Q8NFJ6 (PKR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	384 AA.
Sequence status	Complete.
Protein existence	Evidence 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 the gene represented in this entry (Ref.7). The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Digenic inheritance has been reported in few cases of patients carrying mutations in PROKR2 as well as in a second gene (Ref.7 and Ref.8). Ref.7 Ref.8
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hypogonadotropic hypogonadism Kallmann syndrome
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	circadian rhythm Inferred from electronic annotation. Source: Compara
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	neuropeptide Y receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 384	384	Prokineticin receptor 2		PRO_0000070083
Regions
	Topological domain	1 – 54	54	Extracellular Potential
	Transmembrane	55 – 75	21	Helical; Name=1; Potential
	Topological domain	76 – 89	14	Cytoplasmic Potential
	Transmembrane	90 – 110	21	Helical; Name=2; Potential
	Topological domain	111 – 136	26	Extracellular Potential
	Transmembrane	137 – 157	21	Helical; Name=3; Potential
	Topological domain	158 – 171	14	Cytoplasmic Potential
	Transmembrane	172 – 192	21	Helical; Name=4; Potential
	Topological domain	193 – 223	31	Extracellular Potential
	Transmembrane	224 – 244	21	Helical; Name=5; Potential
	Topological domain	245 – 273	29	Cytoplasmic Potential
	Transmembrane	274 – 294	21	Helical; Name=6; Potential
	Topological domain	295 – 313	19	Extracellular Potential
	Transmembrane	314 – 334	21	Helical; Name=7; Potential
	Topological domain	335 – 384	50	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	7	1	N-linked (GlcNAc...) Potential
	Glycosylation	27	1	N-linked (GlcNAc...) Potential
	Disulfide bond	128 ↔ 208		By similarity
Natural variations
	Natural variant	85	1	R → C in HH3; uncertain pathological significance. Ref.7		VAR_030957
	Natural variant	85	1	R → H in HH3; phenotype consistent with Kallmann syndrome. Ref.7		VAR_030958
	Natural variant	164	1	R → Q in HH3; phenotype consistent with Kallmann syndrome. Ref.7		VAR_030959
	Natural variant	173	1	L → R in HH3; phenotype consistent with Kallmann syndrome; digenic inheritance; the patient also carries the pathogenic mutation Leu-396 in KAL1. Ref.7		VAR_030960
	Natural variant	178	1	W → S in HH3; phenotype consistent with Kallmann syndrome. Ref.7		VAR_030961
	Natural variant	210	1	Q → R in HH3; phenotype consistent with Kallmann syndrome. Ref.7		VAR_030962
	Natural variant	268	1	R → C in HH3; uncertain pathological significance; phenotype consistent with Kallmann syndrome; some patients also carry pathogenic mutations in SEMA3A. Ref.7 Ref.8		VAR_030963
	Natural variant	290	1	P → S in HH3; phenotype consistent with Kallmann syndrome. Ref.7		VAR_030964
	Natural variant	323	1	M → I in HH3; phenotype consistent with Kallmann syndrome. Ref.7		VAR_030965
	Natural variant	331	1	V → M in HH3; uncertain pathological significance. Ref.3 Ref.7		VAR_030966
	Natural variant	335	1	T → M. Ref.7		VAR_030967

Sequences

	Sequence		Length	Mass (Da)
	Q8NFJ6 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 2D5BFA3655347B5E	FASTA	384	43,996
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
+	Additional computationally mapped references.

Web resources

GeneReviews

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.
IPI	IPI00168843.
RefSeq	NP_658986.1. NM_144773.2.
UniGene	Hs.375029.
3D structure databases
ProteinModelPortal	Q8NFJ6.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000217270.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q8NFJ6.
Polymorphism databases
DMDM	33112425.
Proteomic databases
PaxDb	Q8NFJ6.
PRIDE	Q8NFJ6.
Protocols and materials databases
DNASU	128674.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000217270; ENSP00000217270; ENSG00000101292. ENST00000546004; ENSP00000440790; ENSG00000101292.
GeneID	128674.
KEGG	hsa:128674.
UCSC	uc010zqw.2. human.
Organism-specific databases
CTD	128674.
GeneCards	GC20M005282.
HGNC	HGNC:15836. PROKR2.
HPA	HPA047281.
MIM	244200. phenotype. 607123. gene.
neXtProt	NX_Q8NFJ6.
Orphanet	478. Kallmann syndrome. 432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKB	PA30014.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG319668.
HOGENOM	HOG000231664.
HOVERGEN	HBG039631.
InParanoid	Q8NFJ6.
KO	K08380.
OMA	DLPMDED.
OrthoDB	EOG4SF966.
PhylomeDB	Q8NFJ6.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q8NFJ6.
CleanEx	HS_PROKR2.
Genevestigator	Q8NFJ6.
GermOnline	ENSG00000101292. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR000611. NPY_rcpt. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR01012. NRPEPTIDEYR.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q8NFJ6.
ChEMBL	CHEMBL5548.
GenomeRNAi	128674.
NextBio	82420.
SOURCE	Search...

Entry information

Entry name

PKR2_HUMAN

Accession

Primary (citable) accession number: Q8NFJ6
Secondary accession number(s): A5JUU1 , Q2M3C0, Q5TDY1, Q9NTT0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2003
Last sequence update:	October 1, 2002
Last modified:	May 1, 2013
This is version 98 of the entry and version 1 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.