FKB14_HUMAN
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 03-AUG-2022, entry version 183.
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.
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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; 92.
DR IntAct; Q9NWM8; 25.
DR MINT; Q9NWM8; -.
DR STRING; 9606.ENSP00000222803; -.
DR BindingDB; Q9NWM8; -.
DR ChEMBL; CHEMBL2342; -.
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; Q9NWM8; -.
DR PeptideAtlas; Q9NWM8; -.
DR PRIDE; Q9NWM8; -.
DR ProteomicsDB; 82955; -.
DR Antibodypedia; 2831; 217 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 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; VVNDSHH; -.
DR OrthoDB; 1507309at2759; -.
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 1078 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 179 other tissues.
DR ExpressionAtlas; Q9NWM8; baseline and differential.
DR Genevisible; Q9NWM8; HS.
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 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 Pfam; PF13499; EF-hand_7; 1.
DR Pfam; PF00254; FKBP_C; 1.
DR SUPFAM; SSF47473; SSF47473; 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.
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
