PPIL1_HUMAN
ID PPIL1_HUMAN Reviewed; 166 AA.
AC Q9Y3C6; O15001; Q5TDC9;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase-like 1;
DE Short=PPIase;
DE EC=5.2.1.8 {ECO:0000269|PubMed:16595688, ECO:0000269|PubMed:33220177};
DE AltName: Full=Rotamase PPIL1;
GN Name=PPIL1; Synonyms=CYPL1; ORFNames=CGI-124, UNQ2425/PRO4984;
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].
RC TISSUE=Fetal brain;
RX PubMed=8978786; DOI=10.1159/000134199;
RA Ozaki K., Fujiwara T., Kawai A., Shimizu F., Takami S., Okuno S.,
RA Takeda S., Shimada Y., Nagata M., Watanabe T., Takaichi A., Takahashi E.,
RA Nakamura Y., Shin S.;
RT "Cloning, expression and chromosomal mapping of a novel cyclophilin-related
RT gene (PPIL1) from human fetal brain.";
RL Cytogenet. Cell Genet. 72:242-245(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, KINETIC PARAMETERS, ACTIVITY REGULATION,
RP CYCLOSPORIN A BINDING, INTERACTION WITH SNW1, AND STRUCTURE BY NMR.
RX PubMed=16595688; DOI=10.1074/jbc.m511155200;
RA Xu C., Zhang J., Huang X., Sun J., Xu Y., Tang Y., Wu J., Shi Y., Huang Q.,
RA Zhang Q.;
RT "Solution structure of human peptidyl prolyl isomerase-like protein 1 and
RT insights into its interaction with SKIP.";
RL J. Biol. Chem. 281:15900-15908(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE SPLICEOSOMAL C
RP COMPLEX, FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=11991638; DOI=10.1017/s1355838202021088;
RA Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J.;
RT "Purification and characterization of native spliceosomes suitable for
RT three-dimensional structural analysis.";
RL RNA 8:426-439(2002).
RN [9]
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [11]
RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS), AND INTERACTION WITH SNW1.
RX PubMed=20368803; DOI=10.1371/journal.pone.0010013;
RA Stegmann C.M., Luhrmann R., Wahl M.C.;
RT "The crystal structure of PPIL1 bound to cyclosporine A suggests a binding
RT mode for a linear epitope of the SKIP protein.";
RL PLoS ONE 5:E10013-E10013(2010).
RN [12] {ECO:0007744|PDB:5XJC}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS), FUNCTION, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=28502770; DOI=10.1016/j.cell.2017.04.033;
RA Zhang X., Yan C., Hang J., Finci L.I., Lei J., Shi Y.;
RT "An Atomic Structure of the Human Spliceosome.";
RL Cell 169:918-929(2017).
RN [13] {ECO:0007744|PDB:5MQF}
RP STRUCTURE BY ELECTRON MICROSCOPY (5.90 ANGSTROMS), FUNCTION, SUBUNIT,
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=28076346; DOI=10.1038/nature21079;
RA Bertram K., Agafonov D.E., Liu W.T., Dybkov O., Will C.L., Hartmuth K.,
RA Urlaub H., Kastner B., Stark H., Luhrmann R.;
RT "Cryo-EM structure of a human spliceosome activated for step 2 of
RT splicing.";
RL Nature 542:318-323(2017).
RN [14]
RP INVOLVEMENT IN PCH14, VARIANTS PCH14 45-ARG--GLY-166 DEL; CYS-78; SER-82;
RP THR-99; ALA-ASN-ALA-GLY-PRO-ASP-106 INS; ALA-107; CYS-109; ALA-127 AND
RP GLN-131, CHARACTERIZATION OF VARIANT PCH14 CYS-78; SER-82; THR-99;
RP ALA-ASN-ALA-GLY-PRO-ASP-106 INS; ALA-107; ALA-127 AND GLN-131, FUNCTION,
RP INTERACTION WITH CDC40; RBM22 AND SNW1, MUTAGENESIS OF ARG-55, AND
RP CATALYTIC ACTIVITY.
RX PubMed=33220177; DOI=10.1016/j.neuron.2020.10.035;
RA Chai G., Webb A., Li C., Antaki D., Lee S., Breuss M.W., Lang N.,
RA Stanley V., Anzenberg P., Yang X., Marshall T., Gaffney P., Wierenga K.J.,
RA Chung B.H., Tsang M.H., Pais L.S., Lovgren A.K., VanNoy G.E., Rehm H.L.,
RA Mirzaa G., Leon E., Diaz J., Neumann A., Kalverda A.P., Manfield I.W.,
RA Parry D.A., Logan C.V., Johnson C.A., Bonthron D.T., Valleley E.M.A.,
RA Issa M.Y., Abdel-Ghafar S.F., Abdel-Hamid M.S., Jennings P., Zaki M.S.,
RA Sheridan E., Gleeson J.G.;
RT "Mutations in Spliceosomal Genes PPIL1 and PRP17 Cause Neurodegenerative
RT Pontocerebellar Hypoplasia with Microcephaly.";
RL Neuron 109:241-256(2021).
CC -!- FUNCTION: Involved in pre-mRNA splicing as component of the spliceosome
CC (PubMed:11991638, PubMed:28502770, PubMed:28076346, PubMed:33220177).
CC PPIases accelerate the folding of proteins. Catalyzes the cis-trans
CC isomerization of proline imidic peptide bonds in oligopeptides
CC (PubMed:16595688). Catalyzes prolyl peptide bond isomerization in
CC CDC40/PRP17 (PubMed:33220177). Plays an important role in embryonic
CC brain development; this function is independent of its isomerase
CC activity (PubMed:33220177). {ECO:0000269|PubMed:11991638,
CC ECO:0000269|PubMed:16595688, ECO:0000269|PubMed:28076346,
CC ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:33220177}.
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; Evidence={ECO:0000269|PubMed:16595688,
CC ECO:0000269|PubMed:33220177};
CC -!- ACTIVITY REGULATION: Inhibited by Cyclosporin A.
CC {ECO:0000269|PubMed:16595688}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=230 uM for N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide
CC {ECO:0000269|PubMed:16595688};
CC -!- SUBUNIT: Identified in the spliceosome C complex (PubMed:11991638,
CC PubMed:28502770, PubMed:28076346). Interacts with SNW1/SKIP
CC (PubMed:16595688, PubMed:20368803, PubMed:33220177). Interacts with
CC CDC40/PRP17; this interaction leads to CDC40 isomerization
CC (PubMed:33220177). Interacts with RBM22 (PubMed:33220177).
CC {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:16595688,
CC ECO:0000269|PubMed:20368803, ECO:0000269|PubMed:28076346,
CC ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:33220177}.
CC -!- INTERACTION:
CC Q9Y3C6; Q9UMD9: COL17A1; NbExp=3; IntAct=EBI-2557649, EBI-2528742;
CC Q9Y3C6; Q16630: CPSF6; NbExp=3; IntAct=EBI-2557649, EBI-358410;
CC Q9Y3C6; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-2557649, EBI-742054;
CC Q9Y3C6; Q5T749: KPRP; NbExp=3; IntAct=EBI-2557649, EBI-10981970;
CC Q9Y3C6; P50458: LHX2; NbExp=3; IntAct=EBI-2557649, EBI-12179869;
CC Q9Y3C6; Q92802: N4BP2L2; NbExp=3; IntAct=EBI-2557649, EBI-2514973;
CC Q9Y3C6; P78424: POU6F2; NbExp=3; IntAct=EBI-2557649, EBI-12029004;
CC Q9Y3C6; P0CG20: PRR35; NbExp=3; IntAct=EBI-2557649, EBI-11986293;
CC Q9Y3C6; Q9UFD9: RIMBP3; NbExp=3; IntAct=EBI-2557649, EBI-10182375;
CC Q9Y3C6; Q13573: SNW1; NbExp=15; IntAct=EBI-2557649, EBI-632715;
CC Q9Y3C6; A6NLX3: SPDYE4; NbExp=3; IntAct=EBI-2557649, EBI-12047907;
CC Q9Y3C6; P15884: TCF4; NbExp=3; IntAct=EBI-2557649, EBI-533224;
CC Q9Y3C6; P15884-3: TCF4; NbExp=3; IntAct=EBI-2557649, EBI-13636688;
CC Q9Y3C6; Q9BRX9: WDR83; NbExp=2; IntAct=EBI-2557649, EBI-7705033;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11991638,
CC ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770}.
CC -!- TISSUE SPECIFICITY: Ubiquitous, with the most abundant expression in
CC heart and skeletal muscle.
CC -!- DISEASE: Pontocerebellar hypoplasia 14 (PCH14) [MIM:619301]: A form of
CC pontocerebellar hypoplasia, a disorder characterized by structural
CC defects of the pons and cerebellum, evident upon brain imaging. PCH14
CC is a severe autosomal recessive form characterized by progressive
CC microcephaly, and poor or absent psychomotor development with severely
CC impaired intellectual development apparent from birth. Other features
CC may include hypotonia, spastic quadriplegia, and early-onset seizures.
CC Early death may occur in some patients. {ECO:0000269|PubMed:33220177}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the cyclophilin-type PPIase family. PPIL1
CC subfamily. {ECO:0000305}.
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; AF151882; AAD34119.1; -; mRNA.
DR EMBL; AY359032; AAQ89391.1; -; mRNA.
DR EMBL; Z85996; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL122034; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03916.1; -; Genomic_DNA.
DR EMBL; BC003048; AAH03048.1; -; mRNA.
DR CCDS; CCDS4826.1; -.
DR RefSeq; NP_057143.1; NM_016059.4.
DR PDB; 1XWN; NMR; -; A=1-166.
DR PDB; 2K7N; NMR; -; A=1-166.
DR PDB; 2X7K; X-ray; 1.15 A; A=1-166.
DR PDB; 5MQF; EM; 5.90 A; V=1-166.
DR PDB; 5XJC; EM; 3.60 A; S=1-166.
DR PDB; 5YZG; EM; 4.10 A; S=1-166.
DR PDB; 5Z56; EM; 5.10 A; S=1-166.
DR PDB; 5Z57; EM; 6.50 A; S=1-166.
DR PDB; 6FF4; EM; 16.00 A; V=1-166.
DR PDB; 6FF7; EM; 4.50 A; V=1-166.
DR PDB; 6ICZ; EM; 3.00 A; S=1-166.
DR PDB; 6ID0; EM; 2.90 A; S=1-166.
DR PDB; 6ID1; EM; 2.86 A; S=1-166.
DR PDB; 6QDV; EM; 3.30 A; i=3-164.
DR PDB; 6ZYM; EM; 3.40 A; V=1-166.
DR PDBsum; 1XWN; -.
DR PDBsum; 2K7N; -.
DR PDBsum; 2X7K; -.
DR PDBsum; 5MQF; -.
DR PDBsum; 5XJC; -.
DR PDBsum; 5YZG; -.
DR PDBsum; 5Z56; -.
DR PDBsum; 5Z57; -.
DR PDBsum; 6FF4; -.
DR PDBsum; 6FF7; -.
DR PDBsum; 6ICZ; -.
DR PDBsum; 6ID0; -.
DR PDBsum; 6ID1; -.
DR PDBsum; 6QDV; -.
DR PDBsum; 6ZYM; -.
DR AlphaFoldDB; Q9Y3C6; -.
DR BMRB; Q9Y3C6; -.
DR SMR; Q9Y3C6; -.
DR BioGRID; 119654; 81.
DR CORUM; Q9Y3C6; -.
DR IntAct; Q9Y3C6; 36.
DR MINT; Q9Y3C6; -.
DR STRING; 9606.ENSP00000362803; -.
DR BindingDB; Q9Y3C6; -.
DR GlyGen; Q9Y3C6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y3C6; -.
DR MetOSite; Q9Y3C6; -.
DR PhosphoSitePlus; Q9Y3C6; -.
DR SwissPalm; Q9Y3C6; -.
DR BioMuta; PPIL1; -.
DR DMDM; 20177874; -.
DR EPD; Q9Y3C6; -.
DR jPOST; Q9Y3C6; -.
DR MassIVE; Q9Y3C6; -.
DR MaxQB; Q9Y3C6; -.
DR PaxDb; Q9Y3C6; -.
DR PeptideAtlas; Q9Y3C6; -.
DR PRIDE; Q9Y3C6; -.
DR ProteomicsDB; 86015; -.
DR Antibodypedia; 29729; 278 antibodies from 29 providers.
DR DNASU; 51645; -.
DR Ensembl; ENST00000373699.6; ENSP00000362803.5; ENSG00000137168.8.
DR GeneID; 51645; -.
DR KEGG; hsa:51645; -.
DR MANE-Select; ENST00000373699.6; ENSP00000362803.5; NM_016059.5; NP_057143.1.
DR UCSC; uc003omu.3; human.
DR CTD; 51645; -.
DR DisGeNET; 51645; -.
DR GeneCards; PPIL1; -.
DR HGNC; HGNC:9260; PPIL1.
DR HPA; ENSG00000137168; Low tissue specificity.
DR MIM; 601301; gene.
DR MIM; 619301; phenotype.
DR neXtProt; NX_Q9Y3C6; -.
DR OpenTargets; ENSG00000137168; -.
DR PharmGKB; PA33587; -.
DR VEuPathDB; HostDB:ENSG00000137168; -.
DR eggNOG; KOG0881; Eukaryota.
DR GeneTree; ENSGT00940000153189; -.
DR HOGENOM; CLU_012062_16_3_1; -.
DR InParanoid; Q9Y3C6; -.
DR OMA; ELYNDHA; -.
DR PhylomeDB; Q9Y3C6; -.
DR TreeFam; TF300200; -.
DR BRENDA; 5.2.1.8; 2681.
DR PathwayCommons; Q9Y3C6; -.
DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR SABIO-RK; Q9Y3C6; -.
DR SignaLink; Q9Y3C6; -.
DR BioGRID-ORCS; 51645; 523 hits in 1092 CRISPR screens.
DR ChiTaRS; PPIL1; human.
DR EvolutionaryTrace; Q9Y3C6; -.
DR GeneWiki; PPIL1; -.
DR GenomeRNAi; 51645; -.
DR Pharos; Q9Y3C6; Tbio.
DR PRO; PR:Q9Y3C6; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9Y3C6; protein.
DR Bgee; ENSG00000137168; Expressed in heart right ventricle and 179 other tissues.
DR ExpressionAtlas; Q9Y3C6; baseline and differential.
DR Genevisible; Q9Y3C6; HS.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0071007; C:U2-type catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0016018; F:cyclosporin A binding; IDA:UniProtKB.
DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:UniProtKB.
DR GO; GO:1990403; P:embryonic brain development; IMP:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IDA:UniProtKB.
DR GO; GO:0006457; P:protein folding; IEA:InterPro.
DR GO; GO:0000413; P:protein peptidyl-prolyl isomerization; IDA:UniProtKB.
DR Gene3D; 2.40.100.10; -; 1.
DR InterPro; IPR029000; Cyclophilin-like_dom_sf.
DR InterPro; IPR024936; Cyclophilin-type_PPIase.
DR InterPro; IPR020892; Cyclophilin-type_PPIase_CS.
DR InterPro; IPR002130; Cyclophilin-type_PPIase_dom.
DR InterPro; IPR044666; Cyclophilin_A-like.
DR PANTHER; PTHR45625; PTHR45625; 1.
DR Pfam; PF00160; Pro_isomerase; 1.
DR PIRSF; PIRSF001467; Peptidylpro_ismrse; 1.
DR PRINTS; PR00153; CSAPPISMRASE.
DR SUPFAM; SSF50891; SSF50891; 1.
DR PROSITE; PS00170; CSA_PPIASE_1; 1.
DR PROSITE; PS50072; CSA_PPIASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; Intellectual disability; Isomerase;
KW mRNA processing; mRNA splicing; Nucleus; Phosphoprotein;
KW Reference proteome; Rotamase; Spliceosome.
FT CHAIN 1..166
FT /note="Peptidyl-prolyl cis-trans isomerase-like 1"
FT /id="PRO_0000064164"
FT DOMAIN 10..164
FT /note="PPIase cyclophilin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00156"
FT BINDING 54..65
FT /ligand="cyclosporin A"
FT /ligand_id="ChEBI:CHEBI:4031"
FT /evidence="ECO:0000305|PubMed:16595688"
FT BINDING 70..71
FT /ligand="cyclosporin A"
FT /ligand_id="ChEBI:CHEBI:4031"
FT /evidence="ECO:0000305|PubMed:16595688"
FT BINDING 99..104
FT /ligand="cyclosporin A"
FT /ligand_id="ChEBI:CHEBI:4031"
FT /evidence="ECO:0000305|PubMed:16595688"
FT BINDING 109..113
FT /ligand="cyclosporin A"
FT /ligand_id="ChEBI:CHEBI:4031"
FT /evidence="ECO:0000305|PubMed:16595688"
FT BINDING 119
FT /ligand="cyclosporin A"
FT /ligand_id="ChEBI:CHEBI:4031"
FT /evidence="ECO:0000305|PubMed:16595688"
FT BINDING 125
FT /ligand="cyclosporin A"
FT /ligand_id="ChEBI:CHEBI:4031"
FT /evidence="ECO:0000305|PubMed:16595688"
FT MOD_RES 149
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 36
FT /note="C -> S (in dbSNP:rs12194408)"
FT /id="VAR_051772"
FT VARIANT 45..166
FT /note="Missing (in PCH14)"
FT /evidence="ECO:0000269|PubMed:33220177"
FT /id="VAR_085506"
FT VARIANT 78
FT /note="Y -> C (in PCH14; unknown pathological significance;
FT strongly reduced protein levels compared to wild-type after
FT transfection in HEK293T cell line)"
FT /evidence="ECO:0000269|PubMed:33220177"
FT /id="VAR_085507"
FT VARIANT 82
FT /note="F -> S (in PCH14; unknown pathological significance;
FT strongly reduced protein levels compared to wild-type after
FT transfection in HEK293T cell line)"
FT /evidence="ECO:0000269|PubMed:33220177"
FT /id="VAR_085508"
FT VARIANT 99
FT /note="A -> T (in PCH14; strongly reduced interaction with
FT SNW1; strongly reduced protein levels in homozygous
FT patient's fibroblasts compared to heterozygous or wild-type
FT cells; in transgenic knockin mice, produces a
FT pontocerebellar hypoplasia-like phenotype;
FT dbSNP:rs199818754)"
FT /evidence="ECO:0000269|PubMed:33220177"
FT /id="VAR_085509"
FT VARIANT 106
FT /note="D -> DANAGPD (in PCH14; unknown pathological
FT significance; strongly reduced protein levels compared to
FT wild-type after transfection in HEK293T cell line)"
FT /evidence="ECO:0000269|PubMed:33220177"
FT /id="VAR_085510"
FT VARIANT 107
FT /note="T -> A (in PCH14; unknown pathological significance;
FT reduced interaction with SNW1; no effect on protein
FT expression level, but shows reduced thermal stability and
FT increased aggregation propensity in vitro)"
FT /evidence="ECO:0000269|PubMed:33220177"
FT /id="VAR_085511"
FT VARIANT 109
FT /note="G -> C (in PCH14; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33220177"
FT /id="VAR_085512"
FT VARIANT 127
FT /note="T -> A (in PCH14; reduced protein levels in
FT homozygous patient's fibroblasts compared to heterozygous
FT or wild-type cells; dbSNP:rs553128312)"
FT /evidence="ECO:0000269|PubMed:33220177"
FT /id="VAR_085513"
FT VARIANT 131
FT /note="R -> Q (in PCH14; strongly reduced interaction with
FT SNW1; slightly reduced protein levels compared to wild-
FT type, after transfection in HEK293T cell line, reduced
FT thermal stability and increased aggregation propensity in
FT vitro; in transgenic knockin mice, produces a
FT pontocerebellar hypoplasia-like phenotype;
FT dbSNP:rs765668519)"
FT /evidence="ECO:0000269|PubMed:33220177"
FT /id="VAR_085514"
FT MUTAGEN 55
FT /note="R->A: Loss of isomerase activity. Can rescue
FT splicing defects when transfected in knockout cells."
FT /evidence="ECO:0000269|PubMed:33220177"
FT STRAND 12..18
FT /evidence="ECO:0007829|PDB:2X7K"
FT STRAND 21..27
FT /evidence="ECO:0007829|PDB:2X7K"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:2X7K"
FT HELIX 33..45
FT /evidence="ECO:0007829|PDB:2X7K"
FT TURN 46..50
FT /evidence="ECO:0007829|PDB:2X7K"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:2X7K"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:2X7K"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:2X7K"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:2X7K"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:6ID0"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:2X7K"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:2X7K"
FT STRAND 112..117
FT /evidence="ECO:0007829|PDB:2X7K"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:2X7K"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:2X7K"
FT STRAND 128..134
FT /evidence="ECO:0007829|PDB:2X7K"
FT HELIX 136..142
FT /evidence="ECO:0007829|PDB:2X7K"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:1XWN"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:2X7K"
FT STRAND 158..164
FT /evidence="ECO:0007829|PDB:2X7K"
SQ SEQUENCE 166 AA; 18237 MW; 2872DC3336CD05E4 CRC64;
MAAIPPDSWQ PPNVYLETSM GIIVLELYWK HAPKTCKNFA ELARRGYYNG TKFHRIIKDF
MIQGGDPTGT GRGGASIYGK QFEDELHPDL KFTGAGILAM ANAGPDTNGS QFFVTLAPTQ
WLDGKHTIFG RVCQGIGMVN RVGMVETNSQ DRPVDDVKII KAYPSG
