CXCL6_HUMAN
ID CXCL6_HUMAN Reviewed; 114 AA.
AC P80162; B2R4X3; Q4W5D4;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 4.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=C-X-C motif chemokine 6;
DE AltName: Full=Chemokine alpha 3;
DE Short=CKA-3;
DE AltName: Full=Granulocyte chemotactic protein 2;
DE Short=GCP-2;
DE AltName: Full=Small-inducible cytokine B6;
DE Contains:
DE RecName: Full=Small-inducible cytokine B6, N-processed variant 1;
DE Contains:
DE RecName: Full=Small-inducible cytokine B6, N-processed variant 2;
DE Contains:
DE RecName: Full=Small-inducible cytokine B6, N-processed variant 3;
DE Flags: Precursor;
GN Name=CXCL6; Synonyms=GCP2, SCYB6;
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 [GENOMIC DNA].
RX PubMed=9164944;
RA Rovai L.E., Herschman H.R., Smith J.B.;
RT "Cloning and characterization of the human granulocyte chemotactic protein-
RT 2 gene.";
RL J. Immunol. 158:5257-5266(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Ni J., Su J., Li H.;
RT "Cloning, sequencing and biological characterization of a C-X-C chemokine,
RT CKA-3.";
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 38-114, AND FUNCTION.
RX PubMed=9057843; DOI=10.1111/j.1432-1033.1997.00762.x;
RA Froyen G., Proost P., Ronsse I., Mitera T., Haelens A., Wuyts A.,
RA Opdenakker G., van Damme J., Billiau A.;
RT "Cloning, bacterial expression and biological characterization of
RT recombinant human granulocyte chemotactic protein-2 and differential
RT expression of granulocyte chemotactic protein-2 and epithelial cell-derived
RT neutrophil activating peptide-78 mRNAs.";
RL Eur. J. Biochem. 243:762-769(1997).
RN [7]
RP PROTEIN SEQUENCE OF 38-112, FUNCTION, AND PROTEOLYTIC PROCESSING OF
RP N-TERMINAL.
RC TISSUE=Osteosarcoma;
RX PubMed=8399143; DOI=10.1021/bi00089a037;
RA Proost P., Wuyts A., Conings R., Lenaerts J.-P., Billiau A., Opdenakker G.,
RA van Damme J.;
RT "Human and bovine granulocyte chemotactic protein-2: complete amino acid
RT sequence and functional characterization as chemokines.";
RL Biochemistry 32:10170-10177(1993).
RN [8]
RP PROTEIN SEQUENCE OF 38-57, AND FUNCTION.
RC TISSUE=Osteosarcoma;
RX PubMed=8423327;
RA Proost P., de Wolf-Peeters C., Conings R., Opdenakker G., Billiau A.,
RA van Damme J.;
RT "Identification of a novel granulocyte chemotactic protein (GCP-2) from
RT human tumor cells. In vitro and in vivo comparison with natural forms of
RT GRO, IP-10, and IL-8.";
RL J. Immunol. 150:1000-1010(1993).
RN [9]
RP FUNCTION.
RX PubMed=18443119; DOI=10.1128/aac.00028-08;
RA Linge H.M., Collin M., Nordenfelt P., Morgelin M., Malmsten M., Egesten A.;
RT "The human CXC chemokine granulocyte chemotactic protein 2 (GCP-2)/CXCL6
RT possesses membrane-disrupting properties and is antibacterial.";
RL Antimicrob. Agents Chemother. 52:2599-2607(2008).
CC -!- FUNCTION: Chemotactic for neutrophil granulocytes. Signals through
CC binding and activation of its receptors (CXCR1 and CXCR2). In addition
CC to its chemotactic and angiogenic properties, it has strong
CC antibacterial activity against Gram-positive and Gram-negative bacteria
CC (90-fold-higher when compared to CXCL5 and CXCL7).
CC {ECO:0000269|PubMed:18443119, ECO:0000269|PubMed:8399143,
CC ECO:0000269|PubMed:8423327, ECO:0000269|PubMed:9057843}.
CC -!- INTERACTION:
CC P80162; P13501: CCL5; NbExp=2; IntAct=EBI-9214033, EBI-2848366;
CC P80162; P48061: CXCL12; NbExp=2; IntAct=EBI-9214033, EBI-3913254;
CC P80162; P02776: PF4; NbExp=2; IntAct=EBI-9214033, EBI-2565740;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the intercrine alpha (chemokine CxC) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CXCL6 entry;
CC URL="https://en.wikipedia.org/wiki/CXCL6";
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DR EMBL; U83303; AAC51338.1; -; Genomic_DNA.
DR EMBL; U81234; AAD00506.1; -; mRNA.
DR EMBL; AK311981; BAG34920.1; -; mRNA.
DR EMBL; AC108029; AAY40939.1; -; Genomic_DNA.
DR EMBL; BC013744; AAH13744.1; -; mRNA.
DR EMBL; Y08770; CAA70023.1; -; mRNA.
DR CCDS; CCDS3560.1; -.
DR PIR; A54188; A54188.
DR RefSeq; NP_002984.1; NM_002993.3.
DR AlphaFoldDB; P80162; -.
DR SMR; P80162; -.
DR BioGRID; 112274; 34.
DR IntAct; P80162; 12.
DR MINT; P80162; -.
DR STRING; 9606.ENSP00000226317; -.
DR iPTMnet; P80162; -.
DR PhosphoSitePlus; P80162; -.
DR BioMuta; CXCL6; -.
DR DMDM; 2851486; -.
DR MassIVE; P80162; -.
DR MaxQB; P80162; -.
DR PaxDb; P80162; -.
DR PeptideAtlas; P80162; -.
DR PRIDE; P80162; -.
DR ProteomicsDB; 57668; -.
DR Antibodypedia; 13323; 277 antibodies from 22 providers.
DR DNASU; 6372; -.
DR Ensembl; ENST00000226317.10; ENSP00000226317.5; ENSG00000124875.10.
DR GeneID; 6372; -.
DR KEGG; hsa:6372; -.
DR MANE-Select; ENST00000226317.10; ENSP00000226317.5; NM_002993.4; NP_002984.1.
DR UCSC; uc003hhf.4; human.
DR CTD; 6372; -.
DR DisGeNET; 6372; -.
DR GeneCards; CXCL6; -.
DR HGNC; HGNC:10643; CXCL6.
DR HPA; ENSG00000124875; Group enriched (gallbladder, lymphoid tissue, urinary bladder).
DR MIM; 138965; gene.
DR neXtProt; NX_P80162; -.
DR OpenTargets; ENSG00000124875; -.
DR PharmGKB; PA35574; -.
DR VEuPathDB; HostDB:ENSG00000124875; -.
DR eggNOG; ENOG502S7MM; Eukaryota.
DR GeneTree; ENSGT00940000162749; -.
DR InParanoid; P80162; -.
DR OMA; KELRCTC; -.
DR OrthoDB; 1556509at2759; -.
DR PhylomeDB; P80162; -.
DR TreeFam; TF333433; -.
DR PathwayCommons; P80162; -.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P80162; -.
DR BioGRID-ORCS; 6372; 7 hits in 1057 CRISPR screens.
DR ChiTaRS; CXCL6; human.
DR GenomeRNAi; 6372; -.
DR Pharos; P80162; Tbio.
DR PRO; PR:P80162; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P80162; protein.
DR Bgee; ENSG00000124875; Expressed in bronchial epithelial cell and 126 other tissues.
DR ExpressionAtlas; P80162; baseline and differential.
DR Genevisible; P80162; 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; IEA:UniProtKB-KW.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0001776; P:leukocyte homeostasis; IEA:Ensembl.
DR GO; GO:0042119; P:neutrophil activation; IDA:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; IDA:UniProtKB.
DR GO; GO:0032642; P:regulation of chemokine production; IEA:Ensembl.
DR GO; GO:0070951; P:regulation of neutrophil mediated killing of gram-negative bacterium; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd00273; Chemokine_CXC; 1.
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; PTHR10179; PTHR10179; 1.
DR Pfam; PF00048; IL8; 1.
DR PRINTS; PR00437; SMALLCYTKCXC.
DR SMART; SM00199; SCY; 1.
DR SUPFAM; SSF54117; SSF54117; 1.
DR PROSITE; PS00471; SMALL_CYTOKINES_CXC; 1.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Chemotaxis; Cytokine; Direct protein sequencing;
KW Disulfide bond; Heparin-binding; Reference proteome; Secreted; Signal.
FT SIGNAL 1..37
FT /evidence="ECO:0000269|PubMed:8399143,
FT ECO:0000269|PubMed:8423327"
FT CHAIN 38..114
FT /note="C-X-C motif chemokine 6"
FT /id="PRO_0000005084"
FT CHAIN 40..114
FT /note="Small-inducible cytokine B6, N-processed variant 1"
FT /id="PRO_0000005085"
FT CHAIN 43..114
FT /note="Small-inducible cytokine B6, N-processed variant 2"
FT /id="PRO_0000005086"
FT CHAIN 46..114
FT /note="Small-inducible cytokine B6, N-processed variant 3"
FT /id="PRO_0000005087"
FT DISULFID 49..75
FT /evidence="ECO:0000250"
FT DISULFID 51..91
FT /evidence="ECO:0000250"
SQ SEQUENCE 114 AA; 11897 MW; 5A58B38C17F25178 CRC64;
MSLPSSRAAR VPGPSGSLCA LLALLLLLTP PGPLASAGPV SAVLTELRCT CLRVTLRVNP
KTIGKLQVFP AGPQCSKVEV VASLKNGKQV CLDPEAPFLK KVIQKILDSG NKKN
