DISP3_MOUSE
ID DISP3_MOUSE Reviewed; 1347 AA.
AC A3KFU9; Q0EEE3; Q69ZL6; Q6GQX3; Q6NS63;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 1.
DT 25-MAY-2022, entry version 75.
DE RecName: Full=Protein dispatched homolog 3 {ECO:0000250|UniProtKB:Q9P2K9};
DE AltName: Full=Patched domain-containing protein 2 {ECO:0000305};
DE AltName: Full=RND-type protein RNDEu-2 {ECO:0000303|Ref.1};
GN Name=Disp3 {ECO:0000250|UniProtKB:Q9P2K9};
GN Synonyms=Kiaa1337, Ptchd2 {ECO:0000312|MGI:MGI:2444403};
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] (ISOFORM 1).
RC TISSUE=Brain;
RA Hashimoto S., Yamaguchi A.;
RT "Identification of the novel RND-type protein in mice.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
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 MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Brain, and 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 105-1347 (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [5]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=19179482; DOI=10.1210/me.2008-0271;
RA Zikova M., Corlett A., Bendova Z., Pajer P., Bartunek P.;
RT "DISP3, a sterol-sensing domain-containing protein that links thyroid
RT hormone action and cholesterol metabolism.";
RL Mol. Endocrinol. 23:520-528(2009).
CC -!- FUNCTION: Plays a role in neuronal proliferation and differentiation.
CC Plays a role in the accumulation of cellular cholesterol. Involved in
CC intracellular lipid droplet formation. May contribute to cholesterol
CC homeostasis in neuronal cells. {ECO:0000250|UniProtKB:B9U3F2,
CC ECO:0000250|UniProtKB:Q9P2K9}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9P2K9}; Multi-pass membrane protein
CC {ECO:0000305}. Nucleus membrane {ECO:0000250|UniProtKB:Q9P2K9}; Multi-
CC pass membrane protein {ECO:0000305}. Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:B9U3F2}; Multi-pass membrane protein
CC {ECO:0000305}. Note=Predominantly localized to cholesterol-enriched
CC domains within the membrane (By similarity). Localizes to cytoplasmic
CC punctate vesicular structures (By similarity).
CC {ECO:0000250|UniProtKB:B9U3F2, ECO:0000250|UniProtKB:Q9P2K9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A3KFU9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A3KFU9-2; Sequence=VSP_028968, VSP_028969;
CC Name=3;
CC IsoId=A3KFU9-3; Sequence=VSP_028967;
CC -!- TISSUE SPECIFICITY: Expressed in brain, retina, testis and thymus
CC (PubMed:19179482). {ECO:0000269|PubMed:19179482}.
CC -!- INDUCTION: Down-regulated by thyroid hormone T3 (PubMed:19179482).
CC {ECO:0000269|PubMed:19179482}.
CC -!- DOMAIN: The SSD (sterol-sensing) domain is necessary for the increase
CC in cellular cholesterol uptake. {ECO:0000250|UniProtKB:B9U3F2}.
CC -!- SIMILARITY: Belongs to the patched family. {ECO:0000305}.
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DR EMBL; AB235901; BAF32145.1; -; mRNA.
DR EMBL; AL606919; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL645605; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC070441; AAH70441.1; -; mRNA.
DR EMBL; BC072569; AAH72569.1; -; mRNA.
DR EMBL; AK173152; BAD32430.1; -; mRNA.
DR CCDS; CCDS38966.1; -. [A3KFU9-1]
DR RefSeq; XP_011248557.1; XM_011250255.2.
DR AlphaFoldDB; A3KFU9; -.
DR STRING; 10090.ENSMUSP00000038490; -.
DR GlyGen; A3KFU9; 2 sites.
DR PhosphoSitePlus; A3KFU9; -.
DR PaxDb; A3KFU9; -.
DR PRIDE; A3KFU9; -.
DR ProteomicsDB; 277454; -. [A3KFU9-1]
DR ProteomicsDB; 277455; -. [A3KFU9-2]
DR ProteomicsDB; 277456; -. [A3KFU9-3]
DR MGI; MGI:2444403; Disp3.
DR eggNOG; KOG3664; Eukaryota.
DR InParanoid; A3KFU9; -.
DR PhylomeDB; A3KFU9; -.
DR BioGRID-ORCS; 242748; 2 hits in 73 CRISPR screens.
DR PRO; PR:A3KFU9; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; A3KFU9; protein.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0045834; P:positive regulation of lipid metabolic process; ISS:UniProtKB.
DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; ISS:UniProtKB.
DR InterPro; IPR042480; DISP3.
DR InterPro; IPR003392; Ptc/Disp.
DR InterPro; IPR000731; SSD.
DR PANTHER; PTHR46687; PTHR46687; 1.
DR Pfam; PF02460; Patched; 2.
DR PROSITE; PS50156; SSD; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cholesterol metabolism; Cytoplasmic vesicle;
KW Differentiation; Endoplasmic reticulum; Glycoprotein; Lipid metabolism;
KW Membrane; Nucleus; Reference proteome; Steroid metabolism;
KW Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..1347
FT /note="Protein dispatched homolog 3"
FT /id="PRO_0000308330"
FT TOPO_DOM 1..67
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..88
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 89..417
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 418..438
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 439
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 440..460
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 461..463
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 464..484
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 485..528
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 529..549
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 550
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 551..571
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 572..684
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 685..705
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 706..1137
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1138..1158
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1159
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1160..1180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1181..1246
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1247..1267
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1268..1281
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1282..1302
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1303..1310
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1311..1331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1332..1347
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 412..570
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 156..207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 976
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 827..1347
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028967"
FT VAR_SEQ 827..839
FT /note="VYRAPFGDFTKKL -> GCFRRRAPPASGW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028968"
FT VAR_SEQ 840..1347
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028969"
FT CONFLICT 27
FT /note="I -> V (in Ref. 1; BAF32145)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="S -> P (in Ref. 1; BAF32145 and 4; BAD32430)"
FT /evidence="ECO:0000305"
FT CONFLICT 775
FT /note="T -> P (in Ref. 1; BAF32145 and 4; BAD32430)"
FT /evidence="ECO:0000305"
FT CONFLICT 951
FT /note="C -> W (in Ref. 4; BAD32430)"
FT /evidence="ECO:0000305"
FT CONFLICT 1018
FT /note="S -> L (in Ref. 1; BAF32145 and 4; BAD32430)"
FT /evidence="ECO:0000305"
FT CONFLICT 1225..1227
FT /note="LSQ -> QAE (in Ref. 1; BAF32145 and 4; BAD32430)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1347 AA; 148446 MW; 55EBCFB73F9659E0 CRC64;
MDSEDDPLLQ DVWLEEEQPE DEACRGIPGP GLQSGAQGCW RRWTLPSRPP TLGFWSTLGW
AFTNPCCAGL VLFLGCSIPM VLSAFMFLYY PPLDIDISYN AFEIRNHEAS QRFDALALAL
KSQFGSWGRN RRDLADFTSE TLQRLISEQL QQLHLGNHSR PASRAPRSAP RDTVATQTSA
ANSSERRRRE APSPEGQVTN QSRARRGASR WDYSRTYVSA NTQTHAHWRI ELIFLARGDA
ERNIFTSERL VTIHEIERKI MDHPGFREFC WKPHEVLKDL PLGSYSYCSP PSSLMTYFFP
TERGGKIYYD GMGQDLADIR GSLELAMTHP EFYWYVDEGL SVDNLKSSLL RSEILFGAPL
PNYYSVDDRW EEQRAKFQSF VVTYVAMLAK QSTSKVQVLY GGTDLFDYEV RRTFNNDMLL
AFISSSCIAA LVYILTSCSV FLSFFGIASI GLSCLVALFL YHVVFGIQYL GILNGVAAFV
IVGIGVDDVF VFINTYRQAT HLEDPQLRMI HTIQTAGKAT FFTSLTTAAA YAANVFSQIP
AVHDFGLFMS LIVTCCWLAV LFTMPAALGL WSLYMAPLES SCQNSCHQKC GRKSSLHFPG
DLFTAPERAG GGPAQGPLPY LDDDIPLLNV EDEPASLELG DVSLVSVHCE GLQPTPDANS
RGQLLAQLQE LLHHWVLWAA VKSRWVIVGL FASILILSLV FASRLRPASR APLLFRPDTN
IQVLLDLKYN LSAEGISCIT CSGLFQEKPH SLQNNVRTSL EKKKRGSGVS WASRTETTAQ
ESMSTVYISK VKSKGHPAVY RLSLNASLPA PWQAVSPGDG EVPSFQVYRA PFGDFTKKLT
ACMSTVGLLQ AASPSRKWMV TALACDARRG WKFDFSFYVA TKEQQHTRKL YFAQSHKPPF
HGRLCVAPPG CLLSSSPDGP TKGFFYVPSD KVPKARISAT FGFNPCVNTG CGKPAVRPLV
DTGAMVFVVF GIIGLNRTQQ MDNHVIGDPG SVIYDSSFDL FKEIGHLCRL CKAIAGNSEL
VKPGGAQCLP SGYSISSFLQ MLHPECKELP EPNLLPGQLS HGAVGVKEGR VQWISMAFES
TTYKGKSSFQ TYSDYLRWES FLRQQLQTFP EGSALHRGFQ TCEHWKQIFM EIIGVQSALY
GLVLSLLICV AAVAVFTTHV LLLLPVLLSI LGIVCLVVTI MYWSGWEMGA VEAISLSILV
GSSVDYCVHL VEGYLLAGEN LPPQLSQDPS SQRQWRTLEA VRHVGVAIVS SALTTVIATV
PLFFCIIAPF AKFGKIVALN TGVSILYTLT VSTALLGIMA PGSFTRTRTS FLKALGAVLL
AGALGLGACL VLLRSGYKIP LPSGATL
