TT39B_MOUSE
ID TT39B_MOUSE Reviewed; 617 AA.
AC Q8BYY4; B2RX73; Q3V168; Q8BX40; Q9D8N8;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Tetratricopeptide repeat protein 39B;
DE Short=TPR repeat protein 39B;
GN Name=Ttc39b {ECO:0000312|MGI:MGI:1917113};
GN Synonyms=T39 {ECO:0000303|PubMed:27383786};
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] (ISOFORMS 1; 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell, Pancreas, Skin, 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Liver, Pancreas, 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 DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=27383786; DOI=10.1038/nature18628;
RA Hsieh J., Koseki M., Molusky M.M., Yakushiji E., Ichi I., Westerterp M.,
RA Iqbal J., Chan R.B., Abramowicz S., Tascau L., Takiguchi S., Yamashita S.,
RA Welch C.L., Di Paolo G., Hussain M.M., Lefkowitch J.H., Rader D.J.,
RA Tall A.R.;
RT "TTC39B deficiency stabilizes LXR reducing both atherosclerosis and
RT steatohepatitis.";
RL Nature 535:303-307(2016).
CC -!- FUNCTION: Regulates high density lipoprotein (HDL) cholesterol
CC metabolism by promoting the ubiquitination and degradation of the
CC oxysterols receptors LXR (NR1H2 and NR1H3).
CC {ECO:0000269|PubMed:27383786}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8BYY4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BYY4-2; Sequence=VSP_026361, VSP_026362;
CC Name=3;
CC IsoId=Q8BYY4-3; Sequence=VSP_026359, VSP_026360;
CC -!- TISSUE SPECIFICITY: High expression in lung and spleen. Low lower
CC expression in liver and small intestine. Weak expression in heart,
CC brain, kidney, adipose, and adrenal gland.
CC {ECO:0000269|PubMed:27383786}.
CC -!- DISRUPTION PHENOTYPE: Chow-fed deficient mice display increased HDL-
CC cholesterol level, accompanied by increased ABCA1 and MYLIP expression,
CC increased oxysterols receptors LXR (NR1H3 AND NR1H2) protein level
CC without change in NR1H2/3 mRNA levels. Many NR1H2/3 targets are up-
CC regulated, including ABCG5/8, SCD1, ELOVL5, INSIG2 and LPCAT3.
CC Deficiency of TTC39B reduced processing of SREBP1 a pivotal regulator
CC of lipogenesis. When fed with a high-fat/high-cholesterol/bile-salt
CC diet during 20 weeks, used as a model of steatohepatitis resembling
CC human non-alcoholic steatohepatitis, mice show increased HDL
CC cholesterol and APOA1 levels, reduced VLDL (very low density
CC lipoprotein), and reduced mortality compared with wild-type. The livers
CC of deficient mice shown diminished hepatic triglyceride and cholesteryl
CC ester accumulation, fewer inflammatory foci consisting of neutrophils
CC and lymphocytes, less hepatocellular ballooning degeneration and less
CC hepatocyte proliferation compared to control. Knockout mice lacking
CC both TTC39B and LDLR, fed a Western diet for 20 weeks, exhibit a
CC reduction in LDL-cholesterol, but plasma triglyceride levels are not
CC different. Atherosclerotic lesion area of the aorta are reduced
CC compared to LDLR single knockout mice. {ECO:0000269|PubMed:27383786}.
CC -!- SIMILARITY: Belongs to the TTC39 family. {ECO:0000305}.
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DR EMBL; AK007856; BAB25308.1; -; mRNA.
DR EMBL; AK037208; BAC29754.1; -; mRNA.
DR EMBL; AK049108; BAC33545.1; -; mRNA.
DR EMBL; AK132655; BAE21284.1; -; mRNA.
DR EMBL; BX571885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466527; EDL31029.1; -; Genomic_DNA.
DR EMBL; BC151021; AAI51022.1; -; mRNA.
DR CCDS; CCDS18297.1; -. [Q8BYY4-1]
DR RefSeq; NP_081514.1; NM_027238.2. [Q8BYY4-1]
DR AlphaFoldDB; Q8BYY4; -.
DR BioGRID; 213723; 1.
DR STRING; 10090.ENSMUSP00000099887; -.
DR iPTMnet; Q8BYY4; -.
DR PhosphoSitePlus; Q8BYY4; -.
DR EPD; Q8BYY4; -.
DR jPOST; Q8BYY4; -.
DR MaxQB; Q8BYY4; -.
DR PaxDb; Q8BYY4; -.
DR PeptideAtlas; Q8BYY4; -.
DR PRIDE; Q8BYY4; -.
DR ProteomicsDB; 297735; -. [Q8BYY4-1]
DR ProteomicsDB; 297736; -. [Q8BYY4-2]
DR ProteomicsDB; 297737; -. [Q8BYY4-3]
DR Antibodypedia; 24508; 102 antibodies from 22 providers.
DR DNASU; 69863; -.
DR Ensembl; ENSMUST00000030205; ENSMUSP00000030205; ENSMUSG00000038172. [Q8BYY4-3]
DR Ensembl; ENSMUST00000048274; ENSMUSP00000040590; ENSMUSG00000038172. [Q8BYY4-2]
DR Ensembl; ENSMUST00000102823; ENSMUSP00000099887; ENSMUSG00000038172. [Q8BYY4-1]
DR GeneID; 69863; -.
DR KEGG; mmu:69863; -.
DR UCSC; uc008tkq.1; mouse. [Q8BYY4-1]
DR UCSC; uc008tkr.1; mouse. [Q8BYY4-2]
DR UCSC; uc008tks.1; mouse. [Q8BYY4-3]
DR CTD; 158219; -.
DR MGI; MGI:1917113; Ttc39b.
DR VEuPathDB; HostDB:ENSMUSG00000038172; -.
DR eggNOG; KOG3783; Eukaryota.
DR GeneTree; ENSGT00950000182917; -.
DR HOGENOM; CLU_010086_3_0_1; -.
DR InParanoid; Q8BYY4; -.
DR OMA; ELMYVWN; -.
DR OrthoDB; 754120at2759; -.
DR PhylomeDB; Q8BYY4; -.
DR TreeFam; TF313761; -.
DR BioGRID-ORCS; 69863; 5 hits in 72 CRISPR screens.
DR ChiTaRS; Ttc39b; mouse.
DR PRO; PR:Q8BYY4; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8BYY4; protein.
DR Bgee; ENSMUSG00000038172; Expressed in spermatocyte and 202 other tissues.
DR ExpressionAtlas; Q8BYY4; baseline and differential.
DR Genevisible; Q8BYY4; MM.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0010887; P:negative regulation of cholesterol storage; IMP:UniProtKB.
DR GO; GO:0010874; P:regulation of cholesterol efflux; IMP:UniProtKB.
DR GO; GO:0090181; P:regulation of cholesterol metabolic process; IMP:UniProtKB.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR019412; Iml2/TPR_39.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR InterPro; IPR034305; TTC39B.
DR PANTHER; PTHR31859; PTHR31859; 1.
DR PANTHER; PTHR31859:SF4; PTHR31859:SF4; 1.
DR Pfam; PF10300; DUF3808; 1.
DR Pfam; PF13174; TPR_6; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Lipid metabolism; Reference proteome; Repeat;
KW TPR repeat; Ubl conjugation pathway.
FT CHAIN 1..617
FT /note="Tetratricopeptide repeat protein 39B"
FT /id="PRO_0000292002"
FT REPEAT 328..361
FT /note="TPR 1"
FT REPEAT 520..553
FT /note="TPR 2"
FT REPEAT 561..594
FT /note="TPR 3"
FT VAR_SEQ 167..209
FT /note="EMHAEICYAECLLQKAALTFVQDENMINFIKGGLKIRTSYQIY -> TDLRA
FT SLRTRAGTGRPKVFPRQSMRLNWPQYDLHCLFLPGNPM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_026359"
FT VAR_SEQ 210..617
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_026360"
FT VAR_SEQ 474..518
FT /note="EMMYVWNGFSIVGKRKDLSENLLVTVEKAEEALQNQDFTDYSVDD -> VLL
FT LLTVYLPEIRSLLGASRDALTFACEVYSSVENYYVFLYLYVN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_026361"
FT VAR_SEQ 519..617
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_026362"
SQ SEQUENCE 617 AA; 70293 MW; D7FF38C238C6A5BB CRC64;
MALVGSRVEL DADEDIFEDA LETISRSPSD MATSGFHFVP CETKRTSRQL GASAMGRPEG
SSAKVDLKSG LEECAEALNL FLSNKFKDAL ELLRPWAKES MYHALGYSTI VVLQAVMTFE
QQDIQNGISA MKDALQTCQK YRKKCTVVES FSSLLSRGSL EQLSEEEMHA EICYAECLLQ
KAALTFVQDE NMINFIKGGL KIRTSYQIYK ECLSILHVIQ KNKQEQHFFY EFEGGVKLGT
GAFNLMLSLL PARIIRLLEF IGFSGNRDLG LLQLREGASG SSMRSPLCCL TILAFHTYIS
LILGTGEVNV VEAESLLAPF LQQFPNGSLI LFYHARIELL KGNTEKAQET FRKCISVQEE
WKQFHHLCYW ELMWIHIYQQ NWMQAYYYSD LLCKESKWSK ATYVFLKAAI LSMLPEEEVA
ATKENVVSLF RQVDGLKQRI AGKSLPTEKF AVRKARRYSP PSGVPGKLVM PALEMMYVWN
GFSIVGKRKD LSENLLVTVE KAEEALQNQD FTDYSVDDEC LVKLLKGCCL KNLERPLQAE
LCFNHVVESE KLLKYDHYLV PFTLFELAFL YKSQGEIDKA IKVLETARNN YKDYSLESRL
HFRIQAALHL WKKPSTD
