ID   GBRR2_HUMAN             Reviewed;         465 AA.
AC   P28476; A2BDE4; Q9H153;
DT   01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2012, sequence version 5.
DT   24-JAN-2024, entry version 211.
DE   RecName: Full=Gamma-aminobutyric acid receptor subunit rho-2;
DE   AltName: Full=GABA(A) receptor subunit rho-2;
DE   AltName: Full=GABA(C) receptor;
DE   Flags: Precursor;
GN   Name=GABRR2;
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] (ISOFORM 1).
RC   TISSUE=Retina;
RX   PubMed=1315307; DOI=10.1016/0888-7543(92)90312-g;
RA   Cutting G.R., Curristin S., Zoghbi H., O'Hara B., Seldin M.F., Uhl G.R.;
RT   "Identification of a putative gamma-aminobutyric acid (GABA) receptor
RT   subunit rho2 cDNA and colocalization of the genes encoding rho2 (GABRR2)
RT   and rho1 (GABRR1) to human chromosome 6q14-q21 and mouse chromosome 4.";
RL   Genomics 12:801-806(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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).
CC   -!- FUNCTION: GABA, the major inhibitory neurotransmitter in the vertebrate
CC       brain, mediates neuronal inhibition by binding to the
CC       GABA/benzodiazepine receptor and opening an integral chloride channel.
CC       Rho-2 GABA receptor could play a role in retinal neurotransmission.
CC   -!- SUBUNIT: Generally pentameric. There are five types of GABA(A) receptor
CC       chains: alpha, beta, gamma, delta, and rho. Interacts with SQSTM1 (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane; Multi-pass membrane
CC       protein. Cell membrane; Multi-pass membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=1;
CC         IsoId=P28476-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P28476-2; Sequence=VSP_044373;
CC   -!- MISCELLANEOUS: [Isoform 2]: Isoform 2 could be translated from an
CC       upstream initiator ATG located in frame within the first coding exon.
CC       The probability of a signal peptide within this isoform is very low.
CC       {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC       Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRR2 sub-
CC       subfamily. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; M86868; AAA52510.1; -; mRNA.
DR   EMBL; AL121833; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC130352; AAI30353.1; -; mRNA.
DR   EMBL; BC130354; AAI30355.1; -; mRNA.
DR   CCDS; CCDS5020.3; -. [P28476-1]
DR   PIR; A38079; A38079.
DR   RefSeq; NP_002034.3; NM_002043.4. [P28476-1]
DR   AlphaFoldDB; P28476; -.
DR   SMR; P28476; -.
DR   STRING; 9606.ENSP00000386029; -.
DR   BindingDB; P28476; -.
DR   ChEMBL; CHEMBL2375; -.
DR   DrugBank; DB01567; Fludiazepam.
DR   DrugBank; DB16754; TPMPA.
DR   DrugCentral; P28476; -.
DR   GlyCosmos; P28476; 2 sites, No reported glycans.
DR   GlyGen; P28476; 2 sites.
DR   iPTMnet; P28476; -.
DR   PhosphoSitePlus; P28476; -.
DR   BioMuta; GABRR2; -.
DR   DMDM; 410516956; -.
DR   EPD; P28476; -.
DR   PaxDb; 9606-ENSP00000386029; -.
DR   ProteomicsDB; 54487; -. [P28476-1]
DR   Antibodypedia; 18718; 142 antibodies from 23 providers.
DR   DNASU; 2570; -.
DR   Ensembl; ENST00000402938.4; ENSP00000386029.4; ENSG00000111886.11. [P28476-1]
DR   GeneID; 2570; -.
DR   KEGG; hsa:2570; -.
DR   MANE-Select; ENST00000402938.4; ENSP00000386029.4; NM_002043.5; NP_002034.3.
DR   UCSC; uc003pnb.4; human. [P28476-1]
DR   AGR; HGNC:4091; -.
DR   CTD; 2570; -.
DR   DisGeNET; 2570; -.
DR   GeneCards; GABRR2; -.
DR   HGNC; HGNC:4091; GABRR2.
DR   HPA; ENSG00000111886; Tissue enriched (retina).
DR   MIM; 137162; gene.
DR   neXtProt; NX_P28476; -.
DR   OpenTargets; ENSG00000111886; -.
DR   PharmGKB; PA28506; -.
DR   VEuPathDB; HostDB:ENSG00000111886; -.
DR   eggNOG; KOG3643; Eukaryota.
DR   GeneTree; ENSGT00940000156864; -.
DR   HOGENOM; CLU_010920_0_1_1; -.
DR   InParanoid; P28476; -.
DR   OMA; VQKASHI; -.
DR   OrthoDB; 4265336at2759; -.
DR   TreeFam; TF315453; -.
DR   PathwayCommons; P28476; -.
DR   Reactome; R-HSA-977443; GABA receptor activation.
DR   SignaLink; P28476; -.
DR   BioGRID-ORCS; 2570; 9 hits in 1156 CRISPR screens.
DR   ChiTaRS; GABRR2; human.
DR   GeneWiki; GABRR2; -.
DR   GenomeRNAi; 2570; -.
DR   Pharos; P28476; Tchem.
DR   PRO; PR:P28476; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; P28476; Protein.
DR   Bgee; ENSG00000111886; Expressed in vena cava and 132 other cell types or tissues.
DR   GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR   GO; GO:1902711; C:GABA-A receptor complex; IBA:GO_Central.
DR   GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:0005254; F:chloride channel activity; IEA:UniProtKB-KW.
DR   GO; GO:0004890; F:GABA-A receptor activity; TAS:ProtInc.
DR   GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR   GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR   GO; GO:1904315; F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential; IEA:Ensembl.
DR   GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR   GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central.
DR   GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0007601; P:visual perception; IEA:Ensembl.
DR   CDD; cd19005; LGIC_ECD_GABAAR_rho; 1.
DR   CDD; cd19059; LGIC_TM_GABAAR_rho; 1.
DR   Gene3D; 2.70.170.10; Neurotransmitter-gated ion-channel ligand-binding domain; 1.
DR   Gene3D; 1.20.58.390; Neurotransmitter-gated ion-channel transmembrane domain; 1.
DR   InterPro; IPR006028; GABAA/Glycine_rcpt.
DR   InterPro; IPR008059; GABAAa_rho2_rcpt.
DR   InterPro; IPR008057; GABAAa_rho_rcpt.
DR   InterPro; IPR006202; Neur_chan_lig-bd.
DR   InterPro; IPR036734; Neur_chan_lig-bd_sf.
DR   InterPro; IPR006201; Neur_channel.
DR   InterPro; IPR036719; Neuro-gated_channel_TM_sf.
DR   InterPro; IPR038050; Neuro_actylchol_rec.
DR   InterPro; IPR006029; Neurotrans-gated_channel_TM.
DR   InterPro; IPR018000; Neurotransmitter_ion_chnl_CS.
DR   NCBIfam; TIGR00860; LIC; 1.
DR   PANTHER; PTHR18945:SF197; GAMMA-AMINOBUTYRIC ACID RECEPTOR SUBUNIT RHO-2; 1.
DR   PANTHER; PTHR18945; NEUROTRANSMITTER GATED ION CHANNEL; 1.
DR   Pfam; PF02931; Neur_chan_LBD; 1.
DR   Pfam; PF02932; Neur_chan_memb; 1.
DR   PRINTS; PR00253; GABAARECEPTR.
DR   PRINTS; PR01670; GABAARRHO.
DR   PRINTS; PR01672; GABAARRHO2.
DR   PRINTS; PR00252; NRIONCHANNEL.
DR   SUPFAM; SSF90112; Neurotransmitter-gated ion-channel transmembrane pore; 1.
DR   SUPFAM; SSF63712; Nicotinic receptor ligand binding domain-like; 1.
DR   PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
DR   Genevisible; P28476; HS.
PE   2: Evidence at transcript level;
KW   Alternative initiation; Cell membrane; Chloride; Chloride channel;
KW   Disulfide bond; Glycoprotein; Ion channel; Ion transport; Membrane;
KW   Postsynaptic cell membrane; Reference proteome; Signal; Synapse;
KW   Transmembrane; Transmembrane helix; Transport.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..465
FT                   /note="Gamma-aminobutyric acid receptor subunit rho-2"
FT                   /id="PRO_0000000488"
FT   TOPO_DOM        21..260
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        261..281
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        294..314
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        326..346
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        347..443
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        444..464
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        120
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        254
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        178..192
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1
FT                   /note="M -> MVKPGGICSATGYWKAAFCLTDVHKM (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_044373"
FT   CONFLICT        209
FT                   /note="Y -> H (in Ref. 1; AAA52510)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   465 AA;  54151 MW;  209700077636A395 CRC64;
     MPYFTRLILF LFCLMVLVES RKPKRKRWTG QVEMPKPSHL YKKNLDVTKI RKGKPQQLLR
     VDEHDFSMRP AFGGPAIPVG VDVQVESLDS ISEVDMDFTM TLYLRHYWKD ERLAFSSASN
     KSMTFDGRLV KKIWVPDVFF VHSKRSFTHD TTTDNIMLRV FPDGHVLYSM RITVTAMCNM
     DFSHFPLDSQ TCSLELESYA YTDEDLMLYW KNGDESLKTD EKISLSQFLI QKFHTTSRLA
     FYSSTGWYNR LYINFTLRRH IFFFLLQTYF PATLMVMLSW VSFWIDRRAV PARVSLGITT
     VLTMTTIITG VNASMPRVSY VKAVDIYLWV SFVFVFLSVL EYAAVNYLTT VQERKERKLR
     EKFPCMCGML HSKTMMLDGS YSESEANSLA GYPRSHILTE EERQDKIVVH LGLSGEANAA
     RKKGLLKGQT GFRIFQNTHA IDKYSRLIFP ASYIFFNLIY WSVFS
//