IFT57_HUMAN
ID IFT57_HUMAN Reviewed; 429 AA.
AC Q9NWB7; Q96DA9;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Intraflagellar transport protein 57 homolog;
DE AltName: Full=Dermal papilla-derived protein 8;
DE AltName: Full=Estrogen-related receptor beta-like protein 1;
DE AltName: Full=HIP1-interacting protein;
DE AltName: Full=MHS4R2;
GN Name=IFT57; Synonyms=DERP8, ESRRBL1, HIPPI;
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 [MRNA], FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH
RP HIP1, AND MUTAGENESIS OF LYS-409.
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].
RC TISSUE=Testis;
RA Pasutto F., Schickel J., Deufel T., Rohe M.;
RT "Analysis of the coding capacity of the MHS4 critical region on chromosome
RT 3q13.1.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Ikeda A., Ukai Y., Yamashita M., Yoshimoto M.;
RT "Molecular cloning of a dermal papilla derived gene.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Uterus;
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 [8]
RP INTERACTION WITH CHICKEN ANEMIA VIRUS APOPTIN.
RX PubMed=12745083; DOI=10.1016/s0006-291x(03)00764-2;
RA Cheng C.-M., Huang S.-P., Chang Y.-F., Chung W.-Y., Yuo C.-Y.;
RT "The viral death protein Apoptin interacts with Hippi, the protein
RT interactor of Huntingtin-interacting protein 1.";
RL Biochem. Biophys. Res. Commun. 305:359-364(2003).
RN [9]
RP INTERACTION WITH BFAR.
RX PubMed=14502241; DOI=10.1038/sj.cdd.4401287;
RA Roth W., Kermer P., Krajewska M., Welsh K., Davis S., Krajewski S.,
RA Reed J.C.;
RT "Bifunctional apoptosis inhibitor (BAR) protects neurons from diverse cell
RT death pathways.";
RL Cell Death Differ. 10:1178-1187(2003).
RN [10]
RP FUNCTION.
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 [11]
RP DNA-BINDING.
RX PubMed=17173859; DOI=10.1016/j.bbrc.2006.11.138;
RA Majumder P., Chattopadhyay B., Sukanya S., Ray T., Banerjee M.,
RA Mukhopadhyay D., Bhattacharyya N.P.;
RT "Interaction of HIPPI with putative promoter sequence of caspase-1 in vitro
RT and in vivo.";
RL Biochem. Biophys. Res. Commun. 353:80-85(2007).
RN [12]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=17623017; DOI=10.1111/j.1742-4658.2007.05922.x;
RA Majumder P., Choudhury A., Banerjee M., Lahiri A., Bhattacharyya N.P.;
RT "Interactions of HIPPI, a molecular partner of Huntingtin interacting
RT protein HIP1, with the specific motif present at the putative promoter
RT sequence of the caspase-1, caspase-8 and caspase-10 genes.";
RL FEBS J. 274:3886-3899(2007).
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 INVOLVEMENT IN OFD18.
RX PubMed=27060890; DOI=10.1111/cge.12785;
RA Thevenon J., Duplomb L., Phadke S., Eguether T., Saunier A., Avila M.,
RA Carmignac V., Bruel A.L., St-Onge J., Duffourd Y., Pazour G.J., Franco B.,
RA Attie-Bitach T., Masurel-Paulet A., Riviere J.B., Cormier-Daire V.,
RA Philippe C., Faivre L., Thauvin-Robinet C.;
RT "Autosomal recessive IFT57 hypomorphic mutation cause ciliary transport
RT defect in unclassified oral-facial-digital syndrome with short stature and
RT brachymesophalangia.";
RL Clin. Genet. 90:509-517(2016).
RN [15]
RP INTERACTION WITH USH1G.
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 (By similarity). Has pro-apoptotic function via
CC its interaction with HIP1, leading to recruit caspase-8 (CASP8) and
CC trigger apoptosis. Has the ability to bind DNA sequence motif 5'-
CC AAAGACATG-3' present in the promoter of caspase genes such as CASP1,
CC CASP8 and CASP10, suggesting that it may act as a transcription
CC regulator; however the relevance of such function remains unclear.
CC {ECO:0000250, ECO:0000269|PubMed:11788820, ECO:0000269|PubMed:17107665,
CC ECO:0000269|PubMed:17623017}.
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 (By similarity). Interacts with IFT20 (By
CC similarity). Interacts with IFT88 (By similarity). Interacts with
CC IFT80, IFT-81, IFT74, IFT172, TTC30B and KIF17 (By similarity).
CC Interacts with BLOC1S2 (By similarity). Interacts with RYBP (By
CC similarity). Interacts with HOMER1; the interaction possibly prevents
CC the pro-apoptotic effects of IFT57 (By similarity). Interacts with HIP1
CC (PubMed:11788820). In normal conditions, it poorly interacts with HIP1,
CC HIP1 being strongly associated with HTT (PubMed:11788820). However, in
CC mutant HTT proteins with a long poly-Gln region, interaction between
CC HTT and HIP1 is inhibited, promoting the interaction between HIP1 and
CC IFT57, leading to apoptosis (PubMed:11788820). Interacts with BFAR
CC (PubMed:14502241). Interacts with TTC25 (PubMed:25860617). Interacts
CC with USH1G (PubMed:31637240). Interacts with chicken anemia virus
CC protein apoptin (PubMed:12745083). {ECO:0000250|UniProtKB:Q8BXG3,
CC ECO:0000269|PubMed:11788820, ECO:0000269|PubMed:12745083,
CC ECO:0000269|PubMed:14502241, ECO:0000269|PubMed:25860617,
CC ECO:0000269|PubMed:31637240}.
CC -!- INTERACTION:
CC Q9NWB7; Q6QNY1: BLOC1S2; NbExp=3; IntAct=EBI-725672, EBI-465872;
CC Q9NWB7; O00471: EXOC5; NbExp=3; IntAct=EBI-725672, EBI-949824;
CC Q9NWB7; P42858: HTT; NbExp=3; IntAct=EBI-725672, EBI-466029;
CC Q9NWB7; Q8IY31-3: IFT20; NbExp=3; IntAct=EBI-725672, EBI-9091197;
CC Q9NWB7; Q8WVK7: SKA2; NbExp=3; IntAct=EBI-725672, EBI-1773994;
CC Q9NWB7; Q8IY57-5: YAF2; NbExp=3; IntAct=EBI-725672, EBI-12111538;
CC Q9NWB7; Q8IUH5: ZDHHC17; NbExp=2; IntAct=EBI-725672, EBI-524753;
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q8BXG3}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000250|UniProtKB:Q5EA95}. Note=Concentrates within the inner
CC segment of cilia. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Present in many tissues such as brain, thymus,
CC lymph node, lung, liver, skin and kidney (at protein level).
CC {ECO:0000269|PubMed:11788820}.
CC -!- DOMAIN: The pseudo DED region (pDED) mediates the interaction with
CC HIP1.
CC -!- DISEASE: Orofaciodigital syndrome 18 (OFD18) [MIM:617927]: A form of
CC orofaciodigital syndrome, a group of heterogeneous disorders
CC characterized by malformations of the oral cavity, face and digits, and
CC associated phenotypic abnormalities that lead to the delineation of
CC various subtypes. OFD18 is an autosomal recessive form characterized by
CC short stature, brachymesophalangy, pre- and postaxial polysyndactyly,
CC and stocky femoral necks, as well as oral anomalies and dysmorphic
CC facial features. {ECO:0000269|PubMed:27060890}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the IFT57 family. {ECO:0000305}.
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DR EMBL; AF245220; AAK28373.1; -; mRNA.
DR EMBL; AF139576; AAK13588.1; -; mRNA.
DR EMBL; AB014762; BAB87803.1; -; mRNA.
DR EMBL; AK001009; BAA91466.1; -; mRNA.
DR EMBL; CR457251; CAG33532.1; -; mRNA.
DR EMBL; CH471052; EAW79730.1; -; Genomic_DNA.
DR EMBL; BC009690; AAH09690.2; -; mRNA.
DR EMBL; BC011899; AAH11899.1; -; mRNA.
DR CCDS; CCDS2951.1; -.
DR RefSeq; NP_060480.1; NM_018010.3.
DR AlphaFoldDB; Q9NWB7; -.
DR SMR; Q9NWB7; -.
DR BioGRID; 120396; 86.
DR ComplexPortal; CPX-5022; IFT-B complex.
DR CORUM; Q9NWB7; -.
DR IntAct; Q9NWB7; 63.
DR MINT; Q9NWB7; -.
DR STRING; 9606.ENSP00000264538; -.
DR iPTMnet; Q9NWB7; -.
DR PhosphoSitePlus; Q9NWB7; -.
DR BioMuta; IFT57; -.
DR DMDM; 74734638; -.
DR EPD; Q9NWB7; -.
DR jPOST; Q9NWB7; -.
DR MassIVE; Q9NWB7; -.
DR MaxQB; Q9NWB7; -.
DR PaxDb; Q9NWB7; -.
DR PeptideAtlas; Q9NWB7; -.
DR PRIDE; Q9NWB7; -.
DR ProteomicsDB; 82925; -.
DR Antibodypedia; 32363; 314 antibodies from 34 providers.
DR DNASU; 55081; -.
DR Ensembl; ENST00000264538.4; ENSP00000264538.3; ENSG00000114446.5.
DR GeneID; 55081; -.
DR KEGG; hsa:55081; -.
DR MANE-Select; ENST00000264538.4; ENSP00000264538.3; NM_018010.4; NP_060480.1.
DR UCSC; uc003dwx.4; human.
DR CTD; 55081; -.
DR DisGeNET; 55081; -.
DR GeneCards; IFT57; -.
DR HGNC; HGNC:17367; IFT57.
DR HPA; ENSG00000114446; Low tissue specificity.
DR MalaCards; IFT57; -.
DR MIM; 606621; gene.
DR MIM; 617927; phenotype.
DR neXtProt; NX_Q9NWB7; -.
DR OpenTargets; ENSG00000114446; -.
DR Orphanet; 508501; Oral-facial-digital syndrome with short stature and brachymesophalangy.
DR PharmGKB; PA27890; -.
DR VEuPathDB; HostDB:ENSG00000114446; -.
DR eggNOG; KOG0972; Eukaryota.
DR GeneTree; ENSGT00390000006307; -.
DR HOGENOM; CLU_039132_0_0_1; -.
DR InParanoid; Q9NWB7; -.
DR OMA; VHAHDQD; -.
DR OrthoDB; 839892at2759; -.
DR PhylomeDB; Q9NWB7; -.
DR TreeFam; TF106156; -.
DR PathwayCommons; Q9NWB7; -.
DR Reactome; R-HSA-5610787; Hedgehog 'off' state.
DR Reactome; R-HSA-5620924; Intraflagellar transport.
DR SignaLink; Q9NWB7; -.
DR BioGRID-ORCS; 55081; 16 hits in 1071 CRISPR screens.
DR ChiTaRS; IFT57; human.
DR GeneWiki; IFT57; -.
DR GenomeRNAi; 55081; -.
DR Pharos; Q9NWB7; Tbio.
DR PRO; PR:Q9NWB7; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NWB7; protein.
DR Bgee; ENSG00000114446; Expressed in bronchial epithelial cell and 197 other tissues.
DR ExpressionAtlas; Q9NWB7; baseline and differential.
DR Genevisible; Q9NWB7; HS.
DR GO; GO:0005930; C:axoneme; IEA:Ensembl.
DR GO; GO:0005813; C:centrosome; IBA:GO_Central.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0097546; C:ciliary base; IDA:UniProtKB.
DR GO; GO:0097542; C:ciliary tip; TAS:Reactome.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0044292; C:dendrite terminus; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0030992; C:intraciliary transport particle B; IPI:ComplexPortal.
DR GO; GO:0032391; C:photoreceptor connecting cilium; IDA:UniProtKB.
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; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IDA:MGI.
DR GO; GO:0060271; P:cilium assembly; IC:ComplexPortal.
DR GO; GO:0001947; P:heart looping; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0060972; P:left/right pattern formation; IEA:Ensembl.
DR GO; GO:0044458; P:motile cilium assembly; IEA:Ensembl.
DR GO; GO:0010839; P:negative regulation of keratinocyte proliferation; IEA:Ensembl.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:1905515; P:non-motile cilium assembly; IBA:GO_Central.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:MGI.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR InterPro; IPR019530; Intra-flagellar_transport_57.
DR PANTHER; PTHR16011; PTHR16011; 1.
DR Pfam; PF10498; IFT57; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cell projection; Ciliopathy; Cilium; Coiled coil; Cytoplasm;
KW Cytoskeleton; DNA-binding; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..429
FT /note="Intraflagellar transport protein 57 homolog"
FT /id="PRO_0000328884"
FT REGION 335..426
FT /note="pDED"
FT COILED 304..369
FT /evidence="ECO:0000255"
FT MUTAGEN 409
FT /note="K->D: Impairs the interaction with HIP1."
FT /evidence="ECO:0000269|PubMed:11788820"
FT CONFLICT 293
FT /note="I -> V (in Ref. 7; AAH09690)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 429 AA; 49108 MW; D80200D957AE5AC4 CRC64;
MTAALAVVTT SGLEDGVPRS RGEGTGEVVL ERGPGAAYHM FVVMEDLVEK LKLLRYEEEF
LRKSNLKAPS RHYFALPTNP GEQFYMFCTL AAWLINKAGR PFEQPQEYDD PNATISNILS
ELRSFGRTAD FPPSKLKSGY GEHVCYVLDC FAEEALKYIG FTWKRPIYPV EELEEESVAE
DDAELTLNKV DEEFVEEETD NEENFIDLNV LKAQTYHLDM NETAKQEDIL ESTTDAAEWS
LEVERVLPQL KVTIRTDNKD WRIHVDQMHQ HRSGIESALK ETKGFLDKLH NEITRTLEKI
SSREKYINNQ LENLVQEYRA AQAQLSEAKE RYQQGNGGVT ERTRLLSEVM EELEKVKQEM
EEKGSSMTDG APLVKIKQSL TKLKQETVEM DIRIGIVEHT LLQSKLKEKS NMTRNMHATV
IPEPATGFY
