IF122_MOUSE
ID IF122_MOUSE Reviewed; 1182 AA.
AC Q6NWV3; Q6KAU2; Q8C8U5; Q8CD77;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Intraflagellar transport protein 122 homolog {ECO:0000305};
DE AltName: Full=WD repeat-containing protein 10;
GN Name=Ift122 {ECO:0000312|MGI:MGI:1932386};
GN Synonyms=Wdr10 {ECO:0000303|PubMed:19000668};
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=ICR; TISSUE=Fetal brain;
RX PubMed=15449545; DOI=10.1093/dnares/11.2.127;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Kitamura H., Nakagawa T., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of FLJ genes: the
RT complete nucleotide sequences of 110 mouse FLJ-homologous cDNAs identified
RT by screening of terminal sequences of cDNA clones randomly sampled from
RT size-fractionated libraries.";
RL DNA Res. 11:127-135(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Amnion, Placenta, Retina, and Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C3H/He, and C57BL/6J; TISSUE=Brain, and Mesenchymal stem cell;
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 [4]
RP SUBCELLULAR LOCATION.
RX PubMed=19208653; DOI=10.1093/hmg/ddp068;
RA Jiang S.T., Chiou Y.Y., Wang E., Chien Y.L., Ho H.H., Tsai F.J., Lin C.Y.,
RA Tsai S.P., Li H.;
RT "Essential role of nephrocystin in photoreceptor intraflagellar transport
RT in mouse.";
RL Hum. Mol. Genet. 18:1566-1577(2009).
RN [5]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=19000668; DOI=10.1016/j.ydbio.2008.10.020;
RA Cortellino S., Wang C., Wang B., Bassi M.R., Caretti E., Champeval D.,
RA Calmont A., Jarnik M., Burch J., Zaret K.S., Larue L., Bellacosa A.;
RT "Defective ciliogenesis, embryonic lethality and severe impairment of the
RT Sonic Hedgehog pathway caused by inactivation of the mouse complex A
RT intraflagellar transport gene Ift122/Wdr10, partially overlapping with the
RT DNA repair gene Med1/Mbd4.";
RL Dev. Biol. 325:225-237(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, and 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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=21209331; DOI=10.1073/pnas.1011410108;
RA Qin J., Lin Y., Norman R.X., Ko H.W., Eggenschwiler J.T.;
RT "Intraflagellar transport protein 122 antagonizes Sonic Hedgehog signaling
RT and controls ciliary localization of pathway components.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:1456-1461(2011).
CC -!- FUNCTION: As a component of the IFT complex A (IFT-A), a complex
CC required for retrograde ciliary transport and entry into cilia of G
CC protein-coupled receptors (GPCRs), it is required in ciliogenesis and
CC ciliary protein trafficking (By similarity). Involved in cilia
CC formation during neuronal patterning. Acts as a negative regulator of
CC Shh signaling. Required to recruit TULP3 to primary cilia
CC (PubMed:19000668, PubMed:21209331). {ECO:0000250|UniProtKB:Q9HBG6,
CC ECO:0000269|PubMed:19000668, ECO:0000269|PubMed:21209331}.
CC -!- SUBUNIT: Component of the IFT complex A (IFT-A) complex. IFT-A complex
CC is divided into a core subcomplex composed of IFT122:IFT140:WDR19 which
CC is associated with TULP3 and a peripheral subcomplex composed of
CC IFT43:WDR35:TTC21B. Interacts with IFT43:WDR35; the interaction
CC connects the 2 IFT-A subcomplexes. Interacts with IFTAP; the
CC interaction associates IFTAP with IFT-A complex.
CC {ECO:0000250|UniProtKB:Q9HBG6}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000269|PubMed:21209331}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000269|PubMed:21209331}. Note=Localizes to photoreceptor
CC connecting cilia. {ECO:0000269|PubMed:21209331}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6NWV3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6NWV3-2; Sequence=VSP_039810;
CC -!- DEVELOPMENTAL STAGE: Expression at least from 7.5 dpc onwards
CC throughout embryonic development with lower levels at 7.5 dpc and 9.5
CC dpc. Ubiquitously expressed at 11.5 dpc. {ECO:0000269|PubMed:19000668}.
CC -!- DOMAIN: Forms the trimeric core subcomplex IFT122:IFT140:WDR19 via the
CC C-terminal region, whereas it interacts with IFT43:WDR35 via the N-
CC terminal region containing the WD repeats.
CC {ECO:0000250|UniProtKB:Q9HBG6}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal (manifesting between 11.5 dpc
CC and 13.5 dpc). Multiple developmental defects (exencephaly, situs
CC viscerum inversus, delay in turning, hemorrhage and defects in limb
CC development). In the node, primary cilia are absent or malformed in
CC homozygous mutant and heterozygous embryos, respectively. The Shh
CC signaling pathway is impaired in both neural tube patterning (expansion
CC of motoneurons and rostro-caudal level-dependent contraction or
CC expansion of the dorso-lateral interneurons) and limb patterning
CC (ectrosyndactyly). The proteolytic processing of Gli3 is altered.
CC Defects in Ift122 are the cause of the sister of open brain (sopb)
CC phenotype, a mutant that induces embryonic lethality and generates
CC primary cilia with features of defective retrograde intraflagellar
CC transport. {ECO:0000269|PubMed:19000668, ECO:0000269|PubMed:21209331}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD21365.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK131115; BAD21365.1; ALT_INIT; mRNA.
DR EMBL; AK031308; BAC27340.1; -; mRNA.
DR EMBL; AK044456; BAC31930.1; -; mRNA.
DR EMBL; AK167330; BAE39432.1; -; mRNA.
DR EMBL; AK167412; BAE39501.1; -; mRNA.
DR EMBL; BC066083; AAH66083.1; -; mRNA.
DR EMBL; BC067415; AAH67415.1; -; mRNA.
DR CCDS; CCDS20445.1; -. [Q6NWV3-2]
DR CCDS; CCDS51880.1; -. [Q6NWV3-1]
DR RefSeq; NP_001161235.1; NM_001167763.1. [Q6NWV3-1]
DR RefSeq; NP_112454.2; NM_031177.4. [Q6NWV3-2]
DR AlphaFoldDB; Q6NWV3; -.
DR SMR; Q6NWV3; -.
DR BioGRID; 219896; 6.
DR ComplexPortal; CPX-5027; IFT-A complex.
DR IntAct; Q6NWV3; 1.
DR STRING; 10090.ENSMUSP00000045468; -.
DR iPTMnet; Q6NWV3; -.
DR PhosphoSitePlus; Q6NWV3; -.
DR MaxQB; Q6NWV3; -.
DR PaxDb; Q6NWV3; -.
DR PRIDE; Q6NWV3; -.
DR ProteomicsDB; 267256; -. [Q6NWV3-1]
DR ProteomicsDB; 267257; -. [Q6NWV3-2]
DR Antibodypedia; 33252; 71 antibodies from 19 providers.
DR Ensembl; ENSMUST00000038234; ENSMUSP00000045468; ENSMUSG00000030323. [Q6NWV3-2]
DR Ensembl; ENSMUST00000112925; ENSMUSP00000108547; ENSMUSG00000030323. [Q6NWV3-1]
DR GeneID; 81896; -.
DR KEGG; mmu:81896; -.
DR UCSC; uc009djg.2; mouse. [Q6NWV3-2]
DR UCSC; uc009dji.2; mouse. [Q6NWV3-1]
DR CTD; 55764; -.
DR MGI; MGI:1932386; Ift122.
DR VEuPathDB; HostDB:ENSMUSG00000030323; -.
DR eggNOG; KOG1538; Eukaryota.
DR GeneTree; ENSGT00390000001016; -.
DR HOGENOM; CLU_008896_0_0_1; -.
DR InParanoid; Q6NWV3; -.
DR OMA; QSYTIGC; -.
DR OrthoDB; 449704at2759; -.
DR TreeFam; TF105855; -.
DR Reactome; R-MMU-5610787; Hedgehog 'off' state.
DR Reactome; R-MMU-5620924; Intraflagellar transport.
DR BioGRID-ORCS; 81896; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Ift122; mouse.
DR PRO; PR:Q6NWV3; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q6NWV3; protein.
DR Bgee; ENSMUSG00000030323; Expressed in spermatocyte and 215 other tissues.
DR ExpressionAtlas; Q6NWV3; baseline and differential.
DR Genevisible; Q6NWV3; MM.
DR GO; GO:0036064; C:ciliary basal body; IDA:BHF-UCL.
DR GO; GO:0097546; C:ciliary base; IDA:CACAO.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0030991; C:intraciliary transport particle A; IDA:MGI.
DR GO; GO:0097730; C:non-motile cilium; IBA:GO_Central.
DR GO; GO:0032391; C:photoreceptor connecting cilium; IDA:UniProtKB.
DR GO; GO:0048593; P:camera-type eye morphogenesis; IMP:UniProtKB.
DR GO; GO:0060830; P:ciliary receptor clustering involved in smoothened signaling pathway; IGI:MGI.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IMP:MGI.
DR GO; GO:0010172; P:embryonic body morphogenesis; IMP:UniProtKB.
DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IMP:MGI.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:MGI.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IMP:BHF-UCL.
DR GO; GO:0035050; P:embryonic heart tube development; IMP:UniProtKB.
DR GO; GO:0060971; P:embryonic heart tube left/right pattern formation; IMP:BHF-UCL.
DR GO; GO:0072594; P:establishment of protein localization to organelle; IMP:BHF-UCL.
DR GO; GO:0035720; P:intraciliary anterograde transport; IMP:BHF-UCL.
DR GO; GO:0035721; P:intraciliary retrograde transport; IMP:UniProtKB.
DR GO; GO:0042073; P:intraciliary transport; ISS:UniProtKB.
DR GO; GO:0043616; P:keratinocyte proliferation; IMP:MGI.
DR GO; GO:0060173; P:limb development; IMP:UniProtKB.
DR GO; GO:0010839; P:negative regulation of keratinocyte proliferation; IMP:MGI.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IMP:UniProtKB.
DR GO; GO:0021914; P:negative regulation of smoothened signaling pathway involved in ventral spinal cord patterning; IMP:BHF-UCL.
DR GO; GO:0001843; P:neural tube closure; IMP:UniProtKB.
DR GO; GO:1905515; P:non-motile cilium assembly; IMP:MGI.
DR GO; GO:0061512; P:protein localization to cilium; IMP:CACAO.
DR GO; GO:0007227; P:signal transduction downstream of smoothened; IMP:BHF-UCL.
DR GO; GO:0060831; P:smoothened signaling pathway involved in dorsal/ventral neural tube patterning; IGI:MGI.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR039857; Ift122.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR12764; PTHR12764; 1.
DR Pfam; PF00400; WD40; 2.
DR SMART; SM00320; WD40; 8.
DR SUPFAM; SSF50978; SSF50978; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Cilium;
KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton;
KW Developmental protein; Reference proteome; Repeat; WD repeat.
FT CHAIN 1..1182
FT /note="Intraflagellar transport protein 122 homolog"
FT /id="PRO_0000398816"
FT REPEAT 10..50
FT /note="WD 1"
FT REPEAT 51..91
FT /note="WD 2"
FT REPEAT 93..129
FT /note="WD 3"
FT REPEAT 131..169
FT /note="WD 4"
FT REPEAT 174..217
FT /note="WD 5"
FT REPEAT 219..258
FT /note="WD 6"
FT REPEAT 260..300
FT /note="WD 7"
FT REPEAT 453..492
FT /note="WD 8"
FT VAR_SEQ 871
FT /note="Q -> QA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_039810"
FT CONFLICT 19
FT /note="A -> G (in Ref. 2; BAC31930)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="S -> T (in Ref. 2; BAC27340)"
FT /evidence="ECO:0000305"
FT CONFLICT 297
FT /note="H -> Q (in Ref. 2; BAC27340)"
FT /evidence="ECO:0000305"
FT CONFLICT 663
FT /note="A -> V (in Ref. 1; BAD21365)"
FT /evidence="ECO:0000305"
FT CONFLICT 768
FT /note="T -> A (in Ref. 2; BAC31930)"
FT /evidence="ECO:0000305"
FT CONFLICT 776
FT /note="K -> R (in Ref. 2; BAC31930)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1182 AA; 134798 MW; FB5046A4D92C9044 CRC64;
MRAVLTWRDK AEQCIYDLAF KPDGTQLILA AGNRLLVYDT SDGTLLQPLK GHKDTVYCVA
YAKDGKRFAS GSADKSIIIW TSKLEGILKY THNDSIQCVS YNPVTHQLAS CSSSDFGLWS
PEQKSVSKHK SSSKITCCSW TNDGQYLALG MANGIISIRN KNGEEKVKIE RPGGSLSPIW
SICWNPSREE HNDILAVADW GQKLSFYQLS GKQIGKDRPL NFDPCCISYF TKGEYILVGG
SDKQVSLFTK DGVRLGTVGE QNSWVWTCRV KPDSNYVVVG CQDGTISFYQ LIFSTVHGLY
KDRYAYRDSM TDVIVQHLIT EQKVRIKCRE LVKKIAIYKN RLAIQLPEKI LIYELYSEDS
TDMHYRVKEK IVKKFECNLL VVCADHIILC QEKRLQCLSF SGVKEREWQM ESLIRYIKVI
GGPAGREGLL VGLKNGQILK IFVDNLFAIV LLKQATAVRC LDMSASRNKL AVVDENDTCL
VYDIHTKELL FQEPNANSVA WNTQCEDMLC FSGGGYLNIK ASTFPVHQQK LQGFVVGYNG
SKIFCLHVFS MSAVEVPQSA PMYQYLDRKM FKEAYQIACL GVTDADWREL AMEALEGLEF
ETARKAFTRV QDLRYLELIS SIEERKKRGE TNNDLFLADV FSYQGKFHEA AKLYKRSGHE
NLALDMYTDL CMFEYAKDFL GSGDPKETKM LITKQADWAR NINEPKAAVE MYISAGEHAK
AIEISGSHGW VDMLIDIARK LDKAEREPLL MCACYFKKLD SPGYAAETYL KIGDLKSLVQ
LYVDTKRWDE AFALGEKHPE FKDDVYVPYA QWLAENDRFE EAQKAFHKAG RQGEAVRVLE
QLTHNAVVES RFNDAAYYYW MLSMQCLDMA QDPAQKDAML DKFHHFQHLA ELYHGYQTIH
RYTEEPFSFD LPETLFNISK FLLHSLTKAT PLGISKVNTL FTLAKQSKAL GAYKLARHAY
DKLRGLQIPA RIQKSIELGT LTIRSKPFHD SEELVPLCYR CSTNNPLLNN LGNVCINCRQ
PFIFSASSYE VLHLVEFYLE EGITDEEAVA LIDLEAPRHK REGKWRETSS NNSQTLKLDE
TMDSIGEDDP FTAKLSFEQG SSEFVPVVVN RSVLRSMSRR DVLIKRWPPP LQWQYFRSLL
PDASITMCPS CFQMFHSEDY ELLVLQHACC PYCRRRIDDT GP
