ID   GP135_HUMAN             Reviewed;         494 AA.
AC   Q8IZ08; Q7Z604; Q86SM3; Q8NH39;
DT   26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 2.
DT   24-JAN-2024, entry version 150.
DE   RecName: Full=G-protein coupled receptor 135 {ECO:0000305};
GN   Name=GPR135;
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=14623098; DOI=10.1016/s0014-5793(03)01196-7;
RA   Fredriksson R., Hoeglund P.J., Gloriam D.E.I., Lagerstroem M.C.,
RA   Schioeth H.B.;
RT   "Seven evolutionarily conserved human rhodopsin G protein-coupled receptors
RT   lacking close relatives.";
RL   FEBS Lett. 554:381-388(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S.,
RA   Tsutsumi S., Aburatani H., Asai K., Akiyama Y.;
RT   "Genome-wide discovery and analysis of human seven transmembrane helix
RT   receptor genes.";
RL   Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA   Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA   Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA   Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA   Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA   Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA   Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA   Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA   Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA   Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA   Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA   Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA   Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA   Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 99-280.
RX   PubMed=12679517; DOI=10.1073/pnas.0230374100;
RA   Vassilatis D.K., Hohmann J.G., Zeng H., Li F., Ranchalis J.E.,
RA   Mortrud M.T., Brown A., Rodriguez S.S., Weller J.R., Wright A.C.,
RA   Bergmann J.E., Gaitanaris G.A.;
RT   "The G protein-coupled receptor repertoires of human and mouse.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:4903-4908(2003).
RN   [6]
RP   SUBCELLULAR LOCATION, INTERACTION WITH MTNR1B, INTERACTION WITH ARRB1 AND
RP   ARRB2, AND FUNCTION.
RX   PubMed=28827538; DOI=10.1038/s41598-017-08996-7;
RA   Oishi A., Karamitri A., Gerbier R., Lahuna O., Ahmad R., Jockers R.;
RT   "Orphan GPR61, GPR62 and GPR135 receptors and the melatonin MT2 receptor
RT   reciprocally modulate their signaling functions.";
RL   Sci. Rep. 7:8990-8990(2017).
CC   -!- FUNCTION: Orphan receptor. Has spontaneous activity for beta-arrestin
CC       recruitment (PubMed:28827538). Shows a reciprocal regulatory
CC       interaction with the melatonin receptor MTNR1B most likely through
CC       receptor heteromerization (PubMed:28827538).
CC       {ECO:0000269|PubMed:28827538}.
CC   -!- SUBUNIT: Interacts with MTNR1B (PubMed:28827538). Interacts with ARRB1
CC       and ARRB2 in a spontaneous and agonist-independent manner; leading to
CC       the internalization of GPR135 in the endosomal compartment
CC       (PubMed:28827538). {ECO:0000269|PubMed:28827538}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28827538};
CC       Multi-pass membrane protein {ECO:0000255}. Endosome membrane
CC       {ECO:0000269|PubMed:28827538}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=Colocalizes with ARRB2/beta-arrestin-2 in the
CC       endosome. {ECO:0000269|PubMed:28827538}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAC05800.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; AY288418; AAP72127.1; -; mRNA.
DR   EMBL; AB065563; BAC05800.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AL159140; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC032831; AAH32831.2; -; mRNA.
DR   EMBL; AY255588; AAO85100.1; -; mRNA.
DR   CCDS; CCDS9738.1; -.
DR   RefSeq; NP_072093.2; NM_022571.5.
DR   RefSeq; XP_016877085.1; XM_017021596.1.
DR   RefSeq; XP_016877086.1; XM_017021597.1.
DR   RefSeq; XP_016877087.1; XM_017021598.1.
DR   RefSeq; XP_016877088.1; XM_017021599.1.
DR   AlphaFoldDB; Q8IZ08; -.
DR   SMR; Q8IZ08; -.
DR   BioGRID; 122207; 6.
DR   IntAct; Q8IZ08; 4.
DR   STRING; 9606.ENSP00000378548; -.
DR   BindingDB; Q8IZ08; -.
DR   ChEMBL; CHEMBL3309102; -.
DR   iPTMnet; Q8IZ08; -.
DR   PhosphoSitePlus; Q8IZ08; -.
DR   BioMuta; GPR135; -.
DR   DMDM; 62900365; -.
DR   EPD; Q8IZ08; -.
DR   MassIVE; Q8IZ08; -.
DR   PaxDb; 9606-ENSP00000378548; -.
DR   PeptideAtlas; Q8IZ08; -.
DR   ProteomicsDB; 71266; -.
DR   Antibodypedia; 24279; 117 antibodies from 24 providers.
DR   DNASU; 64582; -.
DR   Ensembl; ENST00000395116.2; ENSP00000378548.1; ENSG00000181619.12.
DR   Ensembl; ENST00000481661.1; ENSP00000432696.1; ENSG00000181619.12.
DR   GeneID; 64582; -.
DR   KEGG; hsa:64582; -.
DR   MANE-Select; ENST00000395116.2; ENSP00000378548.1; NM_022571.6; NP_072093.2.
DR   UCSC; uc001xed.3; human.
DR   AGR; HGNC:19991; -.
DR   CTD; 64582; -.
DR   DisGeNET; 64582; -.
DR   GeneCards; GPR135; -.
DR   HGNC; HGNC:19991; GPR135.
DR   HPA; ENSG00000181619; Low tissue specificity.
DR   MIM; 607970; gene.
DR   neXtProt; NX_Q8IZ08; -.
DR   OpenTargets; ENSG00000181619; -.
DR   PharmGKB; PA134863427; -.
DR   VEuPathDB; HostDB:ENSG00000181619; -.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT00950000182998; -.
DR   HOGENOM; CLU_048891_0_0_1; -.
DR   InParanoid; Q8IZ08; -.
DR   OMA; PYCLMGL; -.
DR   OrthoDB; 5322435at2759; -.
DR   PhylomeDB; Q8IZ08; -.
DR   TreeFam; TF333332; -.
DR   PathwayCommons; Q8IZ08; -.
DR   SignaLink; Q8IZ08; -.
DR   BioGRID-ORCS; 64582; 18 hits in 1147 CRISPR screens.
DR   ChiTaRS; GPR135; human.
DR   GeneWiki; GPR135; -.
DR   GenomeRNAi; 64582; -.
DR   Pharos; Q8IZ08; Tbio.
DR   PRO; PR:Q8IZ08; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   RNAct; Q8IZ08; Protein.
DR   Bgee; ENSG00000181619; Expressed in left testis and 100 other cell types or tissues.
DR   GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR   GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:1990763; F:arrestin family protein binding; IDA:UniProtKB.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   PANTHER; PTHR22752; G PROTEIN-COUPLED RECEPTOR; 1.
DR   PANTHER; PTHR22752:SF3; G-PROTEIN COUPLED RECEPTOR 135; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   Genevisible; Q8IZ08; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; Endosome; G-protein coupled receptor; Membrane; Receptor;
KW   Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT   CHAIN           1..494
FT                   /note="G-protein coupled receptor 135"
FT                   /id="PRO_0000069612"
FT   TOPO_DOM        1..12
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        13..33
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        34..37
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        38..58
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        59..81
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        82..102
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        103..125
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        126..146
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        147..164
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        165..185
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        186..226
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        227..247
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        248..262
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        263..283
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        284..494
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..35
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          473..494
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         5
FT                   /note="Q -> P (in dbSNP:rs1752428)"
FT                   /id="VAR_024259"
FT   VARIANT         481
FT                   /note="V -> A (in dbSNP:rs1752427)"
FT                   /id="VAR_049402"
SQ   SEQUENCE   494 AA;  51736 MW;  439A932E2860D4DF CRC64;
     MEEPQPPRPP ASMALLGSQH SGAPSAAGPP GGTSSAATAA VLSFSTVATA ALGNLSDASG
     GGTAAAPGGG GLGGSGAARE AGAAVRRPLG PEAAPLLSHG AAVAAQALVL LLIFLLSSLG
     NCAVMGVIVK HRQLRTVTNA FILSLSLSDL LTALLCLPAA FLDLFTPPGG SAPAAAAGPW
     RGFCAASRFF SSCFGIVSTL SVALISLDRY CAIVRPPREK IGRRRALQLL AGAWLTALGF
     SLPWELLGAP RELAAAQSFH GCLYRTSPDP AQLGAAFSVG LVVACYLLPF LLMCFCHYHI
     CKTVRLSDVR VRPVNTYARV LRFFSEVRTA TTVLIMIVFV ICCWGPYCFL VLLAAARQAQ
     TMQAPSLLSV VAVWLTWANG AINPVIYAIR NPNISMLLGR NREEGYRTRN VDAFLPSQGP
     GLQARSRSRL RNRYANRLGA CNRMSSSNPA SGVAGDVAMW ARKNPVVLFC REGPPEPVTA
     VTKQPKSEAG DTSL
//