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2.A.6.9.1
Dispatched is an exporter of the amino-terminal portion (19 kDa) of the C-terminally cholesterol-modified peptide, hedgehog; sterol sensor protein (Ma et al., 2002). Loss prevents hedgehog signaling. (Nakano et al., 2004; Higgins, 2007). The intracellular movement of this Hedgehog signal is complex, and involves insertion into the apical cell membrane, followed by endocytosis, and then secretion at the basolateral membrane by Dispatched (Nikaido 2018). Dispatched shows a typical RND protein folding pattern, although its overall sequence similarity to Patched or NPC1 is low. However, it contains the typical sterol sensing domain,  similar to those found in NPC1 as well as in Patched. Hedgehog anchored by glycosylphophatidylinositol, rather than cholesterol, was not exported by Dispatched, suggesting that the cholesterol anchor is recognized by the transporter. Finally, the secretion of Hedgehog by Dispatched across the membrane requires help by other proteins, including a secreted soluble protein called Scube (Nikaido 2018).

Accession Number:Q9VNJ5
Protein Name:Protein dispatched
Length:1218
Molecular Weight:138979.00
Species: [7227]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Hedgehog peptide

Cross database links:

eggNOG: inNOG07871
RefSeq: NP_524734.2   
Entrez Gene ID: 44274   
Pfam: PF02460   
KEGG: dme:Dmel_CG2019   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0008158 F:hedgehog receptor activity
GO:0006887 P:exocytosis
GO:0007275 P:multicellular organismal development
GO:0007280 P:pole cell migration
GO:0007224 P:smoothened signaling pathway

References (7)

[1] “Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified hedgehog from signaling cells.”  Burke R.et.al.   10619433
[2] “The genome sequence of Drosophila melanogaster.”  Adams M.D.et.al.   10731132
[3] “Annotation of the Drosophila melanogaster euchromatic genome: a systematic review.”  Misra S.et.al.   12537572
[4] “A Drosophila full-length cDNA resource.”  Stapleton M.et.al.   12537569
[5] “Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of dispatched.”  Ma Y.et.al.   12372301
[6] “Cholesterol modification of hedgehog is required for trafficking and movement, revealing an asymmetric cellular response to hedgehog.”  Gallet A.et.al.   12586063
[7] “Identification of N-glycosylated proteins from the central nervous system of Drosophila melanogaster.”  Koles K.et.al.   17893096

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MLCFDSERMN WYYHVLARRP YLVVVSIAVY CVACIIVALV LNKLPDFSDP TLGFETRGTK 
61:	IGERLTAWYN LLQETDHHGA LFSNPSDLWE RRRVEQGYVE TKLHPNHRRR KNKHKNRNKN 
121:	KRRKEQNQSS HEHHDVAQKM MQFKKRLKAT SSPSPNLGFD TWIGDSGVFR DYEITNDSAS 
181:	SSLEPTRRTE QIEYGHNTTS VDEEEHQQRV QTKKSTWRLL KQAATLPTDG WADMHRRQPI 
241:	EGFFCDSSPR KEYSHFVVQR IGPNATDSLF DLNGLLAMCQ LQDQITEVPS YRAFCEPEML 
301:	TTECCRPWSL PNYAAMLANK SSCFDLTTED VTSLHTLLLG CYEYFHDLKM DNHCNEIPHC 
361:	RAPEECKRLN IVFNVLNFLT DFSFIKSNDS NVYLKYAMIF IPVAQSNRLL PLFHEWEDVE 
421:	LINELVEVVA MDLGLENELF NELLLTDVWL VSLGGTFVMA SVWLYTGSAF ITLMSCVAIC 
481:	FSLGLAYFFY AIVLEFEFFP YMNLLAVVVI IGIGADDVFL FLKIWHCVLT ERFSNRCTLT 
541:	TQSQSALPTL ENSDHTESLE NIMALTMRHA AASMFVTSLT TAGAFYASYS SSITAIKCFG 
601:	IFAGTVVVTN YLLMITWLPA SVSIMERLFA TRMSCHHPMS IKLIHACKKS INRFCQMFEE 
661:	CITKSIMNYA YLWLLIFGAL GASSAVIVFW YPGLQLPEKS HFQLFVSKHP FEVYSSLKQQ 
721:	FWFEKPLQAY ENFKMHMHFV WGVQAVDDGD YTNPNSYGHL HYDNNFNVSS RPAQLWILDF 
781:	CQSVRQQPFY KETLGMLLPN CFIENLIDYM KRRCIDDMDS TRKDRSPCCD AQFPFEPHIF 
841:	EYCLPQSISN MYDTTFFRPG VAGPKFAEAP RLETEDYLGM SGNESAEYST NGSFTPLLVK 
901:	ALVIEFESNV AYSTIYANIR QFYESVEHWF QMQLKTAPPE LQGGWFTSDL KFYNVQDTLS 
961:	HDTFVAICLA MAASLAVLLC FTVNILISIY AVLTVSLSIF NTVAVLILLG WQLNILESIA 
1021:	VSTAIGLAVD FSLHYGIHYR MSPVKERLAA TQFVLSRIIG PTVMAATTTG LAGGIMMASN 
1081:	ILPYIQIGVF LVVVMIVSWF YATFFLMSLL RVAGPQHGFL ELKWPLWSKR SSGSSKFYER 
1141:	KPSQVIASEQ LLTPTSSAIV ELANSETHEL ESLNSNSLIK TISGIESAHA LSSLPRDFEH 
1201:	SFQTMHECKY QTYPSTSN