P25103 (NK1R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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	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 Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	acute inflammatory response Inferred from electronic annotation. Source: Compara aggressive behavior Inferred from electronic annotation. Source: Compara angiotensin-mediated drinking behavior Inferred from electronic annotation. Source: Compara associative learning Inferred from electronic annotation. Source: Compara behavioral response to pain Inferred from electronic annotation. Source: Compara detection of abiotic stimulus Traceable author statement PubMed 9537323. Source: ProtInc eating behavior Inferred from electronic annotation. Source: Compara elevation of cytosolic calcium ion concentration Inferred from electronic annotation. Source: Compara inflammatory response Traceable author statement PubMed 10854844. Source: ProtInc long-term memory Inferred from electronic annotation. Source: Compara mechanosensory behavior Traceable author statement PubMed 9537323. Source: ProtInc operant conditioning Inferred from electronic annotation. Source: Compara phospholipase C-activating G-protein coupled receptor signaling pathway Traceable author statement Ref.3. Source: ProtInc positive regulation of action potential Inferred from electronic annotation. Source: Compara positive regulation of blood pressure Inferred from electronic annotation. Source: Compara positive regulation of epithelial cell migration Inferred from electronic annotation. Source: Compara positive regulation of epithelial cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of hormone secretion Inferred from electronic annotation. Source: Compara positive regulation of leukocyte migration Inferred from electronic annotation. Source: Compara positive regulation of lymphocyte proliferation Inferred from electronic annotation. Source: Compara positive regulation of renal sodium excretion Inferred from electronic annotation. Source: Compara positive regulation of saliva secretion Inferred from electronic annotation. Source: Compara positive regulation of stress fiber assembly Inferred from electronic annotation. Source: Compara positive regulation of synaptic transmission, GABAergic Inferred from electronic annotation. Source: Compara positive regulation of synaptic transmission, cholinergic Inferred from electronic annotation. Source: Compara positive regulation of uterine smooth muscle contraction Inferred from electronic annotation. Source: Compara positive regulation of vascular permeability Inferred from electronic annotation. Source: Compara positive regulation of vasoconstriction Inferred from electronic annotation. Source: Compara regulation of smooth muscle cell migration Inferred from electronic annotation. Source: Compara regulation of smooth muscle cell proliferation Inferred from electronic annotation. Source: Compara response to auditory stimulus Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to heat Inferred from electronic annotation. Source: Compara response to morphine Inferred from electronic annotation. Source: Compara response to nicotine Inferred from electronic annotation. Source: Compara response to ozone Inferred from electronic annotation. Source: Compara response to progesterone stimulus Inferred from electronic annotation. Source: Compara smooth muscle contraction involved in micturition Inferred from electronic annotation. Source: Compara sperm ejaculation Inferred from electronic annotation. Source: Compara
Cellular_component	cell body Inferred from electronic annotation. Source: Compara cell surface Inferred from electronic annotation. Source: Compara cytoplasm Inferred from electronic annotation. Source: Compara dendrite Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.3. Source: ProtInc
Molecular_function	substance P receptor activity Inferred from electronic annotation. Source: Compara tachykinin receptor activity Traceable author statement PubMed 8985172. Source: ProtInc
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

Helical; Name=1; Potential

Topological domain

55 – 64

10

Cytoplasmic Potential

Transmembrane

65 – 86

22

Helical; Name=2; Potential

Topological domain

87 – 106

20

Extracellular Potential

Transmembrane

107 – 128

22

Helical; Name=3; Potential

Topological domain

129 – 148

20

Cytoplasmic Potential

Transmembrane

149 – 169

21

Helical; Name=4; Potential

Topological domain

170 – 194

25

Extracellular Potential

Transmembrane

195 – 219

25

Helical; Name=5; Potential

Topological domain

220 – 248

29

Cytoplasmic Potential

Transmembrane

249 – 270

22

Helical; Name=6; Potential

Topological domain

271 – 283

13

Extracellular Potential

Transmembrane

284 – 308

25

Helical; Name=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

Ref.12

Natural variations

Natural variant

192

1

Y → H Display properties similar to those of the wild-type receptor. Ref.13

VAR_026826

Experimental info

Sequence conflict

116

1

V → C in AAA59936. Ref.3

Sequence conflict

218

1

V → I in AAA59936. Ref.3

Secondary structure

1

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407

Helix Strand Turn

Details...

Beta strand

4 – 8

5

Turn

18 – 20

3

Turn

24 – 26

3

Helix

29 – 59

31

Helix

66 – 83

18

Helix

85 – 95

11

Helix

102 – 135

34

Helix

144 – 162

19

Turn

163 – 168

6

Beta strand

178 – 180

3

Turn

189 – 192

4

Helix

193 – 204

12

Helix

206 – 221

16

Beta strand

229 – 234

6

Helix

238 – 273

36

Beta strand

279 – 281

3

Helix

284 – 308

25

Helix

310 – 320

11

Beta strand

321 – 323

3

Beta strand

335 – 340

6

Beta strand

342 – 344

3

Turn

355 – 358

4

Beta strand

359 – 361

3

Sequences

	Sequence		Length	Mass (Da)
	P25103 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: BINDING TO ANTAGONIST CP 96345.
[12]	"NMR evidence of GM1-induced conformational change of Substance P using isotropic bicelles." Gayen A., Goswami S.K., Mukhopadhyay C. Biochim. Biophys. Acta 1808:127-139(2011) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-364, DISULFIDE BOND.
[13]	"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] [Europe PMC] [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. NM_001058.3.
NP_056542.1. NM_015727.2.

UniGene

Hs.633301.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KS9	NMR	-	A	1-364	[»]
2KSA	NMR	-	A	1-364	[»]
2KSB	NMR	-	A	1-364	[»]

ProteinModelPortal

P25103.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000303522.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P25103.

Polymorphism databases

DMDM

128359.

Proteomic databases

PaxDb

P25103.

PRIDE

P25103.

Protocols and materials databases

DNASU

6869.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000305249; ENSP00000303522; ENSG00000115353.
ENST00000409848; ENSP00000386448; ENSG00000115353.

GeneID

6869.

KEGG

hsa:6869.

UCSC

uc002sng.2. human.

Organism-specific databases

CTD

6869.

GeneCards

GC02M075187.

H-InvDB

HIX0161946.

HGNC

HGNC:11526. TACR1.

MIM

162323. gene.

neXtProt

NX_P25103.

PharmGKB

PA36302.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG331485.

HOGENOM

HOG000013018.

HOVERGEN

HBG103412.

InParanoid

P25103.

KO

K04222.

OMA

LPFHVFF.

OrthoDB

EOG4WQ12N.

PhylomeDB

P25103.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P25103.

Bgee

P25103.

CleanEx

HS_TACR1.

Genevestigator

P25103.

GermOnline

ENSG00000115353. Homo sapiens.

Family and domain databases

InterPro

IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
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

BindingDB

P25103.

ChEMBL

CHEMBL249.

DrugBank

DB00673. Aprepitant.
DB01221. Ketamine.
DB04894. Vapreotide.

EvolutionaryTrace

P25103.

GenomeRNAi

6869.

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:	May 1, 2013
This is version 138 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.