IFT56_HUMAN
ID IFT56_HUMAN Reviewed; 554 AA.
AC A0AVF1; A4D1S3; B7Z5M0; C9J2N7; F8W724; Q9H9S8; Q9NTC0;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Intraflagellar transport protein 56 {ECO:0000250|UniProtKB:Q8BS45};
DE AltName: Full=Tetratricopeptide repeat protein 26 {ECO:0000312|HGNC:HGNC:21882};
DE Short=TPR repeat protein 26 {ECO:0000312|HGNC:HGNC:21882};
GN Name=TTC26 {ECO:0000312|HGNC:HGNC:21882};
GN Synonyms=IFT56 {ECO:0000250|UniProtKB:Q8BS45};
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] (ISOFORMS 1 AND 3).
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-335 (ISOFORM 1/2).
RC TISSUE=Testis;
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 [6]
RP INVOLVEMENT IN BRENS, AND VARIANT BRENS SER-263.
RX PubMed=32617964; DOI=10.1111/cge.13805;
RA David O., Eskin-Schwartz M., Ling G., Dolgin V., Kristal E., Benkowitz E.,
RA Osyntsov L., Gradstein L., Birk O.S., Loewenthal N., Yerushalmi B.;
RT "Pituitary stalk interruption syndrome broadens the clinical spectrum of
RT the TTC26 ciliopathy.";
RL Clin. Genet. 98:303-307(2020).
RN [7]
RP VARIANTS BRENS SER-263 AND LEU-444, CHARACTERIZATION OF VARIANT BRENS
RP SER-263, AND FUNCTION.
RX PubMed=31595528; DOI=10.1002/hep.30982;
RA Shaheen R., Alsahli S., Ewida N., Alzahrani F., Shamseldin H.E., Patel N.,
RA Al Qahtani A., Alhebbi H., Alhashem A., Al-Sheddi T., Alomar R.,
RA Alobeid E., Abouelhoda M., Monies D., Al-Hussaini A., Alzouman M.A.,
RA Shagrani M., Faqeih E., Alkuraya F.S.;
RT "Biallelic Mutations in Tetratricopeptide Repeat Domain 26 (Intraflagellar
RT Transport 56) Cause Severe Biliary Ciliopathy in Humans.";
RL Hepatology 71:2067-2079(2020).
CC -!- FUNCTION: Component of the intraflagellar transport (IFT) complex B
CC required for transport of proteins in the motile cilium. Required for
CC transport of specific ciliary cargo proteins related to motility, while
CC it is neither required for IFT complex B assembly or motion nor for
CC cilium assembly. Required for efficient coupling between the
CC accumulation of GLI2 and GLI3 at the ciliary tips and their
CC dissociation from the negative regulator SUFU. Plays a key role in
CC maintaining the integrity of the IFT complex B and the proper ciliary
CC localization of the IFT complex B components. Not required for IFT
CC complex A ciliary localization or function. Essential for maintaining
CC proper microtubule organization within the ciliary axoneme.
CC {ECO:0000269|PubMed:31595528}.
CC -!- SUBUNIT: Component of the IFT complex B. Interacts with IFT46; the
CC interaction is direct. {ECO:0000250|UniProtKB:Q8BS45}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q8BS45}. Note=Localizes at the base to the
CC ciliary transition zone. {ECO:0000250|UniProtKB:Q8BS45}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A0AVF1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A0AVF1-2; Sequence=VSP_043751;
CC Name=3;
CC IsoId=A0AVF1-3; Sequence=VSP_044791;
CC -!- DISEASE: Biliary, renal, neurologic, and skeletal syndrome (BRENS)
CC [MIM:619534]: An autosomal recessive ciliopathy with multisystemic
CC manifestations including severe neonatal cholestasis that progresses to
CC liver fibrosis and cirrhosis, postaxial polydactyly, hydrocephalus,
CC retinal abnormalities, and situs inversus. Additional features may
CC include congenital cardiac defects, echogenic kidneys with renal
CC failure, ocular abnormalities, joint hyperextensibility, and dysmorphic
CC facial features. Some patients have global developmental delay. Brain
CC imaging typically shows dilated ventricles, hypomyelination, and white
CC matter abnormalities, although some patients have been described with
CC abnormal pituitary development. {ECO:0000269|PubMed:31595528,
CC ECO:0000269|PubMed:32617964}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the IFT56 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAL24039.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK022633; BAB14143.1; -; mRNA.
DR EMBL; AK299132; BAH12956.1; -; mRNA.
DR EMBL; AC009220; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC018644; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236950; EAL24039.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC126331; AAI26332.1; -; mRNA.
DR EMBL; BC130339; AAI30340.1; -; mRNA.
DR EMBL; BC144151; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL137393; CAB70721.2; -; mRNA.
DR CCDS; CCDS55172.1; -. [A0AVF1-2]
DR CCDS; CCDS55173.1; -. [A0AVF1-3]
DR CCDS; CCDS5852.1; -. [A0AVF1-1]
DR PIR; T46452; T46452.
DR RefSeq; NP_001138392.1; NM_001144920.2. [A0AVF1-2]
DR RefSeq; NP_001138395.1; NM_001144923.2. [A0AVF1-3]
DR RefSeq; NP_079202.2; NM_024926.3. [A0AVF1-1]
DR AlphaFoldDB; A0AVF1; -.
DR SMR; A0AVF1; -.
DR BioGRID; 123052; 93.
DR ComplexPortal; CPX-5022; IFT-B complex.
DR CORUM; A0AVF1; -.
DR IntAct; A0AVF1; 19.
DR MINT; A0AVF1; -.
DR STRING; 9606.ENSP00000419279; -.
DR iPTMnet; A0AVF1; -.
DR PhosphoSitePlus; A0AVF1; -.
DR BioMuta; TTC26; -.
DR EPD; A0AVF1; -.
DR jPOST; A0AVF1; -.
DR MassIVE; A0AVF1; -.
DR MaxQB; A0AVF1; -.
DR PaxDb; A0AVF1; -.
DR PeptideAtlas; A0AVF1; -.
DR PRIDE; A0AVF1; -.
DR ProteomicsDB; 16; -. [A0AVF1-1]
DR ProteomicsDB; 17; -. [A0AVF1-2]
DR ProteomicsDB; 29874; -.
DR Antibodypedia; 52471; 100 antibodies from 18 providers.
DR DNASU; 79989; -.
DR Ensembl; ENST00000343187.8; ENSP00000339135.4; ENSG00000105948.13. [A0AVF1-3]
DR Ensembl; ENST00000430935.5; ENSP00000410655.1; ENSG00000105948.13. [A0AVF1-2]
DR Ensembl; ENST00000464848.5; ENSP00000419279.1; ENSG00000105948.13. [A0AVF1-1]
DR GeneID; 79989; -.
DR KEGG; hsa:79989; -.
DR MANE-Select; ENST00000464848.5; ENSP00000419279.1; NM_024926.4; NP_079202.2.
DR UCSC; uc003vus.4; human. [A0AVF1-1]
DR CTD; 79989; -.
DR DisGeNET; 79989; -.
DR GeneCards; TTC26; -.
DR HGNC; HGNC:21882; TTC26.
DR HPA; ENSG00000105948; Low tissue specificity.
DR MIM; 617453; gene.
DR MIM; 619534; phenotype.
DR neXtProt; NX_A0AVF1; -.
DR OpenTargets; ENSG00000105948; -.
DR PharmGKB; PA144596245; -.
DR VEuPathDB; HostDB:ENSG00000105948; -.
DR eggNOG; KOG3785; Eukaryota.
DR GeneTree; ENSGT00390000000159; -.
DR HOGENOM; CLU_036306_2_0_1; -.
DR InParanoid; A0AVF1; -.
DR OMA; FIIRRDY; -.
DR OrthoDB; 383516at2759; -.
DR PhylomeDB; A0AVF1; -.
DR TreeFam; TF105816; -.
DR PathwayCommons; A0AVF1; -.
DR Reactome; R-HSA-5620924; Intraflagellar transport.
DR SignaLink; A0AVF1; -.
DR BioGRID-ORCS; 79989; 5 hits in 1074 CRISPR screens.
DR ChiTaRS; TTC26; human.
DR GenomeRNAi; 79989; -.
DR Pharos; A0AVF1; Tbio.
DR PRO; PR:A0AVF1; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; A0AVF1; protein.
DR Bgee; ENSG00000105948; Expressed in bronchial epithelial cell and 118 other tissues.
DR ExpressionAtlas; A0AVF1; baseline and differential.
DR Genevisible; A0AVF1; HS.
DR GO; GO:0005813; C:centrosome; IEA:Ensembl.
DR GO; GO:0036064; C:ciliary basal body; IBA:GO_Central.
DR GO; GO:0097546; C:ciliary base; IBA:GO_Central.
DR GO; GO:0097542; C:ciliary tip; TAS:Reactome.
DR GO; GO:0005929; C:cilium; IMP:UniProtKB.
DR GO; GO:0030992; C:intraciliary transport particle B; IPI:ComplexPortal.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0120170; F:intraciliary transport particle B binding; IBA:GO_Central.
DR GO; GO:0035082; P:axoneme assembly; ISS:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0035720; P:intraciliary anterograde transport; IBA:GO_Central.
DR GO; GO:0042073; P:intraciliary transport; ISS:UniProtKB.
DR GO; GO:0035735; P:intraciliary transport involved in cilium assembly; IBA:GO_Central.
DR GO; GO:1905198; P:manchette assembly; IEA:Ensembl.
DR GO; GO:0061512; P:protein localization to cilium; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0007224; P:smoothened signaling pathway; ISS:UniProtKB.
DR Gene3D; 1.25.40.10; -; 3.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR InterPro; IPR030511; TTC26.
DR PANTHER; PTHR14781; PTHR14781; 1.
DR SMART; SM00028; TPR; 5.
DR SUPFAM; SSF48452; SSF48452; 2.
DR PROSITE; PS50293; TPR_REGION; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Ciliopathy; Cilium; Disease variant;
KW Protein transport; Reference proteome; Repeat; TPR repeat; Transport.
FT CHAIN 1..554
FT /note="Intraflagellar transport protein 56"
FT /id="PRO_0000289082"
FT REPEAT 57..90
FT /note="TPR 1"
FT REPEAT 92..125
FT /note="TPR 2"
FT REPEAT 151..184
FT /note="TPR 3"
FT REPEAT 468..501
FT /note="TPR 4"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 47..77
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044791"
FT VAR_SEQ 474..554
FT /note="MGQFYYSAKAFDVLERLDPNPEYWEGKRGACVGIFQMIIAGREPKETLREVL
FT HLLRSTGNTQVEYMIRIMKKWAKENRVSI -> RDPSRSAPFTEKHR (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043751"
FT VARIANT 263
FT /note="N -> S (in BRENS; decreased protein abundance;
FT associated with abnormal ciliary structure and function)"
FT /evidence="ECO:0000269|PubMed:31595528,
FT ECO:0000269|PubMed:32617964"
FT /id="VAR_086383"
FT VARIANT 310
FT /note="D -> N (in dbSNP:rs13225917)"
FT /id="VAR_032568"
FT VARIANT 444
FT /note="P -> L (in BRENS; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31595528"
FT /id="VAR_086384"
FT CONFLICT 85
FT /note="K -> E (in Ref. 1; BAB14143)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="E -> V (in Ref. 1; BAH12956)"
FT /evidence="ECO:0000305"
FT CONFLICT 470
FT /note="D -> V (in Ref. 1; BAB14143)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 554 AA; 64178 MW; 188062024DB89B97 CRC64;
MMLSRAKPAV GRGVQHTDKR KKKGRKIPKL EELLSKRDFT GAITLLEFKR HVGEEEEDTN
LWIGYCAFHL GDYKRALEEY ENATKEENCN SEVWVNLACT YFFLGMYKQA EAAGFKASKS
RLQNRLLFHL AHKFNDEKKL MSFHQNLQDV TEDQLSLASI HYMRSHYQEA IDIYKRILLD
NREYLALNVY VALCYYKLDY YDVSQEVLAV YLQQIPDSTI ALNLKACNHF RLYNGRAAEA
ELKSLMDNAS SSFEFAKELI RHNLVVFRGG EGALQVLPPL VDVIPEARLN LVIYYLRQDD
VQEAYNLIKD LEPTTPQEYI LKGVVNAALG QEMGSRDHMK IAQQFFQLVG GSASECDTIP
GRQCMASCFF LLKQFDDVLI YLNSFKSYFY NDDIFNFNYA QAKAATGNTS EGEEAFLLIQ
SEKMKNDYIY LSWLARCYIM NKKPRLAWEL YLKMETSGES FSLLQLIAND CYKMGQFYYS
AKAFDVLERL DPNPEYWEGK RGACVGIFQM IIAGREPKET LREVLHLLRS TGNTQVEYMI
RIMKKWAKEN RVSI
