IF140_HUMAN
ID IF140_HUMAN Reviewed; 1462 AA.
AC Q96RY7; A2A2A8; D3DU75; O60332; Q9UG52;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Intraflagellar transport protein 140 homolog {ECO:0000305};
DE AltName: Full=WD and tetratricopeptide repeats protein 2;
GN Name=IFT140 {ECO:0000312|HGNC:HGNC:29077}; Synonyms=KIAA0590, WDTC2;
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] (ISOFORM 1), AND VARIANT VAL-1070.
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11157797; DOI=10.1093/hmg/10.4.339;
RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C.,
RA Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.;
RT "Sequence, structure and pathology of the fully annotated terminal 2 Mb of
RT the short arm of human chromosome 16.";
RL Hum. Mol. Genet. 10:339-352(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1443, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP FUNCTION, AND IDENTIFICATION IN THE IFT-A COMPLEX.
RX PubMed=20889716; DOI=10.1101/gad.1966210;
RA Mukhopadhyay S., Wen X., Chih B., Nelson C.D., Lane W.S., Scales S.J.,
RA Jackson P.K.;
RT "TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote
RT trafficking of G protein-coupled receptors into primary cilia.";
RL Genes Dev. 24:2180-2193(2010).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, VARIANTS SRTD9 ARG-212; MET-233; MET-292;
RP CYS-311; GLU-522; GLN-576 AND LYS-664, AND CHARACTERIZATION OF VARIANTS
RP SRTD9 ARG-212; CYS-311 AND LYS-664.
RX PubMed=22503633; DOI=10.1016/j.ajhg.2012.03.006;
RA Perrault I., Saunier S., Hanein S., Filhol E., Bizet A.A., Collins F.,
RA Salih M.A., Gerber S., Delphin N., Bigot K., Orssaud C., Silva E.,
RA Baudouin V., Oud M.M., Shannon N., Le Merrer M., Roche O., Pietrement C.,
RA Goumid J., Baumann C., Bole-Feysot C., Nitschke P., Zahrate M., Beales P.,
RA Arts H.H., Munnich A., Kaplan J., Antignac C., Cormier-Daire V.,
RA Rozet J.M.;
RT "Mainzer-Saldino syndrome is a ciliopathy caused by IFT140 mutations.";
RL Am. J. Hum. Genet. 90:864-870(2012).
RN [11]
RP SUBCELLULAR LOCATION, VARIANTS HIS-110; THR-161; GLY-243; SER-459; HIS-514;
RP GLY-787 AND ARG-1353, VARIANTS SRTD9 PHE-152; GLY-267; MET-292; GLU-522 AND
RP ARG-1360, AND CHARACTERIZATION OF VARIANT SRTD9 MET-292.
RX PubMed=23418020; DOI=10.1002/humu.22294;
RA Schmidts M., Frank V., Eisenberger T., Al Turki S., Bizet A.A., Antony D.,
RA Rix S., Decker C., Bachmann N., Bald M., Vinke T., Toenshoff B.,
RA Di Donato N., Neuhann T., Hartley J.L., Maher E.R., Bogdanovic R.,
RA Peco-Antic A., Mache C., Hurles M.E., Joksic I., Guc-Scekic M.,
RA Dobricic J., Brankovic-Magic M., Bolz H.J., Pazour G.J., Beales P.L.,
RA Scambler P.J., Saunier S., Mitchison H.M., Bergmann C.;
RT "Combined NGS approaches identify mutations in the intraflagellar transport
RT gene IFT140 in skeletal ciliopathies with early progressive kidney
RT Disease.";
RL Hum. Mutat. 34:714-724(2013).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-360, 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 [13]
RP INTERACTION WITH TTC25.
RX PubMed=25860617; DOI=10.1371/journal.pone.0124378;
RA Xu Y., Cao J., Huang S., Feng D., Zhang W., Zhu X., Yan X.;
RT "Characterization of tetratricopeptide repeat-containing proteins critical
RT for cilia formation and function.";
RL PLoS ONE 10:E0124378-E0124378(2015).
RN [14]
RP IDENTIFICATION IN THE IFT-A COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=27932497; DOI=10.1091/mbc.e16-11-0813;
RA Hirano T., Katoh Y., Nakayama K.;
RT "Intraflagellar transport-A complex mediates ciliary entry and retrograde
RT trafficking of ciliary G protein-coupled receptors.";
RL Mol. Biol. Cell 28:429-439(2017).
RN [15]
RP IDENTIFICATION IN THE IFT-A COMPLEX.
RX PubMed=29220510; DOI=10.1093/hmg/ddx421;
RA Takahara M., Katoh Y., Nakamura K., Hirano T., Sugawa M., Tsurumi Y.,
RA Nakayama K.;
RT "Ciliopathy-associated mutations of IFT122 impair ciliary protein
RT trafficking but not ciliogenesis.";
RL Hum. Mol. Genet. 27:516-528(2018).
RN [16]
RP INVOLVEMENT IN RP80, AND VARIANTS RP80 LEU-71; ARG-329; PRO-418;
RP 459-TRP--PRO-1462 DEL; MET-484; TRP-663; LYS-790; CYS-871; VAL-974;
RP ARG-1276 AND PRO-1399.
RX PubMed=26216056; DOI=10.1007/s00439-015-1586-x;
RA Xu M., Yang L., Wang F., Li H., Wang X., Wang W., Ge Z., Wang K., Zhao L.,
RA Li H., Li Y., Sui R., Chen R.;
RT "Mutations in human IFT140 cause non-syndromic retinal degeneration.";
RL Hum. Genet. 134:1069-1078(2015).
RN [17]
RP INTERACTION WITH TTC21A.
RX PubMed=30929735; DOI=10.1016/j.ajhg.2019.02.020;
RA Liu W., He X., Yang S., Zouari R., Wang J., Wu H., Kherraf Z.E., Liu C.,
RA Coutton C., Zhao R., Tang D., Tang S., Lv M., Fang Y., Li W., Li H.,
RA Zhao J., Wang X., Zhao S., Zhang J., Arnoult C., Jin L., Zhang Z.,
RA Ray P.F., Cao Y., Zhang F.;
RT "Bi-allelic mutations in TTC21A induce asthenoteratospermia in humans and
RT mice.";
RL Am. J. Hum. Genet. 104:738-748(2019).
RN [18]
RP VARIANT SRTD9 TRP-280.
RX PubMed=24009529; DOI=10.1371/journal.pgen.1003746;
RA Miller K.A., Ah-Cann C.J., Welfare M.F., Tan T.Y., Pope K., Caruana G.,
RA Freckmann M.L., Savarirayan R., Bertram J.F., Dobbie M.S., Bateman J.F.,
RA Farlie P.G.;
RT "Cauli: a mouse strain with an Ift140 mutation that results in a skeletal
RT ciliopathy modelling Jeune syndrome.";
RL PLoS Genet. 9:E1003746-E1003746(2013).
RN [19]
RP VARIANT RP80 LYS-664.
RX PubMed=26359340; DOI=10.1136/bjophthalmol-2015-307555;
RA Bifari I.N., Elkhamary S.M., Bolz H.J., Khan A.O.;
RT "The ophthalmic phenotype of IFT140-related ciliopathy ranges from isolated
RT to syndromic congenital retinal dystrophy.";
RL Br. J. Ophthalmol. 100:829-833(2016).
RN [20]
RP VARIANTS RP80 TYR-333; THR-341; PRO-440; MET-484 AND PRO-939, VARIANT
RP ARG-777, CHARACTERIZATION RP80 PRO-440; MET-484; LYS-664 AND PRO-939,
RP CHARACTERIZATION OF VARIANT ARG-777, AND SUBCELLULAR LOCATION.
RX PubMed=26968735; DOI=10.1167/iovs.15-17976;
RA Hull S., Owen N., Islam F., Tracey-White D., Plagnol V., Holder G.E.,
RA Michaelides M., Carss K., Raymond F.L., Rozet J.M., Ramsden S.C.,
RA Black G.C., Perrault I., Sarkar A., Moosajee M., Webster A.R., Arno G.,
RA Moore A.T.;
RT "Nonsyndromic Retinal Dystrophy due to Bi-Allelic Mutations in the Ciliary
RT Transport Gene IFT140.";
RL Invest. Ophthalmol. Vis. Sci. 57:1053-1062(2016).
RN [21]
RP VARIANTS SRTD9 ARG-212 AND 760-ARG--PRO-1462 DEL.
RX PubMed=28288023; DOI=10.1097/mcd.0000000000000169;
RG DDD Study;
RA Bayat A., Kerr B., Douzgou S.;
RT "The evolving craniofacial phenotype of a patient with Sensenbrenner
RT syndrome caused by IFT140 compound heterozygous mutations.";
RL Clin. Dysmorphol. 26:247-251(2017).
RN [22]
RP VARIANT SRTD9 ARG-212, CHARACTERIZATION OF VARIANT SRTD9 ARG-212, AND
RP FUNCTION.
RX PubMed=28724397; DOI=10.1186/s40246-017-0111-9;
RA Helm B.M., Willer J.R., Sadeghpour A., Golzio C., Crouch E., Vergano S.S.,
RA Katsanis N., Davis E.E.;
RT "Partial uniparental isodisomy of chromosome 16 unmasks a deleterious
RT biallelic mutation in IFT140 that causes Mainzer-Saldino syndrome.";
RL Hum. Genomics 11:16-16(2017).
CC -!- FUNCTION: Component of the IFT complex A (IFT-A), a complex required
CC for retrograde ciliary transport and entry into cilia of G protein-
CC coupled receptors (GPCRs) (PubMed:20889716, PubMed:22503633). Plays a
CC pivotal role in proper development and function of ciliated cells
CC through its role in ciliogenesis and/or cilium maintenance
CC (PubMed:22503633). Required for the development and maintenance of the
CC outer segments of rod and cone photoreceptor cells. Plays a role in
CC maintenance and the delivery of opsin to the outer segment of
CC photoreceptor cells (By similarity). {ECO:0000250|UniProtKB:E9PY46,
CC ECO:0000269|PubMed:20889716, ECO:0000269|PubMed:22503633,
CC ECO:0000269|PubMed:28724397}.
CC -!- SUBUNIT: Component of the IFT complex A (IFT-A) (PubMed:20889716). IFT-
CC A complex is divided into a core subcomplex composed of
CC IFT122:IFT140:WDR19 which is associated with TULP3 and a peripheral
CC subcomplex composed of IFT43:WDR35:TTC21B (PubMed:27932497,
CC PubMed:29220510). Interacts (via C-terminal region) with IFT122 (via C-
CC terminal region) (PubMed:29220510). Interacts with TTC25
CC (PubMed:25860617). Interacts with TTC21A (PubMed:30929735).
CC {ECO:0000269|PubMed:20889716, ECO:0000269|PubMed:25860617,
CC ECO:0000269|PubMed:27932497, ECO:0000269|PubMed:29220510,
CC ECO:0000269|PubMed:30929735}.
CC -!- INTERACTION:
CC Q96RY7; Q8NEZ3: WDR19; NbExp=8; IntAct=EBI-308494, EBI-11903679;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000269|PubMed:22503633, ECO:0000269|PubMed:26968735}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:23418020}. Cell projection, cilium
CC {ECO:0000269|PubMed:22503633, ECO:0000269|PubMed:26968735,
CC ECO:0000269|PubMed:27932497}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96RY7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96RY7-2; Sequence=VSP_056392;
CC -!- DISEASE: Short-rib thoracic dysplasia 9 with or without polydactyly
CC (SRTD9) [MIM:266920]: A form of short-rib thoracic dysplasia, a group
CC of autosomal recessive ciliopathies that are characterized by a
CC constricted thoracic cage, short ribs, shortened tubular bones, and a
CC 'trident' appearance of the acetabular roof. Polydactyly is variably
CC present. Non-skeletal involvement can include cleft lip/palate as well
CC as anomalies of major organs such as the brain, eye, heart, kidneys,
CC liver, pancreas, intestines, and genitalia. Some forms of the disease
CC are lethal in the neonatal period due to respiratory insufficiency
CC secondary to a severely restricted thoracic cage, whereas others are
CC compatible with life. Disease spectrum encompasses Ellis-van Creveld
CC syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-
CC Saldino syndrome, and short rib-polydactyly syndrome. SRTD9 is
CC characterized by phalangeal cone-shaped epiphyses, chronic renal
CC disease, nearly constant retinal dystrophy, and mild radiographic
CC abnormality of the proximal femur. Occasional features include short
CC stature, cerebellar ataxia, and hepatic fibrosis.
CC {ECO:0000269|PubMed:22503633, ECO:0000269|PubMed:23418020,
CC ECO:0000269|PubMed:24009529, ECO:0000269|PubMed:28288023,
CC ECO:0000269|PubMed:28724397}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Retinitis pigmentosa 80 (RP80) [MIM:617781]: A retinal
CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis
CC pigmentosa is characterized by retinal pigment deposits visible on
CC fundus examination and primary loss of rod photoreceptor cells followed
CC by secondary loss of cone photoreceptors. Patients typically have night
CC vision blindness and loss of midperipheral visual field. As their
CC condition progresses, they lose their far peripheral visual field and
CC eventually central vision as well. RP80 inheritance is autosomal
CC recessive. {ECO:0000269|PubMed:26216056, ECO:0000269|PubMed:26359340,
CC ECO:0000269|PubMed:26968735}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25516.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB011162; BAA25516.2; ALT_INIT; mRNA.
DR EMBL; AE006467; AAK61285.1; -; Genomic_DNA.
DR EMBL; AL080069; CAB45696.1; -; mRNA.
DR EMBL; AL031705; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z97633; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL031719; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z97652; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL133297; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85642.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85644.1; -; Genomic_DNA.
DR EMBL; BC035577; AAH35577.1; -; mRNA.
DR CCDS; CCDS10439.1; -. [Q96RY7-1]
DR PIR; T00345; T00345.
DR RefSeq; NP_055529.2; NM_014714.3. [Q96RY7-1]
DR RefSeq; XP_006721053.1; XM_006720990.3. [Q96RY7-1]
DR RefSeq; XP_006721054.1; XM_006720991.3. [Q96RY7-1]
DR RefSeq; XP_016879399.1; XM_017023910.1. [Q96RY7-1]
DR AlphaFoldDB; Q96RY7; -.
DR SMR; Q96RY7; -.
DR BioGRID; 115090; 76.
DR ComplexPortal; CPX-5021; IFT-A complex.
DR CORUM; Q96RY7; -.
DR IntAct; Q96RY7; 24.
DR MINT; Q96RY7; -.
DR STRING; 9606.ENSP00000406012; -.
DR iPTMnet; Q96RY7; -.
DR PhosphoSitePlus; Q96RY7; -.
DR BioMuta; IFT140; -.
DR DMDM; 74761083; -.
DR EPD; Q96RY7; -.
DR jPOST; Q96RY7; -.
DR MassIVE; Q96RY7; -.
DR MaxQB; Q96RY7; -.
DR PaxDb; Q96RY7; -.
DR PeptideAtlas; Q96RY7; -.
DR PRIDE; Q96RY7; -.
DR ProteomicsDB; 78049; -. [Q96RY7-1]
DR Antibodypedia; 23147; 79 antibodies from 20 providers.
DR DNASU; 9742; -.
DR Ensembl; ENST00000361339.9; ENSP00000354895.5; ENSG00000187535.14. [Q96RY7-2]
DR Ensembl; ENST00000426508.7; ENSP00000406012.2; ENSG00000187535.14. [Q96RY7-1]
DR GeneID; 9742; -.
DR KEGG; hsa:9742; -.
DR MANE-Select; ENST00000426508.7; ENSP00000406012.2; NM_014714.4; NP_055529.2.
DR UCSC; uc002cmb.4; human. [Q96RY7-1]
DR CTD; 9742; -.
DR DisGeNET; 9742; -.
DR GeneCards; IFT140; -.
DR GeneReviews; IFT140; -.
DR HGNC; HGNC:29077; IFT140.
DR HPA; ENSG00000187535; Low tissue specificity.
DR MalaCards; IFT140; -.
DR MIM; 266920; phenotype.
DR MIM; 614620; gene.
DR MIM; 617781; phenotype.
DR neXtProt; NX_Q96RY7; -.
DR OpenTargets; ENSG00000187535; -.
DR Orphanet; 730; Autosomal dominant polycystic kidney disease.
DR Orphanet; 474; Jeune syndrome.
DR Orphanet; 65; Leber congenital amaurosis.
DR Orphanet; 791; Retinitis pigmentosa.
DR Orphanet; 140969; Saldino-Mainzer syndrome.
DR PharmGKB; PA142671665; -.
DR VEuPathDB; HostDB:ENSG00000187535; -.
DR eggNOG; KOG3617; Eukaryota.
DR GeneTree; ENSGT00940000153417; -.
DR HOGENOM; CLU_001853_0_0_1; -.
DR InParanoid; Q96RY7; -.
DR OMA; RMCVKTK; -.
DR OrthoDB; 41516at2759; -.
DR PhylomeDB; Q96RY7; -.
DR TreeFam; TF105851; -.
DR PathwayCommons; Q96RY7; -.
DR Reactome; R-HSA-5610787; Hedgehog 'off' state.
DR Reactome; R-HSA-5620924; Intraflagellar transport.
DR SignaLink; Q96RY7; -.
DR BioGRID-ORCS; 9742; 15 hits in 1076 CRISPR screens.
DR ChiTaRS; IFT140; human.
DR GenomeRNAi; 9742; -.
DR Pharos; Q96RY7; Tbio.
DR PRO; PR:Q96RY7; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q96RY7; protein.
DR Bgee; ENSG00000187535; Expressed in right uterine tube and 134 other tissues.
DR ExpressionAtlas; Q96RY7; baseline and differential.
DR Genevisible; Q96RY7; HS.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0005814; C:centriole; IEA:Ensembl.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0097542; C:ciliary tip; TAS:Reactome.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0120199; C:cone photoreceptor outer segment; IEA:Ensembl.
DR GO; GO:0030991; C:intraciliary transport particle A; IDA:UniProtKB.
DR GO; GO:0032391; C:photoreceptor connecting cilium; IEA:Ensembl.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; IEA:Ensembl.
DR GO; GO:1990403; P:embryonic brain development; IEA:Ensembl.
DR GO; GO:0031076; P:embryonic camera-type eye development; IEA:Ensembl.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0035721; P:intraciliary retrograde transport; IMP:UniProtKB.
DR GO; GO:0042073; P:intraciliary transport; IBA:GO_Central.
DR GO; GO:0021532; P:neural tube patterning; IEA:Ensembl.
DR GO; GO:1905515; P:non-motile cilium assembly; IEA:Ensembl.
DR GO; GO:0035845; P:photoreceptor cell outer segment organization; IEA:Ensembl.
DR GO; GO:0061512; P:protein localization to cilium; IMP:UniProtKB.
DR GO; GO:1902017; P:regulation of cilium assembly; IMP:UniProtKB.
DR GO; GO:0008589; P:regulation of smoothened signaling pathway; IEA:Ensembl.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR SMART; SM00320; WD40; 3.
DR SUPFAM; SSF50978; SSF50978; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Ciliopathy; Cilium;
KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; Disease variant;
KW Phosphoprotein; Reference proteome; Repeat; Retinitis pigmentosa;
KW TPR repeat; WD repeat.
FT CHAIN 1..1462
FT /note="Intraflagellar transport protein 140 homolog"
FT /id="PRO_0000051046"
FT REPEAT 4..48
FT /note="WD 1"
FT REPEAT 51..90
FT /note="WD 2"
FT REPEAT 93..132
FT /note="WD 3"
FT REPEAT 139..188
FT /note="WD 4"
FT REPEAT 221..259
FT /note="WD 5"
FT REPEAT 266..305
FT /note="WD 6"
FT REPEAT 322..361
FT /note="WD 7"
FT REPEAT 772..807
FT /note="TPR 1"
FT REPEAT 869..904
FT /note="TPR 2"
FT REPEAT 906..934
FT /note="TPR 3"
FT REPEAT 955..988
FT /note="TPR 4"
FT REPEAT 1010..1043
FT /note="TPR 5"
FT REPEAT 1078..1111
FT /note="TPR 6"
FT REPEAT 1123..1156
FT /note="TPR 7"
FT REPEAT 1189..1222
FT /note="TPR 8"
FT REPEAT 1376..1409
FT /note="TPR 9"
FT REGION 1434..1462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1443
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT VAR_SEQ 1..806
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_056392"
FT VARIANT 71
FT /note="P -> L (in RP80; unknown pathological significance;
FT dbSNP:rs772757427)"
FT /evidence="ECO:0000269|PubMed:26216056"
FT /id="VAR_080667"
FT VARIANT 110
FT /note="R -> H (in dbSNP:rs371077545)"
FT /evidence="ECO:0000269|PubMed:23418020"
FT /id="VAR_070999"
FT VARIANT 152
FT /note="L -> F (in SRTD9; dbSNP:rs1403669200)"
FT /evidence="ECO:0000269|PubMed:23418020"
FT /id="VAR_071000"
FT VARIANT 161
FT /note="P -> T (in dbSNP:rs148462329)"
FT /evidence="ECO:0000269|PubMed:23418020"
FT /id="VAR_071001"
FT VARIANT 165
FT /note="D -> A (in dbSNP:rs35588860)"
FT /id="VAR_053396"
FT VARIANT 212
FT /note="G -> R (in SRTD9; partial to complete loss of basal
FT body localization and increase of cytoplasmic localization;
FT partial loss of function; dbSNP:rs201188361)"
FT /evidence="ECO:0000269|PubMed:22503633,
FT ECO:0000269|PubMed:28288023, ECO:0000269|PubMed:28724397"
FT /id="VAR_068523"
FT VARIANT 233
FT /note="I -> M (in SRTD9)"
FT /evidence="ECO:0000269|PubMed:22503633"
FT /id="VAR_068524"
FT VARIANT 243
FT /note="E -> G (in dbSNP:rs539181813)"
FT /evidence="ECO:0000269|PubMed:23418020"
FT /id="VAR_071002"
FT VARIANT 267
FT /note="E -> G (in SRTD9; disease phenotype consistent with
FT Mainzer-Saldino syndrome)"
FT /evidence="ECO:0000269|PubMed:23418020"
FT /id="VAR_071003"
FT VARIANT 279
FT /note="R -> P (in dbSNP:rs4786350)"
FT /id="VAR_053397"
FT VARIANT 280
FT /note="R -> Q (in dbSNP:rs35404373)"
FT /id="VAR_053398"
FT VARIANT 280
FT /note="R -> W (in SRTD9; dbSNP:rs8058674)"
FT /evidence="ECO:0000269|PubMed:24009529"
FT /id="VAR_078817"
FT VARIANT 292
FT /note="V -> M (in SRTD9; impairs centrosomal localization;
FT dbSNP:rs431905521)"
FT /evidence="ECO:0000269|PubMed:22503633,
FT ECO:0000269|PubMed:23418020"
FT /id="VAR_068525"
FT VARIANT 311
FT /note="Y -> C (in SRTD9; partial to complete loss of basal
FT body localization and increase of cytoplasmic localization;
FT dbSNP:rs387907193)"
FT /evidence="ECO:0000269|PubMed:22503633"
FT /id="VAR_068526"
FT VARIANT 329
FT /note="C -> R (in RP80; unknown pathological significance;
FT dbSNP:rs1441549097)"
FT /evidence="ECO:0000269|PubMed:26216056"
FT /id="VAR_080668"
FT VARIANT 333
FT /note="C -> Y (in RP80; unknown pathological significance;
FT dbSNP:rs773372123)"
FT /evidence="ECO:0000269|PubMed:26968735"
FT /id="VAR_080669"
FT VARIANT 341
FT /note="A -> T (in RP80; unknown pathological significance;
FT dbSNP:rs200292484)"
FT /evidence="ECO:0000269|PubMed:26968735"
FT /id="VAR_080670"
FT VARIANT 398
FT /note="V -> I (in dbSNP:rs34762152)"
FT /id="VAR_053399"
FT VARIANT 418
FT /note="A -> P (in RP80; unknown pathological significance;
FT dbSNP:rs770890983)"
FT /evidence="ECO:0000269|PubMed:26216056"
FT /id="VAR_080671"
FT VARIANT 440
FT /note="L -> P (in RP80; also found in a patient with Leber
FT congenital amaurosis and renal failure; unknown
FT pathological significance; decreased localization to the
FT basal body; dbSNP:rs1555491448)"
FT /evidence="ECO:0000269|PubMed:26968735"
FT /id="VAR_080672"
FT VARIANT 451
FT /note="A -> V (in dbSNP:rs8060532)"
FT /id="VAR_053400"
FT VARIANT 459..1462
FT /note="Missing (in RP80; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26216056"
FT /id="VAR_080673"
FT VARIANT 459
FT /note="W -> S (in dbSNP:rs778311141)"
FT /evidence="ECO:0000269|PubMed:23418020"
FT /id="VAR_071004"
FT VARIANT 484
FT /note="T -> M (in RP80; unknown pathological significance;
FT decreased localization to the basal body;
FT dbSNP:rs758052634)"
FT /evidence="ECO:0000269|PubMed:26216056,
FT ECO:0000269|PubMed:26968735"
FT /id="VAR_080674"
FT VARIANT 514
FT /note="L -> H (in dbSNP:rs150903791)"
FT /evidence="ECO:0000269|PubMed:23418020"
FT /id="VAR_071005"
FT VARIANT 522
FT /note="G -> E (in SRTD9; dbSNP:rs199826737)"
FT /evidence="ECO:0000269|PubMed:22503633,
FT ECO:0000269|PubMed:23418020"
FT /id="VAR_068527"
FT VARIANT 561
FT /note="S -> N (in dbSNP:rs8050974)"
FT /id="VAR_062098"
FT VARIANT 576
FT /note="R -> Q (in SRTD9; dbSNP:rs373111085)"
FT /evidence="ECO:0000269|PubMed:22503633"
FT /id="VAR_068528"
FT VARIANT 621
FT /note="R -> Q (in dbSNP:rs11648609)"
FT /id="VAR_053401"
FT VARIANT 663
FT /note="C -> W (in RP80; unknown pathological significance;
FT dbSNP:rs781117803)"
FT /evidence="ECO:0000269|PubMed:26216056"
FT /id="VAR_080675"
FT VARIANT 664
FT /note="E -> K (in SRTD9 and RP80; unknown pathological
FT significance; partial to complete loss of basal body
FT localization and increase of cytoplasmic localization;
FT dbSNP:rs387907192)"
FT /evidence="ECO:0000269|PubMed:22503633,
FT ECO:0000269|PubMed:26359340, ECO:0000269|PubMed:26968735"
FT /id="VAR_068529"
FT VARIANT 670
FT /note="P -> S (in dbSNP:rs34900355)"
FT /id="VAR_053402"
FT VARIANT 760..1462
FT /note="Missing (in SRTD9; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28288023"
FT /id="VAR_080676"
FT VARIANT 777
FT /note="L -> R (no effect on localization to the basal body;
FT dbSNP:rs34535263)"
FT /evidence="ECO:0000269|PubMed:26968735"
FT /id="VAR_080677"
FT VARIANT 787
FT /note="D -> G (in dbSNP:rs144938800)"
FT /evidence="ECO:0000269|PubMed:23418020"
FT /id="VAR_071006"
FT VARIANT 790
FT /note="E -> K (in RP80; unknown pathological significance;
FT dbSNP:rs751323480)"
FT /evidence="ECO:0000269|PubMed:26216056"
FT /id="VAR_080678"
FT VARIANT 871
FT /note="R -> C (in RP80; unknown pathological significance;
FT dbSNP:rs767213195)"
FT /evidence="ECO:0000269|PubMed:26216056"
FT /id="VAR_080679"
FT VARIANT 939
FT /note="S -> P (in RP80; unknown pathological significance;
FT decreased localization to the basal body;
FT dbSNP:rs145549969)"
FT /evidence="ECO:0000269|PubMed:26968735"
FT /id="VAR_080680"
FT VARIANT 974
FT /note="A -> V (in RP80; unknown pathological significance;
FT dbSNP:rs745576178)"
FT /evidence="ECO:0000269|PubMed:26216056"
FT /id="VAR_080681"
FT VARIANT 1070
FT /note="A -> V (in dbSNP:rs2235638)"
FT /evidence="ECO:0000269|PubMed:9628581"
FT /id="VAR_053403"
FT VARIANT 1276
FT /note="G -> R (in RP80; unknown pathological significance;
FT dbSNP:rs200065348)"
FT /evidence="ECO:0000269|PubMed:26216056"
FT /id="VAR_080682"
FT VARIANT 1353
FT /note="P -> R (in dbSNP:rs146666187)"
FT /evidence="ECO:0000269|PubMed:23418020"
FT /id="VAR_071007"
FT VARIANT 1360
FT /note="C -> R (in SRTD9; disease phenotype consistent with
FT Mainzer-Saldino syndrome; dbSNP:rs431905520)"
FT /evidence="ECO:0000269|PubMed:23418020"
FT /id="VAR_071008"
FT VARIANT 1399
FT /note="L -> P (in RP80; unknown pathological significance;
FT dbSNP:rs559371453)"
FT /evidence="ECO:0000269|PubMed:26216056"
FT /id="VAR_080683"
FT CONFLICT 542
FT /note="H -> L (in Ref. 1; BAA25516)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1462 AA; 165193 MW; 2F3CCBD998F80E3B CRC64;
MALYYDHQIE APDAAGSPSF ISWHPVHPFL AVAYISTTST GSVDIYLEQG ECVPDTHVER
PFRVASLCWH PTRLVLAVGW ETGEVTVFNK QDKEQHTMPL THTADITVLR WSPSGNCLLS
GDRLGVLLLW RLDQRGRVQG TPLLKHEYGK HLTHCIFRLP PPGEDLVQLA KAAVSGDEKA
LDMFNWKKSS SGSLLKMGSH EGLLFFVSLM DGTVHYVDEK GKTTQVVSAD STIQMLFYME
KREALVVVTE NLRLSLYTVP PEGKAEEVMK VKLSGKTGRR ADIALIEGSL LVMAVGEAAL
RFWDIERGEN YILSPDEKFG FEKGENMNCV CYCKVKGLLA AGTDRGRVAM WRKVPDFLGS
PGAEGKDRWA LQTPTELQGN ITQIQWGSRK NLLAVNSVIS VAILSERAMS SHFHQQVAAM
QVSPSLLNVC FLSTGVAHSL RTDMHISGVF ATKDAVAVWN GRQVAIFELS GAAIRSAGTF
LCETPVLAMH EENVYTVESN RVQVRTWQGT VKQLLLFSET EGNPCFLDIC GNFLVVGTDL
AHFKSFDLSR REAKAHCSCR SLAELVPGVG GIASLRCSSS GSTISILPSK ADNSPDSKIC
FYDVEMDTVT VFDFKTGQID RRETLSFNEQ ETNKSHLFVD EGLKNYVPVN HFWDQSEPRL
FVCEAVQETP RSQPQSANGQ PQDGRAGPAA DVLILSFFIS EEHGFLLHES FPRPATSHSL
LGMEVPYYYF TRKPEEADRE DEVEPGCHHI PQMVSRRPLR DFVGLEDCDK ATRDAMLHFS
FFVTIGDMDE AFKSIKLIKS EAVWENMARM CVKTQRLDVA KVCLGNMGHA RGARALREAE
QEPELEARVA VLATQLGMLE DAEQLYRKCK RHDLLNKFYQ AAGRWQEALQ VAEHHDRVHL
RSTYHRYAGH LEASADCSRA LSYYEKSDTH RFEVPRMLSE DLPSLELYVN KMKDKTLWRW
WAQYLESQGE MDAALHYYEL ARDHFSLVRI HCFQGNVQKA AQIANETGNL AASYHLARQY
ESQEEVGQAV HFYTRAQAFK NAIRLCKENG LDDQLMNLAL LSSPEDMIEA ARYYEEKGVQ
MDRAVMLYHK AGHFSKALEL AFATQQFVAL QLIAEDLDET SDPALLARCS DFFIEHSQYE
RAVELLLAAR KYQEALQLCL GQNMSITEEM AEKMTVAKDS SDLPEESRRE LLEQIADCCM
RQGSYHLATK KYTQAGNKLK AMRALLKSGD TEKITFFASV SRQKEIYIMA ANYLQSLDWR
KEPEIMKNII GFYTKGRALD LLAGFYDACA QVEIDEYQNY DKAHGALTEA YKCLAKAKAK
SPLDQETRLA QLQSRMALVK RFIQARRTYT EDPKESIKQC ELLLEEPDLD STIRIGDVYG
FLVEHYVRKE EYQTAYRFLE EMRRRLPLAN MSYYVSPQAV DAVHRGLGLP LPRTVPEQVR
HNSMEDAREL DEEVVEEADD DP
