Q9GZZ7 (GFRA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GDNF family receptor alpha-4
Short name=GDNF receptor alpha-4
Short name=GDNFR-alpha-4
Short name=GFR-alpha-4

Alternative name(s):
Persephin receptor

Gene names

Name:

GFRA4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	299 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for persephin. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor. May be important in C-cell development and, in the postnatal development of the adrenal medulla.
Subcellular location	Isoform GFRalpha4a: Cell membrane; Lipid-anchor › GPI-anchor Ref.1. Isoform GFRalpha4b: Cell membrane; Lipid-anchor › GPI-anchor Ref.1. Isoform GFRalpha4c: Secreted.
Tissue specificity	Predominantly expressed in the adult thyroid gland. Low levels also found in fetal adrenal and thyroid glands.
Sequence similarities	Belongs to the GDNFR family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Receptor
PTM	GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of ossification Inferred from electronic annotation. Source: Compara
Cellular_component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW extracellular space Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	glial cell-derived neurotrophic factor receptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform GFRalpha4b (identifier: Q9GZZ7-1)

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.

Isoform GFRalpha4a (identifier: Q9GZZ7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     132-197: CARAAAGPWR...RLRGPRGVPA → PRLLAFQVSC...RCLRAYAGLV

Isoform GFRalpha4c (identifier: Q9GZZ7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     132-182: CARAAAGPWR...RPRRLPAGPG → PRLLAFQVSC...PPSPLTTWTT
     183-299: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 278	258	GDNF family receptor alpha-4		PRO_0000010793
	Propeptide	279 – 299	21	Removed in mature form Potential		PRO_0000010794
Amino acid modifications
	Lipidation	278	1	GPI-anchor amidated glycine Potential
	Glycosylation	208	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	132 – 197	66	CARAA…RGVPA → PRLLAFQVSCTPAPSAPDGC LLDQGARCLRAYAGLV in isoform GFRalpha4a.		VSP_007223
	Alternative sequence	132 – 182	51	CARAA…PAGPG → PRLLAFQVSCTPAPSAPDGC LLDQGARCLRAYAGLVGSPQ APPSPLTTWTT in isoform GFRalpha4c.		VSP_007224
	Alternative sequence	183 – 299	117	Missing in isoform GFRalpha4c.		VSP_007225

Sequences

	Sequence		Length	Mass (Da)
	Isoform GFRalpha4b [UniParc]. Last modified April 23, 2003. Version 2. Checksum: 8443B8342FF10801	FASTA	299	31,670
	10 20 30 40 50 60 MVRCLGPALL LLLLLGSASS VGGNRCVDAA EACTADARCQ RLRSEYVAQC LGRAAQGGCP 70 80 90 100 110 120 RARCRRALRR FFARGPPALT HALLFCPCAG PACAERRRQT FVPSCAFSGP GPAPPSCLEP 130 140 150 160 170 180 LNFCERSRVC RCARAAAGPW RGWGRGLSPA HRPPAAQASP PGLSGLVHPS AQRPRRLPAG 190 200 210 220 230 240 PGRPLPARLR GPRGVPAGTA VTPNYVDNVS ARVAPWCDCG ASGNRREDCE AFRGLFTRNR 250 260 270 280 290 CLDGAIQAFA SGWPPVLLDQ LNPQGDPEHS LLQVSSTGRA LERRSLLSIL PVLALPALL
	Isoform GFRalpha4a [UniParc]. Checksum: 09E1DE67073974D1	FASTA	269	28,650
	10 20 30 40 50 60 MVRCLGPALL LLLLLGSASS VGGNRCVDAA EACTADARCQ RLRSEYVAQC LGRAAQGGCP 70 80 90 100 110 120 RARCRRALRR FFARGPPALT HALLFCPCAG PACAERRRQT FVPSCAFSGP GPAPPSCLEP 130 140 150 160 170 180 LNFCERSRVC RPRLLAFQVS CTPAPSAPDG CLLDQGARCL RAYAGLVGTA VTPNYVDNVS 190 200 210 220 230 240 ARVAPWCDCG ASGNRREDCE AFRGLFTRNR CLDGAIQAFA SGWPPVLLDQ LNPQGDPEHS 250 260 LLQVSSTGRA LERRSLLSIL PVLALPALL
	Isoform GFRalpha4c [UniParc]. Checksum: DB837797C0688D5D	FASTA	182	19,216
	10 20 30 40 50 60 MVRCLGPALL LLLLLGSASS VGGNRCVDAA EACTADARCQ RLRSEYVAQC LGRAAQGGCP 70 80 90 100 110 120 RARCRRALRR FFARGPPALT HALLFCPCAG PACAERRRQT FVPSCAFSGP GPAPPSCLEP 130 140 150 160 170 180 LNFCERSRVC RPRLLAFQVS CTPAPSAPDG CLLDQGARCL RAYAGLVGSP QAPPSPLTTW TT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human glial cell line-derived neurotrophic factor receptor alpha4 is the receptor for persephin and is predominantly expressed in normal and malignant thyroid medullary cells." Lindahl M., Poteryaev D., Yu L., Arumae U., Timmusk T., Bongarzone I., Aiello A., Pierotti M.A., Airaksinen M.S., Saarma M. J. Biol. Chem. 276:9344-9351(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GFRALPHA4A; GFRALPHA4B AND GFRALPHA4C), GPI-ANCHOR. Tissue: Thyroid.
[2]	Zhou B., Levinson B., Gitschier J. Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ISOFORM GFRALPHA4A).
[3]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ291673 mRNA. Translation: CAC19690.1. AJ291674 mRNA. Translation: CAC19691.1. AJ291675 mRNA. Translation: CAC19692.1. AF253318 mRNA. Translation: AAG25925.1. AL356755 Genomic DNA. Translation: CAC16508.2. AL356755 Genomic DNA. Translation: CAI23466.1.
IPI	IPI00005510. IPI00015537. IPI00015540.
RefSeq	NP_071422.1. NM_022139.3. NP_665705.1. NM_145762.2.
UniGene	Hs.302025.
3D structure databases
ProteinModelPortal	Q9GZZ7.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000313423.
Polymorphism databases
DMDM	30173123.
Proteomic databases
PaxDb	Q9GZZ7.
PRIDE	Q9GZZ7.
Protocols and materials databases
DNASU	64096.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000290417; ENSP00000290417; ENSG00000125861. ENST00000319242; ENSP00000313423; ENSG00000125861. ENST00000477160; ENSP00000435801; ENSG00000125861.
GeneID	64096.
KEGG	hsa:64096.
UCSC	uc002win.3. human. uc002wio.3. human. uc002wip.1. human.
Organism-specific databases
CTD	64096.
GeneCards	GC20M003587.
HGNC	HGNC:13821. GFRA4.
neXtProt	NX_Q9GZZ7.
PharmGKB	PA28656.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG87849.
HOGENOM	HOG000231728.
HOVERGEN	HBG051727.
InParanoid	Q9GZZ7.
OMA	NRCLDGA.
PhylomeDB	Q9GZZ7.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology.
Gene expression databases
Bgee	Q9GZZ7.
CleanEx	HS_GFRA4.
Genevestigator	Q9GZZ7.
GermOnline	ENSG00000125861. Homo sapiens.
Family and domain databases
InterPro	IPR016017. GDNF/GAS1. IPR003438. GDNF_rcpt. [Graphical view]
Pfam	PF02351. GDNF. 2 hits. [Graphical view]
PRINTS	PR01316. GDNFRECEPTOR.
SMART	SM00907. GDNF. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	64096.
NextBio	65918.

Entry information

Entry name

GFRA4_HUMAN

Accession

Primary (citable) accession number: Q9GZZ7
Secondary accession number(s): Q5JT74, Q9H191, Q9H192

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 23, 2003
Last sequence update:	April 23, 2003
Last modified:	May 1, 2013
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.