TULP3_MOUSE
ID TULP3_MOUSE Reviewed; 460 AA.
AC O88413;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Tubby-related protein 3 {ECO:0000305};
DE AltName: Full=Tubby-like protein 3;
GN Name=Tulp3 {ECO:0000312|MGI:MGI:1329045};
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], AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=9828123; DOI=10.1006/geno.1998.5567;
RA Nishina P.M., North M.A., Ikeda A., Yan Y., Naggert J.K.;
RT "Molecular characterization of a novel tubby gene family member, TULP3, in
RT mouse and humans.";
RL Genomics 54:215-220(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ICR;
RA Shirayoshi Y., Kawamura A., Nakatsuji N.;
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; 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 [4]
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=11406614; DOI=10.1093/hmg/10.12.1325;
RA Ikeda A., Ikeda S., Gridley T., Nishina P.M., Naggert J.K.;
RT "Neural tube defects and neuroepithelial cell death in Tulp3 knockout
RT mice.";
RL Hum. Mol. Genet. 10:1325-1334(2001).
RN [5]
RP FUNCTION IN THE SHH PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=19334287; DOI=10.1002/dvdy.21926;
RA Cameron D.A., Pennimpede T., Petkovich M.;
RT "Tulp3 is a critical repressor of mouse hedgehog signaling.";
RL Dev. Dyn. 238:1140-1149(2009).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=19695251; DOI=10.1016/j.febslet.2009.08.015;
RA Caberoy N.B., Li W.;
RT "Unconventional secretion of tubby and tubby-like protein 1.";
RL FEBS Lett. 583:3057-3062(2009).
RN [7]
RP FUNCTION IN THE SHH PATHWAY, DISRUPTION PHENOTYPE, AND SUBCELLULAR
RP LOCATION.
RX PubMed=19286674; DOI=10.1093/hmg/ddp113;
RA Norman R.X., Ko H.W., Huang V., Eun C.M., Abler L.L., Zhang Z., Sun X.,
RA Eggenschwiler J.T.;
RT "Tubby-like protein 3 (TULP3) regulates patterning in the mouse embryo
RT through inhibition of Hedgehog signaling.";
RL Hum. Mol. Genet. 18:1740-1754(2009).
RN [8]
RP SUBCELLULAR LOCATION.
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).
RN [9]
RP FUNCTION.
RX PubMed=31761534; DOI=10.1016/j.cell.2019.11.005;
RA Hilgendorf K.I., Johnson C.T., Mezger A., Rice S.L., Norris A.M.,
RA Demeter J., Greenleaf W.J., Reiter J.F., Kopinke D., Jackson P.K.;
RT "Omega-3 Fatty Acids Activate Ciliary FFAR4 to Control Adipogenesis.";
RL Cell 179:1289-1305(2019).
CC -!- FUNCTION: Negative regulator of the Shh signaling transduction pathway:
CC recruited to primary cilia via association with the IFT complex A (IFT-
CC A) and is required for recruitment of G protein-coupled receptor GPR161
CC to cilia, a promoter of PKA-dependent basal repression machinery in Shh
CC signaling. Binds to phosphorylated inositide (phosphoinositide) lipids.
CC Both IFT-A- and phosphoinositide-binding properties are required to
CC regulate ciliary G protein-coupled receptor trafficking. Not involved
CC in ciliogenesis. During adipogenesis, regulates ciliary trafficking of
CC FFAR4 in preadipocytes. {ECO:0000269|PubMed:19286674,
CC ECO:0000269|PubMed:19334287, ECO:0000269|PubMed:31761534}.
CC -!- SUBUNIT: Associates with the IFT complex A (IFT-A).
CC {ECO:0000250|UniProtKB:O75386}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cell membrane. Cell projection, cilium.
CC Cytoplasm. Secreted. Note=Translocates from the plasma membrane to the
CC nucleus upon activation of guanine nucleotide-binding protein G(q)
CC subunit alpha (By similarity). Does not have a cleavable signal peptide
CC and is secreted by a non-conventional pathway. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed including eyes and adipose depots.
CC {ECO:0000269|PubMed:9828123}.
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed during development.
CC {ECO:0000269|PubMed:11406614}.
CC -!- DISRUPTION PHENOTYPE: Failure of neural tube closure and death by
CC embryonic day 14.5. Failure of cranial neural tube closure coincident
CC with increased neuroepithelial apoptosis specifically in the hindbrain
CC and the caudal neural tube. In addition, the number of tubulin beta-3
CC positive cells is significantly decreased in the embryonic hindbrain.
CC Morphological defects in the embryonic craniofacial regions, the spinal
CC neural tube and the limbs. {ECO:0000269|PubMed:11406614,
CC ECO:0000269|PubMed:19286674, ECO:0000269|PubMed:19334287}.
CC -!- SIMILARITY: Belongs to the TUB family. {ECO:0000305}.
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DR EMBL; AF045582; AAC95430.1; -; mRNA.
DR EMBL; AB016963; BAA74752.1; -; mRNA.
DR EMBL; BC060068; AAH60068.1; -; mRNA.
DR CCDS; CCDS39647.1; -.
DR RefSeq; NP_035787.1; NM_011657.2.
DR AlphaFoldDB; O88413; -.
DR SMR; O88413; -.
DR BioGRID; 204384; 18.
DR STRING; 10090.ENSMUSP00000001562; -.
DR iPTMnet; O88413; -.
DR PhosphoSitePlus; O88413; -.
DR EPD; O88413; -.
DR jPOST; O88413; -.
DR MaxQB; O88413; -.
DR PaxDb; O88413; -.
DR PeptideAtlas; O88413; -.
DR PRIDE; O88413; -.
DR ProteomicsDB; 298384; -.
DR Antibodypedia; 10458; 269 antibodies from 23 providers.
DR DNASU; 22158; -.
DR Ensembl; ENSMUST00000001562; ENSMUSP00000001562; ENSMUSG00000001521.
DR GeneID; 22158; -.
DR KEGG; mmu:22158; -.
DR UCSC; uc009edh.1; mouse.
DR CTD; 7289; -.
DR MGI; MGI:1329045; Tulp3.
DR VEuPathDB; HostDB:ENSMUSG00000001521; -.
DR eggNOG; KOG2502; Eukaryota.
DR GeneTree; ENSGT00940000158155; -.
DR HOGENOM; CLU_028236_1_1_1; -.
DR InParanoid; O88413; -.
DR OMA; FPTYFMH; -.
DR OrthoDB; 1445357at2759; -.
DR PhylomeDB; O88413; -.
DR TreeFam; TF314076; -.
DR Reactome; R-MMU-5610787; Hedgehog 'off' state.
DR BioGRID-ORCS; 22158; 5 hits in 73 CRISPR screens.
DR ChiTaRS; Tulp3; mouse.
DR PRO; PR:O88413; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; O88413; protein.
DR Bgee; ENSMUSG00000001521; Expressed in animal zygote and 239 other tissues.
DR ExpressionAtlas; O88413; baseline and differential.
DR Genevisible; O88413; MM.
DR GO; GO:0097731; C:9+0 non-motile cilium; ISO:MGI.
DR GO; GO:0005930; C:axoneme; IDA:MGI.
DR GO; GO:0097546; C:ciliary base; ISO:MGI.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0001664; F:G protein-coupled receptor binding; ISO:MGI.
DR GO; GO:0120160; F:intraciliary transport particle A binding; ISS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI.
DR GO; GO:0060348; P:bone development; IMP:MGI.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0060434; P:bronchus morphogenesis; IMP:MGI.
DR GO; GO:0021953; P:central nervous system neuron differentiation; IMP:MGI.
DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; IMP:MGI.
DR GO; GO:0031076; P:embryonic camera-type eye development; IMP:MGI.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:MGI.
DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; IMP:MGI.
DR GO; GO:0061548; P:ganglion development; IMP:MGI.
DR GO; GO:0060173; P:limb development; IMP:MGI.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IMP:MGI.
DR GO; GO:1901621; P:negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning; IMP:MGI.
DR GO; GO:0021914; P:negative regulation of smoothened signaling pathway involved in ventral spinal cord patterning; IMP:MGI.
DR GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR GO; GO:0021915; P:neural tube development; IMP:MGI.
DR GO; GO:0001841; P:neural tube formation; IMP:MGI.
DR GO; GO:0061512; P:protein localization to cilium; IMP:UniProtKB.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IMP:MGI.
DR GO; GO:0008589; P:regulation of smoothened signaling pathway; IMP:MGI.
DR GO; GO:0007224; P:smoothened signaling pathway; IMP:MGI.
DR GO; GO:0060831; P:smoothened signaling pathway involved in dorsal/ventral neural tube patterning; IMP:MGI.
DR Gene3D; 3.20.90.10; -; 1.
DR InterPro; IPR025659; Tubby-like_C.
DR InterPro; IPR000007; Tubby_C.
DR InterPro; IPR018066; Tubby_C_CS.
DR InterPro; IPR005398; Tubby_N.
DR Pfam; PF01167; Tub; 1.
DR Pfam; PF16322; Tub_N; 2.
DR PRINTS; PR01573; SUPERTUBBY.
DR PRINTS; PR01574; TUBBYPROTEIN.
DR SUPFAM; SSF54518; SSF54518; 1.
DR PROSITE; PS01200; TUB_1; 1.
DR PROSITE; PS01201; TUB_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cilium; Cytoplasm; Developmental protein;
KW Membrane; Nucleus; Reference proteome; Secreted.
FT CHAIN 1..460
FT /note="Tubby-related protein 3"
FT /id="PRO_0000186471"
FT REGION 37..132
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 151..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 165..193
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 460 AA; 51231 MW; 02EBC62899BB8B3B CRC64;
MEAARCAPGP RGDSAFDDET LRLRQLKLDN QRALLEKKQR KKRLEPLMVQ PNPEARLRRL
KPRGSEEHTP LVDPQMPRSD VILHGIDGPA AFLKPEAQDL ESKPQVLSVG SPAPEEGTEG
SADGESPEET APKPDLQEIL QKHGILSSVN YDEEPDKEED EGGNLSSPSA RSEESAAASQ
KAASETGASG VTAQQGDAQL GEVENLEDFA YSPAPRGVTV KCKVTRDKKG MDRGLFPTYY
MHLEREENRK IFLLAGRKRK KSKTSNYLVS TDPTDLSREG ESYIGKLRSN LMGTKFTVYD
HGVNPVKAQG LVEKAHTRQE LAAICYETNV LGFKGPRKMS VIIPGMNMNH ERIPFRPRNE
HESLLSKWQN KSMENLIELH NKAPVWNDDT QSYVLNFHGR VTQASVKNFQ IVHGNDPDYI
VMQFGRVADD VFTLDYNYPL CALQAFAIGL SSFDSKLACE
