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Protein

GDNF family receptor alpha-like

Gene

GFRAL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Brainstem-restricted receptor for GDF15 which regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099). Upon interaction with its ligand, GDF15, interacts with RET and induces cellular signaling through activation of MAPK- and AKT- signaling pathways.4 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionReceptor

Names & Taxonomyi

Protein namesi
Recommended name:
GDNF family receptor alpha-likeCurated
Gene namesi
Name:GFRALImported
Synonyms:C6orf144
ORF Names:UNQ9356/PRO34128
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000187871.2
HGNCiHGNC:32789 GFRAL
MIMi617837 gene
neXtProtiNX_Q6UXV0

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 351ExtracellularSequence analysisAdd BLAST333
Transmembranei352 – 371HelicalSequence analysisAdd BLAST20
Topological domaini372 – 394CytoplasmicSequence analysisAdd BLAST23

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA145008357

Chemistry databases

GuidetoPHARMACOLOGYi2977

Polymorphism and mutation databases

BioMutaiGFRAL
DMDMi108935991

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000024012419 – 394GDNF family receptor alpha-likeAdd BLAST376

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi23N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi50N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi62N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi67N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi103N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi116N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi131 ↔ 189Combined sources1 Publication
Disulfide bondi138 ↔ 144Combined sources1 Publication
Disulfide bondi155 ↔ 167Combined sources1 Publication
Disulfide bondi162 ↔ 210Combined sources1 Publication
Disulfide bondi191 ↔ 198Combined sources1 Publication
Disulfide bondi220 ↔ 291Combined sources1 Publication
Disulfide bondi227 ↔ 233Combined sources1 Publication
Disulfide bondi244 ↔ 275Combined sources1 Publication
Disulfide bondi252 ↔ 258Combined sources1 Publication
Disulfide bondi269 ↔ 316Combined sources1 Publication
Disulfide bondi293 ↔ 304Combined sources1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ6UXV0
PRIDEiQ6UXV0

Expressioni

Tissue specificityi

Expressed in the brainstem, restricted to cells in the area postrema and the immediately adjacent region of the nucleus tractus solitarius (at protein level) (PubMed:28846097, PubMed:28846098). Detected at low levels in testis and adipose tissue (PubMed:28846097).2 Publications

Gene expression databases

BgeeiENSG00000187871
CleanExiHS_GFRAL

Organism-specific databases

HPAiHPA047372

Interactioni

Subunit structurei

Interacts (via the extracellular domain) with GDF15 and RET; receptor of GDF15, mediates cellular signaling through interaction with RET after GDF15-binding (PubMed:28953886, PubMed:28846097, PubMed:28846099). Interaction with RET requires previous GDF15-binding (PubMed:28846097, PubMed:28846099).3 Publications

Protein-protein interaction databases

STRINGi9606.ENSP00000343636

Structurei

Secondary structure

1394
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi131 – 139Combined sources9
Helixi142 – 154Combined sources13
Beta strandi156 – 161Combined sources6
Helixi164 – 175Combined sources12
Helixi180 – 188Combined sources9
Helixi196 – 205Combined sources10
Helixi208 – 211Combined sources4
Helixi220 – 228Combined sources9
Helixi231 – 244Combined sources14
Helixi246 – 252Combined sources7
Helixi256 – 260Combined sources5
Turni264 – 266Combined sources3
Helixi273 – 280Combined sources8
Turni281 – 284Combined sources4
Helixi286 – 288Combined sources3
Helixi301 – 311Combined sources11
Helixi313 – 315Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5VZ4X-ray2.20B115-351[»]
ProteinModelPortaliQ6UXV0
SMRiQ6UXV0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni149 – 228Required for interaction with GDF151 PublicationAdd BLAST80

Sequence similaritiesi

Belongs to the GDNFR family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IIJI Eukaryota
ENOG4111VG4 LUCA
GeneTreeiENSGT00730000111274
HOGENOMiHOG000112712
HOVERGENiHBG081552
InParanoidiQ6UXV0
OMAiLGKKCIN
OrthoDBiEOG091G087B
PhylomeDBiQ6UXV0
TreeFamiTF331647

Family and domain databases

InterProiView protein in InterPro
IPR016017 GDNF/GAS1
IPR037193 GDNF_alpha
IPR003438 GDNF_rcpt
PANTHERiPTHR10269 PTHR10269, 1 hit
PfamiView protein in Pfam
PF02351 GDNF, 2 hits
SMARTiView protein in SMART
SM00907 GDNF, 3 hits
SUPFAMiSSF110035 SSF110035, 2 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q6UXV0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIVFIFLAMG LSLENEYTSQ TNNCTYLREQ CLRDANGCKH AWRVMEDACN
60 70 80 90 100
DSDPGDPCKM RNSSYCNLSI QYLVESNFQF KECLCTDDFY CTVNKLLGKK
110 120 130 140 150
CINKSDNVKE DKFKWNLTTR SHHGFKGMWS CLEVAEACVG DVVCNAQLAS
160 170 180 190 200
YLKACSANGN PCDLKQCQAA IRFFYQNIPF NIAQMLAFCD CAQSDIPCQQ
210 220 230 240 250
SKEALHSKTC AVNMVPPPTC LSVIRSCQND ELCRRHYRTF QSKCWQRVTR
260 270 280 290 300
KCHEDENCIS TLSKQDLTCS GSDDCKAAYI DILGTVLQVQ CTCRTITQSE
310 320 330 340 350
ESLCKIFQHM LHRKSCFNYP TLSNVKGMAL YTRKHANKIT LTGFHSPFNG
360 370 380 390
EVIYAAMCMT VTCGILLLVM VKLRTSRISS KARDPSSIQI PGEL
Length:394
Mass (Da):44,518
Last modified:June 13, 2006 - v2
Checksum:i641ED7D67CF87428
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05310533R → C. Corresponds to variant dbSNP:rs12199003Ensembl.1
Natural variantiVAR_036234195D → H in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_053106387S → P1 PublicationCorresponds to variant dbSNP:rs9370418Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358198 mRNA Translation: AAQ88565.1
AL592426 Genomic DNA No translation available.
CCDSiCCDS4957.1
RefSeqiNP_997293.2, NM_207410.2
UniGeneiHs.526967

Genome annotation databases

EnsembliENST00000340465; ENSP00000343636; ENSG00000187871
GeneIDi389400
KEGGihsa:389400
UCSCiuc003pcm.1 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGFRAL_HUMAN
AccessioniPrimary (citable) accession number: Q6UXV0
Secondary accession number(s): Q5VTF6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 13, 2006
Last sequence update: June 13, 2006
Last modified: May 23, 2018
This is version 101 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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