IFT27_HUMAN
ID IFT27_HUMAN Reviewed; 186 AA.
AC Q9BW83; O60897;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Intraflagellar transport protein 27 homolog;
DE AltName: Full=Putative GTP-binding protein RAY-like;
DE AltName: Full=Rab-like protein 4;
GN Name=IFT27; Synonyms=RABL4, RAYL;
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 2).
RX PubMed=12529303; DOI=10.1101/gr.695703;
RA Collins J.E., Goward M.E., Cole C.G., Smink L.J., Huckle E.J., Knowles S.,
RA Bye J.M., Beare D.M., Dunham I.;
RT "Reevaluating human gene annotation: a second-generation analysis of
RT chromosome 22.";
RL Genome Res. 13:27-36(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [6]
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 [7]
RP INVOLVEMENT IN BBS19, VARIANT BBS19 TYR-100, AND CHARACTERIZATION OF
RP VARIANT BBS19 TYR-100.
RX PubMed=24488770; DOI=10.1093/hmg/ddu044;
RA Aldahmesh M.A., Li Y., Alhashem A., Anazi S., Alkuraya H., Hashem M.,
RA Awaji A.A., Sogaty S., Alkharashi A., Alzahrani S., Al Hazzaa S.A.,
RA Xiong Y., Kong S., Sun Z., Alkuraya F.S.;
RT "IFT27, encoding a small GTPase component of IFT particles, is mutated in a
RT consanguineous family with Bardet-Biedl syndrome.";
RL Hum. Mol. Genet. 23:3307-3315(2014).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE IFT COMPLEX B,
RP INTERACTION WITH ARL6, AND MUTAGENESIS OF THR-19 AND LYS-68.
RX PubMed=25443296; DOI=10.1016/j.devcel.2014.09.004;
RA Liew G.M., Ye F., Nager A.R., Murphy J.P., Lee J.S., Aguiar M.,
RA Breslow D.K., Gygi S.P., Nachury M.V.;
RT "The intraflagellar transport protein IFT27 promotes BBSome exit from cilia
RT through the GTPase ARL6/BBS3.";
RL Dev. Cell 31:265-278(2014).
CC -!- FUNCTION: Small GTPase-like component of the intraflagellar transport
CC (IFT) complex B that promotes the exit of the BBSome complex from cilia
CC via its interaction with ARL6 (PubMed:25443296). Not involved in entry
CC of the BBSome complex into cilium. Prevents aggregation of GTP-free
CC ARL6 (PubMed:25443296). Required for hedgehog signaling. Forms a
CC subcomplex within the IFT complex B with IFT25. Its role in
CC intraflagellar transport is mainly seen in tissues rich in ciliated
CC cells such as kidney and testis. Essential for male fertility,
CC spermiogenesis and sperm flagella formation. Plays a role in the early
CC development of the kidney. May be involved in the regulation of
CC ureteric bud initiation (By similarity). {ECO:0000250|UniProtKB:A8HN58,
CC ECO:0000269|PubMed:25443296}.
CC -!- SUBUNIT: Component of the IFT complex B, at least composed of IFT20,
CC IFT25/HSPB11, IFT27, IFT52, IFT57, IFT74, IFT81, IFT88 and TRAF3IP1
CC (PubMed:25443296). Interacts with IFT25/HSPB11 (By similarity).
CC Interacts with TTC30B (By similarity). Interacts with RABL2/RABL2A;
CC binding is equal in the presence of GTP or GDP (By similarity).
CC Interacts with ARL6; recognizes and binds with the GTP-free form of
CC ARL6 (PubMed:25443296). {ECO:0000250|UniProtKB:Q9D0P8,
CC ECO:0000269|PubMed:25443296}.
CC -!- INTERACTION:
CC Q9BW83; Q08379: GOLGA2; NbExp=3; IntAct=EBI-747093, EBI-618309;
CC Q9BW83; Q9Y547: HSPB11; NbExp=20; IntAct=EBI-747093, EBI-747101;
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000269|PubMed:25443296}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9D0P8}. Cell projection, cilium, flagellum
CC {ECO:0000250|UniProtKB:Q9D0P8}. Note=Localizes to the sperm flagellum.
CC {ECO:0000250|UniProtKB:Q9D0P8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BW83-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BW83-2; Sequence=VSP_021019;
CC -!- DISEASE: Bardet-Biedl syndrome 19 (BBS19) [MIM:615996]: A syndrome
CC characterized by usually severe pigmentary retinopathy, early-onset
CC obesity, polydactyly, hypogenitalism, renal malformation and
CC intellectual disability. Secondary features include diabetes mellitus,
CC hypertension and congenital heart disease. Bardet-Biedl syndrome
CC inheritance is autosomal recessive, but three mutated alleles (two at
CC one locus, and a third at a second locus) may be required for clinical
CC manifestation of some forms of the disease.
CC {ECO:0000269|PubMed:24488770}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
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DR EMBL; AL022729; CAA18787.1; -; mRNA.
DR EMBL; CR456558; CAG30444.1; -; mRNA.
DR EMBL; BT006815; AAP35461.1; -; mRNA.
DR EMBL; Z80897; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000566; AAH00566.1; -; mRNA.
DR CCDS; CCDS13932.1; -. [Q9BW83-2]
DR CCDS; CCDS54523.1; -. [Q9BW83-1]
DR RefSeq; NP_001171172.1; NM_001177701.2. [Q9BW83-1]
DR RefSeq; NP_006851.1; NM_006860.4. [Q9BW83-2]
DR RefSeq; XP_006724169.1; XM_006724106.2.
DR AlphaFoldDB; Q9BW83; -.
DR SMR; Q9BW83; -.
DR BioGRID; 116210; 41.
DR ComplexPortal; CPX-5022; IFT-B complex.
DR CORUM; Q9BW83; -.
DR IntAct; Q9BW83; 49.
DR STRING; 9606.ENSP00000393541; -.
DR GlyGen; Q9BW83; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BW83; -.
DR MetOSite; Q9BW83; -.
DR PhosphoSitePlus; Q9BW83; -.
DR BioMuta; IFT27; -.
DR DMDM; 20178058; -.
DR EPD; Q9BW83; -.
DR jPOST; Q9BW83; -.
DR MassIVE; Q9BW83; -.
DR MaxQB; Q9BW83; -.
DR PaxDb; Q9BW83; -.
DR PeptideAtlas; Q9BW83; -.
DR PRIDE; Q9BW83; -.
DR ProteomicsDB; 79261; -. [Q9BW83-1]
DR ProteomicsDB; 79262; -. [Q9BW83-2]
DR Antibodypedia; 11783; 125 antibodies from 23 providers.
DR DNASU; 11020; -.
DR Ensembl; ENST00000340630.9; ENSP00000343593.5; ENSG00000100360.15. [Q9BW83-2]
DR Ensembl; ENST00000433985.7; ENSP00000393541.2; ENSG00000100360.15. [Q9BW83-1]
DR GeneID; 11020; -.
DR KEGG; hsa:11020; -.
DR MANE-Select; ENST00000433985.7; ENSP00000393541.2; NM_001177701.3; NP_001171172.1.
DR UCSC; uc003apu.4; human. [Q9BW83-1]
DR CTD; 11020; -.
DR DisGeNET; 11020; -.
DR GeneCards; IFT27; -.
DR GeneReviews; IFT27; -.
DR HGNC; HGNC:18626; IFT27.
DR HPA; ENSG00000100360; Low tissue specificity.
DR MalaCards; IFT27; -.
DR MIM; 615870; gene.
DR MIM; 615996; phenotype.
DR neXtProt; NX_Q9BW83; -.
DR OpenTargets; ENSG00000100360; -.
DR Orphanet; 110; Bardet-Biedl syndrome.
DR PharmGKB; PA38609; -.
DR VEuPathDB; HostDB:ENSG00000100360; -.
DR eggNOG; KOG0079; Eukaryota.
DR GeneTree; ENSGT00870000136549; -.
DR HOGENOM; CLU_041217_10_6_1; -.
DR InParanoid; Q9BW83; -.
DR OMA; EMSVKEM; -.
DR OrthoDB; 1585129at2759; -.
DR PhylomeDB; Q9BW83; -.
DR TreeFam; TF329292; -.
DR PathwayCommons; Q9BW83; -.
DR Reactome; R-HSA-5620924; Intraflagellar transport.
DR SignaLink; Q9BW83; -.
DR BioGRID-ORCS; 11020; 9 hits in 1068 CRISPR screens.
DR ChiTaRS; IFT27; human.
DR GenomeRNAi; 11020; -.
DR Pharos; Q9BW83; Tbio.
DR PRO; PR:Q9BW83; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q9BW83; protein.
DR Bgee; ENSG00000100360; Expressed in right uterine tube and 171 other tissues.
DR ExpressionAtlas; Q9BW83; baseline and differential.
DR Genevisible; Q9BW83; HS.
DR GO; GO:0005813; C:centrosome; IEA:Ensembl.
DR GO; GO:0097542; C:ciliary tip; TAS:Reactome.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IBA:GO_Central.
DR GO; GO:0030992; C:intraciliary transport particle B; IDA:UniProtKB.
DR GO; GO:0031514; C:motile cilium; ISS:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0036126; C:sperm flagellum; ISS:UniProtKB.
DR GO; GO:0097225; C:sperm midpiece; IEA:Ensembl.
DR GO; GO:0097228; C:sperm principal piece; IEA:Ensembl.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0060271; P:cilium assembly; IC:ComplexPortal.
DR GO; GO:0090102; P:cochlea development; IEA:Ensembl.
DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; IEA:Ensembl.
DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB.
DR GO; GO:0035720; P:intraciliary anterograde transport; IC:ComplexPortal.
DR GO; GO:0042073; P:intraciliary transport; IMP:UniProtKB.
DR GO; GO:0001822; P:kidney development; ISS:UniProtKB.
DR GO; GO:0007224; P:smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR CDD; cd04101; RabL4; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR034112; RabL4_euk.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Bardet-Biedl syndrome; Cell projection; Ciliopathy;
KW Cilium; Cytoplasm; Differentiation; Disease variant; Flagellum;
KW GTP-binding; Nucleotide-binding; Obesity; Protein transport;
KW Reference proteome; Spermatogenesis; Transport.
FT CHAIN 1..186
FT /note="Intraflagellar transport protein 27 homolog"
FT /id="PRO_0000082715"
FT BINDING 12..19
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 64..68
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 123..126
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT VAR_SEQ 12
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12529303"
FT /id="VSP_021019"
FT VARIANT 100
FT /note="C -> Y (in BBS19; loss-of-function mutation; results
FT in significantly reduced protein levels;
FT dbSNP:rs587777546)"
FT /evidence="ECO:0000269|PubMed:24488770"
FT /id="VAR_071804"
FT MUTAGEN 19
FT /note="T->N: GDP-locked."
FT /evidence="ECO:0000269|PubMed:25443296"
FT MUTAGEN 68
FT /note="K->A: GTP-locked."
FT /evidence="ECO:0000269|PubMed:25443296"
SQ SEQUENCE 186 AA; 20480 MW; 78CACF9ADF929B02 CRC64;
MVKLAAKCIL AGDPAVGKTA LAQIFRSDGA HFQKSYTLTT GMDLVVKTVP VPDTGDSVEL
FIFDSAGKEL FSEMLDKLWE SPNVLCLVYD VTNEESFNNC SKWLEKARSQ APGISLPGVL
VGNKTDLAGR RAVDSAEARA WALGQGLECF ETSVKEMENF EAPFHCLAKQ FHQLYREKVE
VFRALA
