_dom_sf. DR InterPro; IPR001179; PPIase_FKBP_dom. DR PANTHER; PTHR46222:SF1; PEPTIDYL-PROLYL CIS-TRANS ISOMERASE FKBP14; 1. DR PANTHER; PTHR46222; PEPTIDYL-PROLYL CIS-TRANS ISOMERASE FKBP7/14; 1. DR Pfam; PF00254; FKBP_C; 1. DR SUPFAM; SSF47473; EF-hand; 1. DR SUPFAM; SSF54534; FKBP-like; 1. DR PROSITE; PS00018; EF_HAND_1; 1. DR PROSITE; PS50222; EF_HAND_2; 2. DR PROSITE; PS00014; ER_TARGET; 1. DR PROSITE; PS50059; FKBP_PPIASE; 1. DR Genevisible; Q9NWM8; HS. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Deafness; Direct protein sequencing; Disulfide bond; KW Ehlers-Danlos syndrome; Endoplasmic reticulum; Glycoprotein; Isomerase; KW Metal-binding; Reference proteome; Repeat; Rotamase; Signal. FT SIGNAL 1..19 FT /evidence="ECO:0000269|PubMed:15340161" FT CHAIN 20..211 FT /note="Peptidyl-prolyl cis-trans isomerase FKBP14" FT /id="PRO_0000025521" FT DOMAIN 45..135 FT /note="PPIase FKBP-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00277" FT DOMAIN 135..170 FT /note="EF-hand 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 179..211 FT /note="EF-hand 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT MOTIF 208..211 FT /note="Prevents secretion from ER" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138" FT BINDING 148 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24272907, FT ECO:0000305|PubMed:24821723, ECO:0007744|PDB:4MSP" FT BINDING 150 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24272907, FT ECO:0000305|PubMed:24821723, ECO:0007744|PDB:4MSP" FT BINDING 152 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24272907, FT ECO:0000305|PubMed:24821723, ECO:0007744|PDB:4MSP" FT BINDING 154 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24272907, FT ECO:0000305|PubMed:24821723, ECO:0007744|PDB:4MSP" FT BINDING 159 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24272907, FT ECO:0000305|PubMed:24821723, ECO:0007744|PDB:4MSP" FT BINDING 192 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448, FT ECO:0000269|PubMed:24272907, ECO:0000305|PubMed:24821723, FT ECO:0007744|PDB:4MSP" FT BINDING 194 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448, FT ECO:0000269|PubMed:24272907, ECO:0000305|PubMed:24821723, FT ECO:0007744|PDB:4MSP" FT BINDING 196 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448, FT ECO:0000269|PubMed:24272907, ECO:0000305|PubMed:24821723, FT ECO:0007744|PDB:4MSP" FT BINDING 198 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:24272907, FT ECO:0000305|PubMed:24821723, ECO:0007744|PDB:4MSP" FT BINDING 203 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448, FT ECO:0000269|PubMed:24272907, ECO:0000305|PubMed:24821723, FT ECO:0007744|PDB:4MSP" FT CARBOHYD 176 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 38..96 FT /evidence="ECO:0000269|Ref.7, ECO:0000305|PubMed:24821723, FT ECO:0007744|PDB:4DIP, ECO:0007744|PDB:4MSP" FT HELIX 19..21 FT /evidence="ECO:0007829|PDB:4DIP" FT STRAND 28..33 FT /evidence="ECO:0007829|PDB:4DIP" FT STRAND 47..56 FT /evidence="ECO:0007829|PDB:4DIP" FT TURN 57..59 FT /evidence="ECO:0007829|PDB:4DIP" FT STRAND 62..65 FT /evidence="ECO:0007829|PDB:4DIP" FT HELIX 66..69 FT /evidence="ECO:0007829|PDB:4DIP" FT TURN 70..72 FT /evidence="ECO:0007829|PDB:4DIP" FT STRAND 75..78 FT /evidence="ECO:0007829|PDB:4DIP" FT TURN 79..82 FT /evidence="ECO:0007829|PDB:4MSP" FT HELIX 86..91 FT /evidence="ECO:0007829|PDB:4DIP" FT STRAND 100..105 FT /evidence="ECO:0007829|PDB:4DIP" FT HELIX 107..109 FT /evidence="ECO:0007829|PDB:4DIP" FT TURN 110..114 FT /evidence="ECO:0007829|PDB:4DIP" FT STRAND 125..135 FT /evidence="ECO:0007829|PDB:4DIP" FT HELIX 141..147 FT /evidence="ECO:0007829|PDB:4MSP" FT STRAND 152..156 FT /evidence="ECO:0007829|PDB:4MSP" FT HELIX 157..170 FT /evidence="ECO:0007829|PDB:4MSP" FT HELIX 177..191 FT /evidence="ECO:0007829|PDB:4MSP" FT STRAND 196..200 FT /evidence="ECO:0007829|PDB:4MSP" FT HELIX 201..205 FT /evidence="ECO:0007829|PDB:4MSP" SQ SEQUENCE 211 AA; 24172 MW; 858184954FE10029 CRC64; MRLFLWNAVL TLFVTSLIGA LIPEPEVKIE VLQKPFICHR KTKGGDLMLV HYEGYLEKDG SLFHSTHKHN NGQPIWFTLG ILEALKGWDQ GLKGMCVGEK RKLIIPPALG YGKEGKGKIP PESTLIFNID LLEIRNGPRS HESFQEMDLN DDWKLSKDEV KAYLKKEFEK HGAVVNESHH DALVEDIFDK EDEDKDGFIS AREFTYKHDE L //