MREG_HUMAN
ID MREG_HUMAN Reviewed; 214 AA.
AC Q8N565; Q53R89; Q53TC1; Q5XKB6; Q9NWC9; Q9P1S1;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Melanoregulin;
DE AltName: Full=Dilute suppressor protein homolog;
GN Name=MREG; Synonyms=DSU; ORFNames=HDCGA21P;
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 2), AND VARIANT ARG-15.
RC TISSUE=Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-15.
RC TISSUE=Duodenum, and Skin;
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 70-214 (ISOFORM 1).
RC TISSUE=Dendritic cell;
RA Zhao Z., Huang X., Li N., Zhu X., Cao X.;
RT "A novel gene from human dendritic cell.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=17260955; DOI=10.1021/bi061466i;
RA Boesze-Battaglia K., Song H., Sokolov M., Lillo C., Pankoski-Walker L.,
RA Gretzula C., Gallagher B., Rachel R.A., Jenkins N.A., Copeland N.G.,
RA Morris F., Jacob J., Yeagle P., Williams D.S., Damek-Poprawa M.;
RT "The tetraspanin protein peripherin-2 forms a complex with melanoregulin, a
RT putative membrane fusion regulator.";
RL Biochemistry 46:1256-1272(2007).
RN [6]
RP FUNCTION.
RX PubMed=19240024; DOI=10.1074/jbc.m808857200;
RA Damek-Poprawa M., Diemer T., Lopes V.S., Lillo C., Harper D.C., Marks M.S.,
RA Wu Y., Sparrow J.R., Rachel R.A., Williams D.S., Boesze-Battaglia K.;
RT "Melanoregulin (MREG) modulates lysosome function in pigment epithelial
RT cells.";
RL J. Biol. Chem. 284:10877-10889(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Probably functions as cargo-recognition protein that couples
CC cytoplasmic vesicles to the transport machinery. Plays a role in hair
CC pigmentation, a process that involves shedding of melanosome-containing
CC vesicles from melanocytes, followed by phagocytosis of the melanosome-
CC containing vesicles by keratinocytes. Functions on melanosomes as
CC receptor for RILP and the complex formed by RILP and DCTN1, and thereby
CC contributes to retrograde melanosome transport from the cell periphery
CC to the center. Overexpression causes accumulation of late endosomes
CC and/or lysosomes at the microtubule organising center (MTOC) at the
CC center of the cell. Probably binds cholesterol and requires the
CC presence of cholesterol in membranes to function in microtubule-
CC mediated retrograde organelle transport. Binds phosphatidylinositol 3-
CC phosphate, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-
CC phosphate and phosphatidylinositol 3,5-bisphosphate, but not
CC phosphatidylinositol 3,4-bisphosphate or phosphatidylinositol 4,5-
CC bisphosphate (By similarity). Required for normal phagosome clearing
CC and normal activation of lysosomal enzymes in lysosomes from retinal
CC pigment epithelium cells (PubMed:19240024). Required for normal
CC degradation of the lipofuscin component N-retinylidene-N-
CC retinylethanolamine (A2E) in the eye. May function in membrane fusion
CC and regulate the biogenesis of disk membranes of photoreceptor rod
CC cells (By similarity). {ECO:0000250|UniProtKB:Q6NVG5,
CC ECO:0000269|PubMed:19240024}.
CC -!- SUBUNIT: Identified in a complex with RILP and DCTN1; interacts
CC directly with RILP, but does not interact directly with DCTN1.
CC Interacts with PRPH2. {ECO:0000250|UniProtKB:Q6NVG5}.
CC -!- INTERACTION:
CC Q8N565; Q8N9N8: EIF1AD; NbExp=3; IntAct=EBI-10978787, EBI-750700;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:Q6NVG5}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q6NVG5}. Melanosome membrane
CC {ECO:0000250|UniProtKB:Q6NVG5}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q6NVG5}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q6NVG5}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q6NVG5}. Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:Q6NVG5}. Note=Localizes to the inner segment and
CC basal outer segment of rods in the retina.
CC {ECO:0000250|UniProtKB:Q6NVG5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8N565-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N565-2; Sequence=VSP_026387;
CC -!- TISSUE SPECIFICITY: Expressed in photoreceptor cells (at protein
CC level). {ECO:0000269|PubMed:17260955}.
CC -!- PTM: Palmitoylated. Palmitoylation is required to maintain the protein
CC at the melanosome membrane. {ECO:0000250|UniProtKB:Q6NVG5}.
CC -!- SIMILARITY: Belongs to the melanoregulin family. {ECO:0000305}.
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DR EMBL; AK000978; BAA91453.1; -; mRNA.
DR EMBL; AC010686; AAY14656.1; -; Genomic_DNA.
DR EMBL; AC093382; AAY14719.1; -; Genomic_DNA.
DR EMBL; BC032747; AAH32747.1; -; mRNA.
DR EMBL; BC082990; AAH82990.1; -; mRNA.
DR EMBL; AF068290; AAF65179.1; -; mRNA.
DR CCDS; CCDS46513.1; -. [Q8N565-1]
DR RefSeq; NP_060470.2; NM_018000.2. [Q8N565-1]
DR AlphaFoldDB; Q8N565; -.
DR SMR; Q8N565; -.
DR BioGRID; 120813; 21.
DR IntAct; Q8N565; 9.
DR STRING; 9606.ENSP00000484331; -.
DR iPTMnet; Q8N565; -.
DR PhosphoSitePlus; Q8N565; -.
DR SwissPalm; Q8N565; -.
DR BioMuta; MREG; -.
DR DMDM; 74751016; -.
DR EPD; Q8N565; -.
DR jPOST; Q8N565; -.
DR MassIVE; Q8N565; -.
DR MaxQB; Q8N565; -.
DR PaxDb; Q8N565; -.
DR PeptideAtlas; Q8N565; -.
DR PRIDE; Q8N565; -.
DR ProteomicsDB; 72005; -. [Q8N565-1]
DR ProteomicsDB; 72006; -. [Q8N565-2]
DR Antibodypedia; 34232; 182 antibodies from 20 providers.
DR DNASU; 55686; -.
DR Ensembl; ENST00000263268.11; ENSP00000263268.6; ENSG00000118242.16. [Q8N565-1]
DR Ensembl; ENST00000620139.4; ENSP00000484331.1; ENSG00000118242.16. [Q8N565-1]
DR GeneID; 55686; -.
DR KEGG; hsa:55686; -.
DR MANE-Select; ENST00000263268.11; ENSP00000263268.6; NM_018000.3; NP_060470.2.
DR UCSC; uc002vfo.4; human. [Q8N565-1]
DR CTD; 55686; -.
DR DisGeNET; 55686; -.
DR GeneCards; MREG; -.
DR HGNC; HGNC:25478; MREG.
DR HPA; ENSG00000118242; Tissue enhanced (retina).
DR MIM; 609207; gene.
DR neXtProt; NX_Q8N565; -.
DR OpenTargets; ENSG00000118242; -.
DR PharmGKB; PA162396174; -.
DR VEuPathDB; HostDB:ENSG00000118242; -.
DR eggNOG; ENOG502S05X; Eukaryota.
DR GeneTree; ENSGT00390000008926; -.
DR HOGENOM; CLU_105265_0_0_1; -.
DR InParanoid; Q8N565; -.
DR OMA; CRCLEEP; -.
DR OrthoDB; 1250643at2759; -.
DR PhylomeDB; Q8N565; -.
DR TreeFam; TF334733; -.
DR PathwayCommons; Q8N565; -.
DR SignaLink; Q8N565; -.
DR BioGRID-ORCS; 55686; 14 hits in 1079 CRISPR screens.
DR ChiTaRS; MREG; human.
DR GenomeRNAi; 55686; -.
DR Pharos; Q8N565; Tbio.
DR PRO; PR:Q8N565; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8N565; protein.
DR Bgee; ENSG00000118242; Expressed in amniotic fluid and 154 other tissues.
DR ExpressionAtlas; Q8N565; baseline and differential.
DR Genevisible; Q8N565; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0031300; C:intrinsic component of organelle membrane; ISS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042470; C:melanosome; IBA:GO_Central.
DR GO; GO:0033162; C:melanosome membrane; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0030318; P:melanocyte differentiation; IBA:GO_Central.
DR GO; GO:0032400; P:melanosome localization; ISS:UniProtKB.
DR GO; GO:0032402; P:melanosome transport; IBA:GO_Central.
DR GO; GO:0072385; P:minus-end-directed organelle transport along microtubule; IEA:Ensembl.
DR GO; GO:0090382; P:phagosome maturation; ISS:UniProtKB.
DR InterPro; IPR031638; Melanoregulin.
DR PANTHER; PTHR34340; PTHR34340; 1.
DR Pfam; PF15812; MREG; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasmic vesicle; Lipid-binding;
KW Lipoprotein; Lysosome; Membrane; Palmitate; Phosphoprotein;
KW Reference proteome; Transport.
FT CHAIN 1..214
FT /note="Melanoregulin"
FT /id="PRO_0000292175"
FT MOTIF 162..172
FT /note="Cholesterol-binding sequence motif"
FT /evidence="ECO:0000250|UniProtKB:Q6NVG5"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT VAR_SEQ 208..214
FT /note="YLPFPSP -> LWGDLSCRLAHMQGVLH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_026387"
FT VARIANT 15
FT /note="G -> R (in dbSNP:rs1864253)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_053923"
FT CONFLICT 154
FT /note="N -> S (in Ref. 1; BAA91453)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="F -> L (in Ref. 4; AAF65179)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 214 AA; 24927 MW; 48D9780706C27DF7 CRC64;
MGLRDWLRTV CCCCGCECLE ERALPEKEPL VSDNNPYSSF GATLVRDDEK NLWSMPHDVS
HTEADDDRTL YNLIVIRNQQ AKDSEEWQKL NYDIHTLRQV RREVRNRWKC ILEDLGFQKE
ADSLLSVTKL STISDSKNTR KAREMLLKLA EETNIFPTSW ELSERYLFVV DRLIALDAAE
EFFKLARRTY PKKPGVPCLA DGQKELHYLP FPSP
