ID   CCL11_HUMAN             Reviewed;          97 AA.
AC   P51671; P50877; Q92490; Q92491;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   04-NOV-2026, entry version 221.
DE   RecName: Full=Eotaxin;
DE   AltName: Full=C-C motif chemokine 11;
DE   AltName: Full=Eosinophil chemotactic protein;
DE   AltName: Full=Small-inducible cytokine A11;
DE   Flags: Precursor;
GN   Name=CCL11; Synonyms=SCYA11;
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], FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX   PubMed=8597956; DOI=10.1038/nm0496-449;
RA   Garcia-Zepeda E.A., Rothenberg M.E., Ownbey T.R., Leder P., Luster A.D.;
RT   "Human eotaxin is a specific chemoattractant for eosinophil cells and
RT   provides a new mechanism to explain tissue eosinophilia.";
RL   Nat. Med. 2:449-456(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8609214; DOI=10.1172/jci118456;
RA   Ponath P.D., Qin S., Ringler D.J., Clark-Lewis I., Wang J., Kassam N.,
RA   Smith H., Shi X., Gonzalo J.A., Newman W., Gutierrez-Ramos J.-C.,
RA   Mackay C.R.;
RT   "Cloning of the human eosinophil chemoattractant, eotaxin. Expression,
RT   receptor binding, and functional properties suggest a mechanism for the
RT   selective recruitment of eosinophils.";
RL   J. Clin. Invest. 97:604-612(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC   TISSUE=Small intestine;
RX   PubMed=8631813; DOI=10.1074/jbc.271.13.7725;
RA   Kitaura M., Nakajima T., Imai T., Harada S., Combadiere C., Tiffany H.L.,
RA   Murphy P.M., Yoshie O.;
RT   "Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine,
RT   and identification of a specific eosinophil eotaxin receptor, CC chemokine
RT   receptor 3.";
RL   J. Biol. Chem. 271:7725-7730(1996).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 60-65 AND 75-88, AND
RP   VARIANTS.
RC   TISSUE=Foreskin;
RX   PubMed=8780731; DOI=10.1006/bbrc.1996.1292;
RA   Bartels J., Schlueter C., Richter E., Noso N., Kulke R., Christophers E.,
RA   Schroeder J.-M.;
RT   "Human dermal fibroblasts express eotaxin: molecular cloning, mRNA
RT   expression, and identification of eotaxin sequence variants.";
RL   Biochem. Biophys. Res. Commun. 225:1045-1051(1996).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Placenta;
RX   PubMed=9169149; DOI=10.1006/geno.1997.4656;
RA   Garcia-Zepeda E.A., Rothenberg M.E., Weremowicz S., Sarafi M.N.,
RA   Morton C.C., Luster A.D.;
RT   "Genomic organization, complete sequence, and chromosomal location of the
RT   gene for human eotaxin (SCYA11), an eosinophil-specific CC chemokine.";
RL   Genomics 41:471-476(1997).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Lung;
RX   PubMed=9299399; DOI=10.1006/bbrc.1997.7169;
RA   Hein H., Schlueter C., Kulke R., Christophers E., Schroeder J.-M.,
RA   Bartels J.;
RT   "Genomic organization, sequence, and transcriptional regulation of the
RT   human eotaxin gene.";
RL   Biochem. Biophys. Res. Commun. 237:537-542(1997).
RN   [7]
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   [8]
RP   GLYCOSYLATION AT THR-94.
RC   TISSUE=Blood;
RX   PubMed=9578468; DOI=10.1046/j.1432-1327.1998.2530114.x;
RA   Noso N., Bartels J., Mallet A.I., Mochizuki M., Christophers E.,
RA   Schroeder J.-M.;
RT   "Delayed production of biologically active O-glycosylated forms of human
RT   eotaxin by tumor-necrosis-factor-alpha-stimulated dermal fibroblasts.";
RL   Eur. J. Biochem. 253:114-122(1998).
RN   [9]
RP   FUNCTION.
RX   PubMed=28279120; DOI=10.1080/10799893.2017.1298132;
RA   Park J.Y., Kang Y.W., Choi B.Y., Yang Y.C., Cho B.P., Cho W.G.;
RT   "CCL11 promotes angiogenic activity by activating the PI3K/Akt pathway in
RT   HUVECs.";
RL   J. Recept. Signal Transduct. 37:416-421(2017).
RN   [10]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION BY TNF.
RX   PubMed=33846499; DOI=10.1038/s41598-021-87199-7;
RA   Wakabayashi K., Isozaki T., Tsubokura Y., Fukuse S., Kasama T.;
RT   "Eotaxin-1/CCL11 is involved in cell migration in rheumatoid arthritis.";
RL   Sci. Rep. 11:7937-7937(2021).
RN   [11]
RP   STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX   PubMed=9712872; DOI=10.1074/jbc.273.35.22471;
RA   Crump M.P., Rajarathnam K., Kim K.S., Clark-Lewis I., Sykes B.D.;
RT   "Solution structure of eotaxin, a chemokine that selectively recruits
RT   eosinophils in allergic inflammation.";
RL   J. Biol. Chem. 273:22471-22479(1998).
CC   -!- FUNCTION: Chemokine that plays a central role in both allergic and non-
CC       allergic inflammatory reactions by inducing the migration of different
CC       leukocyte types including eosinophils, basophils, macrophages and
CC       dendritic cells (PubMed:8597956, PubMed:33846499). Exerts its effects
CC       primarily by binding to the CCR3 receptor (PubMed:8631813). Induces
CC       also chemotaxis of endothelial cells and promotes angiogenesis by
CC       activating the PI3K/Akt pathway (PubMed:28279120).
CC       {ECO:0000269|PubMed:28279120, ECO:0000269|PubMed:33846499,
CC       ECO:0000269|PubMed:8597956, ECO:0000269|PubMed:8631813}.
CC   -!- INTERACTION:
CC       P51671; Q9Y4X3: CCL27; NbExp=2; IntAct=EBI-727357, EBI-16744026;
CC       P51671; Q9NRJ3: CCL28; NbExp=2; IntAct=EBI-727357, EBI-7783254;
CC       P51671; P13501: CCL5; NbExp=2; IntAct=EBI-727357, EBI-2848366;
CC       P51671; P51677: CCR3; NbExp=2; IntAct=EBI-727357, EBI-6625120;
CC       P51671; P02778: CXCL10; NbExp=2; IntAct=EBI-727357, EBI-7815386;
CC       P51671; P48061: CXCL12; NbExp=2; IntAct=EBI-727357, EBI-3913254;
CC       P51671; P27487: DPP4; NbExp=2; IntAct=EBI-727357, EBI-2871277;
CC       P51671; P02776: PF4; NbExp=2; IntAct=EBI-727357, EBI-2565740;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:33846499,
CC       ECO:0000305|PubMed:8597956}.
CC   -!- INDUCTION: Induced by TNF, IL1A/interleukin-1 alpha and IFNG/IFN-gamma.
CC       {ECO:0000269|PubMed:33846499, ECO:0000269|PubMed:8597956}.
CC   -!- PTM: O-linked glycan consists of a Gal-GalNAc disaccharide which is
CC       modified with up to 2 sialic acid residues.
CC       {ECO:0000269|PubMed:9578468}.
CC   -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=CCL11 entry;
CC       URL="https://en.wikipedia.org/wiki/CCL11";
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DR   EMBL; U46573; AAA98957.1; -; mRNA.
DR   EMBL; U34780; AAC50369.1; -; Genomic_DNA.
DR   EMBL; D49372; BAA08370.1; -; mRNA.
DR   EMBL; Z69291; CAA93258.1; -; mRNA.
DR   EMBL; Z75668; CAA99997.1; -; mRNA.
DR   EMBL; Z75669; CAA99998.1; -; mRNA.
DR   EMBL; U46572; AAC51297.1; -; Genomic_DNA.
DR   EMBL; Z92709; CAB07027.1; -; Genomic_DNA.
DR   EMBL; BC017850; AAH17850.1; -; mRNA.
DR   CCDS; CCDS11279.1; -.
DR   PIR; JC4912; JC4912.
DR   RefSeq; NP_002977.1; NM_002986.3.
DR   PDB; 1EOT; NMR; -; A=24-97.
DR   PDB; 2EOT; NMR; -; A=24-97.
DR   PDB; 2MPM; NMR; -; A=24-97.
DR   PDB; 7SCS; X-ray; 1.51 A; B=24-97.
DR   AlphaFoldDB; P51671; -.
DR   BMRB; P51671; -.
DR   MDposit; P51671; -.
DR   SMR; P51671; -.
DR   BioGRID; 112259; 29.
DR   DIP; DIP-5858N; -.
DR   FunCoup; P51671; 605.
DR   IntAct; P51671; 28.
DR   NDEx; IQUERY-CP-CCL11; 9 NDEx IQuery Curated Pathways.
DR   STRING; 9606.ENSP00000302234; -.
DR   BindingDB; P51671; -.
DR   ChEMBL; CHEMBL3286077; -.
DR   DrugBank; DB05429; Bertilimumab.
DR   GlyCosmos; P51671; 1 site, No reported glycans.
DR   GlyGen; P51671; 2 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; P51671; -.
DR   PhosphoSitePlus; P51671; -.
DR   BioMuta; CCL11; -.
DR   DMDM; 1706661; -.
DR   PaxDb; 9606-ENSP00000302234; -.
DR   PeptideAtlas; P51671; -.
DR   ABCD; P51671; 3 sequenced antibodies.
DR   Antibodypedia; 15485; 506 antibodies from 46 providers.
DR   DNASU; 6356; -.
DR   Ensembl; ENST00000305869.4; ENSP00000302234.3; ENSG00000172156.4.
DR   GeneID; 6356; -.
DR   KEGG; hsa:6356; -.
DR   MANE-Select; ENST00000305869.4; ENSP00000302234.3; NM_002986.3; NP_002977.1.
DR   AGR; HGNC:10610; -.
DR   ClinPGx; PA35543; -.
DR   CTD; 6356; -.
DR   DisGeNET; 6356; -.
DR   GeneCards; CCL11; -.
DR   HGNC; HGNC:10610; CCL11.
DR   HPA; ENSG00000172156; Tissue enhanced (intestine, lymphoid tissue, stomach, urinary bladder).
DR   MalaCards; CCL11; -.
DR   MIM; 601156; gene.
DR   OpenTargets; ENSG00000172156; -.
DR   VEuPathDB; HostDB:ENSG00000172156; -.
DR   eggNOG; ENOG502S8M4; Eukaryota.
DR   GeneTree; ENSGT01130000278316; -.
DR   HOGENOM; CLU_141716_1_0_1; -.
DR   InParanoid; P51671; -.
DR   OMA; AATFXFV; -.
DR   OrthoDB; 8934837at2759; -.
DR   PAN-GO; P51671; 8 GO annotations based on evolutionary models.
DR   PhylomeDB; P51671; -.
DR   PathwayCommons; P51671; -.
DR   Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR   Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR   SignaLink; P51671; -.
DR   SIGNOR; P51671; -.
DR   Agora; ENSG00000172156; -.
DR   BioGRID-ORCS; 6356; 11 hits in 1137 CRISPR screens.
DR   ChiTaRS; CCL11; human.
DR   EvolutionaryTrace; P51671; -.
DR   GeneWiki; CCL11; -.
DR   GenomeRNAi; 6356; -.
DR   Pharos; P51671; Tbio.
DR   PRO; PR:P51671; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; P51671; protein.
DR   Bgee; ENSG00000172156; Expressed in pylorus and 87 other cell types or tissues.
DR   ExpressionAtlas; P51671; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IDA:BHF-UCL.
DR   GO; GO:0048020; F:CCR chemokine receptor binding; IBA:GO_Central.
DR   GO; GO:0031728; F:CCR3 chemokine receptor binding; IDA:CAFA.
DR   GO; GO:0008009; F:chemokine activity; IDA:UniProtKB.
DR   GO; GO:0046983; F:protein dimerization activity; IDA:CAFA.
DR   GO; GO:0048018; F:receptor ligand activity; IDA:CAFA.
DR   GO; GO:0007015; P:actin filament organization; IEA:Ensembl.
DR   GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IBA:GO_Central.
DR   GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR   GO; GO:0060326; P:cell chemotaxis; IDA:UniProt.
DR   GO; GO:0070098; P:chemokine-mediated signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR   GO; GO:0002544; P:chronic inflammatory response; IEA:Ensembl.
DR   GO; GO:0007010; P:cytoskeleton organization; IDA:UniProtKB.
DR   GO; GO:0048245; P:eosinophil chemotaxis; IDA:UniProtKB.
DR   GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR   GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR   GO; GO:0006874; P:intracellular calcium ion homeostasis; TAS:ProtInc.
DR   GO; GO:0007611; P:learning or memory; ISS:ARUK-UCL.
DR   GO; GO:0002551; P:mast cell chemotaxis; IEA:Ensembl.
DR   GO; GO:0050768; P:negative regulation of neurogenesis; ISS:ARUK-UCL.
DR   GO; GO:0030838; P:positive regulation of actin filament polymerization; IDA:BHF-UCL.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR   GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL.
DR   GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:BHF-UCL.
DR   GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR   GO; GO:0008360; P:regulation of cell shape; IDA:UniProtKB.
DR   GO; GO:0035962; P:response to interleukin-13; IEA:Ensembl.
DR   GO; GO:0070670; P:response to interleukin-4; IEA:Ensembl.
DR   GO; GO:0009314; P:response to radiation; TAS:ProtInc.
DR   GO; GO:0009615; P:response to virus; TAS:ProtInc.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   CDD; cd00272; Chemokine_CC; 1.
DR   DisProt; DP00641; -.
DR   FunFam; 2.40.50.40:FF:000002; C-C motif chemokine; 1.
DR   Gene3D; 2.40.50.40; -; 1.
DR   InterPro; IPR039809; Chemokine_b/g/d.
DR   InterPro; IPR000827; Chemokine_CC_CS.
DR   InterPro; IPR001811; Chemokine_IL8-like_dom.
DR   InterPro; IPR036048; Interleukin_8-like_sf.
DR   PANTHER; PTHR12015:SF146; EOTAXIN; 1.
DR   PANTHER; PTHR12015; SMALL INDUCIBLE CYTOKINE A; 1.
DR   Pfam; PF00048; IL8; 1.
DR   SMART; SM00199; SCY; 1.
DR   SUPFAM; SSF54117; Interleukin 8-like chemokines; 1.
DR   PROSITE; PS00472; SMALL_CYTOKINES_CC; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Chemotaxis; Cytokine; Direct protein sequencing;
KW   Disulfide bond; Glycoprotein; Inflammatory response; Reference proteome;
KW   Secreted; Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..97
FT                   /note="Eotaxin"
FT                   /id="PRO_0000005195"
FT   CARBOHYD        94
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:9578468"
FT   DISULFID        32..57
FT                   /evidence="ECO:0000269|PubMed:9712872"
FT   DISULFID        33..73
FT                   /evidence="ECO:0000269|PubMed:9712872"
FT   VARIANT         7
FT                   /note="L -> P"
FT                   /id="VAR_001634"
FT   VARIANT         23
FT                   /note="A -> T (in dbSNP:rs1129844)"
FT                   /id="VAR_001635"
FT   VARIANT         51
FT                   /note="R -> S"
FT                   /id="VAR_001636"
FT   VARIANT         79
FT                   /note="K -> R"
FT                   /id="VAR_001637"
FT   VARIANT         86
FT                   /note="K -> T (in dbSNP:rs34262946)"
FT                   /id="VAR_048705"
FT   STRAND          26..29
FT                   /evidence="ECO:0007829|PDB:1EOT"
FT   STRAND          30..32
FT                   /evidence="ECO:0007829|PDB:7SCS"
FT   HELIX           43..45
FT                   /evidence="ECO:0007829|PDB:7SCS"
FT   STRAND          46..52
FT                   /evidence="ECO:0007829|PDB:7SCS"
FT   STRAND          57..59
FT                   /evidence="ECO:0007829|PDB:7SCS"
FT   STRAND          61..66
FT                   /evidence="ECO:0007829|PDB:7SCS"
FT   STRAND          67..70
FT                   /evidence="ECO:0007829|PDB:2MPM"
FT   STRAND          71..74
FT                   /evidence="ECO:0007829|PDB:7SCS"
FT   HELIX           79..90
FT                   /evidence="ECO:0007829|PDB:7SCS"
SQ   SEQUENCE   97 AA;  10732 MW;  B433C30FDA4C71A7 CRC64;
     MKVSAALLWL LLIAAAFSPQ GLAGPASVPT TCCFNLANRK IPLQRLESYR RITSGKCPQK
     AVIFKTKLAK DICADPKKKW VQDSMKYLDQ KSPTPKP
//