P25024 (CXCR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-X-C chemokine receptor type 1
Short name=CXC-R1
Short name=CXCR-1

Alternative name(s):
CDw128a
High affinity interleukin-8 receptor A
Short name=IL-8R A
IL-8 receptor type 1
CD_antigen=CD181

Gene names

Name:	CXCR1
Synonyms:	CMKAR1, IL8RA

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

General annotation (Comments)

Function	Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activate a phosphatidylinositol-calcium second messenger system. This receptor binds to IL-8 with a high affinity and to MGSA (GRO) with a low affinity.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Biological process	Chemotaxis
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
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of phospholipase D activity Inferred from electronic annotation. Source: InterPro dendritic cell chemotaxis Traceable author statement PubMed 16621978. Source: BHF-UCL elevation of cytosolic calcium ion concentration Inferred from electronic annotation. Source: InterPro inflammatory response Traceable author statement PubMed 10725748. Source: ProtInc negative regulation of cAMP biosynthetic process Inferred from electronic annotation. Source: InterPro receptor internalization Inferred from direct assay PubMed 10734056. Source: UniProtKB
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	interleukin-8 receptor activity Inferred from direct assay PubMed 10734056. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 350

350

C-X-C chemokine receptor type 1

PRO_0000069330

Regions

Topological domain

1 – 39

39

Extracellular Potential

Transmembrane

40 – 66

27

Helical; Name=1; Potential

Topological domain

67 – 75

9

Cytoplasmic Potential

Transmembrane

76 – 96

21

Helical; Name=2; Potential

Topological domain

97 – 111

15

Extracellular Potential

Transmembrane

112 – 133

22

Helical; Name=3; Potential

Topological domain

134 – 154

21

Cytoplasmic Potential

Transmembrane

155 – 174

20

Helical; Name=4; Potential

Topological domain

175 – 199

25

Extracellular Potential

Transmembrane

200 – 220

21

Helical; Name=5; Potential

Topological domain

221 – 242

22

Cytoplasmic Potential

Transmembrane

243 – 264

22

Helical; Name=6; Potential

Topological domain

265 – 285

21

Extracellular Potential

Transmembrane

286 – 308

23

Helical; Name=7; Potential

Topological domain

309 – 350

42

Cytoplasmic Potential

Amino acid modifications

Glycosylation

3

1

N-linked (GlcNAc...) Potential

Glycosylation

16

1

N-linked (GlcNAc...) Potential

Disulfide bond

110 ↔ 187

By similarity

Natural variations

Natural variant

31

1

M → R. Ref.5 Ref.8 Ref.11
Corresponds to variant rs16858811 [ dbSNP | Ensembl ].

VAR_021061

Natural variant

71

1

R → C.
Corresponds to variant rs1805038 [ dbSNP | Ensembl ].

VAR_016236

Natural variant

268

1

M → L.
Corresponds to variant rs9282752 [ dbSNP | Ensembl ].

VAR_026525

Natural variant

276

1

S → T Common polymorphism. Ref.1 Ref.5 Ref.8 Ref.12
Corresponds to variant rs2234671 [ dbSNP | Ensembl ].

VAR_003479

Natural variant

306

1

A → T. Ref.12

VAR_016237

Natural variant

335

1

R → C. Ref.5 Ref.8 Ref.11 Ref.12
Corresponds to variant rs16858808 [ dbSNP | Ensembl ].

VAR_016238

Natural variant

342

1

S → L. Ref.8
Corresponds to variant rs16858806 [ dbSNP | Ensembl ].

VAR_021062

Experimental info

Sequence conflict

154

1

K → N in AAH72397. Ref.11

Secondary structure

1

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350

Helix Strand Turn

Details...

Helix

38 – 66

29

Helix

75 – 100

26

Beta strand

101 – 103

3

Helix

108 – 138

31

Beta strand

139 – 141

3

Beta strand

143 – 146

4

Helix

149 – 173

25

Turn

195 – 197

3

Helix

201 – 204

4

Turn

205 – 207

3

Helix

208 – 225

18

Turn

226 – 228

3

Beta strand

229 – 231

3

Helix

235 – 238

4

Helix

240 – 267

28

Beta strand

270 – 272

3

Helix

276 – 282

7

Helix

285 – 293

9

Helix

294 – 298

5

Helix

300 – 308

9

Helix

311 – 322

12

Sequences

	Sequence		Length	Mass (Da)
	P25024 [UniParc]. Last modified May 30, 2006. Version 2. Checksum: 2463E868C0EB0DE2	FASTA	350	39,791
	10 20 30 40 50 60 MSNITDPQMW DFDDLNFTGM PPADEDYSPC MLETETLNKY VVIIAYALVF LLSLLGNSLV 70 80 90 100 110 120 MLVILYSRVG RSVTDVYLLN LALADLLFAL TLPIWAASKV NGWIFGTFLC KVVSLLKEVN 130 140 150 160 170 180 FYSGILLLAC ISVDRYLAIV HATRTLTQKR HLVKFVCLGC WGLSMNLSLP FFLFRQAYHP 190 200 210 220 230 240 NNSSPVCYEV LGNDTAKWRM VLRILPHTFG FIVPLFVMLF CYGFTLRTLF KAHMGQKHRA 250 260 270 280 290 300 MRVIFAVVLI FLLCWLPYNL VLLADTLMRT QVIQESCERR NNIGRALDAT EILGFLHSCL 310 320 330 340 350 NPIIYAFIGQ NFRHGFLKIL AMHGLVSKEF LARHRVTSYT SSSVNVSSNL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and functional expression of a human interleukin-8 receptor." Holmes W.E., Lee J., Kuang W.-J., Rice G.C., Wood W.I. Science 253:1278-1280(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT THR-276.
[2]	"Molecular characterization of receptors for human interleukin-8, GRO/melanoma growth-stimulatory activity and neutrophil activating peptide-2." Cerretti D.P., Kozlosky C.J., Vanden Bos T., Nelson N., Gearing D.P., Beckmann M.P. Mol. Immunol. 30:359-367(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
[3]	"The high-affinity interleukin 8 receptor gene (IL8RA) maps to the 2q33-q36 region of the human genome: cloning of a pseudogene (IL8RBP) for the low-affinity receptor." Mollereau C., Passage E., Mattei M.-G., Vassart G., Parmentier M. Genomics 16:248-251(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Comparison of the genomic organization and promoter function for human interleukin-8 receptors A and B." Ahuja S.K., Shetty A., Tiffany H.L., Murphy P.M. J. Biol. Chem. 269:26381-26389(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[5]	"Molecular evolution of CXCR1, a G protein-coupled receptor involved in signal transduction of neutrophils." Liu Y., Yang S., Lin A.A., Cavalli-Sforza L.L., Su B. J. Mol. Evol. 61:691-696(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-31; THR-276 AND CYS-335.
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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].
[8]	SeattleSNPs variation discovery resource Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-31; THR-276; CYS-335 AND LEU-342.
[9]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	"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], VARIANTS ARG-31 AND CYS-335. Tissue: Blood.
[12]	"Single nucleotide polymorphisms in the coding regions of human CXC-chemokine receptors CXCR1, CXCR2 and CXCR3." Kato H., Tsuchiya N., Tokunaga K. Genes Immun. 1:330-337(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 223-350, VARIANTS THR-276; THR-306 AND CYS-335.
[13]	"Characterization of two high affinity human interleukin-8 receptors." Lee J., Horuk R., Rice G.C., Bennett G.L., Camerato T., Wood W.I. J. Biol. Chem. 267:16283-16287(1992) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[14]	"Structure of a CXC chemokine-receptor fragment in complex with interleukin-8." Skelton N.J., Quan C., Reilly D., Lowman H. Structure 7:157-168(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 9-29 IN COMPLEX WITH IL-8.
+	Additional computationally mapped references.

Web resources

Wikipedia

CXC chemokine receptors entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L19591 mRNA. Translation: AAB59436.1.
L19592 Genomic DNA. Translation: AAA59160.1.
M68932 mRNA. Translation: AAA59159.1.
X65858 Genomic DNA. Translation: CAA46688.1.
U11870 Genomic DNA. Translation: AAA64378.1.
AY916762 Genomic DNA. Translation: AAY21512.1.
AY916763 Genomic DNA. Translation: AAY21513.1.
AY916764 Genomic DNA. Translation: AAY21514.1.
AY916765 Genomic DNA. Translation: AAY21515.1.
AY916766 Genomic DNA. Translation: AAY21516.1.
AY916769 Genomic DNA. Translation: AAY21519.1.
AY916772 Genomic DNA. Translation: AAY21522.1.
AY916773 Genomic DNA. Translation: AAY21523.1.
CR541994 mRNA. Translation: CAG46791.1.
CR542029 mRNA. Translation: CAG46826.1.
AK312668 mRNA. Translation: BAG35550.1.
AY651785 Genomic DNA. Translation: AAT46689.1.
AC097483 Genomic DNA. Translation: AAX93212.1.
CH471063 Genomic DNA. Translation: EAW70590.1.
BC028221 mRNA. Translation: AAH28221.1.
BC072397 mRNA. Translation: AAH72397.1.
AB032728 Genomic DNA. Translation: BAA92290.1.
AB032729 Genomic DNA. Translation: BAA92291.1.
AB032730 Genomic DNA. Translation: BAA92292.1.
AB032731 Genomic DNA. Translation: BAA92293.1.
AB032732 Genomic DNA. Translation: BAA92294.1.

IPI

IPI00296618.

PIR

A39445. I37449.

RefSeq

NP_000625.1. NM_000634.2.

UniGene

Hs.194778.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ILP	NMR	-	C	9-29	[»]
1ILQ	NMR	-	C	9-29	[»]
2LNL	NMR	-	A	29-324	[»]

ProteinModelPortal

P25024.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-3779N.

IntAct

P25024. 4 interactions.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P25024.

Polymorphism databases

DMDM

108936015.

Proteomic databases

PaxDb

P25024.

PRIDE

P25024.

Protocols and materials databases

DNASU

3577.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000295683; ENSP00000295683; ENSG00000163464.

GeneID

3577.

KEGG

hsa:3577.

UCSC

uc002vhc.3. human.

Organism-specific databases

CTD

3577.

GeneCards

GC02M219028.

H-InvDB

HIX0203926.

HGNC

HGNC:6026. CXCR1.

MIM

146929. gene.

neXtProt

NX_P25024.

PharmGKB

PA29842.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG146068.

HOVERGEN

HBG106917.

InParanoid

P25024.

KO

K04175.

OMA

PVCYEVL.

OrthoDB

EOG4M0F2B.

PhylomeDB

P25024.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

Bgee

P25024.

Genevestigator

P25024.

GermOnline

ENSG00000163464. Homo sapiens.

Family and domain databases

InterPro

IPR000174. Chemokine_CXCR.
IPR001355. Chemokine_CXCR1.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]

Pfam

PF00001. 7tm_1. 1 hit.
[Graphical view]

PRINTS

PR00237. GPCRRHODOPSN.
PR00427. INTRLEUKIN8R.
PR00572. INTRLEUKN8AR.

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P25024.

ChEMBL

CHEMBL4029.

EvolutionaryTrace

P25024.

GenomeRNAi

3577.

NextBio

13982.

SOURCE

Search...

Entry information

Entry name

CXCR1_HUMAN

Accession

Primary (citable) accession number: P25024
Secondary accession number(s): B2R6Q3 , Q2YEF8, Q2YEG4, Q2YEG5, Q2YEG7, Q2YEG8, Q53R18, Q6IN95, Q8N6T6, Q9P2T8, Q9P2T9, Q9P2U0, Q9P2U1, Q9P2U2

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	May 30, 2006
Last modified:	May 1, 2013
This is version 139 of the entry and version 2 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.