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Q8NFJ6 (PKR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Prokineticin receptor 2

Short name=PK-R2
Alternative name(s):
G-protein coupled receptor 73-like 1
GPR73b
GPRg2
Gene names
Name:PROKR2
Synonyms:GPR73L1, PKR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length384 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for prokineticin 2. Exclusively coupled to the G(q) subclass of heteromeric G proteins. Activation leads to mobilization of calcium, stimulation of phosphoinositide turnover and activation of p44/p42 mitogen-activated protein kinase.

Subunit structure

Homodimer. Ref.6

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Expressed in the ileocecum, thyroid gland, pituitary gland, salivary gland, adrenal gland, testis, ovary and brain.

Involvement in disease

Hypogonadotropic hypogonadism 3 with or without anosmia (HH3) [MIM:244200]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
Note: The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in PROKR2 as well as in other HH-associated genes including KAL1, SEMA3A, PROK2, GNRH1 and FGFR1 (Ref.7, Ref.8, Ref.9). Ref.7 Ref.8 Ref.9

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 384384Prokineticin receptor 2
PRO_0000070083

Regions

Topological domain1 – 5454Extracellular Potential
Transmembrane55 – 7521Helical; Name=1; Potential
Topological domain76 – 8914Cytoplasmic Potential
Transmembrane90 – 11021Helical; Name=2; Potential
Topological domain111 – 13626Extracellular Potential
Transmembrane137 – 15721Helical; Name=3; Potential
Topological domain158 – 17114Cytoplasmic Potential
Transmembrane172 – 19221Helical; Name=4; Potential
Topological domain193 – 22331Extracellular Potential
Transmembrane224 – 24421Helical; Name=5; Potential
Topological domain245 – 27329Cytoplasmic Potential
Transmembrane274 – 29421Helical; Name=6; Potential
Topological domain295 – 31319Extracellular Potential
Transmembrane314 – 33421Helical; Name=7; Potential
Topological domain335 – 38450Cytoplasmic Potential

Amino acid modifications

Glycosylation71N-linked (GlcNAc...) Potential
Glycosylation271N-linked (GlcNAc...) Potential
Disulfide bond128 ↔ 208 By similarity

Natural variations

Natural variant851R → C in HH3; uncertain pathological significance. Ref.7
VAR_030957
Natural variant851R → H in HH3; phenotype consistent with Kallmann syndrome. Ref.7
Corresponds to variant rs74315418 [ dbSNP | Ensembl ].
VAR_030958
Natural variant1151V → M in HH3; phenotype consistent with Kallmann syndrome; digenic inheritance; the patient also carries a mutation in PROK2. Ref.9
VAR_069964
Natural variant1641R → Q in HH3; phenotype consistent with Kallmann syndrome. Ref.7
VAR_030959
Natural variant1731L → R in HH3; phenotype consistent with Kallmann syndrome; digenic inheritance; the patient also carries the pathogenic mutation Leu-396 in KAL1. Ref.7
Corresponds to variant rs74315416 [ dbSNP | Ensembl ].
VAR_030960
Natural variant1781W → S in HH3; phenotype consistent with Kallmann syndrome. Ref.7
Corresponds to variant rs201835496 [ dbSNP | Ensembl ].
VAR_030961
Natural variant2021S → G in HH3; triallelic inheritance; the patient also carries mutations in GNRH1 and FGFR1. Ref.9
VAR_069965
Natural variant2101Q → R in HH3; phenotype consistent with Kallmann syndrome. Ref.7
VAR_030962
Natural variant2681R → C in HH3; uncertain pathological significance; phenotype consistent with Kallmann syndrome; some patients also carry pathogenic mutations in SEMA3A. Ref.7 Ref.8
Corresponds to variant rs78861628 [ dbSNP | Ensembl ].
VAR_030963
Natural variant2901P → S in HH3; phenotype consistent with Kallmann syndrome. Ref.7
VAR_030964
Natural variant3231M → I in HH3; phenotype consistent with Kallmann syndrome. Ref.7
VAR_030965
Natural variant3311V → M in HH3; uncertain pathological significance. Ref.3 Ref.7
VAR_030966
Natural variant3351T → M. Ref.7
VAR_030967

Sequences

Sequence LengthMass (Da)Tools
Q8NFJ6 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 2D5BFA3655347B5E

FASTA38443,996
        10         20         30         40         50         60 
MAAQNGNTSF TPNFNPPQDH ASSLSFNFSY GDYDLPMDED EDMTKTRTFF AAKIVIGIAL 

        70         80         90        100        110        120 
AGIMLVCGIG NFVFIAALTR YKKLRNLTNL LIANLAISDF LVAIICCPFE MDYYVVRQLS 

       130        140        150        160        170        180 
WEHGHVLCAS VNYLRTVSLY VSTNALLAIA IDRYLAIVHP LKPRMNYQTA SFLIALVWMV 

       190        200        210        220        230        240 
SILIAIPSAY FATETVLFIV KSQEKIFCGQ IWPVDQQLYY KSYFLFIFGV EFVGPVVTMT 

       250        260        270        280        290        300 
LCYARISREL WFKAVPGFQT EQIRKRLRCR RKTVLVLMCI LTAYVLCWAP FYGFTIVRDF 

       310        320        330        340        350        360 
FPTVFVKEKH YLTAFYVVEC IAMSNSMINT VCFVTVKNNT MKYFKKMMLL HWRPSQRGSK 

       370        380 
SSADLDLRTN GVPTTEEVDC IRLK 

« Hide

References

« Hide 'large scale' references
[1]"Identification and molecular characterization of two closely related G protein-coupled receptors activated by prokineticins/endocrine gland vascular endothelial growth factor."
Lin D.C.-H., Bullock C.M., Ehlert F.J., Chen J.-L., Tian H., Zhou Q.-Y.
J. Biol. Chem. 277:19276-19280(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Molecular cloning and characterization of prokineticin receptors."
Soga T., Matsumoto S., Oda T., Saito T., Hiyama H., Takasaki J., Kamohara M., Ohishi T., Matsushime H., Furuichi K.
Biochim. Biophys. Acta 1579:173-179(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]Martin A.L., Kaighin V.A., Aronstam R.S.
Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT MET-331.
Tissue: Testis.
[4]"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. expand/collapse author list , 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].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[6]"Evidence that prokineticin receptor 2 exists as a dimer in vivo."
Marsango S., Bonaccorsi di Patti M.C., Barra D., Miele R.
Cell. Mol. Life Sci. 68:2919-2929(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[7]"Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2."
Dode C., Teixeira L., Levilliers J., Fouveaut C., Bouchard P., Kottler M.-L., Lespinasse J., Lienhardt-Roussie A., Mathieu M., Moerman A., Morgan G., Murat A., Toublanc J.-E., Wolczynski S., Delpech M., Petit C., Young J., Hardelin J.-P.
PLoS Genet. 2:1648-1652(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HH3 CYS-85; HIS-85; GLN-164; ARG-173; SER-178; ARG-210; CYS-268; SER-290; ILE-323 AND MET-331, VARIANT MET-335.
[8]"SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome."
Hanchate N.K., Giacobini P., Lhuillier P., Parkash J., Espy C., Fouveaut C., Leroy C., Baron S., Campagne C., Vanacker C., Collier F., Cruaud C., Meyer V., Garcia-Pinero A., Dewailly D., Cortet-Rudelli C., Gersak K., Metz C. expand/collapse author list , Chabrier G., Pugeat M., Young J., Hardelin J.P., Prevot V., Dode C.
PLoS Genet. 8:E1002896-E1002896(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HH3 CYS-268.
[9]"Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism."
Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B., Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M., Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A., Kumanov P. expand/collapse author list , Young J., Yialamas M.A., Hall J.E., Van Vliet G., Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K., Pitteloud N.
Am. J. Hum. Genet. 92:725-743(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HH3 MET-115 AND GLY-202.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF506288 mRNA. Translation: AAM48128.1.
AB084081 mRNA. Translation: BAC24022.1.
EF577398 mRNA. Translation: ABQ52418.1.
AL121755 Genomic DNA. Translation: CAI22379.1.
BC104959 mRNA. Translation: AAI04960.1.
BC104961 mRNA. Translation: AAI04962.1.
RefSeqNP_658986.1. NM_144773.2.
XP_005260720.1. XM_005260663.1.
UniGeneHs.375029.

3D structure databases

ProteinModelPortalQ8NFJ6.
SMRQ8NFJ6. Positions 54-349.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid126143. 1 interaction.
STRING9606.ENSP00000217270.

Chemistry

BindingDBQ8NFJ6.
ChEMBLCHEMBL5548.
GuidetoPHARMACOLOGY336.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ8NFJ6.

Polymorphism databases

DMDM33112425.

Proteomic databases

PaxDbQ8NFJ6.
PRIDEQ8NFJ6.

Protocols and materials databases

DNASU128674.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000217270; ENSP00000217270; ENSG00000101292.
ENST00000546004; ENSP00000440790; ENSG00000101292.
GeneID128674.
KEGGhsa:128674.
UCSCuc010zqw.2. human.

Organism-specific databases

CTD128674.
GeneCardsGC20M005282.
HGNCHGNC:15836. PROKR2.
HPAHPA047281.
MIM244200. phenotype.
607123. gene.
neXtProtNX_Q8NFJ6.
Orphanet478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
3157. Septo-optic dysplasia.
PharmGKBPA30014.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG319668.
HOGENOMHOG000231664.
HOVERGENHBG039631.
InParanoidQ8NFJ6.
KOK08380.
OMADYDLPMD.
OrthoDBEOG73NG3D.
PhylomeDBQ8NFJ6.
TreeFamTF315303.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeQ8NFJ6.
CleanExHS_PROKR2.
GenevestigatorQ8NFJ6.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000611. NPY_rcpt.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR01012. NRPEPTIDEYR.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiProkineticin_receptor_2.
GenomeRNAi128674.
NextBio82420.
PROQ8NFJ6.
SOURCESearch...

Entry information

Entry namePKR2_HUMAN
AccessionPrimary (citable) accession number: Q8NFJ6
Secondary accession number(s): A5JUU1 expand/collapse secondary AC list , Q2M3C0, Q5TDY1, Q9NTT0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2003
Last sequence update: October 1, 2002
Last modified: April 16, 2014
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries