GABR2_HUMAN
ID GABR2_HUMAN Reviewed; 941 AA.
AC O75899; O75974; O75975; Q5VXZ2; Q8WX04; Q9P1R2; Q9UNR1; Q9UNS9;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Gamma-aminobutyric acid type B receptor subunit 2;
DE Short=GABA-B receptor 2;
DE Short=GABA-B-R2;
DE Short=GABA-BR2;
DE Short=GABABR2;
DE Short=Gb2;
DE AltName: Full=G-protein coupled receptor 51;
DE AltName: Full=HG20;
DE Flags: Precursor;
GN Name=GABBR2; Synonyms=GPR51, GPRC3B;
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], FUNCTION, SUBUNIT, INTERACTION WITH GABBR1, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Cerebellum {ECO:0000303|PubMed:9872316};
RX PubMed=9872316; DOI=10.1038/25354;
RA White J.H., Wise A., Main M.J., Green A., Fraser N.J., Disney G.H.,
RA Barnes A.A., Emson P., Foord S.M., Marshall F.H.;
RT "Heterodimerization is required for the formation of a functional GABA(B)
RT receptor.";
RL Nature 396:679-682(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain {ECO:0000303|PubMed:10087195};
RX PubMed=10087195; DOI=10.1006/geno.1998.5706;
RA Ng G.Y.K., McDonald T., Bonnert T., Rigby M., Heavens R., Whiting P.,
RA Chateauneuf A., Coulombe N., Kargman S., Caskey T., Evans J.F.,
RA O'Neill G.P., Liu Q.;
RT "Cloning of a novel G-protein-coupled receptor GPR 51 resembling GABAB
RT receptors expressed predominantly in nervous tissues and mapped proximal to
RT the hereditary sensory neuropathy type 1 locus on chromosome 9.";
RL Genomics 56:288-295(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND VARIANTS PHE-628 AND ALA-869.
RC TISSUE=Brain {ECO:0000303|PubMed:10328880};
RX PubMed=10328880; DOI=10.1006/mcne.1999.0741;
RA Martin S.C., Russek S.J., Farb D.H.;
RT "Molecular identification of the human GABABR2: cell surface expression and
RT coupling to adenylyl cyclase in the absence of GABABR1.";
RL Mol. Cell. Neurosci. 13:180-191(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain {ECO:0000303|PubMed:10727622};
RX PubMed=10727622; DOI=10.1016/s0006-8993(00)01958-2;
RA Clark J.A., Mezey E., Lam A.S., Bonner T.I.;
RT "Distribution of the GABA(B) receptor subunit gb2 in rat CNS.";
RL Brain Res. 860:41-52(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Liu M., Parker R., McCrea K., Watson J., Baker E., Sutherland G.,
RA Herzog H.;
RT "Cloning and characterization of a novel human GABA-B receptor subtype with
RT high affinity for GABA and low affinity for baclofen.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hippocampus {ECO:0000303|Ref.6};
RA Borowsky B., Laz T., Gerald C.;
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-941.
RC TISSUE=Hippocampus {ECO:0000303|PubMed:15489334};
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 [9]
RP FUNCTION.
RX PubMed=10075644; DOI=10.1074/jbc.274.12.7607;
RA Ng G.Y.K., Clark J., Coulombe N., Ethier N., Hebert T.E., Sullivan R.,
RA Kargman S., Chateauneuf A., Tsukamoto N., McDonald T., Whiting P.,
RA Mezey E., Johnson M.P., Liu Q., Kolakowski L.F. Jr., Evans J.F.,
RA Bonner T.I., O'Neill G.P.;
RT "Identification of a GABAB receptor subunit, gb2, required for functional
RT GABAB receptor activity.";
RL J. Biol. Chem. 274:7607-7610(1999).
RN [10]
RP FUNCTION, INTERACTION WITH GABBR1, TISSUE SPECIFICITY, AND DOMAIN.
RX PubMed=9872744; DOI=10.1126/science.283.5398.74;
RA Kuner R., Koehr G., Gruenewald S., Eisenhardt G., Bach A., Kornau H.-C.;
RT "Role of heteromer formation in GABAB receptor function.";
RL Science 283:74-77(1999).
RN [11]
RP FUNCTION, AND INTERACTION WITH GABBR1.
RX PubMed=10906333; DOI=10.1074/jbc.m005333200;
RA Schwarz D.A., Barry G., Eliasof S.D., Petroski R.E., Conlon P.J.,
RA Maki R.A.;
RT "Characterization of gamma-aminobutyric acid receptor GABAB(1e), a GABAB(1)
RT splice variant encoding a truncated receptor.";
RL J. Biol. Chem. 275:32174-32181(2000).
RN [12]
RP FUNCTION, AND INTERACTION WITH GABBR1.
RX PubMed=10773016;
RA Sullivan R., Chateauneuf A., Coulombe N., Kolakowski L.F. Jr.,
RA Johnson M.P., Hebert T.E., Ethier N., Belley M., Metters K., Abramovitz M.,
RA O'Neill G.P., Ng G.Y.K.;
RT "Coexpression of full-length gamma-aminobutyric acid(B) (GABA(B)) receptors
RT with truncated receptors and metabotropic glutamate receptor 4 supports the
RT GABA(B) heterodimer as the functional receptor.";
RL J. Pharmacol. Exp. Ther. 293:460-467(2000).
RN [13]
RP VARIANT NDPLHS THR-567.
RX PubMed=26740508; DOI=10.1136/jmedgenet-2015-103568;
RA Lopes F., Barbosa M., Ameur A., Soares G., de Sa J., Dias A.I.,
RA Oliveira G., Cabral P., Temudo T., Calado E., Cruz I.F., Vieira J.P.,
RA Oliveira R., Esteves S., Sauer S., Jonasson I., Syvaenen A.C.,
RA Gyllensten U., Pinto D., Maciel P.;
RT "Identification of novel genetic causes of Rett syndrome-like phenotypes.";
RL J. Med. Genet. 53:190-199(2016).
RN [14]
RP FUNCTION, INTERACTION WITH GABBR1, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=15617512; DOI=10.1042/bj20041435;
RA Villemure J.F., Adam L., Bevan N.J., Gearing K., Chenier S., Bouvier M.;
RT "Subcellular distribution of GABA(B) receptor homo- and hetero-dimers.";
RL Biochem. J. 388:47-55(2005).
RN [15]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH GABBR1.
RX PubMed=18165688; DOI=10.1074/jbc.m705202200;
RA Nomura R., Suzuki Y., Kakizuka A., Jingami H.;
RT "Direct detection of the interaction between recombinant soluble
RT extracellular regions in the heterodimeric metabotropic gamma-aminobutyric
RT acid receptor.";
RL J. Biol. Chem. 283:4665-4673(2008).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) OF 42-466, PARTIAL PROTEIN SEQUENCE,
RP FUNCTION, INTERACTION WITH GABBR1, MUTAGENESIS OF TYR-118, GLYCOSYLATION AT
RP ASN-90; ASN-389; ASN-404 AND ASN-453, AND DISULFIDE BONDS.
RX PubMed=22660477; DOI=10.1038/nn.3133;
RA Geng Y., Xiong D., Mosyak L., Malito D.L., Kniazeff J., Chen Y.,
RA Burmakina S., Quick M., Bush M., Javitch J.A., Pin J.P., Fan Q.R.;
RT "Structure and functional interaction of the extracellular domain of human
RT GABA(B) receptor GBR2.";
RL Nat. Neurosci. 15:970-978(2012).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 42-466 IN COMPLEXES WITH GABBR1;
RP AGONISTS AND ANTAGONISTS, FUNCTION, SUBUNIT, GLYCOSYLATION AT ASN-404, AND
RP DISULFIDE BOND.
RX PubMed=24305054; DOI=10.1038/nature12725;
RA Geng Y., Bush M., Mosyak L., Wang F., Fan Q.R.;
RT "Structural mechanism of ligand activation in human GABA(B) receptor.";
RL Nature 504:254-259(2013).
RN [18]
RP INVOLVEMENT IN DEE59, AND VARIANT DEE59 TRP-693.
RX PubMed=29100083; DOI=10.1016/j.ajhg.2017.09.008;
RG Deciphering Developmental Disorders Study;
RA Hamdan F.F., Myers C.T., Cossette P., Lemay P., Spiegelman D.,
RA Laporte A.D., Nassif C., Diallo O., Monlong J., Cadieux-Dion M.,
RA Dobrzeniecka S., Meloche C., Retterer K., Cho M.T., Rosenfeld J.A., Bi W.,
RA Massicotte C., Miguet M., Brunga L., Regan B.M., Mo K., Tam C.,
RA Schneider A., Hollingsworth G., FitzPatrick D.R., Donaldson A., Canham N.,
RA Blair E., Kerr B., Fry A.E., Thomas R.H., Shelagh J., Hurst J.A.,
RA Brittain H., Blyth M., Lebel R.R., Gerkes E.H., Davis-Keppen L., Stein Q.,
RA Chung W.K., Dorison S.J., Benke P.J., Fassi E., Corsten-Janssen N.,
RA Kamsteeg E.J., Mau-Them F.T., Bruel A.L., Verloes A., Ounap K.,
RA Wojcik M.H., Albert D.V.F., Venkateswaran S., Ware T., Jones D., Liu Y.C.,
RA Mohammad S.S., Bizargity P., Bacino C.A., Leuzzi V., Martinelli S.,
RA Dallapiccola B., Tartaglia M., Blumkin L., Wierenga K.J., Purcarin G.,
RA O'Byrne J.J., Stockler S., Lehman A., Keren B., Nougues M.C., Mignot C.,
RA Auvin S., Nava C., Hiatt S.M., Bebin M., Shao Y., Scaglia F., Lalani S.R.,
RA Frye R.E., Jarjour I.T., Jacques S., Boucher R.M., Riou E., Srour M.,
RA Carmant L., Lortie A., Major P., Diadori P., Dubeau F., D'Anjou G.,
RA Bourque G., Berkovic S.F., Sadleir L.G., Campeau P.M., Kibar Z.,
RA Lafreniere R.G., Girard S.L., Mercimek-Mahmutoglu S., Boelman C.,
RA Rouleau G.A., Scheffer I.E., Mefford H.C., Andrade D.M., Rossignol E.,
RA Minassian B.A., Michaud J.L.;
RT "High rate of recurrent de novo mutations in developmental and epileptic
RT encephalopathies.";
RL Am. J. Hum. Genet. 101:664-685(2017).
RN [19]
RP INVOLVEMENT IN NDPLHS, INVOLVEMENT IN DEE59, VARIANT NDPLHS THR-567,
RP VARIANTS DEE59 ILE-695 AND ASN-705, CHARACTERIZATION OF VARIANT NDPLHS
RP THR-567, AND CHARACTERIZATION OF VARIANTS DEE59 ILE-695 AND ASN-705.
RX PubMed=28856709; DOI=10.1002/ana.25032;
RA Yoo Y., Jung J., Lee Y.N., Lee Y., Cho H., Na E., Hong J., Kim E.,
RA Lee J.S., Lee J.S., Hong C., Park S.Y., Wie J., Miller K., Shur N.,
RA Clow C., Ebel R.S., DeBrosse S.D., Henderson L.B., Willaert R.,
RA Castaldi C., Tikhonova I., Bilguevar K., Mane S., Kim K.J., Hwang Y.S.,
RA Lee S.G., So I., Lim B.C., Choi H.J., Seong J.Y., Shin Y.B., Jung H.,
RA Chae J.H., Choi M.;
RT "GABBR2 mutations determine phenotype in rett syndrome and epileptic
RT encephalopathy.";
RL Ann. Neurol. 82:466-478(2017).
RN [20]
RP INVOLVEMENT IN NDPLHS, VARIANT NDPLHS THR-707, CHARACTERIZATION OF VARIANTS
RP NDPLHS THR-567 AND THR-707, AND CHARACTERIZATION OF VARIANTS DEE59 ILE-695
RP AND ASN-705.
RX PubMed=29369404; DOI=10.1002/ana.25155;
RA Vuillaume M.L., Jeanne M., Xue L., Blesson S., Denomme-Pichon A.S.,
RA Alirol S., Brulard C., Colin E., Isidor B., Gilbert-Dussardier B.,
RA Odent S., Parent P., Donnart A., Redon R., Bezieau S., Rondard P.,
RA Laumonnier F., Toutain A.;
RT "A novel mutation in the transmembrane 6 domain of GABBR2 leads to a Rett-
RT like phenotype.";
RL Ann. Neurol. 83:437-439(2018).
CC -!- FUNCTION: Component of a heterodimeric G-protein coupled receptor for
CC GABA, formed by GABBR1 and GABBR2 (PubMed:9872316, PubMed:9872744,
CC PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054).
CC Within the heterodimeric GABA receptor, only GABBR1 seems to bind
CC agonists, while GABBR2 mediates coupling to G proteins
CC (PubMed:18165688). Ligand binding causes a conformation change that
CC triggers signaling via guanine nucleotide-binding proteins (G proteins)
CC and modulates the activity of down-stream effectors, such as adenylate
CC cyclase (PubMed:10075644, PubMed:10773016, PubMed:24305054). Signaling
CC inhibits adenylate cyclase, stimulates phospholipase A2, activates
CC potassium channels, inactivates voltage-dependent calcium-channels and
CC modulates inositol phospholipid hydrolysis (PubMed:10075644,
CC PubMed:9872744, PubMed:10906333, PubMed:10773016). Plays a critical
CC role in the fine-tuning of inhibitory synaptic transmission
CC (PubMed:9872744, PubMed:22660477). Pre-synaptic GABA receptor inhibits
CC neurotransmitter release by down-regulating high-voltage activated
CC calcium channels, whereas postsynaptic GABA receptor decreases neuronal
CC excitability by activating a prominent inwardly rectifying potassium
CC (Kir) conductance that underlies the late inhibitory postsynaptic
CC potentials (PubMed:9872316, PubMed:10075644, PubMed:9872744,
CC PubMed:22660477). Not only implicated in synaptic inhibition but also
CC in hippocampal long-term potentiation, slow wave sleep, muscle
CC relaxation and antinociception (Probable).
CC {ECO:0000269|PubMed:10075644, ECO:0000269|PubMed:10328880,
CC ECO:0000269|PubMed:15617512, ECO:0000269|PubMed:18165688,
CC ECO:0000269|PubMed:22660477, ECO:0000269|PubMed:24305054,
CC ECO:0000269|PubMed:9872316, ECO:0000269|PubMed:9872744, ECO:0000305}.
CC -!- SUBUNIT: Heterodimer of GABBR1 and GABBR2 (PubMed:9872316,
CC PubMed:9872744, PubMed:10906333, PubMed:10773016, PubMed:15617512,
CC PubMed:18165688, PubMed:22660477, PubMed:24305054). Homodimers may
CC form, but are inactive (PubMed:15617512). Interacts (via C-terminus)
CC with ATF4 (via leucine zipper domain) (By similarity).
CC {ECO:0000250|UniProtKB:Q9Z0U4, ECO:0000269|PubMed:10773016,
CC ECO:0000269|PubMed:15617512, ECO:0000269|PubMed:18165688,
CC ECO:0000269|PubMed:22660477, ECO:0000269|PubMed:24305054,
CC ECO:0000269|PubMed:9872316, ECO:0000269|PubMed:9872744}.
CC -!- INTERACTION:
CC O75899; Q9UBS5: GABBR1; NbExp=4; IntAct=EBI-715469, EBI-724156;
CC O75899; Q9UBS5-2: GABBR1; NbExp=6; IntAct=EBI-715469, EBI-16084001;
CC O75899; P46459: NSF; NbExp=4; IntAct=EBI-715469, EBI-712251;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10328880,
CC ECO:0000269|PubMed:15617512, ECO:0000269|PubMed:9872316}; Multi-pass
CC membrane protein {ECO:0000305}. Postsynaptic cell membrane
CC {ECO:0000250|UniProtKB:O88871}; Multi-pass membrane protein
CC {ECO:0000305}. Note=Coexpression of GABBR1 and GABBR2 is required for
CC GABBR1 maturation and transport to the plasma membrane. In contrast,
CC GABBR2 does not depend on GABBR1 for transport to the cell membrane.
CC {ECO:0000269|PubMed:15617512}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, especially in cerebral
CC cortex, thalamus, hippocampus, frontal, occipital and temporal lobe,
CC occipital pole and cerebellum, followed by corpus callosum, caudate
CC nucleus, spinal cord, amygdala and medulla (PubMed:10087195,
CC PubMed:10328880, PubMed:10727622, PubMed:9872744). Weakly expressed in
CC heart, testis and skeletal muscle (PubMed:10087195, PubMed:10727622).
CC {ECO:0000269|PubMed:10087195, ECO:0000269|PubMed:10328880,
CC ECO:0000269|PubMed:10727622, ECO:0000269|PubMed:9872744}.
CC -!- DOMAIN: Alpha-helical parts of the C-terminal intracellular region
CC mediate heterodimeric interaction with GABBR1.
CC {ECO:0000305|PubMed:9872744}.
CC -!- DISEASE: Neurodevelopmental disorder with poor language and loss of
CC hand skills (NDPLHS) [MIM:617903]: An autosomal dominant disorder
CC characterized by psychomotor developmental stagnation or regression.
CC NDPLHS manifest in the first years of life as loss of purposeful hand
CC movements, loss of language, and intellectual disability.
CC {ECO:0000269|PubMed:26740508, ECO:0000269|PubMed:28856709,
CC ECO:0000269|PubMed:29369404}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Developmental and epileptic encephalopathy 59 (DEE59)
CC [MIM:617904]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE59 is an autosomal dominant condition characterized
CC by onset of refractory seizures in early infancy.
CC {ECO:0000269|PubMed:28856709, ECO:0000269|PubMed:29100083,
CC ECO:0000269|PubMed:29369404}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family. GABA-B
CC receptor subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH35071.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AJ012188; CAA09942.1; -; mRNA.
DR EMBL; AF069755; AAC99345.1; -; mRNA.
DR EMBL; AF099033; AAD45867.1; -; mRNA.
DR EMBL; AF056085; AAC63228.1; -; mRNA.
DR EMBL; AF095784; AAD30389.1; -; mRNA.
DR EMBL; AF074483; AAD03336.1; -; mRNA.
DR EMBL; AL445495; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353782; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356282; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591502; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035071; AAH35071.2; ALT_INIT; mRNA.
DR CCDS; CCDS6736.1; -.
DR RefSeq; NP_005449.5; NM_005458.7.
DR PDB; 4F11; X-ray; 2.38 A; A=42-466.
DR PDB; 4F12; X-ray; 3.02 A; A=42-466.
DR PDB; 4MQE; X-ray; 2.35 A; B=42-466.
DR PDB; 4MQF; X-ray; 2.22 A; B=42-466.
DR PDB; 4MR7; X-ray; 2.15 A; B=42-466.
DR PDB; 4MR8; X-ray; 2.15 A; B=42-466.
DR PDB; 4MR9; X-ray; 2.35 A; B=42-466.
DR PDB; 4MRM; X-ray; 2.86 A; B=42-466.
DR PDB; 4MS1; X-ray; 2.25 A; B=42-466.
DR PDB; 4MS3; X-ray; 2.50 A; B=42-466.
DR PDB; 4MS4; X-ray; 1.90 A; B=42-466.
DR PDB; 4PAS; X-ray; 1.62 A; B=779-819.
DR PDB; 6M8R; X-ray; 3.20 A; K/L=876-913.
DR PDB; 6OCP; X-ray; 2.35 A; P/Q/R=895-909.
DR PDB; 6UO8; EM; 3.63 A; B=41-819.
DR PDB; 6UO9; EM; 4.80 A; B=41-819.
DR PDB; 6UOA; EM; 6.30 A; B=41-819.
DR PDB; 6VJM; EM; 3.97 A; B=41-819.
DR PDB; 6W2X; EM; 3.60 A; B=42-941.
DR PDB; 6WIV; EM; 3.30 A; B=1-819.
DR PDB; 7C7Q; EM; 3.00 A; B=41-780.
DR PDB; 7C7S; EM; 2.90 A; B=41-819.
DR PDB; 7CA3; EM; 4.50 A; B=1-787.
DR PDB; 7CA5; EM; 7.60 A; B=1-787.
DR PDB; 7CUM; EM; 3.52 A; B=1-787.
DR PDB; 7EB2; EM; 3.50 A; D=41-819.
DR PDBsum; 4F11; -.
DR PDBsum; 4F12; -.
DR PDBsum; 4MQE; -.
DR PDBsum; 4MQF; -.
DR PDBsum; 4MR7; -.
DR PDBsum; 4MR8; -.
DR PDBsum; 4MR9; -.
DR PDBsum; 4MRM; -.
DR PDBsum; 4MS1; -.
DR PDBsum; 4MS3; -.
DR PDBsum; 4MS4; -.
DR PDBsum; 4PAS; -.
DR PDBsum; 6M8R; -.
DR PDBsum; 6OCP; -.
DR PDBsum; 6UO8; -.
DR PDBsum; 6UO9; -.
DR PDBsum; 6UOA; -.
DR PDBsum; 6VJM; -.
DR PDBsum; 6W2X; -.
DR PDBsum; 6WIV; -.
DR PDBsum; 7C7Q; -.
DR PDBsum; 7C7S; -.
DR PDBsum; 7CA3; -.
DR PDBsum; 7CA5; -.
DR PDBsum; 7CUM; -.
DR PDBsum; 7EB2; -.
DR AlphaFoldDB; O75899; -.
DR SMR; O75899; -.
DR BioGRID; 114938; 12.
DR ComplexPortal; CPX-2955; GABA-B receptor complex.
DR CORUM; O75899; -.
DR DIP; DIP-42851N; -.
DR IntAct; O75899; 7.
DR MINT; O75899; -.
DR STRING; 9606.ENSP00000259455; -.
DR BindingDB; O75899; -.
DR ChEMBL; CHEMBL5034; -.
DR DrugBank; DB08891; Arbaclofen.
DR DrugBank; DB08892; Arbaclofen Placarbil.
DR DrugBank; DB00181; Baclofen.
DR DrugBank; DB02530; gamma-Aminobutyric acid.
DR DrugBank; DB05010; SGS-742.
DR DrugCentral; O75899; -.
DR GuidetoPHARMACOLOGY; 241; -.
DR TCDB; 9.A.14.15.1; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; O75899; 5 sites.
DR iPTMnet; O75899; -.
DR PhosphoSitePlus; O75899; -.
DR BioMuta; GABBR2; -.
DR EPD; O75899; -.
DR MassIVE; O75899; -.
DR PaxDb; O75899; -.
DR PeptideAtlas; O75899; -.
DR PRIDE; O75899; -.
DR ProteomicsDB; 50252; -.
DR ABCD; O75899; 2 sequenced antibodies.
DR Antibodypedia; 2939; 588 antibodies from 42 providers.
DR DNASU; 9568; -.
DR Ensembl; ENST00000259455.4; ENSP00000259455.2; ENSG00000136928.7.
DR GeneID; 9568; -.
DR KEGG; hsa:9568; -.
DR MANE-Select; ENST00000259455.4; ENSP00000259455.2; NM_005458.8; NP_005449.5.
DR UCSC; uc004ays.4; human.
DR CTD; 9568; -.
DR DisGeNET; 9568; -.
DR GeneCards; GABBR2; -.
DR HGNC; HGNC:4507; GABBR2.
DR HPA; ENSG00000136928; Tissue enriched (brain).
DR MalaCards; GABBR2; -.
DR MIM; 607340; gene.
DR MIM; 617903; phenotype.
DR MIM; 617904; phenotype.
DR neXtProt; NX_O75899; -.
DR OpenTargets; ENSG00000136928; -.
DR Orphanet; 3095; Atypical Rett syndrome.
DR PharmGKB; PA28896; -.
DR VEuPathDB; HostDB:ENSG00000136928; -.
DR eggNOG; KOG1055; Eukaryota.
DR GeneTree; ENSGT00940000155783; -.
DR HOGENOM; CLU_005240_0_0_1; -.
DR InParanoid; O75899; -.
DR OMA; LLKHYHW; -.
DR OrthoDB; 590810at2759; -.
DR PhylomeDB; O75899; -.
DR TreeFam; TF313965; -.
DR PathwayCommons; O75899; -.
DR Reactome; R-HSA-1296041; Activation of G protein gated Potassium channels.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-420499; Class C/3 (Metabotropic glutamate/pheromone receptors).
DR Reactome; R-HSA-977444; GABA B receptor activation.
DR Reactome; R-HSA-997272; Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
DR SignaLink; O75899; -.
DR SIGNOR; O75899; -.
DR BioGRID-ORCS; 9568; 8 hits in 1076 CRISPR screens.
DR ChiTaRS; GABBR2; human.
DR GeneWiki; GABBR2; -.
DR GenomeRNAi; 9568; -.
DR Pharos; O75899; Tclin.
DR PRO; PR:O75899; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O75899; protein.
DR Bgee; ENSG00000136928; Expressed in Brodmann (1909) area 23 and 141 other tissues.
DR ExpressionAtlas; O75899; baseline and differential.
DR Genevisible; O75899; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:1902712; C:G protein-coupled GABA receptor complex; IPI:ComplexPortal.
DR GO; GO:0038039; C:G protein-coupled receptor heterodimeric complex; IPI:UniProtKB.
DR GO; GO:1902710; C:GABA receptor complex; IDA:CAFA.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004965; F:G protein-coupled GABA receptor activity; TAS:ProtInc.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:CAFA.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:ComplexPortal.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IDA:UniProtKB.
DR GO; GO:0007194; P:negative regulation of adenylate cyclase activity; TAS:ProtInc.
DR GO; GO:0150099; P:neuron-glial cell signaling; ISS:ARUK-UCL.
DR GO; GO:0051932; P:synaptic transmission, GABAergic; IC:ComplexPortal.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR041689; GBR2_CC.
DR InterPro; IPR002455; GPCR3_GABA-B.
DR InterPro; IPR000337; GPCR_3.
DR InterPro; IPR017978; GPCR_3_C.
DR InterPro; IPR017979; GPCR_3_CS.
DR InterPro; IPR002457; GPCR_3_GABA_rcpt_B2.
DR InterPro; IPR028082; Peripla_BP_I.
DR PANTHER; PTHR10519; PTHR10519; 1.
DR Pfam; PF00003; 7tm_3; 1.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF18455; GBR2_CC; 1.
DR PRINTS; PR01178; GABAB2RECPTR.
DR PRINTS; PR00248; GPCRMGR.
DR SUPFAM; SSF53822; SSF53822; 1.
DR PROSITE; PS00981; G_PROTEIN_RECEP_F3_3; 1.
DR PROSITE; PS50259; G_PROTEIN_RECEP_F3_4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Coiled coil; Direct protein sequencing;
KW Disease variant; Disulfide bond; Epilepsy; G-protein coupled receptor;
KW Glycoprotein; Intellectual disability; Membrane; Phosphoprotein;
KW Postsynaptic cell membrane; Receptor; Reference proteome; Signal; Synapse;
KW Transducer; Transmembrane; Transmembrane helix.
FT SIGNAL 1..41
FT /evidence="ECO:0000255"
FT CHAIN 42..941
FT /note="Gamma-aminobutyric acid type B receptor subunit 2"
FT /id="PRO_0000012952"
FT TOPO_DOM 42..483
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 484..504
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 505..522
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 523..543
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 544..551
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 552..572
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 573..597
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 598..618
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 619..654
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 655..675
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 676..691
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 692..712
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 713..720
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 721..741
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 742..941
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 763..790
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 781..819
FT /evidence="ECO:0000255"
FT MOD_RES 776
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80T41"
FT MOD_RES 779
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80T41"
FT MOD_RES 819
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q80T41"
FT MOD_RES 884
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80T41"
FT MOD_RES 893
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80T41"
FT MOD_RES 913
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80T41"
FT MOD_RES 916
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80T41"
FT MOD_RES 920
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80T41"
FT MOD_RES 924
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80T41"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22660477"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22660477"
FT CARBOHYD 404
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22660477,
FT ECO:0000269|PubMed:24305054"
FT CARBOHYD 453
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22660477"
FT DISULFID 108..135
FT DISULFID 237..266
FT DISULFID 265..302
FT VARIANT 163
FT /note="L -> P (in dbSNP:rs35449008)"
FT /id="VAR_049280"
FT VARIANT 567
FT /note="A -> T (in NDPLHS; increased basal signaling
FT activity and only weak stimulation by GABA agonist; when
FT injected into Xenopus tadpoles, causes abnormal swimming
FT patterns and increased frequencies of seizure-like behavior
FT compared to wild-type-injected animals; no effect on cell
FT surface expression; dbSNP:rs922847767)"
FT /evidence="ECO:0000269|PubMed:26740508,
FT ECO:0000269|PubMed:28856709, ECO:0000269|PubMed:29369404"
FT /id="VAR_079029"
FT VARIANT 628
FT /note="Y -> F"
FT /evidence="ECO:0000269|PubMed:10328880"
FT /id="VAR_010148"
FT VARIANT 693
FT /note="G -> W (in DEE59; unknown pathological significance;
FT dbSNP:rs1554689320)"
FT /evidence="ECO:0000269|PubMed:29100083"
FT /id="VAR_080569"
FT VARIANT 695
FT /note="S -> I (in DEE59; full signaling activity in the
FT absence of GABA agonist; when injected into Xenopus
FT tadpoles, causes abnormal swimming patterns and increased
FT frequencies of seizure-like behavior compared to wild-type-
FT injected animals; no effect on cell surface expression;
FT dbSNP:rs1554689319)"
FT /evidence="ECO:0000269|PubMed:28856709,
FT ECO:0000269|PubMed:29369404"
FT /id="VAR_080570"
FT VARIANT 705
FT /note="I -> N (in DEE59; increased basal signaling activity
FT and no stimulation by GABA agonist; when injected into
FT Xenopus tadpoles, causes abnormal swimming patterns and
FT increased frequencies of seizure-like behavior compared to
FT wild-type-injected animals; no effect on cell surface
FT expression; dbSNP:rs1554689315)"
FT /evidence="ECO:0000269|PubMed:28856709,
FT ECO:0000269|PubMed:29369404"
FT /id="VAR_080571"
FT VARIANT 707
FT /note="A -> T (in NDPLHS; increased basal signaling
FT activity and only weak stimulation by GABA agonist; no
FT effect on cell surface expression; dbSNP:rs1554689313)"
FT /evidence="ECO:0000269|PubMed:29369404"
FT /id="VAR_080572"
FT VARIANT 869
FT /note="T -> A (in dbSNP:rs10985765)"
FT /evidence="ECO:0000269|PubMed:10328880"
FT /id="VAR_010149"
FT MUTAGEN 118
FT /note="Y->A: Impairs interaction with GABBR1. Decreases
FT signaling via G-proteins."
FT /evidence="ECO:0000269|PubMed:22660477"
FT CONFLICT 6
FT /note="S -> R (in Ref. 2; AAC99345)"
FT /evidence="ECO:0000305"
FT CONFLICT 12
FT /note="P -> R (in Ref. 2; AAC99345)"
FT /evidence="ECO:0000305"
FT CONFLICT 424
FT /note="G -> E (in Ref. 5; AAD30389)"
FT /evidence="ECO:0000305"
FT CONFLICT 797
FT /note="R -> H (in Ref. 8; AAH35071)"
FT /evidence="ECO:0000305"
FT STRAND 55..62
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:4MQE"
FT HELIX 71..90
FT /evidence="ECO:0007829|PDB:4MS4"
FT TURN 91..96
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 98..105
FT /evidence="ECO:0007829|PDB:4MS4"
FT HELIX 110..123
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:4MS4"
FT HELIX 136..145
FT /evidence="ECO:0007829|PDB:4MS4"
FT HELIX 146..149
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 152..157
FT /evidence="ECO:0007829|PDB:4MS4"
FT HELIX 161..164
FT /evidence="ECO:0007829|PDB:4MS4"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 172..176
FT /evidence="ECO:0007829|PDB:4MS4"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:4MS4"
FT HELIX 182..192
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 197..205
FT /evidence="ECO:0007829|PDB:4MS4"
FT HELIX 206..219
FT /evidence="ECO:0007829|PDB:4MS4"
FT TURN 220..223
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 225..234
FT /evidence="ECO:0007829|PDB:4MS4"
FT HELIX 237..245
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:4MS4"
FT HELIX 257..269
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:6WIV"
FT STRAND 278..283
FT /evidence="ECO:0007829|PDB:4MS4"
FT TURN 287..290
FT /evidence="ECO:0007829|PDB:4MS4"
FT HELIX 304..311
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 315..319
FT /evidence="ECO:0007829|PDB:4MS4"
FT HELIX 335..345
FT /evidence="ECO:0007829|PDB:4MS4"
FT TURN 346..348
FT /evidence="ECO:0007829|PDB:4MR7"
FT HELIX 355..372
FT /evidence="ECO:0007829|PDB:4MS4"
FT HELIX 378..387
FT /evidence="ECO:0007829|PDB:4MS4"
FT HELIX 393..404
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 407..410
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 413..418
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 425..431
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 436..443
FT /evidence="ECO:0007829|PDB:4MS4"
FT TURN 444..447
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 448..451
FT /evidence="ECO:0007829|PDB:4MS4"
FT TURN 453..455
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 459..462
FT /evidence="ECO:0007829|PDB:4MS4"
FT STRAND 470..474
FT /evidence="ECO:0007829|PDB:7C7Q"
FT HELIX 479..505
FT /evidence="ECO:0007829|PDB:7C7S"
FT TURN 506..508
FT /evidence="ECO:0007829|PDB:7C7S"
FT HELIX 510..513
FT /evidence="ECO:0007829|PDB:7C7S"
FT HELIX 517..538
FT /evidence="ECO:0007829|PDB:7C7S"
FT STRAND 541..544
FT /evidence="ECO:0007829|PDB:7C7S"
FT HELIX 546..550
FT /evidence="ECO:0007829|PDB:7C7S"
FT HELIX 553..583
FT /evidence="ECO:0007829|PDB:7C7S"
FT TURN 596..598
FT /evidence="ECO:0007829|PDB:7C7S"
FT HELIX 599..618
FT /evidence="ECO:0007829|PDB:7C7S"
FT STRAND 622..627
FT /evidence="ECO:0007829|PDB:7C7S"
FT STRAND 638..641
FT /evidence="ECO:0007829|PDB:7C7S"
FT STRAND 644..649
FT /evidence="ECO:0007829|PDB:7C7S"
FT HELIX 653..677
FT /evidence="ECO:0007829|PDB:7C7S"
FT TURN 680..682
FT /evidence="ECO:0007829|PDB:7C7Q"
FT TURN 684..686
FT /evidence="ECO:0007829|PDB:7C7Q"
FT HELIX 690..712
FT /evidence="ECO:0007829|PDB:7C7S"
FT TURN 713..715
FT /evidence="ECO:0007829|PDB:7EB2"
FT HELIX 717..740
FT /evidence="ECO:0007829|PDB:7C7S"
FT HELIX 742..748
FT /evidence="ECO:0007829|PDB:7C7S"
FT HELIX 780..816
FT /evidence="ECO:0007829|PDB:4PAS"
FT HELIX 885..890
FT /evidence="ECO:0007829|PDB:6M8R"
FT HELIX 899..902
FT /evidence="ECO:0007829|PDB:6OCP"
FT STRAND 908..911
FT /evidence="ECO:0007829|PDB:6M8R"
SQ SEQUENCE 941 AA; 105821 MW; 09F1773DB0673C5D CRC64;
MASPRSSGQP GPPPPPPPPP ARLLLLLLLP LLLPLAPGAW GWARGAPRPP PSSPPLSIMG
LMPLTKEVAK GSIGRGVLPA VELAIEQIRN ESLLRPYFLD LRLYDTECDN AKGLKAFYDA
IKYGPNHLMV FGGVCPSVTS IIAESLQGWN LVQLSFAATT PVLADKKKYP YFFRTVPSDN
AVNPAILKLL KHYQWKRVGT LTQDVQRFSE VRNDLTGVLY GEDIEISDTE SFSNDPCTSV
KKLKGNDVRI ILGQFDQNMA AKVFCCAYEE NMYGSKYQWI IPGWYEPSWW EQVHTEANSS
RCLRKNLLAA MEGYIGVDFE PLSSKQIKTI SGKTPQQYER EYNNKRSGVG PSKFHGYAYD
GIWVIAKTLQ RAMETLHASS RHQRIQDFNY TDHTLGRIIL NAMNETNFFG VTGQVVFRNG
ERMGTIKFTQ FQDSREVKVG EYNAVADTLE IINDTIRFQG SEPPKDKTII LEQLRKISLP
LYSILSALTI LGMIMASAFL FFNIKNRNQK LIKMSSPYMN NLIILGGMLS YASIFLFGLD
GSFVSEKTFE TLCTVRTWIL TVGYTTAFGA MFAKTWRVHA IFKNVKMKKK IIKDQKLLVI
VGGMLLIDLC ILICWQAVDP LRRTVEKYSM EPDPAGRDIS IRPLLEHCEN THMTIWLGIV
YAYKGLLMLF GCFLAWETRN VSIPALNDSK YIGMSVYNVG IMCIIGAAVS FLTRDQPNVQ
FCIVALVIIF CSTITLCLVF VPKLITLRTN PDAATQNRRF QFTQNQKKED SKTSTSVTSV
NQASTSRLEG LQSENHRLRM KITELDKDLE EVTMQLQDTP EKTTYIKQNH YQELNDILNL
GNFTESTDGG KAILKNHLDQ NPQLQWNTTE PSRTCKDPIE DINSPEHIQR RLSLQLPILH
HAYLPSIGGV DASCVSPCVS PTASPRHRHV PPSFRVMVSG L
