Reviewed, UniProtKB/Swiss-Prot P25103 (NK1R_HUMAN)

Names and origin

Protein names

Recommended name:
    Substance-P receptor
      Short name=SPR
Alternative name(s):
    NK-1 receptor
      Short name=NK-1R
    Tachykinin receptor 1

Gene names

Name:	TACR1
Synonyms:	NK1R, TAC1R

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	407 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance P > substance K > neuromedin-K.
Subunit structure	Interacts with ARRB1 By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	activation of phospholipase C activity by G-protein coupled receptor protein signaling pathway coupled to IP3 second messenger Ref.3 Traceable author statement. Source: ProtInc detection of abiotic stimulus Traceable author statement. Source: ProtInc mechanosensory behavior Traceable author statement. Source: ProtInc tachykinin receptor signaling pathway Inferred from direct assay. Source: UniProtKB
Cellular component	integral to plasma membrane Ref.3 Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 407	407	Substance-P receptor		PRO_0000069885
Regions
	Topological domain	1 – 31	31	Extracellular Potential
	Transmembrane	32 – 54	23	1 Potential
	Topological domain	55 – 64	10	Cytoplasmic Potential
	Transmembrane	65 – 86	22	2 Potential
	Topological domain	87 – 106	20	Extracellular Potential
	Transmembrane	107 – 128	22	3 Potential
	Topological domain	129 – 148	20	Cytoplasmic Potential
	Transmembrane	149 – 169	21	4 Potential
	Topological domain	170 – 194	25	Extracellular Potential
	Transmembrane	195 – 219	25	5 Potential
	Topological domain	220 – 248	29	Cytoplasmic Potential
	Transmembrane	249 – 270	22	6 Potential
	Topological domain	271 – 283	13	Extracellular Potential
	Transmembrane	284 – 308	25	7 Potential
	Topological domain	309 – 407	99	Cytoplasmic Potential
Sites
	Binding site	197	1	Antagonist CP 96345
Amino acid modifications
	Lipidation	322	1	S-palmitoyl cysteine Potential
	Glycosylation	14	1	N-linked (GlcNAc...) Potential
	Glycosylation	18	1	N-linked (GlcNAc...) Potential
	Disulfide bond	105 ↔ 180		By similarity
Natural variations
	Natural variant	192	1	Y → H Display properties similar to those of the wild-type receptor. Ref.12		VAR_026826
Experimental info
	Sequence conflict	116	1	V → C in AAA59936. Ref.3
	Sequence conflict	218	1	V → I in AAA59936. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P25103-1 [UniParc]. Last modified May 1, 1992. Version 1. Checksum: 2AFFD3F61B1A3041	FASTA	407	46,251
	10 20 30 40 50 60 MDNVLPVDSD LSPNISTNTS EPNQFVQPAW QIVLWAAAYT VIVVTSVVGN VVVMWIILAH 70 80 90 100 110 120 KRMRTVTNYF LVNLAFAEAS MAAFNTVVNF TYAVHNEWYY GLFYCKFHNF FPIAAVFASI 130 140 150 160 170 180 YSMTAVAFDR YMAIIHPLQP RLSATATKVV ICVIWVLALL LAFPQGYYST TETMPSRVVC 190 200 210 220 230 240 MIEWPEHPNK IYEKVYHICV TVLIYFLPLL VIGYAYTVVG ITLWASEIPG DSSDRYHEQV 250 260 270 280 290 300 SAKRKVVKMM IVVVCTFAIC WLPFHIFFLL PYINPDLYLK KFIQQVYLAI MWLAMSSTMY 310 320 330 340 350 360 NPIIYCCLND RFRLGFKHAF RCCPFISAGD YEGLEMKSTR YLQTQGSVYK VSRLETTIST 370 380 390 400 VVGAHEEEPE DGPKATPSSL DLTSNCSSRS DSKTMTESFS FSSNVLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, structural characterization and functional expression of the human substance P receptor." Takeda Y., Chou K.B., Takeda J., Sachais B.S., Krause J.E. Biochem. Biophys. Res. Commun. 179:1232-1240(1991) [PubMed: 1718267] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Isolation and characterisation of the human lung NK-1 receptor cDNA." Hopkins B., Powell S.J., Danks P., Briggs I., Graham A. Biochem. Biophys. Res. Commun. 180:1110-1117(1991) [PubMed: 1659396] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[3]	"Human substance P receptor (NK-1): organization of the gene, chromosome localization, and functional expression of cDNA clones." Gerard N.P., Garraway L.A., Eddy R.L. Jr., Shows T.B., Iijima H., Paquet J.L., Gerard C. Biochemistry 30:10640-10646(1991) [PubMed: 1657150] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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: 1312928] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[5]	"Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor." Fong T.M., Anderson S.A., Yu H., Huang R.-R.C., Strader C.D. Mol. Pharmacol. 41:24-30(1992) [PubMed: 1310144] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"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.
[7]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[10]	"The human tachykinin NK1 (short form) and tachykinin NK4 receptor: a reappraisal." Page N.M., Bell N.J. Eur. J. Pharmacol. 437:27-30(2002) [PubMed: 11864635] [Abstract] Cited for: SHOWS THAT THERE IS NO SHORT SPLICED ISOFORM.
[11]	"Amino-aromatic interaction between histidine 197 of the neurokinin-1 receptor and CP 96345." Fong T.M., Cascieri M.A., Yu H., Bansai A., Swain C., Strader C.D. Nature 362:350-353(1993) [PubMed: 8384323] [Abstract] Cited for: BINDING TO ANTAGONIST CP 96345.
[12]	"Identification of single-nucleotide polymorphisms of the human neurokinin 1 receptor gene and pharmacological characterization of a Y192H variant." Randolph G.P., Simon J.S., Arreaza M.G., Qiu P., Lachowicz J.E., Duffy R.A. Pharmacogenomics J. 4:394-402(2004) [PubMed: 15452552] [Abstract] Cited for: VARIANT HIS-192, CHARACTERIZATION OF VARIANT HIS-192.
+	Additional computationally mapped references.

Web resources

Wikipedia

Tachykinin entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	S62045 mRNA. Translation: AAB20168.2. M74290 mRNA. Translation: AAA60601.1. M81797 mRNA. Translation: AAA59933.1. M76675 mRNA. Translation: AAA59936.1. X65177 , X65178, X65179, X65180, X65181 Genomic DNA. Translation: CAA46292.1. M84425 mRNA. Translation: AAA36641.1. M84426 mRNA. Translation: AAA36644.1. AY462098 mRNA. Translation: AAR23925.1. AK289765 mRNA. Translation: BAF82454.1. CH471053 Genomic DNA. Translation: EAW99596.1. BC074911 mRNA. Translation: AAH74911.1. BC074912 mRNA. Translation: AAH74912.1.
IPI	IPI00012729.
PIR	JQ1274. A41134.
RefSeq	NP_001049.1. NP_056542.1.
UniGene	Hs.633301
3D structure databases
SMR	P25103. Positions 22-324.
ModBase	Search...
Protein-protein interaction databases
STRING	P25103.
Protein family/group databases
GPCRDB	Search...
Proteomic databases
PRIDE	P25103.
Genome annotation databases
Ensembl	ENST00000305249; ENSP00000303522; ENSG00000115353; Homo sapiens. [Genome view]
GeneID	6869.
KEGG	hsa:6869.
UCSC	uc002sng.1. human.
Organism-specific databases
CTD	6869.
GeneCards	GC02M075187.
H-InvDB	HIX0029906.
HGNC	HGNC:11526. TACR1.
MIM	162323. gene.
PharmGKB	PA36302.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17440.
HOGENOM	HBG443644.
HOVERGEN	P25103.
InParanoid	P25103.
OMA	PVDSDLF.
OrthoDB	EOG9W6RFC.
PhylomeDB	P25103.
Enzyme and pathway databases
Reactome	REACT_14797. Signaling by GPCR.
Gene expression databases
ArrayExpress	P25103.
Bgee	P25103.
CleanEx	HS_TACR1.
Genevestigator	P25103.
GermOnline	ENSG00000115353. Homo sapiens.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_supfam. IPR001681. Neurokn_rcpt. IPR000046. NK1_rcpt. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR01024. NEUROKININ1R. PR00244. NEUROKININR.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00673. Aprepitant. DB01221. Ketamine. DB04894. Vapreotide.
NextBio	26811.
SOURCE	Search...

Entry information

Entry name

NK1R_HUMAN

Accession

Primary (citable) accession number: P25103
Secondary accession number(s): A8K150

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	May 1, 1992
Last modified:	January 19, 2010
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.