TUB_MOUSE
ID TUB_MOUSE Reviewed; 505 AA.
AC P50586;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Tubby protein;
GN Name=Tub; Synonyms=Rd5;
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].
RC STRAIN=C57BL/6J;
RX PubMed=8612280; DOI=10.1016/s0092-8674(00)81104-6;
RA Kleyn P.W., Fan W., Kovats S.G., Lee J.L., Pulido J.C., Wu Y.,
RA Berkemeier L.R., Misumi D.J., Holmgren L., Charlat O., Woolf E.A.,
RA Tayber O., Brody T., Shu P., Hawkins F., Kennedy B., Baldini L.,
RA Ebeling C., Alperin G.D., Deeds J., Lakey N.D., Culpepper J., Chen H.,
RA Gluecksmann-Kuis M.A., Carlson G.A., Duyk G.M., Moore K.J.;
RT "Identification and characterization of the mouse obesity gene tubby: a
RT member of a novel gene family.";
RL Cell 85:281-290(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J, and CD-1; TISSUE=Brain, and Testis;
RX PubMed=8606774; DOI=10.1038/380534a0;
RA Noben-Trauth K., Naggert J.K., North M.A., Nishina P.M.;
RT "A candidate gene for the mouse mutation tubby.";
RL Nature 380:534-538(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Brueckmann T., Winterpacht A., Hankeln T., Schmidt E.R., Zabel B.U.;
RT "Mouse chromosome 7 BAC clone 287P4, sequenced in DHGP-project: comparative
RT sequencing of 1 Mb region in man (Chromosome 11p15) and mouse (Chromosome
RT 7).";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-330 AND ARG-332.
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 [5]
RP INTERACTION WITH TULP1.
RX PubMed=19837063; DOI=10.1016/j.yexcr.2009.10.008;
RA Caberoy N.B., Maiguel D., Kim Y., Li W.;
RT "Identification of tubby and tubby-like protein 1 as eat-me signals by
RT phage display.";
RL Exp. Cell Res. 316:245-257(2010).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 241-505, SUBCELLULAR LOCATION,
RP DNA-BINDING, AND FUNCTION.
RX PubMed=10591637; DOI=10.1126/science.286.5447.2119;
RA Boggon T.J., Shan W.-S., Santagata S., Myers S.C., Shapiro L.;
RT "Implication of tubby proteins as transcription factors by structure-based
RT functional analysis.";
RL Science 286:2119-2125(1999).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 243-505, SUBCELLULAR LOCATION,
RP INTERACTION WITH GNAQ, PHOSPHOLIPID BINDING, MUTAGENESIS OF LYS-330 AND
RP ARG-332, AND FUNCTION.
RX PubMed=11375483; DOI=10.1126/science.1061233;
RA Santagata S., Boggon T.J., Baird C.L., Gomez C.A., Zhao J., Shan W.S.,
RA Myszka D.G., Shapiro L.;
RT "G-protein signaling through tubby proteins.";
RL Science 292:2041-2050(2001).
CC -!- FUNCTION: Functions in signal transduction from heterotrimeric G
CC protein-coupled receptors. Binds to membranes containing
CC phosphatidylinositol 4,5-bisphosphate. Can bind DNA (in vitro). May
CC contribute to the regulation of transcription in the nucleus. Could be
CC involved in the hypothalamic regulation of body weight. Contribute to
CC stimulation of phagocytosis of apoptotic retinal pigment epithelium
CC (RPE) cells and macrophages (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:10591637, ECO:0000269|PubMed:11375483}.
CC -!- SUBUNIT: Interacts with GNAQ. Interacts with TULP1.
CC {ECO:0000269|PubMed:11375483, ECO:0000269|PubMed:19837063}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Secreted. Cell membrane;
CC Peripheral membrane protein; Cytoplasmic side. Note=Binds phospholipid
CC and is anchored to the plasma membrane through binding
CC phosphatidylinositol 4,5-bisphosphate. Is released upon activation of
CC phospholipase C. Translocates from the plasma membrane to the nucleus
CC upon activation of guanine nucleotide-binding protein G(q) subunit
CC alpha. Does not have a cleavable signal peptide and is secreted by a
CC non-conventional pathway.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P50586-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P50586-2; Sequence=VSP_006675;
CC -!- DISEASE: Note=Defects in Tub are the cause of maturity-onset obesity,
CC insulin resistance and sensory deficits.
CC -!- SIMILARITY: Belongs to the TUB family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC52512.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U54643; AAB53495.1; -; mRNA.
DR EMBL; U52433; AAC52510.1; -; mRNA.
DR EMBL; U52824; AAC52512.1; ALT_INIT; mRNA.
DR EMBL; AJ296303; CAC39309.1; -; Genomic_DNA.
DR CCDS; CCDS21732.1; -. [P50586-1]
DR PIR; S68518; S68518.
DR RefSeq; NP_068685.1; NM_021885.4. [P50586-1]
DR PDB; 1C8Z; X-ray; 1.90 A; A=243-505.
DR PDB; 1I7E; X-ray; 1.95 A; A=243-505.
DR PDBsum; 1C8Z; -.
DR PDBsum; 1I7E; -.
DR AlphaFoldDB; P50586; -.
DR SMR; P50586; -.
DR BioGRID; 204371; 7.
DR IntAct; P50586; 1.
DR MINT; P50586; -.
DR STRING; 10090.ENSMUSP00000033341; -.
DR iPTMnet; P50586; -.
DR PhosphoSitePlus; P50586; -.
DR MaxQB; P50586; -.
DR PaxDb; P50586; -.
DR PeptideAtlas; P50586; -.
DR PRIDE; P50586; -.
DR ProteomicsDB; 298026; -. [P50586-1]
DR ProteomicsDB; 298027; -. [P50586-2]
DR Antibodypedia; 11439; 90 antibodies from 25 providers.
DR DNASU; 22141; -.
DR Ensembl; ENSMUST00000033341; ENSMUSP00000033341; ENSMUSG00000031028. [P50586-1]
DR GeneID; 22141; -.
DR KEGG; mmu:22141; -.
DR UCSC; uc009jdf.1; mouse. [P50586-1]
DR CTD; 7275; -.
DR MGI; MGI:2651573; Tub.
DR VEuPathDB; HostDB:ENSMUSG00000031028; -.
DR eggNOG; KOG2502; Eukaryota.
DR GeneTree; ENSGT00940000158372; -.
DR InParanoid; P50586; -.
DR OMA; MTSKHHS; -.
DR PhylomeDB; P50586; -.
DR TreeFam; TF314076; -.
DR BioGRID-ORCS; 22141; 1 hit in 71 CRISPR screens.
DR EvolutionaryTrace; P50586; -.
DR PRO; PR:P50586; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P50586; protein.
DR Bgee; ENSMUSG00000031028; Expressed in retinal neural layer and 212 other tissues.
DR ExpressionAtlas; P50586; baseline and differential.
DR Genevisible; P50586; MM.
DR GO; GO:0005929; C:cilium; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IMP:MGI.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001664; F:G protein-coupled receptor binding; ISO:MGI.
DR GO; GO:0120160; F:intraciliary transport particle A binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0042073; P:intraciliary transport; ISO:MGI.
DR GO; GO:0006910; P:phagocytosis, recognition; IDA:MGI.
DR GO; GO:0045494; P:photoreceptor cell maintenance; IMP:MGI.
DR GO; GO:0050766; P:positive regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:1903441; P:protein localization to ciliary membrane; ISO:MGI.
DR GO; GO:0061512; P:protein localization to cilium; IMP:MGI.
DR GO; GO:1903546; P:protein localization to photoreceptor outer segment; IMP:MGI.
DR GO; GO:0097500; P:receptor localization to non-motile cilium; IMP:MGI.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IMP:MGI.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0060041; P:retina development in camera-type eye; IMP:MGI.
DR GO; GO:0007605; P:sensory perception of sound; 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; 1.
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 3D-structure; Alternative splicing; Cell membrane; Cytoplasm; Membrane;
KW Nucleus; Obesity; Phagocytosis; Reference proteome; Secreted;
KW Sensory transduction.
FT CHAIN 1..505
FT /note="Tubby protein"
FT /id="PRO_0000186464"
FT REGION 35..243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..93
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..229
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 153..208
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_006675"
FT MUTAGEN 330
FT /note="K->A: Abolishes interaction with
FT phosphatidylinositol 4,5-bisphosphate and reduces secretion
FT by 40%; when associated with A-332."
FT /evidence="ECO:0000269|PubMed:11375483,
FT ECO:0000269|PubMed:19695251"
FT MUTAGEN 332
FT /note="R->A: Abolishes interaction with
FT phosphatidylinositol 4,5-bisphosphate and reduces secretion
FT by 40%; when associated with A-330."
FT /evidence="ECO:0000269|PubMed:11375483,
FT ECO:0000269|PubMed:19695251"
FT HELIX 250..255
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 264..270
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 275..278
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 282..288
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 294..315
FT /evidence="ECO:0007829|PDB:1C8Z"
FT HELIX 317..320
FT /evidence="ECO:0007829|PDB:1C8Z"
FT TURN 321..323
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 328..333
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 337..343
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 345..347
FT /evidence="ECO:0007829|PDB:1C8Z"
FT HELIX 349..351
FT /evidence="ECO:0007829|PDB:1C8Z"
FT HELIX 356..358
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 359..362
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 365..371
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 384..389
FT /evidence="ECO:0007829|PDB:1C8Z"
FT HELIX 405..407
FT /evidence="ECO:0007829|PDB:1I7E"
FT HELIX 409..414
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 419..426
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:1C8Z"
FT TURN 433..436
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 437..442
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 445..448
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 453..457
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 464..473
FT /evidence="ECO:0007829|PDB:1C8Z"
FT STRAND 476..481
FT /evidence="ECO:0007829|PDB:1C8Z"
FT HELIX 487..499
FT /evidence="ECO:0007829|PDB:1C8Z"
SQ SEQUENCE 505 AA; 55362 MW; 32E160BBF5265211 CRC64;
MTSKPHSDWI PYSVLDDEGS NLRQQKLDRQ RALLEQKQKK KRQEPLMVQA NADGRPRSRR
ARQSEEQAPL VESYLSSSGS TSYQVQEADS IASVQLGATR PPAPASAKKS KGAAASGGQG
GAPRKEKKGK HKGTSGPATL AEDKSEAQGP VQILTVGQSD HDKDAGETAA GGGAQPSGQD
LRATMQRKGI SSSMSFDEDE DEDENSSSSS QLNSNTRPSS ATSRKSIREA ASAPSPAAPE
PPVDIEVQDL EEFALRPAPQ GITIKCRITR DKKGMDRGMY PTYFLHLDRE DGKKVFLLAG
RKRKKSKTSN YLISVDPTDL SRGGDSYIGK LRSNLMGTKF TVYDNGVNPQ KASSSTLESG
TLRQELAAVC YETNVLGFKG PRKMSVIVPG MNMVHERVCI RPRNEHETLL ARWQNKNTES
IIELQNKTPV WNDDTQSYVL NFHGRVTQAS VKNFQIIHGN DPDYIVMQFG RVAEDVFTMD
YNYPLCALQA FAIALSSFDS KLACE
