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   24-JAN-2024, entry version 190.
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, IFT27, IFT52, IFT57, IFT74, IFT81, IFT88 and TRAF3IP1
CC       (PubMed:25443296). Interacts with IFT25 (By similarity). Interacts with
CC       IFT70B (By similarity). Interacts with RABL2/RABL2A; binding is equal
CC       in the presence of GTP or GDP (By similarity). Interacts with ARL6;
CC       recognizes and binds with the GTP-free form of ARL6 (PubMed:25443296).
CC       {ECO:0000250|UniProtKB:Q9D0P8, ECO:0000269|PubMed:25443296}.
CC   -!- INTERACTION:
CC       Q9BW83; Q08379: GOLGA2; NbExp=3; IntAct=EBI-747093, EBI-618309;
CC       Q9BW83; Q9Y547: IFT25; 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; 45.
DR   ComplexPortal; CPX-5022; Intraflagellar transport complex B.
DR   CORUM; Q9BW83; -.
DR   IntAct; Q9BW83; 49.
DR   STRING; 9606.ENSP00000393541; -.
DR   TCDB; 1.X.1.1.1; the intraflagellar transporter-a complex (ift-a) family.
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; 9606-ENSP00000393541; -.
DR   PeptideAtlas; Q9BW83; -.
DR   ProteomicsDB; 79261; -. [Q9BW83-1]
DR   ProteomicsDB; 79262; -. [Q9BW83-2]
DR   Pumba; Q9BW83; -.
DR   Antibodypedia; 11783; 146 antibodies from 24 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   AGR; HGNC:18626; -.
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; KMWGQPS; -.
DR   OrthoDB; 3662662at2759; -.
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 1146 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 173 other cell types or tissues.
DR   ExpressionAtlas; Q9BW83; baseline and differential.
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; NAS: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; NAS: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; P-loop containing nucleotide triphosphate hydrolases; 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   NCBIfam; TIGR00231; small_GTP; 1.
DR   PANTHER; PTHR47979; DRAB11-RELATED; 1.
DR   PANTHER; PTHR47979:SF7; INTRAFLAGELLAR TRANSPORT PROTEIN 27 HOMOLOG; 1.
DR   Pfam; PF00071; Ras; 1.
DR   PRINTS; PR00449; RASTRNSFRMNG.
DR   SMART; SM00175; RAB; 1.
DR   SMART; SM00173; RAS; 1.
DR   SMART; SM00174; RHO; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   PROSITE; PS51419; RAB; 1.
DR   Genevisible; Q9BW83; HS.
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
//