IFT57_MOUSE
ID IFT57_MOUSE Reviewed; 429 AA.
AC Q8BXG3; Q924M2; Q9CUS6;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Intraflagellar transport protein 57 homolog;
DE AltName: Full=HIP1-interacting protein;
GN Name=Ift57; Synonyms=Hippi;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11788820; DOI=10.1038/ncb735;
RA Gervais F.G., Singaraja R., Xanthoudakis S., Gutekunst C.-A., Leavitt B.R.,
RA Metzler M., Hackam A.S., Tam J., Vaillancourt J.P., Houtzager V.,
RA Rasper D.M., Roy S., Hayden M.R., Nicholson D.W.;
RT "Recruitment and activation of caspase-8 by the Huntingtin-interacting
RT protein Hip-1 and a novel partner Hippi.";
RL Nat. Cell Biol. 4:95-105(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J;
RA Pazour G.J., Walker B.L., Witman G.B., Rosenbaum J.L., Cole D.G.;
RT "Mouse intraflagellar transport protein IFT57.";
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-357 (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, and Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP INTERACTION WITH IFT88.
RX PubMed=11062270; DOI=10.1083/jcb.151.3.709;
RA Pazour G.J., Dickert B.L., Vucica Y., Seeley E.S., Rosenbaum J.L.,
RA Witman G.B., Cole D.G.;
RT "Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease
RT gene tg737, are required for assembly of cilia and flagella.";
RL J. Cell Biol. 151:709-718(2000).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=11916979; DOI=10.1083/jcb.200107108;
RA Pazour G.J., Baker S.A., Deane J.A., Cole D.G., Dickert B.L.,
RA Rosenbaum J.L., Witman G.B., Besharse J.C.;
RT "The intraflagellar transport protein, IFT88, is essential for vertebrate
RT photoreceptor assembly and maintenance.";
RL J. Cell Biol. 157:103-113(2002).
RN [6]
RP INTERACTION WITH IFT20.
RX PubMed=12821668; DOI=10.1074/jbc.m300156200;
RA Baker S.A., Freeman K., Luby-Phelps K., Pazour G.J., Besharse J.C.;
RT "IFT20 links kinesin II with a mammalian intraflagellar transport complex
RT that is conserved in motile flagella and sensory cilia.";
RL J. Biol. Chem. 278:34211-34218(2003).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=17027958; DOI=10.1016/j.ydbio.2006.09.001;
RA Houde C., Dickinson R.J., Houtzager V.M., Cullum R., Montpetit R.,
RA Metzler M., Simpson E.M., Roy S., Hayden M.R., Hoodless P.A.,
RA Nicholson D.W.;
RT "Hippi is essential for node cilia assembly and Sonic hedgehog signaling.";
RL Dev. Biol. 300:523-533(2006).
RN [8]
RP INTERACTION WITH RYBP.
RX PubMed=17874297; DOI=10.1007/s10495-007-0131-3;
RA Stanton S.E., Blanck J.K., Locker J., Schreiber-Agus N.;
RT "Rybp interacts with Hippi and enhances Hippi-mediated apoptosis.";
RL Apoptosis 12:2197-2206(2007).
RN [9]
RP TISSUE SPECIFICITY, AND INTERACTION WITH HOMER1.
RX PubMed=17107665; DOI=10.1016/j.bbrc.2006.10.167;
RA Sakamoto K., Yoshida S., Ikegami K., Minakami R., Kato A., Udo H.,
RA Sugiyama H.;
RT "Homer1c interacts with Hippi and protects striatal neurons from
RT apoptosis.";
RL Biochem. Biophys. Res. Commun. 352:1-5(2007).
RN [10]
RP INTERACTION WITH BLOC1S2.
RX PubMed=18188704; DOI=10.1007/s10495-007-0176-3;
RA Gdynia G., Lehmann-Koch J., Sieber S., Tagscherer K.E., Fassl A.,
RA Zentgraf H., Matsuzawa S., Reed J.C., Roth W.;
RT "BLOC1S2 interacts with the HIPPI protein and sensitizes NCH89 glioblastoma
RT cells to apoptosis.";
RL Apoptosis 13:437-447(2008).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=17931679; DOI=10.1016/j.visres.2007.08.022;
RA Luby-Phelps K., Fogerty J., Baker S.A., Pazour G.J., Besharse J.C.;
RT "Spatial distribution of intraflagellar transport proteins in vertebrate
RT photoreceptors.";
RL Vision Res. 48:413-423(2008).
RN [12]
RP IDENTIFICATION IN THE IFT COMPLEX B, INTERACTION WITH IFT88, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19253336; DOI=10.1002/cm.20346;
RA Follit J.A., Xu F., Keady B.T., Pazour G.J.;
RT "Characterization of mouse IFT complex B.";
RL Cell Motil. Cytoskeleton 66:457-468(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [14]
RP IDENTIFICATION IN THE IFT B COMPLEX, AND INTERACTION WITH IFT80; IFT81;
RP IFT74; IFT172; IFT88; TTC30B AND KIF17.
RX PubMed=23810713; DOI=10.1016/j.yexcr.2013.06.010;
RA Howard P.W., Jue S.F., Maurer R.A.;
RT "Interaction of mouse TTC30/DYF-1 with multiple intraflagellar transport
RT complex B proteins and KIF17.";
RL Exp. Cell Res. 319:2275-2281(2013).
RN [15]
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 [16]
RP SUBCELLULAR LOCATION.
RX PubMed=31637240; DOI=10.3389/fcell.2019.00216;
RA Sorusch N., Yildirim A., Knapp B., Janson J., Fleck W., Scharf C.,
RA Wolfrum U.;
RT "SANS (USH1G) Molecularly Links the Human Usher Syndrome Protein Network to
RT the Intraflagellar Transport Module by Direct Binding to IFT-B Proteins.";
RL Front. Cell Dev. Biol. 7:216-216(2019).
CC -!- FUNCTION: Required for the formation of cilia. Plays an indirect role
CC in sonic hedgehog signaling, cilia being required for all activity of
CC the hedgehog pathway. Has pro-apoptotic function via its interaction
CC with HIP1, leading to recruit caspase-8 (CASP8) and trigger apoptosis.
CC Has the ability to bind DNA sequence motif 5'-AAAGACATG-3' present in
CC the promoter of caspase genes such as CASP1, CASP8 and CASP10,
CC suggesting that it may act as a transcription regulator; however the
CC relevance of such function remains unclear.
CC {ECO:0000269|PubMed:17027958}.
CC -!- SUBUNIT: Component of the IFT complex B, at least composed of IFT20,
CC IFT22, HSPB11/IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74,
CC IFT80, IFT81, and IFT88 (PubMed:19253336, PubMed:23810713). Interacts
CC with IFT20 (PubMed:12821668). Interacts with IFT88 (PubMed:11062270,
CC PubMed:19253336, PubMed:23810713). Interacts with IFT80, IFT-81, IFT74,
CC IFT172, TTC30B and KIF17 (PubMed:23810713). Interacts with BLOC1S2
CC (PubMed:18188704). Interacts with RYBP (PubMed:17874297). Interacts
CC with HOMER1; the interaction possibly prevents the pro-apoptotic
CC effects of IFT57 (PubMed:17107665). Interacts with HIP1 (By
CC similarity). In normal conditions, it poorly interacts with HIP1, HIP1
CC being strongly associated with HTT (By similarity). However, in mutant
CC HTT proteins with a long poly-Gln region, interaction between HTT and
CC HIP1 is inhibited, promoting the interaction between HIP1 and IFT57,
CC leading to apoptosis (By similarity). Interacts with BFAR (By
CC similarity). Interacts with TTC25 (PubMed:25860617). Interacts with
CC USH1G (By similarity). {ECO:0000250|UniProtKB:Q9NWB7,
CC ECO:0000269|PubMed:11062270, ECO:0000269|PubMed:12821668,
CC ECO:0000269|PubMed:17107665, ECO:0000269|PubMed:17874297,
CC ECO:0000269|PubMed:18188704, ECO:0000269|PubMed:19253336,
CC ECO:0000269|PubMed:23810713, ECO:0000269|PubMed:25860617}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000269|PubMed:31637240}. Cytoplasm, cytoskeleton, cilium basal
CC body. Golgi apparatus. Note=Concentrates within the inner segment of
CC cilia.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BXG3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BXG3-2; Sequence=VSP_032843;
CC -!- TISSUE SPECIFICITY: Present in retina and testis. In brain, it is
CC present in the cortex, striatum, globus pallidus, hypothalamus and
CC cerebellum. Present at high level in neurons and neuropil throughout
CC the brain (at protein level). Expressed in hippocampal neurons, where
CC it colocalizes with HOMER1 at postsynaptic regions.
CC {ECO:0000269|PubMed:11788820, ECO:0000269|PubMed:11916979,
CC ECO:0000269|PubMed:17107665}.
CC -!- DEVELOPMENTAL STAGE: Ubiquitous through the epiblast. Expression is
CC detected in mesoderm and most strongly in ectoderm, but not in
CC endoderm. Highly expressed in the region of the node, a depression at
CC the surface of the embryo proposed to have a role in left-right axis
CC patterning. At 8.5 dpc, it is widely expressed except in the heart.
CC Stronger expression is observed in the anterior midline, the forebrain
CC and the somites. Strong expression remains in the forebrain at 9.5 dpc
CC and 10.5 dpc and extends to all regions of the neural tube. At those
CC stages, high expression is also found in the branchial arches and in
CC the limb buds. Embryo section at 9.5 dpc also shows expression
CC throughout the neural tube and the mesoderm, but not in the surface
CC ectoderm. The strongest expression is observed on the luminal edge of
CC the neural tube and in the ventral foregut.
CC {ECO:0000269|PubMed:17027958}.
CC -!- DOMAIN: The pseudo DED region (pDED) mediates the interaction with
CC HIP1. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice show randomization of the embryo turning
CC process and heart looping, which are hallmarks of defective left-right
CC (LR) axis patterning. Motile monocilia normally present at the surface
CC of the embryonic node, and proposed to initiate the break in LR
CC symmetry, are absent. Furthermore, defects in central nervous system
CC development are observed. The Sonic hedgehog (Shh) pathway is down-
CC regulated in the neural tube, resulting in failure to establish ventral
CC neural cell fate. {ECO:0000269|PubMed:17027958}.
CC -!- SIMILARITY: Belongs to the IFT57 family. {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; AF274590; AAK69403.1; -; mRNA.
DR EMBL; DQ266091; ABB72788.1; -; mRNA.
DR EMBL; AK014731; BAB29522.1; -; mRNA.
DR EMBL; AK047217; BAC32995.1; -; mRNA.
DR CCDS; CCDS28211.1; -. [Q8BXG3-1]
DR RefSeq; NP_082956.2; NM_028680.3. [Q8BXG3-1]
DR AlphaFoldDB; Q8BXG3; -.
DR SMR; Q8BXG3; -.
DR BioGRID; 216353; 4.
DR ComplexPortal; CPX-5028; IFT-B complex.
DR STRING; 10090.ENSMUSP00000046645; -.
DR iPTMnet; Q8BXG3; -.
DR PhosphoSitePlus; Q8BXG3; -.
DR MaxQB; Q8BXG3; -.
DR PaxDb; Q8BXG3; -.
DR PRIDE; Q8BXG3; -.
DR ProteomicsDB; 266958; -. [Q8BXG3-1]
DR ProteomicsDB; 266959; -. [Q8BXG3-2]
DR Antibodypedia; 32363; 314 antibodies from 34 providers.
DR DNASU; 73916; -.
DR Ensembl; ENSMUST00000046777; ENSMUSP00000046645; ENSMUSG00000032965. [Q8BXG3-1]
DR Ensembl; ENSMUST00000142682; ENSMUSP00000117882; ENSMUSG00000032965. [Q8BXG3-2]
DR GeneID; 73916; -.
DR KEGG; mmu:73916; -.
DR UCSC; uc007zkf.1; mouse. [Q8BXG3-1]
DR CTD; 55081; -.
DR MGI; MGI:1921166; Ift57.
DR VEuPathDB; HostDB:ENSMUSG00000032965; -.
DR eggNOG; KOG0972; Eukaryota.
DR GeneTree; ENSGT00390000006307; -.
DR InParanoid; Q8BXG3; -.
DR OMA; VHAHDQD; -.
DR PhylomeDB; Q8BXG3; -.
DR TreeFam; TF106156; -.
DR Reactome; R-MMU-5610787; Hedgehog 'off' state.
DR Reactome; R-MMU-5620924; Intraflagellar transport.
DR BioGRID-ORCS; 73916; 4 hits in 71 CRISPR screens.
DR ChiTaRS; Ift57; mouse.
DR PRO; PR:Q8BXG3; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q8BXG3; protein.
DR Bgee; ENSMUSG00000032965; Expressed in choroid plexus epithelium and 244 other tissues.
DR ExpressionAtlas; Q8BXG3; baseline and differential.
DR Genevisible; Q8BXG3; MM.
DR GO; GO:0005930; C:axoneme; IDA:CACAO.
DR GO; GO:0005813; C:centrosome; IDA:MGI.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0097546; C:ciliary base; ISS:UniProtKB.
DR GO; GO:0005929; C:cilium; IDA:BHF-UCL.
DR GO; GO:0044292; C:dendrite terminus; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0030992; C:intraciliary transport particle B; IDA:UniProtKB.
DR GO; GO:0032391; C:photoreceptor connecting cilium; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR GO; GO:0060271; P:cilium assembly; IC:ComplexPortal.
DR GO; GO:0001947; P:heart looping; IMP:MGI.
DR GO; GO:0035720; P:intraciliary anterograde transport; IC:ComplexPortal.
DR GO; GO:0042073; P:intraciliary transport; IBA:GO_Central.
DR GO; GO:0043616; P:keratinocyte proliferation; IMP:MGI.
DR GO; GO:0060972; P:left/right pattern formation; IMP:MGI.
DR GO; GO:0044458; P:motile cilium assembly; IMP:MGI.
DR GO; GO:0010839; P:negative regulation of keratinocyte proliferation; IMP:MGI.
DR GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR GO; GO:1905515; P:non-motile cilium assembly; IMP:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:MGI.
DR GO; GO:0007224; P:smoothened signaling pathway; IMP:MGI.
DR InterPro; IPR019530; Intra-flagellar_transport_57.
DR PANTHER; PTHR16011; PTHR16011; 1.
DR Pfam; PF10498; IFT57; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Cell projection; Cilium; Coiled coil;
KW Cytoplasm; Cytoskeleton; DNA-binding; Golgi apparatus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..429
FT /note="Intraflagellar transport protein 57 homolog"
FT /id="PRO_0000328885"
FT REGION 335..426
FT /note="pDED"
FT COILED 305..369
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..85
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_032843"
FT CONFLICT 311
FT /note="L -> P (in Ref. 1; AAK69403)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 429 AA; 48772 MW; 6498169407BD49D2 CRC64;
MAAAAAVIPP SGLDDGVSRA RGEGAGEAVV ERGPGAAYHM FVVMEDLVEK LKLLRYEEEL
LRKSNLKPPS RHYFALPTNP GEQFYMFCTL AAWLINKTGR AFEQPQEYDD PNATISNILS
ELRSFGRTAD FPPSKLKSGY GEQVCYVLDC LAEEALKYIG FTWKRPSYPV EELEEETVPE
DDAELTLSKV DEEFVEEETD NEENFIDLNV LKAQTYRLDT NESAKQEDIL ESTTDAAEWS
LEVERVLPQL KVTIRTDNKD WRIHVDQMHQ HKSGIESALK ETKGFLDKLH NEISRTLEKI
GSREKYINNQ LEHLVQEYRG AQAQLSEARE RYQQGNGGVT ERTRLLSEVT EELEKVKQEM
EEKGSSMTDG TPLVKIKQSL TKLKQETVQM DIRIGVVEHT LLQSKLKEKC NMTRDMHAAV
TPESAIGFY
