DISP3_HUMAN
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 03-AUG-2022, entry version 134.
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; 8.
DR IntAct; Q9P2K9; 6.
DR STRING; 9606.ENSP00000294484; -.
DR GlyGen; Q9P2K9; 2 sites.
DR iPTMnet; Q9P2K9; -.
DR PhosphoSitePlus; Q9P2K9; -.
DR BioMuta; DISP3; -.
DR DMDM; 160017977; -.
DR MassIVE; Q9P2K9; -.
DR PaxDb; Q9P2K9; -.
DR PeptideAtlas; Q9P2K9; -.
DR PRIDE; Q9P2K9; -.
DR ProteomicsDB; 83841; -. [Q9P2K9-1]
DR ProteomicsDB; 83842; -. [Q9P2K9-2]
DR Antibodypedia; 57337; 159 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 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; WDYSRTY; -.
DR OrthoDB; 56949at2759; -.
DR PhylomeDB; Q9P2K9; -.
DR TreeFam; TF331579; -.
DR PathwayCommons; Q9P2K9; -.
DR SignaLink; Q9P2K9; -.
DR BioGRID-ORCS; 57540; 10 hits in 1073 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 79 other tissues.
DR ExpressionAtlas; Q9P2K9; baseline and differential.
DR Genevisible; Q9P2K9; HS.
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:0016021; C:integral component of 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 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..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
