P29371 (NK3R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neuromedin-K receptor
Short name=NKR

Alternative name(s):
NK-3 receptor
Short name=NK-3R
Neurokinin B receptor
Tachykinin receptor 3

Gene names

Name:	TACR3
Synonyms:	NK3R, TAC3R

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	465 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This is a receptor for the tachykinin neuropeptide neuromedin-K (neurokinin B). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: neuromedin-K > substance K > substance P.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Post-translational modification	The anchoring of this receptor to the plasma membrane is probably mediated by the palmitoylation of a cysteine residue.
Involvement in disease	Hypogonadotropic hypogonadism 11 with or without anosmia (HH11) [MIM:614840]: 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.6
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
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from electronic annotation. Source: Compara hyperosmotic salinity response Inferred from electronic annotation. Source: Compara positive regulation of blood pressure Inferred from electronic annotation. Source: Compara positive regulation of heart rate Inferred from electronic annotation. Source: Compara positive regulation of uterine smooth muscle contraction Inferred from electronic annotation. Source: Compara regulation of dopamine metabolic process Inferred from electronic annotation. Source: Compara regulation of feeding behavior Inferred from electronic annotation. Source: Compara response to cocaine Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from electronic annotation. Source: Compara response to morphine Inferred from electronic annotation. Source: Compara
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	tachykinin receptor activity Traceable author statement PubMed 8990205. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 465	465	Neuromedin-K receptor		PRO_0000069899
Regions
	Topological domain	1 – 84	84	Extracellular Potential
	Transmembrane	85 – 107	23	Helical; Name=1; Potential
	Topological domain	108 – 117	10	Cytoplasmic Potential
	Transmembrane	118 – 139	22	Helical; Name=2; Potential
	Topological domain	140 – 159	20	Extracellular Potential
	Transmembrane	160 – 181	22	Helical; Name=3; Potential
	Topological domain	182 – 201	20	Cytoplasmic Potential
	Transmembrane	202 – 222	21	Helical; Name=4; Potential
	Topological domain	223 – 245	23	Extracellular Potential
	Transmembrane	246 – 270	25	Helical; Name=5; Potential
	Topological domain	271 – 299	29	Cytoplasmic Potential
	Transmembrane	300 – 321	22	Helical; Name=6; Potential
	Topological domain	322 – 334	13	Extracellular Potential
	Transmembrane	335 – 359	25	Helical; Name=7; Potential
	Topological domain	360 – 465	106	Cytoplasmic Potential
Amino acid modifications
	Lipidation	374	1	S-palmitoyl cysteine Potential
	Glycosylation	23	1	N-linked (GlcNAc...) Potential
	Glycosylation	50	1	N-linked (GlcNAc...) Potential
	Glycosylation	73	1	N-linked (GlcNAc...) Potential
	Disulfide bond	158 ↔ 233		By similarity
Natural variations
	Natural variant	93	1	G → D in HH11; unequivocal evidence of impaired receptor signaling; rs121918124. Ref.6		VAR_069177
	Natural variant	286	1	K → R. Corresponds to variant rs2276973 [ dbSNP | Ensembl ].		VAR_049422
	Natural variant	353	1	P → S in HH11; unequivocal evidence of impaired receptor signaling; rs121918125. Ref.6		VAR_069178
	Natural variant	449	1	A → T. Corresponds to variant rs17033889 [ dbSNP | Ensembl ].		VAR_049423
Experimental info
	Sequence conflict	3	1	T → I in AAB21706. Ref.2
	Sequence conflict	63	1	A → R in AAB21706. Ref.2
	Sequence conflict	439	1	C → F in CAA46291. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P29371 [UniParc]. Last modified December 1, 1992. Version 1. Checksum: 98E88D4BC9DBD315	FASTA	465	52,202
	10 20 30 40 50 60 MATLPAAETW IDGGGGVGAD AVNLTASLAA GAATGAVETG WLQLLDQAGN LSSSPSALGL 70 80 90 100 110 120 PVASPAPSQP WANLTNQFVQ PSWRIALWSL AYGVVVAVAV LGNLIVIWII LAHKRMRTVT 130 140 150 160 170 180 NYFLVNLAFS DASMAAFNTL VNFIYALHSE WYFGANYCRF QNFFPITAVF ASIYSMTAIA 190 200 210 220 230 240 VDRYMAIIDP LKPRLSATAT KIVIGSIWIL AFLLAFPQCL YSKTKVMPGR TLCFVQWPEG 250 260 270 280 290 300 PKQHFTYHII VIILVYCFPL LIMGITYTIV GITLWGGEIP GDTCDKYHEQ LKAKRKVVKM 310 320 330 340 350 360 MIIVVMTFAI CWLPYHIYFI LTAIYQQLNR WKYIQQVYLA SFWLAMSSTM YNPIIYCCLN 370 380 390 400 410 420 KRFRAGFKRA FRWCPFIKVS SYDELELKTT RFHPNRQSSM YTVTRMESMT VVFDPNDADT 430 440 450 460 TRSSRKKRAT PRDPSFNGCS RRNSKSASAT SSFISSPYTS VDEYS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA sequence and heterologous expression of the human neurokinin-3 receptor." Huang R.-R.C., Cheung A.H., Mazina K.E., Strader C.D., Fong T.M. Biochem. Biophys. Res. Commun. 184:966-972(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Molecular characterisation, expression and localisation of human neurokinin-3 receptor." Buell G., Schulz M.F., Arkinstall S.J., Maury K., Missotten M., Adami N., Talabot F., Kawashima E. FEBS Lett. 299:90-95(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The primary structure and gene organization of human substance P and neuromedin K receptors." Takahashi K., Tanaka A., Hara M., Nakanishi S. Eur. J. Biochem. 204:1025-1033(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[4]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[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].
[6]	"TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction." Topaloglu A.K., Reimann F., Guclu M., Yalin A.S., Kotan L.D., Porter K.M., Serin A., Mungan N.O., Cook J.R., Ozbek M.N., Imamoglu S., Akalin N.S., Yuksel B., O'Rahilly S., Semple R.K. Nat. Genet. 41:354-358(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HH11 ASP-93 AND SER-353, CHARACTERIZATION OF VARIANTS HH11 ASP-93 AND SER-353.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M89473 mRNA. Translation: AAA36366.1. S86392 , S86371, S86382, S86388, S86390 Genomic DNA. Translation: AAB21706.1. X65172 , X65173, X65174, X65175, X65176 Genomic DNA. Translation: CAA46291.1. AY462099 mRNA. Translation: AAR23926.1. BC121806 mRNA. Translation: AAI21807.1.
IPI	IPI00021358.
PIR	JQ1517.
RefSeq	NP_001050.1. NM_001059.2.
UniGene	Hs.942.
3D structure databases
ProteinModelPortal	P29371.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000303325.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P29371.
Polymorphism databases
DMDM	128364.
Proteomic databases
PaxDb	P29371.
PRIDE	P29371.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000304883; ENSP00000303325; ENSG00000169836.
GeneID	6870.
KEGG	hsa:6870.
UCSC	uc003hxe.1. human.
Organism-specific databases
CTD	6870.
GeneCards	GC04M104507.
HGNC	HGNC:11528. TACR3.
HPA	HPA009418.
MIM	162332. gene. 614840. phenotype.
neXtProt	NX_P29371.
Orphanet	432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKB	PA36304.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG331485.
HOGENOM	HOG000013018.
HOVERGEN	HBG103412.
InParanoid	P29371.
KO	K04224.
OMA	PTRQSSM.
OrthoDB	EOG41NTM9.
PhylomeDB	P29371.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	P29371.
CleanEx	HS_TACR3.
Genevestigator	P29371.
GermOnline	ENSG00000169836. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR001681. Neurokn_rcpt. IPR001013. NK3_rcpt. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR01026. NEUROKININ3R. PR00244. NEUROKININR.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P29371.
ChEMBL	CHEMBL4429.
GenomeRNAi	6870.
NextBio	26817.
SOURCE	Search...

Entry information

Entry name

NK3R_HUMAN

Accession

Primary (citable) accession number: P29371
Secondary accession number(s): Q0P510

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	May 1, 2013
This is version 115 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.