GPR35_HUMAN
ID GPR35_HUMAN Reviewed; 309 AA.
AC Q9HC97; J3KR30; O43495; Q17R58; Q4VBN5; Q4ZFV2; Q6FHI8; Q86UH4;
DT 14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 4.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=G-protein coupled receptor 35;
DE AltName: Full=Kynurenic acid receptor;
DE Short=KYNA receptor;
GN Name=GPR35;
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 [GENOMIC DNA], AND VARIANT ARG-294.
RX PubMed=9479505; DOI=10.1006/geno.1998.5095;
RA O'Dowd B.F., Nguyen T., Marchese A., Cheng R., Lynch K.R., Heng H.H.Q.,
RA Kolakowski L.F. Jr., George S.R.;
RT "Discovery of three novel G-protein-coupled receptor genes.";
RL Genomics 47:310-313(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS THR-25; ILE-29;
RP MET-108; SER-125 AND MET-253.
RX PubMed=11017071; DOI=10.1038/79876;
RA Horikawa Y., Oda N., Cox N.J., Li X., Orho-Melander M., Hara M.,
RA Hinokio Y., Lindner T.H., Mashima H., Schwarz P.E.H., del Bosque-Plata L.,
RA Horikawa Y., Oda Y., Yoshiuchi I., Colilla S., Polonsky K.S., Wei S.,
RA Concannon P., Iwasaki N., Schulze J., Baier L.J., Bogardus C., Groop L.,
RA Boerwinkle E., Hanis C.L., Bell G.I.;
RT "Genetic variation in the gene encoding calpain-10 is associated with type
RT 2 diabetes mellitus.";
RL Nat. Genet. 26:163-175(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Warren C.N., Aronstam R.S., Sharma S.V.;
RT "Isolation of complete coding sequence for G-protein coupled receptor 35
RT (GPR35).";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ARG-294.
RC TISSUE=Hepatoma;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-294.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-294.
RC TISSUE=Brain;
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 [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16754668; DOI=10.1074/jbc.m603503200;
RA Wang J., Simonavicius N., Wu X., Swaminath G., Reagan J., Tian H., Ling L.;
RT "Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35.";
RL J. Biol. Chem. 281:22021-22028(2006).
CC -!- FUNCTION: Acts as a receptor for kynurenic acid, an intermediate in the
CC tryptophan metabolic pathway. The activity of this receptor is mediated
CC by G-proteins that elicit calcium mobilization and inositol phosphate
CC production through G(qi/o) proteins. {ECO:0000269|PubMed:16754668}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16754668};
CC Multi-pass membrane protein {ECO:0000269|PubMed:16754668}.
CC Note=Internalized to the cytoplasm after exposure to kynurenic acid.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9HC97-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HC97-2; Sequence=VSP_045871;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in immune and
CC gastrointestinal tissues. {ECO:0000269|PubMed:16754668}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF027957; AAC52028.1; -; Genomic_DNA.
DR EMBL; AF089087; AAG17965.1; -; mRNA.
DR EMBL; AY275467; AAP32299.1; -; Genomic_DNA.
DR EMBL; AK172786; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CR541765; CAG46564.1; -; mRNA.
DR EMBL; AC124862; AAX88945.1; -; Genomic_DNA.
DR EMBL; BC095500; AAH95500.1; -; mRNA.
DR EMBL; BC117453; AAI17454.2; -; mRNA.
DR EMBL; BC117455; AAI17456.2; -; mRNA.
DR CCDS; CCDS2541.1; -. [Q9HC97-1]
DR CCDS; CCDS56174.1; -. [Q9HC97-2]
DR RefSeq; NP_001182310.1; NM_001195381.1. [Q9HC97-2]
DR RefSeq; NP_001182311.1; NM_001195382.1. [Q9HC97-2]
DR RefSeq; NP_005292.2; NM_005301.3. [Q9HC97-1]
DR AlphaFoldDB; Q9HC97; -.
DR SMR; Q9HC97; -.
DR BioGRID; 109117; 146.
DR IntAct; Q9HC97; 64.
DR MINT; Q9HC97; -.
DR STRING; 9606.ENSP00000411788; -.
DR BindingDB; Q9HC97; -.
DR ChEMBL; CHEMBL1293267; -.
DR DrugBank; DB00695; Furosemide.
DR DrugBank; DB11937; Kynurenic Acid.
DR DrugBank; DB11156; Pyrantel.
DR DrugCentral; Q9HC97; -.
DR GuidetoPHARMACOLOGY; 102; -.
DR TCDB; 9.A.14.13.8; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; Q9HC97; 1 site.
DR iPTMnet; Q9HC97; -.
DR PhosphoSitePlus; Q9HC97; -.
DR BioMuta; GPR35; -.
DR DMDM; 68068087; -.
DR jPOST; Q9HC97; -.
DR MassIVE; Q9HC97; -.
DR PaxDb; Q9HC97; -.
DR PeptideAtlas; Q9HC97; -.
DR PRIDE; Q9HC97; -.
DR Antibodypedia; 34526; 234 antibodies from 29 providers.
DR DNASU; 2859; -.
DR Ensembl; ENST00000319838.10; ENSP00000322731.5; ENSG00000178623.13. [Q9HC97-1]
DR Ensembl; ENST00000403859.1; ENSP00000385140.1; ENSG00000178623.13. [Q9HC97-1]
DR Ensembl; ENST00000407714.2; ENSP00000384263.1; ENSG00000178623.13. [Q9HC97-1]
DR Ensembl; ENST00000430267.2; ENSP00000411788.2; ENSG00000178623.13. [Q9HC97-2]
DR Ensembl; ENST00000438013.3; ENSP00000415890.3; ENSG00000178623.13. [Q9HC97-1]
DR GeneID; 2859; -.
DR KEGG; hsa:2859; -.
DR MANE-Select; ENST00000407714.2; ENSP00000384263.1; NM_005301.5; NP_005292.2.
DR UCSC; uc002vzs.4; human. [Q9HC97-1]
DR CTD; 2859; -.
DR DisGeNET; 2859; -.
DR GeneCards; GPR35; -.
DR HGNC; HGNC:4492; GPR35.
DR HPA; ENSG00000178623; Tissue enhanced (intestine).
DR MalaCards; GPR35; -.
DR MIM; 602646; gene.
DR neXtProt; NX_Q9HC97; -.
DR OpenTargets; ENSG00000178623; -.
DR Orphanet; 171; Primary sclerosing cholangitis.
DR PharmGKB; PA28880; -.
DR VEuPathDB; HostDB:ENSG00000178623; -.
DR eggNOG; ENOG502S0QN; Eukaryota.
DR GeneTree; ENSGT01040000240444; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; Q9HC97; -.
DR OMA; MVWANLV; -.
DR OrthoDB; 966250at2759; -.
DR PhylomeDB; Q9HC97; -.
DR TreeFam; TF335578; -.
DR PathwayCommons; Q9HC97; -.
DR Reactome; R-HSA-373076; Class A/1 (Rhodopsin-like receptors).
DR SignaLink; Q9HC97; -.
DR SIGNOR; Q9HC97; -.
DR BioGRID-ORCS; 2859; 12 hits in 1070 CRISPR screens.
DR ChiTaRS; GPR35; human.
DR GenomeRNAi; 2859; -.
DR Pharos; Q9HC97; Tchem.
DR PRO; PR:Q9HC97; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9HC97; protein.
DR Bgee; ENSG00000178623; Expressed in mucosa of transverse colon and 107 other tissues.
DR Genevisible; Q9HC97; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0016494; F:C-X-C chemokine receptor activity; IMP:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:UniProtKB.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IDA:MGI.
DR GO; GO:0007010; P:cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:1904456; P:negative regulation of neuronal action potential; IEA:Ensembl.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; IMP:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:UniProtKB.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; IBA:GO_Central.
DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; IBA:GO_Central.
DR CDD; cd15164; 7tmA_GPR35-like; 1.
DR InterPro; IPR044734; 7tmA_GPR35.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..309
FT /note="G-protein coupled receptor 35"
FT /id="PRO_0000069563"
FT TOPO_DOM 1..24
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..45
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..56
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 57..77
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 78..90
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 91..112
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 113..135
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..156
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 157..174
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 175..195
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 196..218
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 219..239
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 240..258
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 259..279
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 280..309
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 2
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 89..162
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 1
FT /note="M -> MLSGSRAVPTPHRGSEELLKYMLHSPCVSLTM (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045871"
FT VARIANT 25
FT /note="A -> T (in dbSNP:rs35146537)"
FT /evidence="ECO:0000269|PubMed:11017071"
FT /id="VAR_013601"
FT VARIANT 29
FT /note="V -> I (in dbSNP:rs139197368)"
FT /evidence="ECO:0000269|PubMed:11017071"
FT /id="VAR_013602"
FT VARIANT 76
FT /note="V -> M (in dbSNP:rs13387859)"
FT /id="VAR_033467"
FT VARIANT 108
FT /note="T -> M (in dbSNP:rs3749171)"
FT /evidence="ECO:0000269|PubMed:11017071"
FT /id="VAR_013603"
FT VARIANT 125
FT /note="R -> S (in dbSNP:rs34778053)"
FT /evidence="ECO:0000269|PubMed:11017071"
FT /id="VAR_013604"
FT VARIANT 253
FT /note="T -> M (in dbSNP:rs12468485)"
FT /evidence="ECO:0000269|PubMed:11017071"
FT /id="VAR_013605"
FT VARIANT 294
FT /note="S -> R (in dbSNP:rs3749172)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9479505,
FT ECO:0000269|Ref.5"
FT /id="VAR_013606"
FT CONFLICT 174
FT /note="A -> R (in Ref. 1; AAC52028)"
FT /evidence="ECO:0000305"
FT CONFLICT Q9HC97-2:13
FT /note="R -> H (in Ref. 4; AK172786)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 309 AA; 34072 MW; 97734FB7231B26F0 CRC64;
MNGTYNTCGS SDLTWPPAIK LGFYAYLGVL LVLGLLLNSL ALWVFCCRMQ QWTETRIYMT
NLAVADLCLL CTLPFVLHSL RDTSDTPLCQ LSQGIYLTNR YMSISLVTAI AVDRYVAVRH
PLRARGLRSP RQAAAVCAVL WVLVIGSLVA RWLLGIQEGG FCFRSTRHNF NSMAFPLLGF
YLPLAVVVFC SLKVVTALAQ RPPTDVGQAE ATRKAARMVW ANLLVFVVCF LPLHVGLTVR
LAVGWNACAL LETIRRALYI TSKLSDANCC LDAICYYYMA KEFQEASALA VAPSAKAHKS
QDSLCVTLA
