ID IL8_HUMAN Reviewed; 99 AA.
AC P10145; B2R4L8; Q6FGF6; Q6LAE6; Q96RG6; Q9C077; Q9UCE1; Q9UCR8; Q9UCR9;
AC Q9UCS0;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 27-MAR-2024, entry version 245.
DE RecName: Full=Interleukin-8;
DE Short=IL-8;
DE AltName: Full=C-X-C motif chemokine 8;
DE AltName: Full=Chemokine (C-X-C motif) ligand 8;
DE AltName: Full=Emoctakin;
DE AltName: Full=Granulocyte chemotactic protein 1;
DE Short=GCP-1;
DE AltName: Full=Monocyte-derived neutrophil chemotactic factor;
DE Short=MDNCF;
DE AltName: Full=Monocyte-derived neutrophil-activating peptide;
DE Short=MONAP;
DE AltName: Full=Neutrophil-activating protein 1;
DE Short=NAP-1;
DE AltName: Full=Protein 3-10C;
DE AltName: Full=T-cell chemotactic factor;
DE Contains:
DE RecName: Full=MDNCF-a;
DE AltName: Full=GCP/IL-8 protein IV;
DE AltName: Full=IL8/NAP1 form I;
DE Contains:
DE RecName: Full=Interleukin-8;
DE AltName: Full=(Ala-IL-8)77;
DE AltName: Full=GCP/IL-8 protein II;
DE AltName: Full=IL-8(1-77);
DE AltName: Full=IL8/NAP1 form II;
DE AltName: Full=MDNCF-b;
DE Contains:
DE RecName: Full=IL-8(5-77);
DE Contains:
DE RecName: Full=IL-8(6-77);
DE AltName: Full=(Ser-IL-8)72;
DE AltName: Full=GCP/IL-8 protein I;
DE AltName: Full=IL8/NAP1 form III;
DE AltName: Full=Lymphocyte-derived neutrophil-activating factor;
DE Short=LYNAP;
DE AltName: Full=MDNCF-c;
DE AltName: Full=Neutrophil-activating factor;
DE Short=NAF;
DE Contains:
DE RecName: Full=IL-8(7-77);
DE AltName: Full=GCP/IL-8 protein V;
DE AltName: Full=IL8/NAP1 form IV;
DE Contains:
DE RecName: Full=IL-8(8-77);
DE AltName: Full=GCP/IL-8 protein VI;
DE AltName: Full=IL8/NAP1 form V;
DE Contains:
DE RecName: Full=IL-8(9-77);
DE AltName: Full=GCP/IL-8 protein III;
DE AltName: Full=IL8/NAP1 form VI;
DE Flags: Precursor;
GN Name=CXCL8; Synonyms=IL8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2953813;
RA Schmid J., Weissmann C.;
RT "Induction of mRNA for a serine protease and a beta-thromboglobulin-like
RT protein in mitogen-stimulated human leukocytes.";
RL J. Immunol. 139:250-256(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3260265; DOI=10.1084/jem.167.6.1883;
RA Matsushima K., Morishita K., Yoshimura T., Lavu S., Kobayashi Y., Lew W.,
RA Appella E., Kung H., Leonard E.J., Oppenheim J.J.;
RT "Molecular cloning of a human monocyte-derived neutrophil chemotactic
RT factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor
RT necrosis factor.";
RL J. Exp. Med. 167:1883-1893(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2663993;
RA Mukaida N., Shiroo M., Matsushima K.;
RT "Genomic structure of the human monocyte-derived neutrophil chemotactic
RT factor IL-8.";
RL J. Immunol. 143:1366-1371(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2664463; DOI=10.1128/mcb.9.5.1946-1957.1989;
RA Kowalski J., Denhardt D.T.;
RT "Regulation of the mRNA for monocyte-derived neutrophil-activating peptide
RT in differentiating HL60 promyelocytes.";
RL Mol. Cell. Biol. 9:1946-1957(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Lung carcinoma;
RX PubMed=2200751; DOI=10.1016/0165-2478(90)90043-p;
RA Hotta K., Hayashi K., Ishikawa J., Tagawa M., Hashimoto K., Mizuno S.,
RA Suzuki K.;
RT "Coding region structure of interleukin-8 gene of human lung giant cell
RT carcinoma LU65C cells that produce LUCT/interleukin-8: homogeneity in
RT interleukin-8 genes.";
RL Immunol. Lett. 24:165-169(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neutrophil;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-91.
RC TISSUE=Peripheral blood leukocyte;
RA Jang J.S., Kim B.E.;
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-97.
RC TISSUE=Kidney;
RA King C.H., Gordon G.S., Konieczkowski M., Sedor J.R.;
RT "cDNA cloning of human mesangial cell interleukin 8 by polymerase chain
RT reaction.";
RL Submitted (FEB-1992) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP PROTEIN SEQUENCE OF 21-41, IDENTIFICATION OF MDNCF-A; IL-8(1-77);
RP IL-8(6-77); IL-8(7-77); IL-8(8-77) AND IL-8(9-77), AND PROTEOLYTIC
RP PROCESSING OF N-TERMINUS.
RX PubMed=2523801; DOI=10.1111/j.1432-1033.1989.tb14729.x;
RA van Damme J., van Beeumen J., Conings R., Decock B., Billiau A.;
RT "Purification of granulocyte chemotactic peptide/interleukin-8 reveals N-
RT terminal sequence heterogeneity similar to that of beta-thromboglobulin.";
RL Eur. J. Biochem. 181:337-344(1989).
RN [15]
RP PROTEIN SEQUENCE OF 21-41, IDENTIFICATION OF MDNCF-A; IL-8(1-77);
RP IL-8(6-77); IL-8(7-77); IL-8(8-77) AND IL-8(9-77), PROTEOLYTIC PROCESSING
RP OF N-TERMINUS, AND FUNCTION.
RX PubMed=2145175; DOI=10.1002/eji.1830200933;
RA van Damme J., Rampart M., Coning R., Decock B., van Osselaer N.,
RA Willems J., Billiau A.;
RT "The neutrophil-activating proteins interleukin 8 and beta-thromboglobulin:
RT in vitro and in vivo comparison of NH2-terminally processed forms.";
RL Eur. J. Immunol. 20:2113-2118(1990).
RN [16]
RP PROTEIN SEQUENCE OF 21-32, IDENTIFICATION OF MDNCF-A; IL-8(1-77) AND
RP IL-8(6-77), AND PROTEOLYTIC PROCESSING OF N-TERMINUS.
RX PubMed=2648135; DOI=10.1016/0161-5890(89)90024-2;
RA Yoshimura T., Robinson E.A., Appella E., Matsushima K., Showalter S.D.,
RA Skeel A., Leonard E.J.;
RT "Three forms of monocyte-derived neutrophil chemotactic factor (MDNCF)
RT distinguished by different lengths of the amino-terminal sequence.";
RL Mol. Immunol. 26:87-93(1989).
RN [17]
RP PROTEIN SEQUENCE OF 23-54, AND IDENTIFICATION OF IL-8(1-77).
RX PubMed=2659722; DOI=10.1084/jem.169.6.1895;
RA Suzuki K., Miyasaka H., Ota H., Yamakawa Y., Tagawa M., Kuramoto A.,
RA Mizuno S.;
RT "Purification and partial primary sequence of a chemotactic protein for
RT polymorphonuclear leukocytes derived from human lung giant cell carcinoma
RT LU65C cells.";
RL J. Exp. Med. 169:1895-1901(1989).
RN [18]
RP PROTEIN SEQUENCE OF 23-47.
RC TISSUE=Skin;
RX PubMed=1755384; DOI=10.1007/978-1-4684-6009-4_12;
RA Schroeder J.-M.;
RT "Biochemical and biological characterization of NAP-1/IL-8-related
RT cytokines in lesional psoriatic scale.";
RL Adv. Exp. Med. Biol. 305:97-107(1991).
RN [19]
RP PROTEIN SEQUENCE OF 23-46, AND IDENTIFICATION OF IL-8(1-77).
RX PubMed=2655583; DOI=10.1042/bj2590585;
RA Golds E.E., Mason P., Nyirkos P.;
RT "Inflammatory cytokines induce synthesis and secretion of gro protein and a
RT neutrophil chemotactic factor but not beta 2-microglobulin in human
RT synovial cells and fibroblasts.";
RL Biochem. J. 259:585-588(1989).
RN [20]
RP PROTEIN SEQUENCE OF 23-42.
RC TISSUE=Chronic myeloid leukemia cell;
RX PubMed=8344717; DOI=10.1016/0165-2478(93)90071-9;
RA Suzuki K., Yamakawa Y., Matsuo Y., Kamiya T., Minowada J., Mizuno S.;
RT "Isolation and amino acid sequence of a chemotactic protein,
RT LECT/interleukin 8, from a human myeloid leukemia cell line, ML-1.";
RL Immunol. Lett. 36:71-81(1993).
RN [21]
RP PROTEIN SEQUENCE OF 28-99, AND IDENTIFICATION OF IL-8(6-77).
RX PubMed=3279957; DOI=10.1016/s0006-291x(88)80364-4;
RA Gregory H., Young J., Schroeder J.-M., Mrowietz U., Christophers E.;
RT "Structure determination of a human lymphocyte derived neutrophil
RT activating peptide (LYNAP).";
RL Biochem. Biophys. Res. Commun. 151:883-890(1988).
RN [22]
RP PROTEIN SEQUENCE OF 28-69, AND IDENTIFICATION OF IL-8(6-77).
RX PubMed=3480540; DOI=10.1073/pnas.84.24.9233;
RA Yoshimura T., Matsushima K., Tanaka S., Robinson E.A., Appella E.,
RA Oppenheim J.J., Leonard E.J.;
RT "Purification of a human monocyte-derived neutrophil chemotactic factor
RT that has peptide sequence similarity to other host defense cytokines.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:9233-9237(1987).
RN [23]
RP PROTEIN SEQUENCE OF 28-59, AND IDENTIFICATION OF IL-8(6-77).
RX PubMed=3322281; DOI=10.1016/0006-291x(87)90432-3;
RA Walz A., Peveri P., Aschauer H., Baggiolini M.;
RT "Purification and amino acid sequencing of NAF, a novel neutrophil-
RT activating factor produced by monocytes.";
RL Biochem. Biophys. Res. Commun. 149:755-761(1987).
RN [24]
RP PROTEOLYTIC PROCESSING OF N-TERMINUS BY THROMBIN, AND FUNCTION.
RX PubMed=2212672;
RA Hebert C.A., Luscinskas F.W., Kiely J.-M., Luis E.A., Darbonne W.C.,
RA Bennett G.L., Liu C.C., Obin M.S., Gimbrone M.A. Jr., Baker J.B.;
RT "Endothelial and leukocyte forms of IL-8. Conversion by thrombin and
RT interactions with neutrophils.";
RL J. Immunol. 145:3033-3040(1990).
RN [25]
RP SYNTHESIS OF 28-99.
RX PubMed=2007144; DOI=10.1021/bi00226a021;
RA Clark-Lewis I., Mose B., Walz A., Baggiolini M., Scott G.J., Aebersold R.;
RT "Chemical synthesis, purification, and characterization of two inflammatory
RT proteins, neutrophil activating peptide 1 (interleukin-8) and neutrophil
RT activating peptide.";
RL Biochemistry 30:3128-3135(1991).
RN [26]
RP FUNCTION.
RX PubMed=1840701; DOI=10.1126/science.1840701;
RA Holmes W.E., Lee J., Kuang W.-J., Rice G.C., Wood W.I.;
RT "Structure and functional expression of a human interleukin-8 receptor.";
RL Science 253:1278-1280(1991).
RN [27]
RP FUNCTION.
RX PubMed=1891716; DOI=10.1126/science.1891716;
RA Murphy P.M., Tiffany H.L.;
RT "Cloning of complementary DNA encoding a functional human interleukin-8
RT receptor.";
RL Science 253:1280-1283(1991).
RN [28]
RP FUNCTION.
RX PubMed=7636208;
RA Hammond M.E., Lapointe G.R., Feucht P.H., Hilt S., Gallegos C.A.,
RA Gordon C.A., Giedlin M.A., Mullenbach G., Tekamp-Olson P.;
RT "IL-8 induces neutrophil chemotaxis predominantly via type I IL-8
RT receptors.";
RL J. Immunol. 155:1428-1433(1995).
RN [29]
RP FUNCTION.
RX PubMed=8662698; DOI=10.1074/jbc.271.22.12783;
RA Damaj B.B., McColl S.R., Mahana W., Crouch M.F., Naccache P.H.;
RT "Physical association of Gi2alpha with interleukin-8 receptors.";
RL J. Biol. Chem. 271:12783-12789(1996).
RN [30]
RP FUNCTION.
RX PubMed=9623510; DOI=10.1159/000023925;
RA Jacobi H.H., Poulsen L.K., Reimert C.M., Skov P.S., Ulfgren A.K., Jones I.,
RA Elfman L.B., Malling H.J., Mygind N.;
RT "IL-8 and the activation of eosinophils and neutrophils following nasal
RT allergen challenge.";
RL Int. Arch. Allergy Immunol. 116:53-59(1998).
RN [31]
RP PROTEOLYTIC PROCESSING OF N-TERMINUS BY MMP9.
RX PubMed=11023497;
RA Van den Steen P.E., Proost P., Wuyts A., Van Damme J., Opdenakker G.;
RT "Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal
RT processing, whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves
RT RANTES and MCP-2 intact.";
RL Blood 96:2673-2681(2000).
RN [32]
RP IDENTIFICATION OF IL-8(5-77) AND IL-8(6-77), FUNCTION, AND PROTEOLYTIC
RP PROCESSING OF N-TERMINUS.
RX PubMed=11978786; DOI=10.1074/jbc.m112275200;
RA Schutyser E., Struyf S., Proost P., Opdenakker G., Laureys G.,
RA Verhasselt B., Peperstraete L., Van de Putte I., Saccani A., Allavena P.,
RA Mantovani A., Van Damme J.;
RT "Identification of biologically active chemokine isoforms from ascitic
RT fluid and elevated levels of CCL18/pulmonary and activation-regulated
RT chemokine in ovarian carcinoma.";
RL J. Biol. Chem. 277:24584-24593(2002).
RN [33]
RP FUNCTION.
RX PubMed=11971003; DOI=10.4049/jimmunol.168.9.4559;
RA Takami M., Terry V., Petruzzelli L.;
RT "Signaling pathways involved in IL-8-dependent activation of adhesion
RT through Mac-1.";
RL J. Immunol. 168:4559-4566(2002).
RN [34]
RP REVIEW.
RX PubMed=1639201; DOI=10.1016/0014-5793(92)80909-z;
RA Baggiolini M., Clark-Lewis I.;
RT "Interleukin-8, a chemotactic and inflammatory cytokine.";
RL FEBS Lett. 307:97-101(1992).
RN [35]
RP REVIEW.
RX PubMed=14711052; DOI=10.1016/s0065-2776(03)81001-5;
RA Struyf S., Proost P., Van Damme J.;
RT "Regulation of the immune response by the interaction of chemokines and
RT proteases.";
RL Adv. Immunol. 81:1-44(2003).
RN [36]
RP CITRULLINATION AT ARG-27.
RX PubMed=18710930; DOI=10.1084/jem.20080305;
RA Proost P., Loos T., Mortier A., Schutyser E., Gouwy M., Noppen S.,
RA Dillen C., Ronsse I., Conings R., Struyf S., Opdenakker G., Maudgal P.C.,
RA Van Damme J.;
RT "Citrullination of CXCL8 by peptidylarginine deiminase alters receptor
RT usage, prevents proteolysis, and dampens tissue inflammation.";
RL J. Exp. Med. 205:2085-2097(2008).
RN [37]
RP FUNCTION, AND CLEAVAGE BY STREPTOCOCCUS PROTEASE SPYCEP (MICROBIAL
RP INFECTION).
RX PubMed=18692776; DOI=10.1016/j.chom.2008.07.002;
RA Zinkernagel A.S., Timmer A.M., Pence M.A., Locke J.B., Buchanan J.T.,
RA Turner C.E., Mishalian I., Sriskandan S., Hanski E., Nizet V.;
RT "The IL-8 protease SpyCEP/ScpC of group A Streptococcus promotes resistance
RT to neutrophil killing.";
RL Cell Host Microbe 4:170-178(2008).
RN [38]
RP CITRULLINATION AT ARG-27.
RX PubMed=19608678; DOI=10.3324/haematol.2009.006973;
RA Loos T., Opdenakker G., Van Damme J., Proost P.;
RT "Citrullination of CXCL8 increases this chemokine's ability to mobilize
RT neutrophils into the blood circulation.";
RL Haematologica 94:1346-1353(2009).
RN [39]
RP INDUCTION.
RX PubMed=20829347; DOI=10.1074/jbc.m110.136259;
RA Park S.H., Choi H.J., Yang H., Do K.H., Kim J., Lee D.W., Moon Y.;
RT "Endoplasmic reticulum stress-activated C/EBP homologous protein enhances
RT nuclear factor-kappaB signals via repression of peroxisome proliferator-
RT activated receptor gamma.";
RL J. Biol. Chem. 285:35330-35339(2010).
RN [40]
RP INTERACTION WITH TNFAIP6, AND MUTAGENESIS OF LYS-91; LYS-94 AND ARG-95.
RX PubMed=24501198; DOI=10.4049/jimmunol.1300194;
RA Dyer D.P., Thomson J.M., Hermant A., Jowitt T.A., Handel T.M.,
RA Proudfoot A.E., Day A.J., Milner C.M.;
RT "TSG-6 inhibits neutrophil migration via direct interaction with the
RT chemokine CXCL8.";
RL J. Immunol. 192:2177-2185(2014).
RN [41]
RP SUBUNIT.
RX PubMed=31235521; DOI=10.1074/jbc.ra119.008902;
RA Denisov S.S., Ippel J.H., Heinzmann A.C.A., Koenen R.R., Ortega-Gomez A.,
RA Soehnlein O., Hackeng T.M., Dijkgraaf I.;
RT "Tick saliva protein Evasin-3 modulates chemotaxis by disrupting CXCL8
RT interactions with glycosaminoglycans and CXCR2.";
RL J. Biol. Chem. 294:12370-12379(2019).
RN [42]
RP STRUCTURE BY NMR OF 28-99.
RX PubMed=2681204; DOI=10.1016/s0021-9258(19)47243-8;
RA Clore G.M., Appella E., Yamada M., Matsushima K., Gronenborn A.M.;
RT "Determination of the secondary structure of interleukin-8 by nuclear
RT magnetic resonance spectroscopy.";
RL J. Biol. Chem. 264:18907-18911(1989).
RN [43]
RP STRUCTURE BY NMR.
RX PubMed=2184886; DOI=10.1021/bi00459a004;
RA Clore G.M., Appella E., Yamada M., Matsushima K., Gronenborn A.M.;
RT "Three-dimensional structure of interleukin 8 in solution.";
RL Biochemistry 29:1689-1696(1990).
RN [44]
RP STRUCTURE BY NMR OF 28-80.
RX PubMed=8631339; DOI=10.1111/j.1432-1033.1996.00026.x;
RA Sticht H., Auer M., Schmitt B., Besemer J., Horcher M., Kirsch T.,
RA Lindley I.J., Rosch P.;
RT "Structure and activity of a chimeric interleukin-8-melanoma-growth-
RT stimulatory-activity protein.";
RL Eur. J. Biochem. 235:26-35(1996).
RN [45]
RP STRUCTURE BY NMR OF COMPLEX TO RECEPTOR.
RX PubMed=10368283; DOI=10.1016/s0969-2126(99)80022-7;
RA Skelton N.J., Quan C., Reilly D., Lowman H.;
RT "Structure of a CXC chemokine-receptor fragment in complex with
RT interleukin-8.";
RL Structure 7:157-168(1999).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
RX PubMed=2182630; DOI=10.1016/s0021-9258(19)39226-9;
RA Baldwin E.T., Franklin K.A., Appella E., Yamada M., Matsushima K.,
RA Wlodawer A., Weber I.T.;
RT "Crystallization of human interleukin-8. A protein chemotactic for
RT neutrophils and T-lymphocytes.";
RL J. Biol. Chem. 265:6851-6853(1990).
RN [47]
RP STRUCTURE BY NMR, AND COMPARISON WITH X-RAY STRUCTURE.
RX PubMed=2005614; DOI=10.1016/0022-2836(91)90518-b;
RA Clore G.M., Gronenborn A.M.;
RT "Comparison of the solution nuclear magnetic resonance and crystal
RT structures of interleukin-8. Possible implications for the mechanism of
RT receptor binding.";
RL J. Mol. Biol. 217:611-620(1991).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), AND STRUCTURE BY NMR.
RX PubMed=1988949; DOI=10.1073/pnas.88.2.502;
RA Baldwin E.T., Weber I.T., St Charles R., Xuan J.C., Appella E., Yamada M.,
RA Matsushima K., Edwards B.F., Clore G.M., Gronenborn A.M.;
RT "Crystal structure of interleukin 8: symbiosis of NMR and
RT crystallography.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:502-506(1991).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF MUTANT.
RX PubMed=10707023;
RX DOI=10.1002/(sici)1097-0134(20000301)38:4<361::aid-prot2>3.3.co;2-s;
RA Gerber N., Lowman H., Artis D.R., Eigenbrot C.;
RT "Receptor-binding conformation of the 'ELR' motif of IL-8: X-ray structure
RT of the L5C/H33C variant at 2.35 A resolution.";
RL Proteins 38:361-367(2000).
CC -!- FUNCTION: Chemotactic factor that mediates inflammatory response by
CC attracting neutrophils, basophils, and T-cells to clear pathogens and
CC protect the host from infection (PubMed:7636208, PubMed:18692776). Also
CC plays an important role in neutrophil activation (PubMed:9623510,
CC PubMed:2145175). Released in response to an inflammatory stimulus,
CC exerts its effect by binding to the G-protein-coupled receptors CXCR1
CC and CXCR2, primarily found in neutrophils, monocytes and endothelial
CC cells (PubMed:1840701, PubMed:1891716). G-protein heterotrimer (alpha,
CC beta, gamma subunits) constitutively binds to CXCR1/CXCR2 receptor and
CC activation by IL8 leads to beta and gamma subunits release from Galpha
CC (GNAI2 in neutrophils) and activation of several downstream signaling
CC pathways including PI3K and MAPK pathways (PubMed:8662698,
CC PubMed:11971003). {ECO:0000269|PubMed:11971003,
CC ECO:0000269|PubMed:11978786, ECO:0000269|PubMed:1840701,
CC ECO:0000269|PubMed:18692776, ECO:0000269|PubMed:1891716,
CC ECO:0000269|PubMed:2145175, ECO:0000269|PubMed:2212672,
CC ECO:0000269|PubMed:7636208, ECO:0000269|PubMed:8662698,
CC ECO:0000269|PubMed:9623510}.
CC -!- SUBUNIT: Homodimer (PubMed:31235521). Dimer formation is disrupted by
CC tick evasin-3 (PubMed:31235521). Interacts with TNFAIP6 (via Link
CC domain); this interaction interferes with chemokine binding to
CC glycosaminoglycans. {ECO:0000269|PubMed:24501198,
CC ECO:0000269|PubMed:31235521}.
CC -!- INTERACTION:
CC P10145; P25025: CXCR2; NbExp=3; IntAct=EBI-3917999, EBI-2835281;
CC P10145; P02776: PF4; NbExp=2; IntAct=EBI-3917999, EBI-2565740;
CC P10145; P98066: TNFAIP6; NbExp=15; IntAct=EBI-3917999, EBI-11700693;
CC P10145; P9WGV3: ahcY; Xeno; NbExp=3; IntAct=EBI-3917999, EBI-11740468;
CC P10145; Q6MX51: atsG; Xeno; NbExp=3; IntAct=EBI-3917999, EBI-11740572;
CC P10145; P9WMN3: glmU; Xeno; NbExp=3; IntAct=EBI-3917999, EBI-11740532;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- INDUCTION: By ER stress in a DDIT3/CHOP-dependent manner.
CC {ECO:0000269|PubMed:20829347}.
CC -!- PTM: Several N-terminal processed forms are produced by proteolytic
CC cleavage after secretion from at least peripheral blood monocytes,
CC leukcocytes and endothelial cells. In general, IL-8(1-77) is referred
CC to as interleukin-8. IL-8(6-77) is the most promiment form.
CC {ECO:0000269|PubMed:11023497, ECO:0000269|PubMed:11978786,
CC ECO:0000269|PubMed:2145175, ECO:0000269|PubMed:2212672,
CC ECO:0000269|PubMed:2523801, ECO:0000269|PubMed:2648135}.
CC -!- PTM: Citrullination at Arg-27 prevents proteolysis, and dampens tissue
CC inflammation, it also enhances leukocytosis, possibly through impaired
CC chemokine clearance from the blood circulation.
CC {ECO:0000269|PubMed:18710930, ECO:0000269|PubMed:19608678}.
CC -!- PTM: (Microbial infection) Cleaved by group A Streptococcus protease
CC SpyCEP; leading to impaired neutrophil endothelial transmigration and
CC thus increased virulence. {ECO:0000269|PubMed:18692776}.
CC -!- SIMILARITY: Belongs to the intercrine alpha (chemokine CxC) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK00048.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-8 entry;
CC URL="https://en.wikipedia.org/wiki/Interleukin_8";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/il8/";
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DR EMBL; M17017; AAA35611.1; -; mRNA.
DR EMBL; Y00787; CAA68742.1; -; mRNA.
DR EMBL; M28130; AAA59158.1; -; Genomic_DNA.
DR EMBL; M26383; AAA36323.1; -; mRNA.
DR EMBL; D14283; BAA03245.1; -; Genomic_DNA.
DR EMBL; BT007067; AAP35730.1; -; mRNA.
DR EMBL; AK311874; BAG34815.1; -; mRNA.
DR EMBL; CR542151; CAG46948.1; -; mRNA.
DR EMBL; AF385628; AAK60276.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471057; EAX05688.1; -; Genomic_DNA.
DR EMBL; BC013615; AAH13615.1; -; mRNA.
DR EMBL; Z11686; CAA77745.1; -; mRNA.
DR EMBL; AF043337; AAK00048.1; ALT_SEQ; mRNA.
DR CCDS; CCDS34005.1; -.
DR PIR; A37034; A37034.
DR RefSeq; NP_000575.1; NM_000584.3.
DR PDB; 1ICW; X-ray; 2.01 A; A/B=28-99.
DR PDB; 1IKL; NMR; -; A=28-99.
DR PDB; 1IKM; NMR; -; A=28-99.
DR PDB; 1IL8; NMR; -; A/B=28-99.
DR PDB; 1ILP; NMR; -; A/B=28-99.
DR PDB; 1ILQ; NMR; -; A/B=28-99.
DR PDB; 1QE6; X-ray; 2.35 A; A/B/C/D=28-99.
DR PDB; 1ROD; NMR; -; A/B=28-80.
DR PDB; 2IL8; NMR; -; A/B=28-99.
DR PDB; 3IL8; X-ray; 2.00 A; A=28-99.
DR PDB; 4XDX; X-ray; 0.95 A; A=30-99.
DR PDB; 5D14; X-ray; 1.00 A; A=30-99.
DR PDB; 5WDZ; NMR; -; A=28-93.
DR PDB; 6LFM; EM; 3.50 A; D/E=28-99.
DR PDB; 6LFO; EM; 3.40 A; D=28-92.
DR PDB; 6N2U; X-ray; 1.25 A; A=1-99.
DR PDB; 6WZM; X-ray; 2.28 A; E/F=28-93.
DR PDB; 6XMN; NMR; -; A=28-93.
DR PDB; 8IC0; EM; 3.41 A; F=28-99.
DR PDBsum; 1ICW; -.
DR PDBsum; 1IKL; -.
DR PDBsum; 1IKM; -.
DR PDBsum; 1IL8; -.
DR PDBsum; 1ILP; -.
DR PDBsum; 1ILQ; -.
DR PDBsum; 1QE6; -.
DR PDBsum; 1ROD; -.
DR PDBsum; 2IL8; -.
DR PDBsum; 3IL8; -.
DR PDBsum; 4XDX; -.
DR PDBsum; 5D14; -.
DR PDBsum; 5WDZ; -.
DR PDBsum; 6LFM; -.
DR PDBsum; 6LFO; -.
DR PDBsum; 6N2U; -.
DR PDBsum; 6WZM; -.
DR PDBsum; 6XMN; -.
DR PDBsum; 8IC0; -.
DR AlphaFoldDB; P10145; -.
DR BMRB; P10145; -.
DR EMDB; EMD-0877; -.
DR EMDB; EMD-0879; -.
DR EMDB; EMD-35351; -.
DR SMR; P10145; -.
DR BioGRID; 109790; 18.
DR DIP; DIP-3778N; -.
DR IntAct; P10145; 14.
DR STRING; 9606.ENSP00000306512; -.
DR BindingDB; P10145; -.
DR ChEMBL; CHEMBL2157; -.
DR DrugBank; DB05434; ABT-510.
DR DrugBank; DB05484; MDX-018.
DR DrugBank; DB12843; Oleandrin.
DR DrugBank; DB05855; Rivanicline.
DR DrugCentral; P10145; -.
DR BioMuta; CXCL8; -.
DR DMDM; 124359; -.
DR EPD; P10145; -.
DR MassIVE; P10145; -.
DR PaxDb; 9606-ENSP00000306512; -.
DR PeptideAtlas; P10145; -.
DR ABCD; P10145; 15 sequenced antibodies.
DR Antibodypedia; 13311; 1869 antibodies from 48 providers.
DR DNASU; 3576; -.
DR Ensembl; ENST00000307407.8; ENSP00000306512.3; ENSG00000169429.12.
DR GeneID; 3576; -.
DR KEGG; hsa:3576; -.
DR MANE-Select; ENST00000307407.8; ENSP00000306512.3; NM_000584.4; NP_000575.1.
DR UCSC; uc003hhe.3; human.
DR AGR; HGNC:6025; -.
DR CTD; 3576; -.
DR DisGeNET; 3576; -.
DR GeneCards; CXCL8; -.
DR HGNC; HGNC:6025; CXCL8.
DR HPA; ENSG00000169429; Tissue enriched (bone).
DR MIM; 146930; gene.
DR neXtProt; NX_P10145; -.
DR OpenTargets; ENSG00000169429; -.
DR PharmGKB; PA29841; -.
DR VEuPathDB; HostDB:ENSG00000169429; -.
DR eggNOG; ENOG502S7MM; Eukaryota.
DR GeneTree; ENSGT00940000160757; -.
DR InParanoid; P10145; -.
DR OMA; IGTELRC; -.
DR OrthoDB; 5343536at2759; -.
DR PhylomeDB; P10145; -.
DR TreeFam; TF333433; -.
DR PathwayCommons; P10145; -.
DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-HSA-380994; ATF4 activates genes in response to endoplasmic reticulum stress.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-6783783; Interleukin-10 signaling.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR SignaLink; P10145; -.
DR SIGNOR; P10145; -.
DR BioGRID-ORCS; 3576; 9 hits in 1147 CRISPR screens.
DR ChiTaRS; CXCL8; human.
DR EvolutionaryTrace; P10145; -.
DR GeneWiki; Interleukin_8; -.
DR GenomeRNAi; 3576; -.
DR Pharos; P10145; Tchem.
DR PRO; PR:P10145; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P10145; Protein.
DR Bgee; ENSG00000169429; Expressed in periodontal ligament and 171 other cell types or tissues.
DR ExpressionAtlas; P10145; baseline and differential.
DR Genevisible; P10145; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0008009; F:chemokine activity; IDA:UniProtKB.
DR GO; GO:0045236; F:CXCR chemokine receptor binding; IBA:GO_Central.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0005153; F:interleukin-8 receptor binding; IPI:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; TAS:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IBA:GO_Central.
DR GO; GO:0019722; P:calcium-mediated signaling; TAS:UniProtKB.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEP:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:BHF-UCL.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:UniProtKB.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; TAS:UniProtKB.
DR GO; GO:0048566; P:embryonic digestive tract development; IEP:DFLAT.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0050930; P:induction of positive chemotaxis; IGI:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0060354; P:negative regulation of cell adhesion molecule production; IDA:ARUK-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0045744; P:negative regulation of G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:ARUK-UCL.
DR GO; GO:0042119; P:neutrophil activation; IDA:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:CACAO.
DR GO; GO:0031328; P:positive regulation of cellular biosynthetic process; IDA:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:ARUK-UCL.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; TAS:BHF-UCL.
DR GO; GO:0031623; P:receptor internalization; IDA:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; IDA:UniProtKB.
DR GO; GO:2000535; P:regulation of entry of bacterium into host cell; IMP:AgBase.
DR GO; GO:0045091; P:regulation of single stranded viral RNA replication via double stranded DNA intermediate; IDA:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0002237; P:response to molecule of bacterial origin; IDA:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd00273; Chemokine_CXC; 1.
DR Gene3D; 2.40.50.40; -; 1.
DR InterPro; IPR039809; Chemokine_b/g/d.
DR InterPro; IPR001089; Chemokine_CXC.
DR InterPro; IPR018048; Chemokine_CXC_CS.
DR InterPro; IPR001811; Chemokine_IL8-like_dom.
DR InterPro; IPR033899; CXC_Chemokine_domain.
DR InterPro; IPR036048; Interleukin_8-like_sf.
DR PANTHER; PTHR12015:SF211; INTERLEUKIN-8; 1.
DR PANTHER; PTHR12015; SMALL INDUCIBLE CYTOKINE A; 1.
DR Pfam; PF00048; IL8; 1.
DR PRINTS; PR00436; INTERLEUKIN8.
DR PRINTS; PR00437; SMALLCYTKCXC.
DR SMART; SM00199; SCY; 1.
DR SUPFAM; SSF54117; Interleukin 8-like chemokines; 1.
DR PROSITE; PS00471; SMALL_CYTOKINES_CXC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chemotaxis; Citrullination; Cytokine;
KW Direct protein sequencing; Disulfide bond; Inflammatory response;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:2145175,
FT ECO:0000269|PubMed:2523801, ECO:0000269|PubMed:2648135"
FT CHAIN 21..99
FT /note="MDNCF-a"
FT /id="PRO_0000005126"
FT CHAIN 23..99
FT /note="Interleukin-8"
FT /id="PRO_0000005127"
FT CHAIN 27..99
FT /note="IL-8(5-77)"
FT /id="PRO_0000041948"
FT CHAIN 28..99
FT /note="IL-8(6-77)"
FT /id="PRO_0000005128"
FT CHAIN 29..99
FT /note="IL-8(7-77)"
FT /id="PRO_0000005129"
FT CHAIN 30..99
FT /note="IL-8(8-77)"
FT /id="PRO_0000005130"
FT CHAIN 31..99
FT /note="IL-8(9-77)"
FT /id="PRO_0000005131"
FT SITE 27..28
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000305"
FT SITE 28..29
FT /note="Cleavage; by MMP9"
FT MOD_RES 27
FT /note="Citrulline"
FT /evidence="ECO:0000269|PubMed:18710930,
FT ECO:0000269|PubMed:19608678"
FT DISULFID 34..61
FT DISULFID 36..77
FT MUTAGEN 91
FT /note="K->A: Decreases heparin-binding activity. Impairs
FT heparin-binding activity and leukocyte transendothelial
FT migration; when associated with A-94 and A-95."
FT /evidence="ECO:0000269|PubMed:24501198"
FT MUTAGEN 94
FT /note="K->A: Impairs heparin-binding activity and leukocyte
FT transendothelial migration; when associated with A-91 and
FT A-95."
FT /evidence="ECO:0000269|PubMed:24501198"
FT MUTAGEN 95
FT /note="R->A: Impairs heparin-binding activity and leukocyte
FT transendothelial migration; when associated with A-91 and
FT A-94."
FT /evidence="ECO:0000269|PubMed:24501198"
FT CONFLICT 53
FT /note="R -> L (in Ref. 17; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:1ROD"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:4XDX"
FT STRAND 49..55
FT /evidence="ECO:0007829|PDB:4XDX"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:1ICW"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:4XDX"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:4XDX"
FT TURN 71..73
FT /evidence="ECO:0007829|PDB:1IKL"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:4XDX"
FT HELIX 83..97
FT /evidence="ECO:0007829|PDB:4XDX"
SQ SEQUENCE 99 AA; 11098 MW; 15C649996E89319F CRC64;
MTSKLAVALL AAFLISAALC EGAVLPRSAK ELRCQCIKTY SKPFHPKFIK ELRVIESGPH
CANTEIIVKL SDGRELCLDP KENWVQRVVE KFLKRAENS
//
