Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

GDNF family receptor alpha-like

Gene

Gfral

Organism
Mus musculus (Mouse)
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:28846099, PubMed:28846097, PubMed:28846098). Upon interaction with its ligand, GDF15, interacts with RET and induces cellular signaling through activation of MAPK- and AKT- signaling pathways (PubMed:28846098, PubMed:28846099).4 Publications

GO - Molecular functioni

  • glial cell-derived neurotrophic factor receptor activity Source: UniProtKB
  • receptor tyrosine kinase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionReceptor

Names & Taxonomyi

Protein namesi
Recommended name:
GDNF family receptor alpha-like
Gene namesi
Name:Gfral
Synonyms:Gral
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:3607786 Gfral

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 domaini20 – 349ExtracellularSequence analysisAdd BLAST330
Transmembranei350 – 370HelicalSequence analysisAdd BLAST21
Topological domaini371 – 393CytoplasmicSequence analysisAdd BLAST23

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

On a chow diet, mutants show no difference in food intake, energy expenditure or body weight compare to wild-type controls. On high-fat diet, they gain substantially more weight and are more glucose intolerant. Diet-induced obese mutants are hyperphagic and have 32% greater total mass and 9% greater lean mass than diet-induced obese wild-type mice (PubMed:28953886, PubMed:28846097, PubMed:28846099). Upon chronical administration of GDF15, mutants are refractory to the GDF15 effects in comparison to wild-types that show attenuated food-intake and sustained weightloss (PubMed:28846098, PubMed:28953886, PubMed:28846097, PubMed:28846099).4 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000024012520 – 393GDNF family receptor alpha-likeAdd BLAST374

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi59N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi65N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi101N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi115N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi131 ↔ 189By similarity
Disulfide bondi138 ↔ 144By similarity
Disulfide bondi155 ↔ 167By similarity
Disulfide bondi162 ↔ 210By similarity
Disulfide bondi191 ↔ 198By similarity
Disulfide bondi220 ↔ 291By similarity
Disulfide bondi227 ↔ 233By similarity
Disulfide bondi244 ↔ 275By similarity
Disulfide bondi252 ↔ 258By similarity
Disulfide bondi269 ↔ 316By similarity
Disulfide bondi293 ↔ 304By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ6SJE0
PRIDEiQ6SJE0

Expressioni

Tissue specificityi

Expressed in the brainstem, restricted to cells in the area postrema and the immediately adjacent region of the nucleus tractus solitarius.3 Publications

Gene expression databases

BgeeiENSMUSG00000059383 Expressed in 1 organ(s), highest expression level in lung
CleanExiMM_GFRAL

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:28846098, PubMed:28846099). Interaction with RET requires previous GDF15-binding (PubMed:28846099).2 Publications

GO - Molecular functioni

Structurei

3D structure databases

ProteinModelPortaliQ6SJE0
SMRiQ6SJE0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni149 – 228Required for interaction with GDF15By similarityAdd BLAST80

Sequence similaritiesi

Belongs to the GDNFR family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IIJI Eukaryota
ENOG4111VG4 LUCA
GeneTreeiENSGT00730000111274
HOGENOMiHOG000112712
HOVERGENiHBG081552
InParanoidiQ6SJE0
OMAiCLNVIHS
OrthoDBiEOG091G087B
PhylomeDBiQ6SJE0
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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform A (identifier: Q6SJE0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MLVFIFLAVT LSSENESSSQ TNDCAHLIQK CLIDANGCEQ SWRSMEDTCL
60 70 80 90 100
TPGDSCKINN SLHCNLSIQA LVEKNFQFKE CLCMDDLHCT VNKLFGKKCT
110 120 130 140 150
NKTDNMEKDN KDKWNLTTTP FYHGFKQMQS CLEVTEACVG DVVCNAQLAL
160 170 180 190 200
YLKACSANGN LCDVKHCQAA IRFFYQNMPF NTAQMLAFCD CAQSDIPCQQ
210 220 230 240 250
SKETLHSKPC ALNIVPPPTC LSVIHTCRND ELCRTHYRTF QTECWPHITG
260 270 280 290 300
KCHEDETCIS MLGKQDLTCS GSESCRAAFL GTFGTVLQVP CACRGVTQAE
310 320 330 340 350
EHVCMIFQHM LHSKSCFNYP TPNVKDISSY EKKNSKEITL TGFNSFFNGE
360 370 380 390
LLYVVVCMAV TCGILFLVML KLRIQSEKRD PSSIEIAGGV IIQ
Length:393
Mass (Da):43,964
Last modified:August 16, 2004 - v2
Checksum:iE3585E89712694B8
GO
Isoform B (identifier: Q6SJE0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     235-238: THYR → LPNS
     239-393: Missing.

Show »
Length:238
Mass (Da):26,637
Checksum:i3CDD4722C60902AA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti20Q → P in AAS13633 (Ref. 1) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_019295235 – 238THYR → LPNS in isoform B. 1 Publication4
Alternative sequenceiVSP_019296239 – 393Missing in isoform B. 1 PublicationAdd BLAST155

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY457637 mRNA Translation: AAS13632.2
AY457638 mRNA Translation: AAS13633.1
CCDSiCCDS40694.1 [Q6SJE0-1]
RefSeqiNP_995316.2, NM_205844.3 [Q6SJE0-1]
UniGeneiMm.213862

Genome annotation databases

EnsembliENSMUST00000074880; ENSMUSP00000074421; ENSMUSG00000059383 [Q6SJE0-1]
ENSMUST00000184693; ENSMUSP00000139120; ENSMUSG00000059383 [Q6SJE0-2]
GeneIDi404194
KEGGimmu:404194
UCSCiuc009qsy.1 mouse [Q6SJE0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY457637 mRNA Translation: AAS13632.2
AY457638 mRNA Translation: AAS13633.1
CCDSiCCDS40694.1 [Q6SJE0-1]
RefSeqiNP_995316.2, NM_205844.3 [Q6SJE0-1]
UniGeneiMm.213862

3D structure databases

ProteinModelPortaliQ6SJE0
SMRiQ6SJE0
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PaxDbiQ6SJE0
PRIDEiQ6SJE0

Protocols and materials databases

DNASUi404194
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000074880; ENSMUSP00000074421; ENSMUSG00000059383 [Q6SJE0-1]
ENSMUST00000184693; ENSMUSP00000139120; ENSMUSG00000059383 [Q6SJE0-2]
GeneIDi404194
KEGGimmu:404194
UCSCiuc009qsy.1 mouse [Q6SJE0-1]

Organism-specific databases

CTDi389400
MGIiMGI:3607786 Gfral

Phylogenomic databases

eggNOGiENOG410IIJI Eukaryota
ENOG4111VG4 LUCA
GeneTreeiENSGT00730000111274
HOGENOMiHOG000112712
HOVERGENiHBG081552
InParanoidiQ6SJE0
OMAiCLNVIHS
OrthoDBiEOG091G087B
PhylomeDBiQ6SJE0
TreeFamiTF331647

Miscellaneous databases

PROiPR:Q6SJE0
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000059383 Expressed in 1 organ(s), highest expression level in lung
CleanExiMM_GFRAL

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
ProtoNetiSearch...

Entry informationi

Entry nameiGFRAL_MOUSE
AccessioniPrimary (citable) accession number: Q6SJE0
Secondary accession number(s): Q6SJD9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 13, 2006
Last sequence update: August 16, 2004
Last modified: November 7, 2018
This is version 87 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again