OBRG_HUMAN
ID OBRG_HUMAN Reviewed; 131 AA.
AC O15243; Q6FHL5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Leptin receptor gene-related protein;
DE AltName: Full=Endospanin-1;
DE AltName: Full=Leptin receptor overlapping transcript protein;
DE AltName: Full=OB-R gene-related protein;
DE Short=OB-RGRP;
GN Name=LEPROT; Synonyms=LEPR, OBR;
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 [MRNA].
RX PubMed=9207021; DOI=10.1093/nar/25.14.2752;
RA Bailleul B., Akerblom I., Strosberg A.D.;
RT "The leptin receptor promoter controls expression of a second distinct
RT protein.";
RL Nucleic Acids Res. 25:2752-2758(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate, and Skeletal muscle;
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 [7]
RP FUNCTION.
RX PubMed=18042720; DOI=10.1073/pnas.0706671104;
RA Couturier C., Sarkis C., Seron K., Belouzard S., Chen P., Lenain A.,
RA Corset L., Dam J., Vauthier V., Dubart A., Mallet J., Froguel P.,
RA Rouille Y., Jockers R.;
RT "Silencing of OB-RGRP in mouse hypothalamic arcuate nucleus increases
RT leptin receptor signaling and prevents diet-induced obesity.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:19476-19481(2007).
RN [8]
RP FUNCTION.
RX PubMed=19907080; DOI=10.1172/jci34997;
RA Touvier T., Conte-Auriol F., Briand O., Cudejko C., Paumelle R., Caron S.,
RA Bauge E., Rouille Y., Salles J.P., Staels B., Bailleul B.;
RT "LEPROT and LEPROTL1 cooperatively decrease hepatic growth hormone action
RT in mice.";
RL J. Clin. Invest. 119:3830-3838(2009).
CC -!- FUNCTION: Negatively regulates leptin receptor (LEPR) cell surface
CC expression, and thus decreases response to leptin. Negatively regulates
CC growth hormone (GH) receptor cell surface expression in liver. May play
CC a role in liver resistance to GH during periods of reduced nutrient
CC availability. {ECO:0000269|PubMed:18042720,
CC ECO:0000269|PubMed:19907080}.
CC -!- SUBUNIT: Interacts with LEPR. Interacts with RAB13 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC O15243; Q13520: AQP6; NbExp=3; IntAct=EBI-15672507, EBI-13059134;
CC O15243; P36382: GJA5; NbExp=3; IntAct=EBI-15672507, EBI-750433;
CC O15243; P48357: LEPR; NbExp=2; IntAct=EBI-15672507, EBI-518596;
CC O15243; Q8TBJ4: PLPPR1; NbExp=3; IntAct=EBI-15672507, EBI-18063495;
CC O15243; Q9UBD6: RHCG; NbExp=3; IntAct=EBI-15672507, EBI-15853497;
CC O15243; P30825: SLC7A1; NbExp=3; IntAct=EBI-15672507, EBI-4289564;
CC O15243; O43759-2: SYNGR1; NbExp=3; IntAct=EBI-15672507, EBI-12187159;
CC O15243; Q9BXJ8: TMEM120A; NbExp=3; IntAct=EBI-15672507, EBI-727322;
CC O15243; O95807: TMEM50A; NbExp=3; IntAct=EBI-15672507, EBI-12903814;
CC O15243; P56557: TMEM50B; NbExp=3; IntAct=EBI-15672507, EBI-12366453;
CC O15243; Q9Y320: TMX2; NbExp=3; IntAct=EBI-15672507, EBI-6447886;
CC O15243; Q9Y548: YIPF1; NbExp=3; IntAct=EBI-15672507, EBI-7850136;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Multi-
CC pass membrane protein {ECO:0000250}. Endosome membrane {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed at the highest levels in heart and
CC placenta and at a lesser extent in lung, liver, skeletal muscle, kidney
CC and pancreas.
CC -!- SIMILARITY: Belongs to the OB-RGRP/VPS55 family. {ECO:0000305}.
CC -!- CAUTION: This protein is encoded by LEPR gene, but shares with LEPR
CC only the first two 5'-UTR exons. It therefore does not share any
CC sequence similarity with LEPR. {ECO:0000305}.
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DR EMBL; Y12670; CAA73211.1; -; mRNA.
DR EMBL; CR541647; CAG46448.1; -; mRNA.
DR EMBL; CR541737; CAG46537.1; -; mRNA.
DR EMBL; AK074841; BAG52014.1; -; mRNA.
DR EMBL; AC119800; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06527.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06531.1; -; Genomic_DNA.
DR EMBL; BC011027; AAH11027.2; -; mRNA.
DR EMBL; BC056250; AAH56250.1; -; mRNA.
DR CCDS; CCDS630.1; -.
DR RefSeq; NP_001185612.1; NM_001198683.1.
DR RefSeq; NP_059996.1; NM_017526.4.
DR AlphaFoldDB; O15243; -.
DR BioGRID; 120123; 13.
DR DIP; DIP-29969N; -.
DR IntAct; O15243; 14.
DR MINT; O15243; -.
DR STRING; 9606.ENSP00000483521; -.
DR SwissPalm; O15243; -.
DR BioMuta; LEPROT; -.
DR EPD; O15243; -.
DR jPOST; O15243; -.
DR MassIVE; O15243; -.
DR MaxQB; O15243; -.
DR PaxDb; O15243; -.
DR PeptideAtlas; O15243; -.
DR PRIDE; O15243; -.
DR ProteomicsDB; 48532; -.
DR Antibodypedia; 67309; 8 antibodies from 6 providers.
DR DNASU; 54741; -.
DR Ensembl; ENST00000371065.9; ENSP00000360104.4; ENSG00000213625.9.
DR GeneID; 54741; -.
DR KEGG; hsa:54741; -.
DR MANE-Select; ENST00000371065.9; ENSP00000360104.4; NM_017526.5; NP_059996.1.
DR UCSC; uc001dcf.4; human.
DR CTD; 54741; -.
DR DisGeNET; 54741; -.
DR GeneCards; LEPROT; -.
DR HGNC; HGNC:29477; LEPROT.
DR HPA; ENSG00000213625; Low tissue specificity.
DR MIM; 613461; gene.
DR neXtProt; NX_O15243; -.
DR OpenTargets; ENSG00000213625; -.
DR PharmGKB; PA134913422; -.
DR VEuPathDB; HostDB:ENSG00000213625; -.
DR eggNOG; KOG2174; Eukaryota.
DR GeneTree; ENSGT00390000006503; -.
DR HOGENOM; CLU_134810_2_2_1; -.
DR InParanoid; O15243; -.
DR OMA; GGDEFSW; -.
DR PhylomeDB; O15243; -.
DR TreeFam; TF313689; -.
DR PathwayCommons; O15243; -.
DR SignaLink; O15243; -.
DR BioGRID-ORCS; 54741; 15 hits in 1075 CRISPR screens.
DR ChiTaRS; LEPROT; human.
DR GenomeRNAi; 54741; -.
DR Pharos; O15243; Tbio.
DR PRO; PR:O15243; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O15243; protein.
DR Bgee; ENSG00000213625; Expressed in metanephric glomerulus and 216 other tissues.
DR ExpressionAtlas; O15243; baseline and differential.
DR Genevisible; O15243; HS.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005102; F:signaling receptor binding; IDA:UniProtKB.
DR GO; GO:0032511; P:late endosome to vacuole transport via multivesicular body sorting pathway; IBA:GO_Central.
DR GO; GO:0060400; P:negative regulation of growth hormone receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:2000009; P:negative regulation of protein localization to cell surface; IDA:UniProtKB.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; IDA:UniProtKB.
DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; HMP:ParkinsonsUK-UCL.
DR InterPro; IPR007262; Vps55/LEPROT.
DR PANTHER; PTHR12050; PTHR12050; 1.
DR Pfam; PF04133; Vps55; 1.
PE 1: Evidence at protein level;
KW Endosome; Golgi apparatus; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..131
FT /note="Leptin receptor gene-related protein"
FT /id="PRO_0000215194"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 32..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 69..89
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 131 AA; 14254 MW; 0F9CE741C2C5ED9C CRC64;
MAGVKALVAL SFSGAIGLTF LMLGCALEDY GVYWPLFVLI FHAISPIPHF IAKRVTYDSD
ATSSACRELA YFFTTGIVVS AFGFPVILAR VAVIKWGACG LVLAGNAVIF LTIQGFFLIF
GRGDDFSWEQ W
