ID   DISP3_HUMAN             Reviewed;        1392 AA.
AC   Q9P2K9; Q5VTU9; Q9UJD6;
DT   23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT   23-OCT-2007, sequence version 2.
DT   24-JAN-2024, entry version 142.
DE   RecName: Full=Protein dispatched homolog 3 {ECO:0000303|PubMed:15645143};
DE   AltName: Full=Patched domain-containing protein 2 {ECO:0000305};
GN   Name=DISP3 {ECO:0000303|PubMed:15645143, ECO:0000312|HGNC:HGNC:29251};
GN   Synonyms=KIAA1337, PTCHD2;
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 [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS SER-182
RP   AND THR-650.
RC   TISSUE=Brain;
RX   PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA   Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XVI. The
RT   complete sequences of 150 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 7:65-73(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 315-1392 (ISOFORM 2).
RA   Rhodes S., Huckle E.;
RL   Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   IDENTIFICATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=15645143;
RA   Katoh Y., Katoh M.;
RT   "Identification and characterization of DISP3 gene in silico.";
RL   Int. J. Oncol. 26:551-556(2005).
RN   [5]
RP   SUBCELLULAR LOCATION, 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).
RN   [6]
RP   FUNCTION.
RX   PubMed=25281927; DOI=10.1016/j.febslet.2014.09.036;
RA   Zikova M., Konirova J., Ditrychova K., Corlett A., Kolar M., Bartunek P.;
RT   "DISP3 promotes proliferation and delays differentiation of neural
RT   progenitor cells.";
RL   FEBS Lett. 588:4071-4077(2014).
CC   -!- FUNCTION: Plays a role in neuronal proliferation and differentiation
CC       (PubMed:25281927). Plays a role in the accumulation of cellular
CC       cholesterol (By similarity). Involved in intracellular lipid droplet
CC       formation (PubMed:25281927). May contribute to cholesterol homeostasis
CC       in neuronal cells (By similarity). {ECO:0000250|UniProtKB:B9U3F2,
CC       ECO:0000269|PubMed:25281927}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:19179482}; Multi-pass membrane protein
CC       {ECO:0000305}. Nucleus membrane {ECO:0000269|PubMed:19179482}; 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 (PubMed:19179482). Localizes to cytoplasmic
CC       punctate vesicular structures (By similarity).
CC       {ECO:0000250|UniProtKB:B9U3F2, ECO:0000269|PubMed:19179482}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9P2K9-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9P2K9-2; Sequence=VSP_028966;
CC   -!- TISSUE SPECIFICITY: Expressed in brain and testis (PubMed:15645143).
CC       {ECO:0000269|PubMed:15645143}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in fetal brain (PubMed:15645143).
CC       {ECO:0000269|PubMed:15645143}.
CC   -!- INDUCTION: Up-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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA92575.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=CAB55303.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AB037758; BAA92575.1; ALT_INIT; mRNA.
DR   EMBL; AL031735; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL590989; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL117236; CAB55303.1; ALT_INIT; mRNA.
DR   CCDS; CCDS41247.1; -. [Q9P2K9-1]
DR   RefSeq; NP_065831.1; NM_020780.1. [Q9P2K9-1]
DR   RefSeq; XP_011540130.1; XM_011541828.2. [Q9P2K9-1]
DR   AlphaFoldDB; Q9P2K9; -.
DR   BioGRID; 121599; 9.
DR   IntAct; Q9P2K9; 6.
DR   STRING; 9606.ENSP00000294484; -.
DR   GlyCosmos; Q9P2K9; 2 sites, No reported glycans.
DR   GlyGen; Q9P2K9; 3 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9P2K9; -.
DR   PhosphoSitePlus; Q9P2K9; -.
DR   BioMuta; DISP3; -.
DR   DMDM; 160017977; -.
DR   MassIVE; Q9P2K9; -.
DR   PaxDb; 9606-ENSP00000294484; -.
DR   PeptideAtlas; Q9P2K9; -.
DR   ProteomicsDB; 83841; -. [Q9P2K9-1]
DR   ProteomicsDB; 83842; -. [Q9P2K9-2]
DR   Antibodypedia; 57337; 174 antibodies from 25 providers.
DR   DNASU; 57540; -.
DR   Ensembl; ENST00000294484.7; ENSP00000294484.6; ENSG00000204624.8. [Q9P2K9-1]
DR   GeneID; 57540; -.
DR   KEGG; hsa:57540; -.
DR   MANE-Select; ENST00000294484.7; ENSP00000294484.6; NM_020780.2; NP_065831.1.
DR   UCSC; uc001ash.5; human. [Q9P2K9-1]
DR   AGR; HGNC:29251; -.
DR   CTD; 57540; -.
DR   DisGeNET; 57540; -.
DR   GeneCards; DISP3; -.
DR   HGNC; HGNC:29251; DISP3.
DR   HPA; ENSG00000204624; Group enriched (brain, pituitary gland, retina, testis).
DR   MIM; 611251; gene.
DR   neXtProt; NX_Q9P2K9; -.
DR   OpenTargets; ENSG00000204624; -.
DR   PharmGKB; PA142671116; -.
DR   VEuPathDB; HostDB:ENSG00000204624; -.
DR   eggNOG; KOG3664; Eukaryota.
DR   GeneTree; ENSGT00940000157931; -.
DR   HOGENOM; CLU_007038_0_0_1; -.
DR   InParanoid; Q9P2K9; -.
DR   OMA; RWDYSRT; -.
DR   OrthoDB; 2909370at2759; -.
DR   PhylomeDB; Q9P2K9; -.
DR   TreeFam; TF331579; -.
DR   PathwayCommons; Q9P2K9; -.
DR   SignaLink; Q9P2K9; -.
DR   BioGRID-ORCS; 57540; 10 hits in 1142 CRISPR screens.
DR   GenomeRNAi; 57540; -.
DR   Pharos; Q9P2K9; Tbio.
DR   PRO; PR:Q9P2K9; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q9P2K9; Protein.
DR   Bgee; ENSG00000204624; Expressed in ganglionic eminence and 81 other cell types or tissues.
DR   ExpressionAtlas; Q9P2K9; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR   GO; GO:0031965; C:nuclear membrane; ISS:UniProtKB.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR   GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0045665; P:negative regulation of neuron differentiation; IDA:UniProtKB.
DR   GO; GO:0045834; P:positive regulation of lipid metabolic process; IDA:UniProtKB.
DR   GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IDA:UniProtKB.
DR   GO; GO:0032368; P:regulation of lipid transport; NAS:UniProtKB.
DR   GO; GO:0007224; P:smoothened signaling pathway; NAS:UniProtKB.
DR   Gene3D; 1.20.1640.10; Multidrug efflux transporter AcrB transmembrane domain; 2.
DR   InterPro; IPR042480; DISP3.
DR   InterPro; IPR004869; MMPL_dom.
DR   InterPro; IPR003392; Ptc/Disp.
DR   InterPro; IPR000731; SSD.
DR   PANTHER; PTHR46687; PROTEIN DISPATCHED HOMOLOG 3; 1.
DR   PANTHER; PTHR46687:SF1; PROTEIN DISPATCHED HOMOLOG 3; 1.
DR   Pfam; PF03176; MMPL; 1.
DR   Pfam; PF02460; Patched; 1.
DR   SUPFAM; SSF82866; Multidrug efflux transporter AcrB transmembrane domain; 2.
DR   PROSITE; PS50156; SSD; 1.
DR   Genevisible; Q9P2K9; HS.
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..1392
FT                   /note="Protein dispatched homolog 3"
FT                   /id="PRO_0000308329"
FT   TOPO_DOM        1..73
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        74..94
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        95..462
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        463..483
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        484
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        485..505
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        506..508
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        509..529
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        530..573
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        574..594
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        595
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        596..616
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        617..729
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        730..750
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        751..1182
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1183..1203
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1204
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1205..1225
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1226..1291
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1292..1312
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1313..1320
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1321..1341
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1342..1358
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        1359..1379
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1380..1392
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   DOMAIN          457..615
FT                   /note="SSD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT   REGION          16..40
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          162..248
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        217..231
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        163
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1021
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         934..1392
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.3"
FT                   /id="VSP_028966"
FT   VARIANT         39
FT                   /note="G -> R (in dbSNP:rs41274528)"
FT                   /id="VAR_061496"
FT   VARIANT         51
FT                   /note="L -> V (in dbSNP:rs3738159)"
FT                   /id="VAR_036796"
FT   VARIANT         182
FT                   /note="G -> S (in dbSNP:rs2817580)"
FT                   /evidence="ECO:0000269|PubMed:10718198"
FT                   /id="VAR_036797"
FT   VARIANT         650
FT                   /note="A -> T (in dbSNP:rs2072994)"
FT                   /evidence="ECO:0000269|PubMed:10718198"
FT                   /id="VAR_036798"
FT   VARIANT         661
FT                   /note="G -> A (in dbSNP:rs2072993)"
FT                   /id="VAR_036799"
FT   VARIANT         948
FT                   /note="R -> H (in dbSNP:rs12096312)"
FT                   /id="VAR_036800"
SQ   SEQUENCE   1392 AA;  153048 MW;  D72303B2F94CD5DF CRC64;
     MDTEDDPLLQ DVWLEEEQEE EEATGETFLG AQKPGPQPGA GGQCCWRHWP LASRPPASGF
     WSTLGWAFTN PCCAGLVLFL GCSIPMALSA FMFLYYPPLD IDISYNAFEI RNHEASQRFD
     ALTLALKSQF GSWGRNRRDL ADFTSETLQR LISEQLQQLH LGNRSRQASR APRVIPAASL
     GGPGPYRDTS AAQKPTANRS GRLRRETPPL EDLAANQSED PRNQRLSKNG RYQPSIPPHA
     AVAANQSRAR RGASRWDYSR AYVSANTQTH AHWRIELIFL ARGDAERNIF TSERLVTIHE
     IERKIMDHPG FREFCWKPHE VLKDLPLGSY SYCSPPSSLM TYFFPTERGG KIYYDGMGQD
     LADIRGSLEL AMTHPEFYWY VDEGLSADNL KSSLLRSEIL FGAPLPNYYS VDDRWEEQRA
     KFQSFVVTYV AMLAKQSTSK VQVLYGGTDL FDYEVRRTFN NDMLLAFISS SCIAALVYIL
     TSCSVFLSFF GIASIGLSCL VALFLYHVVF GIQYLGILNG VAAFVIVGIG VDDVFVFINT
     YRQATHLEDP QLRMIHTVQT AGKATFFTSL TTAAAYAANV FSQIPAVHDF GLFMSLIVSC
     CWLAVLVTMP AALGLWSLYL APLESSCQTS CHQNCSRKTS LHFPGDVFAA PEQVGGSPAQ
     GPIPYLDDDI PLLEVEEEPV SLELGDVSLV SVSPEGLQPA SNTGSRGHLI VQLQELLHHW
     VLWSAVKSRW VIVGLFVSIL ILSLVFASRL RPASRAPLLF RPDTNIQVLL DLKYNLSAEG
     ISCITCSGLF QEKPHSLQNN IRTSLEKKRR GSGVPWASRP EATLQDFPGT VYISKVKSQG
     HPAVYRLSLN ASLPAPWQAV SPGDGEVPSF QVYRAPFGNF TKKLTACMST VGLLQAASPS
     RKWMLTTLAC DAKRGWKFDF SFYVATKEQQ HTRKLYFAQS HKPPFHGRVC MAPPGCLLSS
     SPDGPTKGFF FVPSEKVPKA RLSATFGFNP CVNTGCGKPA VRPLVDTGAM VFVVFGIIGV
     NRTRQVDNHV IGDPGSVVYD SSFDLFKEIG HLCHLCKAIA ANSELVKPGG AQCLPSGYSI
     SSFLQMLHPE CKELPEPNLL PGQLSHGAVG VREGRVQWIS MAFESTTYKG KSSFQTYSDY
     LRWESFLQQQ LQALPEGSVL RRGFQTCEHW KQIFMEIVGV QSALCGLVLS LLICVAAVAV
     FTTHILLLLP VLLSILGIVC LVVTIMYWSG WEMGAVEAIS LSILVGSSVD YCVHLVEGYL
     LAGENLPPHQ AEDARTQRQW RTLEAVRHVG VAIVSSALTT VIATVPLFFC IIAPFAKFGK
     IVALNTGVSI LYTLTVSTAL LGIMAPSSFT RTRTSFLKAL GAVLLAGALG LGACLVLLQS
     GYKIPLPAGA SL
//