ID TUB_HUMAN Reviewed; 506 AA.
AC P50607; D3DQU4; O00293; Q6B007;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 24-JAN-2024, entry version 173.
DE RecName: Full=Tubby protein homolog;
GN Name=TUB;
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] (ISOFORM 1).
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] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9096357; DOI=10.1073/pnas.94.7.3128;
RA North M.A., Naggert J.K., Yan Y., Noben-Trauth K., Nishina P.M.;
RT "Molecular characterization of TUB, TULP1, and TULP2, members of the novel
RT tubby gene family and their possible relation to ocular diseases.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:3128-3133(1997).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal 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 [5]
RP FUNCTION.
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 INVOLVEMENT IN RDOB.
RX PubMed=24375934; DOI=10.1002/humu.22482;
RA Borman A.D., Pearce L.R., Mackay D.S., Nagel-Wolfrum K., Davidson A.E.,
RA Henderson R., Garg S., Waseem N.H., Webster A.R., Plagnol V., Wolfrum U.,
RA Farooqi I.S., Moore A.T.;
RT "A homozygous mutation in the TUB gene associated with retinal dystrophy
RT and obesity.";
RL Hum. Mutat. 35:289-293(2014).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 234-506.
RA Boutboul S., Carroll K.J., Basdevant A., Gomez C., Nandrot E., Clement K.,
RA Shapiro L., Abitbol M.;
RT "A novel human obesity and sensory deficit syndrome resulting from a
RT mutation in the TUB gene.";
RL Submitted (FEB-2009) to the PDB data bank.
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 (By similarity).
CC Contribute to stimulation of phagocytosis of apoptotic retinal pigment
CC epithelium (RPE) cells and macrophages. {ECO:0000250,
CC ECO:0000269|PubMed:19837063}.
CC -!- SUBUNIT: Interacts with GNAQ. Interacts with TULP1. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Secreted {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}.
CC Note=Binds phospholipid and is anchored to the plasma membrane through
CC binding phosphatidylinositol 4,5-bisphosphate. Is released upon
CC activation of phospholipase C. Translocates from the plasma membrane to
CC the nucleus upon activation of guanine nucleotide-binding protein G(q)
CC subunit alpha. Does not have a cleavable signal peptide and is secreted
CC by a non-conventional pathway (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P50607-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P50607-2; Sequence=VSP_023030;
CC -!- DISEASE: Retinal dystrophy and obesity (RDOB) [MIM:616188]: A disease
CC characterized by obesity, night blindness, decreased visual acuity, and
CC electrophysiological features of a rod cone dystrophy.
CC {ECO:0000269|PubMed:24375934}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TUB family. {ECO:0000305}.
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DR EMBL; U54644; AAB53494.1; -; mRNA.
DR EMBL; U82467; AAB53699.1; -; mRNA.
DR EMBL; CH471064; EAW68634.1; -; Genomic_DNA.
DR EMBL; BC075031; AAH75031.1; -; mRNA.
DR EMBL; BC075032; AAH75032.1; -; mRNA.
DR CCDS; CCDS7786.1; -. [P50607-2]
DR CCDS; CCDS7787.1; -. [P50607-1]
DR RefSeq; NP_003311.2; NM_003320.4. [P50607-2]
DR RefSeq; NP_813977.1; NM_177972.2. [P50607-1]
DR PDB; 1S31; X-ray; 2.70 A; A=234-506.
DR PDBsum; 1S31; -.
DR AlphaFoldDB; P50607; -.
DR SMR; P50607; -.
DR BioGRID; 113126; 26.
DR IntAct; P50607; 2.
DR MINT; P50607; -.
DR STRING; 9606.ENSP00000305426; -.
DR DrugBank; DB02028; (1R,2R,3S,4R,6S)-3,4,6-Trihydroxy-5-{[(S)-hydroxy(3-hydroxy-2-oxopropoxy)phosphoryl]oxy}-1,2-cyclohexanediyl bis[dihydrogen (phosphate)].
DR GlyGen; P50607; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P50607; -.
DR PhosphoSitePlus; P50607; -.
DR BioMuta; TUB; -.
DR DMDM; 1717821; -.
DR EPD; P50607; -.
DR jPOST; P50607; -.
DR MassIVE; P50607; -.
DR PaxDb; 9606-ENSP00000305426; -.
DR PeptideAtlas; P50607; -.
DR ProteomicsDB; 56256; -. [P50607-1]
DR ProteomicsDB; 56257; -. [P50607-2]
DR Pumba; P50607; -.
DR Antibodypedia; 11439; 104 antibodies from 26 providers.
DR DNASU; 7275; -.
DR Ensembl; ENST00000299506.3; ENSP00000299506.3; ENSG00000166402.9. [P50607-1]
DR Ensembl; ENST00000305253.8; ENSP00000305426.4; ENSG00000166402.9. [P50607-2]
DR GeneID; 7275; -.
DR KEGG; hsa:7275; -.
DR MANE-Select; ENST00000299506.3; ENSP00000299506.3; NM_177972.3; NP_813977.1.
DR UCSC; uc001mfy.4; human. [P50607-1]
DR AGR; HGNC:12406; -.
DR CTD; 7275; -.
DR DisGeNET; 7275; -.
DR GeneCards; TUB; -.
DR HGNC; HGNC:12406; TUB.
DR HPA; ENSG00000166402; Tissue enhanced (retina).
DR MalaCards; TUB; -.
DR MIM; 601197; gene.
DR MIM; 616188; phenotype.
DR neXtProt; NX_P50607; -.
DR OpenTargets; ENSG00000166402; -.
DR Orphanet; 791; Retinitis pigmentosa.
DR PharmGKB; PA37070; -.
DR VEuPathDB; HostDB:ENSG00000166402; -.
DR eggNOG; KOG2502; Eukaryota.
DR GeneTree; ENSGT00940000158372; -.
DR HOGENOM; CLU_028236_1_1_1; -.
DR InParanoid; P50607; -.
DR OMA; WSYDTLD; -.
DR OrthoDB; 603296at2759; -.
DR PhylomeDB; P50607; -.
DR TreeFam; TF314076; -.
DR PathwayCommons; P50607; -.
DR SignaLink; P50607; -.
DR BioGRID-ORCS; 7275; 18 hits in 1178 CRISPR screens.
DR ChiTaRS; TUB; human.
DR EvolutionaryTrace; P50607; -.
DR GeneWiki; TUB_(gene); -.
DR GenomeRNAi; 7275; -.
DR Pharos; P50607; Tbio.
DR PRO; PR:P50607; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P50607; Protein.
DR Bgee; ENSG00000166402; Expressed in substantia nigra pars reticulata and 165 other cell types or tissues.
DR ExpressionAtlas; P50607; baseline and differential.
DR Genevisible; P50607; HS.
DR GO; GO:0005929; C:cilium; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IDA:MGI.
DR GO; GO:0120160; F:intraciliary transport particle A binding; IDA:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:MGI.
DR GO; GO:0042073; P:intraciliary transport; IDA:MGI.
DR GO; GO:0006910; P:phagocytosis, recognition; IEA:Ensembl.
DR GO; GO:0045494; P:photoreceptor cell maintenance; IEA:Ensembl.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IDA:UniProtKB.
DR GO; GO:0061512; P:protein localization to cilium; IBA:GO_Central.
DR GO; GO:1903546; P:protein localization to photoreceptor outer segment; IEA:Ensembl.
DR GO; GO:0097500; P:receptor localization to non-motile cilium; IEA:Ensembl.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR InterPro; IPR025659; Tubby-like_C.
DR InterPro; IPR000007; Tubby_C.
DR InterPro; IPR018066; Tubby_C_CS.
DR InterPro; IPR005398; Tubby_N.
DR PANTHER; PTHR16517:SF20; TUBBY PROTEIN HOMOLOG; 1.
DR PANTHER; PTHR16517; TUBBY-RELATED; 1.
DR Pfam; PF01167; Tub; 1.
DR Pfam; PF16322; Tub_N; 1.
DR PRINTS; PR01573; SUPERTUBBY.
DR PRINTS; PR01574; TUBBYPROTEIN.
DR SUPFAM; SSF54518; Tubby C-terminal domain-like; 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..506
FT /note="Tubby protein homolog"
FT /id="PRO_0000186463"
FT REGION 36..244
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..100
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 208..231
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..13
FT /note="MTSKPHSDWIPYS -> MGARTPLPSFWVSFFAETGILFPGGTPWPMGSQHS
FT KQHRKPGPLKRGHRRDRRTTRRKYWKEGREIAR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9096357"
FT /id="VSP_023030"
FT HELIX 251..255
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 265..272
FT /evidence="ECO:0007829|PDB:1S31"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 283..289
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 295..303
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 311..316
FT /evidence="ECO:0007829|PDB:1S31"
FT HELIX 318..322
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 329..334
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 338..348
FT /evidence="ECO:0007829|PDB:1S31"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 358..363
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 366..372
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 385..390
FT /evidence="ECO:0007829|PDB:1S31"
FT HELIX 406..408
FT /evidence="ECO:0007829|PDB:1S31"
FT HELIX 410..415
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 421..427
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 431..433
FT /evidence="ECO:0007829|PDB:1S31"
FT TURN 434..437
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 438..440
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 455..459
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 467..474
FT /evidence="ECO:0007829|PDB:1S31"
FT STRAND 477..482
FT /evidence="ECO:0007829|PDB:1S31"
FT HELIX 488..500
FT /evidence="ECO:0007829|PDB:1S31"
SQ SEQUENCE 506 AA; 55651 MW; B2A7D230795346C3 CRC64;
MTSKPHSDWI PYSVLDDEGR NLRQQKLDRQ RALLEQKQKK KRQEPLMVQA NADGRPRSRR
ARQSEEQAPL VESYLSSSGS TSYQVQEADS LASVQLGATR PTAPASAKRT KAAATAGGQG
GAARKEKKGK HKGTSGPAAL AEDKSEAQGP VQILTVGQSD HAQDAGETAA GGGERPSGQD
LRATMQRKGI SSSMSFDEDE EDEEENSSSS SQLNSNTRPS SATSRKSVRE AASAPSPTAP
EQPVDVEVQD LEEFALRPAP QGITIKCRIT RDKKGMDRGM YPTYFLHLDR EDGKKVFLLA
GRKRKKSKTS NYLISVDPTD LSRGGDSYIG KLRSNLMGTK FTVYDNGVNP QKASSSTLES
GTLRQELAAV CYETNVLGFK GPRKMSVIVP GMNMVHERVS IRPRNEHETL LARWQNKNTE
SIIELQNKTP VWNDDTQSYV LNFHGRVTQA SVKNFQIIHG NDPDYIVMQF GRVAEDVFTM
DYNYPLCALQ AFAIALSSFD SKLACE
//
