CXL17_HUMAN
ID CXL17_HUMAN Reviewed; 119 AA.
AC Q6UXB2; A8KAC0;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=C-X-C motif chemokine 17;
DE Short=6-Cys CXCL17 {ECO:0000303|PubMed:23115081};
DE AltName: Full=Dendritic cell and monocyte chemokine-like protein;
DE Short=DMC;
DE AltName: Full=VEGF coregulated chemokine 1;
DE Contains:
DE RecName: Full=4-Cys CXCL17 {ECO:0000303|PubMed:23115081};
DE Flags: Precursor;
GN Name=CXCL17; Synonyms=VCC1; ORFNames=UNQ473/PRO842;
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, AND TISSUE SPECIFICITY.
RC TISSUE=Colon cancer, and Lung;
RX PubMed=16989774; DOI=10.1016/j.bbrc.2006.08.194;
RA Weinstein E.J., Head R., Griggs D.W., Sun D., Evans R.J., Swearingen M.L.,
RA Westlin M.M., Mazzarella R.;
RT "VCC-1, a novel chemokine, promotes tumor growth.";
RL Biochem. Biophys. Res. Commun. 350:74-81(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Trachea;
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=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart, and 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 [6]
RP PROTEIN SEQUENCE OF 22-37.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [7]
RP PROTEIN SEQUENCE OF 23-61 AND 97-112, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Tear;
RX PubMed=25946035; DOI=10.1021/acs.jproteome.5b00179;
RA Azkargorta M., Soria J., Ojeda C., Guzman F., Acera A., Iloro I.,
RA Suarez T., Elortza F.;
RT "Human basal tear peptidome characterization by CID, HCD, and ETD followed
RT by in silico and in vitro analyses for antimicrobial peptide
RT identification.";
RL J. Proteome Res. 14:2649-2658(2015).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, CIRCULAR DICHROISM, 3D-STRUCTURE MODELING,
RP DISULFIDE BONDS, AND MUTAGENESIS OF CYS-50; CYS-52; CYS-75; CYS-77; CYS-103
RP AND CYS-110.
RX PubMed=16455961; DOI=10.4049/jimmunol.176.4.2069;
RA Pisabarro M.T., Leung B., Kwong M., Corpuz R., Frantz G.D., Chiang N.,
RA Vandlen R., Diehl L.J., Skelton N., Kim H.S., Eaton D., Schmidt K.N.;
RT "Novel human dendritic cell- and monocyte-attracting chemokine-like protein
RT identified by fold recognition methods.";
RL J. Immunol. 176:2069-2073(2006).
RN [9]
RP FUNCTION, AND INDUCTION.
RX PubMed=17307946; DOI=10.1128/iai.01900-06;
RA Flach C.F., Qadri F., Bhuiyan T.R., Alam N.H., Jennische E., Lonnroth I.,
RA Holmgren J.;
RT "Broad up-regulation of innate defense factors during acute cholera.";
RL Infect. Immun. 75:2343-2350(2007).
RN [10]
RP SUBCELLULAR LOCATION, AND FUNCTION (6-CYS CXCL17 AND 4-CYS CXCL17).
RX PubMed=23115081; DOI=10.1152/ajpendo.00083.2012;
RA Lee W.Y., Wang C.J., Lin T.Y., Hsiao C.L., Luo C.W.;
RT "CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-
RT inflammatory factor.";
RL Am. J. Physiol. 304:E32-E40(2013).
RN [11]
RP INTERACTION WITH GPR35.
RX PubMed=25411203; DOI=10.4049/jimmunol.1401704;
RA Maravillas-Montero J.L., Burkhardt A.M., Hevezi P.A., Carnevale C.D.,
RA Smit M.J., Zlotnik A.;
RT "GPR35/CXCR8 is the receptor of the mucosal chemokine CXCL17.";
RL J. Immunol. 194:29-33(2015).
CC -!- FUNCTION: Chemokine that acts as chemoattractant for monocytes,
CC macrophages and dendritic cells (PubMed:16455961, PubMed:23115081).
CC Plays a role in angiogenesis and possibly in the development of tumors
CC (PubMed:16989774, PubMed:23115081). Acts as an anti-inflammatory in the
CC stomach (PubMed:23115081). May play a role in the innate defense
CC against infections (PubMed:17307946). Activates the C-X-C chemokine
CC receptor GPR35 to induce a rapid and transient rise in the level of
CC intracellular calcium ions (PubMed:25411203).
CC {ECO:0000269|PubMed:16455961, ECO:0000269|PubMed:16989774,
CC ECO:0000269|PubMed:17307946, ECO:0000269|PubMed:23115081,
CC ECO:0000269|PubMed:25411203}.
CC -!- FUNCTION: [4-Cys CXCL17]: Seems to exhibit much higher chemoattractant
CC potency on monocytes and macrophages than 6-Cys CXCL17.
CC {ECO:0000269|PubMed:23115081}.
CC -!- INTERACTION:
CC Q6UXB2; P13501: CCL5; NbExp=2; IntAct=EBI-16804198, EBI-2848366;
CC Q6UXB2; P48061: CXCL12; NbExp=2; IntAct=EBI-16804198, EBI-3913254;
CC Q6UXB2; P02776: PF4; NbExp=2; IntAct=EBI-16804198, EBI-2565740;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23115081}.
CC -!- TISSUE SPECIFICITY: Detected in trachea, stomach, lung and skeletal
CC muscle. Detected in intestine and in normal and asthmatic lung (at
CC protein level). Breast tumors showed 3- to 24-fold up-regulation.
CC {ECO:0000269|PubMed:16455961, ECO:0000269|PubMed:16989774}.
CC -!- DEVELOPMENTAL STAGE: Detected in fetal lung.
CC -!- INDUCTION: Found to be up-regulated in duodenal mucosa during acute
CC cholera. {ECO:0000269|PubMed:17307946}.
CC -!- PTM: Likely to undergo an endoproteolytic process to form a four-
CC cysteine-containing mature peptide with a canonical CXC chemokine
CC scaffold after secretion. {ECO:0000250|UniProtKB:D4A875}.
CC -!- SIMILARITY: Belongs to the intercrine alpha (chemokine CxC) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CXCL17 entry;
CC URL="https://en.wikipedia.org/wiki/CXCL17";
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DR EMBL; AY598464; AAU04875.1; -; mRNA.
DR EMBL; AY358433; AAQ88799.1; -; mRNA.
DR EMBL; AK292985; BAF85674.1; -; mRNA.
DR EMBL; AC011497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC093946; AAH93946.1; -; mRNA.
DR EMBL; BC112095; AAI12096.1; -; mRNA.
DR CCDS; CCDS12608.1; -.
DR RefSeq; NP_940879.1; NM_198477.2.
DR AlphaFoldDB; Q6UXB2; -.
DR BioGRID; 129832; 17.
DR IntAct; Q6UXB2; 17.
DR STRING; 9606.ENSP00000472467; -.
DR BioMuta; CXCL17; -.
DR DMDM; 74738198; -.
DR MassIVE; Q6UXB2; -.
DR PaxDb; Q6UXB2; -.
DR PeptideAtlas; Q6UXB2; -.
DR PRIDE; Q6UXB2; -.
DR ProteomicsDB; 67583; -.
DR Antibodypedia; 66724; 97 antibodies from 18 providers.
DR DNASU; 284340; -.
DR Ensembl; ENST00000601181.6; ENSP00000472467.1; ENSG00000189377.9.
DR GeneID; 284340; -.
DR KEGG; hsa:284340; -.
DR MANE-Select; ENST00000601181.6; ENSP00000472467.1; NM_198477.3; NP_940879.1.
DR UCSC; uc002otu.4; human.
DR CTD; 284340; -.
DR DisGeNET; 284340; -.
DR GeneCards; CXCL17; -.
DR HGNC; HGNC:19232; CXCL17.
DR HPA; ENSG00000189377; Group enriched (esophagus, lung, salivary gland, stomach).
DR MIM; 611387; gene.
DR neXtProt; NX_Q6UXB2; -.
DR OpenTargets; ENSG00000189377; -.
DR PharmGKB; PA162383045; -.
DR VEuPathDB; HostDB:ENSG00000189377; -.
DR eggNOG; ENOG502TDC2; Eukaryota.
DR GeneTree; ENSGT00390000002861; -.
DR HOGENOM; CLU_166962_0_0_1; -.
DR InParanoid; Q6UXB2; -.
DR OMA; KRCQLAS; -.
DR OrthoDB; 1577529at2759; -.
DR PhylomeDB; Q6UXB2; -.
DR TreeFam; TF342477; -.
DR PathwayCommons; Q6UXB2; -.
DR SignaLink; Q6UXB2; -.
DR BioGRID-ORCS; 284340; 21 hits in 1064 CRISPR screens.
DR GenomeRNAi; 284340; -.
DR Pharos; Q6UXB2; Tbio.
DR PRO; PR:Q6UXB2; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q6UXB2; protein.
DR Bgee; ENSG00000189377; Expressed in nasal cavity epithelium and 140 other tissues.
DR ExpressionAtlas; Q6UXB2; baseline and differential.
DR Genevisible; Q6UXB2; HS.
DR GO; GO:0005615; C:extracellular space; IMP:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0048246; P:macrophage chemotaxis; IBA:GO_Central.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:GO_Central.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IMP:UniProtKB.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IMP:UniProtKB.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IMP:UniProtKB.
DR InterPro; IPR029183; CXCL17.
DR PANTHER; PTHR37351; PTHR37351; 1.
DR Pfam; PF15211; CXCL17; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Chemotaxis; Cleavage on pair of basic residues;
KW Developmental protein; Differentiation; Direct protein sequencing;
KW Disulfide bond; Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 22..119
FT /note="C-X-C motif chemokine 17"
FT /id="PRO_0000311097"
FT CHAIN 64..119
FT /note="4-Cys CXCL17"
FT /evidence="ECO:0000305"
FT /id="PRO_0000438487"
FT REGION 81..100
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 84..100
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 63..64
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:D4A875"
FT DISULFID 75..103
FT /evidence="ECO:0000305|PubMed:23115081"
FT DISULFID 77..110
FT /evidence="ECO:0000305|PubMed:23115081"
FT MUTAGEN 50
FT /note="C->S: Inhibits migration of nonactivated dendritic
FT cells and monocytes; when associated with S-52; S-75; S-77;
FT S-103 and S-110."
FT /evidence="ECO:0000269|PubMed:16455961"
FT MUTAGEN 52
FT /note="C->S: Inhibits migration of nonactivated dendritic
FT cells and monocytes; when associated with S-50; S-75; S-77;
FT S-103 and S-110."
FT /evidence="ECO:0000269|PubMed:16455961"
FT MUTAGEN 75
FT /note="C->S: Inhibits migration of nonactivated dendritic
FT cells and monocytes; when associated with S-50; S-52; S-77;
FT S-103 and S-110."
FT /evidence="ECO:0000269|PubMed:16455961"
FT MUTAGEN 77
FT /note="C->S: Inhibits migration of nonactivated dendritic
FT cells and monocytes; when associated with S-50; S-52; S-75;
FT S-103 and S-110."
FT /evidence="ECO:0000269|PubMed:16455961"
FT MUTAGEN 103
FT /note="C->S: Inhibits migration of nonactivated dendritic
FT cells and monocytes; when associated with S-50; S-52; S-75;
FT S-77 and S-110."
FT /evidence="ECO:0000269|PubMed:16455961"
FT MUTAGEN 110
FT /note="C->S: Inhibits migration of nonactivated dendritic
FT cells and monocytes; when associated with S-50; S-52; S-75;
FT S-77 and S-103."
FT /evidence="ECO:0000269|PubMed:16455961"
SQ SEQUENCE 119 AA; 13819 MW; F2D2FD686E47CC9B CRC64;
MKVLISSLLL LLPLMLMSMV SSSLNPGVAR GHRDRGQASR RWLQEGGQEC ECKDWFLRAP
RRKFMTVSGL PKKQCPCDHF KGNVKKTRHQ RHHRKPNKHS RACQQFLKQC QLRSFALPL
