GFRAL_RAT
ID GFRAL_RAT Reviewed; 394 AA.
AC D3ZB94;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 2.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=GDNF family receptor alpha-like {ECO:0000305};
DE Flags: Precursor;
GN Name=Gfral {ECO:0000312|RGD:1565220};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=28846097; DOI=10.1038/nm.4392;
RA Mullican S.E., Lin-Schmidt X., Chin C.N., Chavez J.A., Furman J.L.,
RA Armstrong A.A., Beck S.C., South V.J., Dinh T.Q., Cash-Mason T.D.,
RA Cavanaugh C.R., Nelson S., Huang C., Hunter M.J., Rangwala S.M.;
RT "GFRAL is the receptor for GDF15 and the ligand promotes weight loss in
RT mice and nonhuman primates.";
RL Nat. Med. 23:1150-1157(2017).
RN [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28846099; DOI=10.1038/nm.4394;
RA Yang L., Chang C.C., Sun Z., Madsen D., Zhu H., Padkjaer S.B., Wu X.,
RA Huang T., Hultman K., Paulsen S.J., Wang J., Bugge A., Frantzen J.B.,
RA Noergaard P., Jeppesen J.F., Yang Z., Secher A., Chen H., Li X., John L.M.,
RA Shan B., He Z., Gao X., Su J., Hansen K.T., Yang W., Joergensen S.B.;
RT "GFRAL is the receptor for GDF15 and is required for the anti-obesity
RT effects of the ligand.";
RL Nat. Med. 23:1158-1166(2017).
RN [4]
RP FUNCTION.
RX PubMed=28846098; DOI=10.1038/nm.4393;
RA Emmerson P.J., Wang F., Du Y., Liu Q., Pickard R.T., Gonciarz M.D.,
RA Coskun T., Hamang M.J., Sindelar D.K., Ballman K.K., Foltz L.A.,
RA Muppidi A., Alsina-Fernandez J., Barnard G.C., Tang J.X., Liu X., Mao X.,
RA Siegel R., Sloan J.H., Mitchell P.J., Zhang B.B., Gimeno R.E., Shan B.,
RA Wu X.;
RT "The metabolic effects of GDF15 are mediated by the orphan receptor
RT GFRAL.";
RL Nat. Med. 23:1215-1219(2017).
CC -!- FUNCTION: Brainstem-restricted receptor for GDF15 which regulates food
CC intake, energy expenditure and body weight in response to metabolic and
CC toxin-induced stresses (Probable). Upon interaction with its ligand,
CC GDF15, interacts with RET and induces cellular signaling through
CC activation of MAPK- and AKT- signaling pathways (By similarity).
CC {ECO:0000250|UniProtKB:Q6SJE0, ECO:0000250|UniProtKB:Q6UXV0,
CC ECO:0000305|PubMed:28846098, ECO:0000305|PubMed:28846099}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:28846098};
CC Single-pass membrane protein {ECO:0000255}; Extracellular side
CC {ECO:0000305|PubMed:28846098}.
CC -!- TISSUE SPECIFICITY: Expressed in the brainstem, restricted to cells in
CC the area postrema and the immediately adjacent region of the nucleus
CC tractus solitarius (PubMed:28846097, PubMed:28846099). Detected at low
CC levels in testis (PubMed:28846099). {ECO:0000269|PubMed:28846097,
CC ECO:0000269|PubMed:28846099}.
CC -!- SIMILARITY: Belongs to the GDNFR family. {ECO:0000305}.
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DR EMBL; AABR07070759; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07070760; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001178927.1; NM_001191998.1.
DR AlphaFoldDB; D3ZB94; -.
DR SMR; D3ZB94; -.
DR STRING; 10116.ENSRNOP00000043286; -.
DR GlyGen; D3ZB94; 3 sites.
DR PaxDb; D3ZB94; -.
DR GeneID; 501023; -.
DR KEGG; rno:501023; -.
DR CTD; 389400; -.
DR RGD; 1565220; Gfral.
DR VEuPathDB; HostDB:ENSRNOG00000032063; -.
DR eggNOG; ENOG502RCJT; Eukaryota.
DR HOGENOM; CLU_058745_1_0_1; -.
DR InParanoid; D3ZB94; -.
DR OMA; CLNVIHS; -.
DR OrthoDB; 1089046at2759; -.
DR TreeFam; TF331647; -.
DR PRO; PR:D3ZB94; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000032063; Expressed in brain and 1 other tissue.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005925; C:focal adhesion; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0016167; F:glial cell-derived neurotrophic factor receptor activity; ISO:RGD.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:RGD.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0035860; P:glial cell-derived neurotrophic factor receptor signaling pathway; ISO:RGD.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:0002023; P:reduction of food intake in response to dietary excess; ISO:RGD.
DR GO; GO:0031098; P:stress-activated protein kinase signaling cascade; ISO:RGD.
DR InterPro; IPR016017; GDNF/GAS1.
DR InterPro; IPR037193; GDNF_alpha.
DR InterPro; IPR003438; GDNF_rcpt.
DR PANTHER; PTHR10269; PTHR10269; 1.
DR Pfam; PF02351; GDNF; 2.
DR SMART; SM00907; GDNF; 3.
DR SUPFAM; SSF110035; SSF110035; 2.
PE 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..394
FT /note="GDNF family receptor alpha-like"
FT /id="PRO_5003053356"
FT TOPO_DOM 20..350
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 351..371
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 372..394
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 150..229
FT /note="Required for interaction with GDF15"
FT /evidence="ECO:0000250|UniProtKB:Q6UXV0"
FT CARBOHYD 65
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 132..190
FT /evidence="ECO:0000250|UniProtKB:Q6UXV0"
FT DISULFID 139..145
FT /evidence="ECO:0000250|UniProtKB:Q6UXV0"
FT DISULFID 156..168
FT /evidence="ECO:0000250|UniProtKB:Q6UXV0"
FT DISULFID 163..211
FT /evidence="ECO:0000250|UniProtKB:Q6UXV0"
FT DISULFID 192..199
FT /evidence="ECO:0000250|UniProtKB:Q6UXV0"
FT DISULFID 221..292
FT /evidence="ECO:0000250|UniProtKB:Q6UXV0"
FT DISULFID 228..234
FT /evidence="ECO:0000250|UniProtKB:Q6UXV0"
FT DISULFID 245..276
FT /evidence="ECO:0000250|UniProtKB:Q6UXV0"
FT DISULFID 253..259
FT /evidence="ECO:0000250|UniProtKB:Q6UXV0"
FT DISULFID 270..317
FT /evidence="ECO:0000250|UniProtKB:Q6UXV0"
FT DISULFID 294..305
FT /evidence="ECO:0000250|UniProtKB:Q6UXV0"
SQ SEQUENCE 394 AA; 43946 MW; 0097F27254BD2D1F CRC64;
MLVFIFLAVR LSSENESSSQ TNDCAYFMRQ CLTDTDGCKQ SWRSMEDACL VSGDSCKINN
PLPCNLSIQS LVEKHFQFKG CLCTDDLHCT VNKIFGKKCT NKTDSMKKDN KYKRNLTTPL
YHDTGFKQMQ SCLEVTEACV GDVVCNAQLA LYLKACTANG NLCDVKHCQA AIRFFYQNMP
FNTAQMLAFC DCAQSDIPCQ QSKETLHSKP CALNVVPPPT CLSVIHTCRN DELCRTYYRT
FQTECWPHVA GKCREDETCI SMLGKQDLTC SGSDSCRAAY LGTFGTVLQV PCACRSITQG
EEPLCMAFQH MLHSKSCFNY PTPNVKDISS YERKHSKEIT LTGFNSPFSG ELIYVVVCMV
VTSGILSLVM LKLRIPSKKR DPAPIEIAGA VIIQ
