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C-X-C motif chemokine 17 (6-Cys CXCL17) (Dendritic cell and monocyte chemokine-like protein) (DMC) (VEGF coregulated chemokine 1) [Cleaved into: 4-Cys CXCL17]

 CXL17_HUMAN             Reviewed;         119 AA.
Q6UXB2; A8KAC0;
13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
05-JUL-2004, sequence version 1.
22-NOV-2017, entry version 96.
RecName: Full=C-X-C motif chemokine 17;
Short=6-Cys CXCL17 {ECO:0000303|PubMed:23115081};
AltName: Full=Dendritic cell and monocyte chemokine-like protein;
Short=DMC;
AltName: Full=VEGF coregulated chemokine 1;
Contains:
RecName: Full=4-Cys CXCL17 {ECO:0000303|PubMed:23115081};
Flags: Precursor;
Name=CXCL17; Synonyms=VCC1; ORFNames=UNQ473/PRO842;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
TISSUE=Colon cancer, and Lung;
PubMed=16989774; DOI=10.1016/j.bbrc.2006.08.194;
Weinstein E.J., Head R., Griggs D.W., Sun D., Evans R.J.,
Swearingen M.L., Westlin M.M., Mazzarella R.;
"VCC-1, a novel chemokine, promotes tumor growth.";
Biochem. Biophys. Res. Commun. 350:74-81(2006).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=12975309; DOI=10.1101/gr.1293003;
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
Wood W.I., Godowski P.J., Gray A.M.;
"The secreted protein discovery initiative (SPDI), a large-scale
effort to identify novel human secreted and transmembrane proteins: a
bioinformatics assessment.";
Genome Res. 13:2265-2270(2003).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Trachea;
PubMed=14702039; DOI=10.1038/ng1285;
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.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15057824; DOI=10.1038/nature02399;
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
Rubin E.M., Lucas S.M.;
"The DNA sequence and biology of human chromosome 19.";
Nature 428:529-535(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Heart, and Lung;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
PROTEIN SEQUENCE OF 22-37.
PubMed=15340161; DOI=10.1110/ps.04682504;
Zhang Z., Henzel W.J.;
"Signal peptide prediction based on analysis of experimentally
verified cleavage sites.";
Protein Sci. 13:2819-2824(2004).
[7]
PROTEIN SEQUENCE OF 23-61 AND 97-112, AND IDENTIFICATION BY MASS
SPECTROMETRY.
TISSUE=Tear;
PubMed=25946035; DOI=10.1021/acs.jproteome.5b00179;
Azkargorta M., Soria J., Ojeda C., Guzman F., Acera A., Iloro I.,
Suarez T., Elortza F.;
"Human basal tear peptidome characterization by CID, HCD, and ETD
followed by in silico and in vitro analyses for antimicrobial peptide
identification.";
J. Proteome Res. 14:2649-2658(2015).
[8]
FUNCTION, TISSUE SPECIFICITY, CIRCULAR DICHROISM, 3D-STRUCTURE
MODELING, DISULFIDE BONDS, AND MUTAGENESIS OF CYS-50; CYS-52; CYS-75;
CYS-77; CYS-103 AND CYS-110.
PubMed=16455961; DOI=10.4049/jimmunol.176.4.2069;
Pisabarro M.T., Leung B., Kwong M., Corpuz R., Frantz G.D., Chiang N.,
Vandlen R., Diehl L.J., Skelton N., Kim H.S., Eaton D., Schmidt K.N.;
"Novel human dendritic cell- and monocyte-attracting chemokine-like
protein identified by fold recognition methods.";
J. Immunol. 176:2069-2073(2006).
[9]
FUNCTION, AND INDUCTION.
PubMed=17307946; DOI=10.1128/IAI.01900-06;
Flach C.F., Qadri F., Bhuiyan T.R., Alam N.H., Jennische E.,
Lonnroth I., Holmgren J.;
"Broad up-regulation of innate defense factors during acute cholera.";
Infect. Immun. 75:2343-2350(2007).
[10]
SUBCELLULAR LOCATION, AND FUNCTION (6-CYS CXCL17 AND 4-CYS CXCL17).
PubMed=23115081; DOI=10.1152/ajpendo.00083.2012;
Lee W.Y., Wang C.J., Lin T.Y., Hsiao C.L., Luo C.W.;
"CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-
inflammatory factor.";
Am. J. Physiol. 304:E32-E40(2013).
[11]
INTERACTION WITH GPR35.
PubMed=25411203; DOI=10.4049/jimmunol.1401704;
Maravillas-Montero J.L., Burkhardt A.M., Hevezi P.A., Carnevale C.D.,
Smit M.J., Zlotnik A.;
"GPR35/CXCR8 is the receptor of the mucosal chemokine CXCL17.";
J. Immunol. 194:29-33(2015).
-!- FUNCTION: Chemokine that acts as chemoattractant for monocytes,
macrophages and dendritic cells (PubMed:16455961,
PubMed:23115081). Plays a role in angiogenesis and possibly in the
development of tumors (PubMed:16989774, PubMed:23115081). Acts as
an anti-inflammatory in the stomach (PubMed:23115081). May play a
role in the innate defense against infections (PubMed:17307946).
Activates the C-X-C chemokine receptor GPR35 to induce a rapid and
transient rise in the level of intracellular calcium ions
(PubMed:25411203). {ECO:0000269|PubMed:16455961,
ECO:0000269|PubMed:16989774, ECO:0000269|PubMed:17307946,
ECO:0000269|PubMed:23115081, ECO:0000269|PubMed:25411203}.
-!- FUNCTION: 4-Cys CXCL17: seems exhibit much higher chemoattractant
potency on monocytes and macrophages than 6-Cys CXCL17.
{ECO:0000269|PubMed:23115081}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23115081}.
-!- TISSUE SPECIFICITY: Detected in trachea, stomach, lung and
skeletal muscle. Detected in intestine and in normal and asthmatic
lung (at protein level). Breast tumors showed 3- to 24-fold up-
regulation. {ECO:0000269|PubMed:16455961,
ECO:0000269|PubMed:16989774}.
-!- DEVELOPMENTAL STAGE: Detected in fetal lung.
-!- INDUCTION: Found to be up-regulated in duodenal mucosa during
acute cholera. {ECO:0000269|PubMed:17307946}.
-!- PTM: Likely to undergo an endoproteolytic process to form a four-
cysteine-containing mature peptide with a canonical CXC chemokine
scaffold after secretion. {ECO:0000250|UniProtKB:D4A875}.
-!- SIMILARITY: Belongs to the intercrine alpha (chemokine CxC)
family. {ECO:0000305}.
-!- WEB RESOURCE: Name=Wikipedia; Note=CXCL17 entry;
URL="https://en.wikipedia.org/wiki/CXCL17";
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; AY598464; AAU04875.1; -; mRNA.
EMBL; AY358433; AAQ88799.1; -; mRNA.
EMBL; AK292985; BAF85674.1; -; mRNA.
EMBL; AC011497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC093946; AAH93946.1; -; mRNA.
EMBL; BC112095; AAI12096.1; -; mRNA.
CCDS; CCDS12608.1; -.
RefSeq; NP_940879.1; NM_198477.2.
UniGene; Hs.445586; -.
ProteinModelPortal; Q6UXB2; -.
STRING; 9606.ENSP00000472467; -.
BioMuta; CXCL17; -.
DMDM; 74738198; -.
PaxDb; Q6UXB2; -.
PeptideAtlas; Q6UXB2; -.
PRIDE; Q6UXB2; -.
Ensembl; ENST00000601181; ENSP00000472467; ENSG00000189377.
GeneID; 284340; -.
KEGG; hsa:284340; -.
UCSC; uc002otu.4; human.
CTD; 284340; -.
DisGeNET; 284340; -.
EuPathDB; HostDB:ENSG00000189377.8; -.
GeneCards; CXCL17; -.
HGNC; HGNC:19232; CXCL17.
MIM; 611387; gene.
neXtProt; NX_Q6UXB2; -.
OpenTargets; ENSG00000189377; -.
PharmGKB; PA162383045; -.
eggNOG; ENOG410J1ND; Eukaryota.
eggNOG; ENOG41118M3; LUCA.
GeneTree; ENSGT00390000002861; -.
HOGENOM; HOG000154812; -.
HOVERGEN; HBG097374; -.
InParanoid; Q6UXB2; -.
OMA; KRCQLAS; -.
OrthoDB; EOG091G0Y5M; -.
PhylomeDB; Q6UXB2; -.
TreeFam; TF342477; -.
GenomeRNAi; 284340; -.
PRO; PR:Q6UXB2; -.
Proteomes; UP000005640; Chromosome 19.
Bgee; ENSG00000189377; -.
CleanEx; HS_CXCL17; -.
ExpressionAtlas; Q6UXB2; baseline and differential.
Genevisible; Q6UXB2; HS.
GO; GO:0005615; C:extracellular space; IMP:UniProtKB.
GO; GO:0000187; P:activation of MAPK activity; IMP:UniProtKB.
GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
GO; GO:0050728; P:negative regulation of inflammatory response; IMP:UniProtKB.
GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IMP:UniProtKB.
GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IMP:UniProtKB.
GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IMP:UniProtKB.
InterPro; IPR029183; CXCL17.
PANTHER; PTHR37351; PTHR37351; 1.
Pfam; PF15211; CXCL17; 1.
1: Evidence at protein level;
Angiogenesis; Chemotaxis; Cleavage on pair of basic residues;
Complete proteome; Developmental protein; Differentiation;
Direct protein sequencing; Disulfide bond; Reference proteome;
Secreted; Signal.
SIGNAL 1 21 {ECO:0000269|PubMed:15340161}.
CHAIN 22 119 C-X-C motif chemokine 17.
/FTId=PRO_0000311097.
CHAIN 64 119 4-Cys CXCL17. {ECO:0000305}.
/FTId=PRO_0000438487.
SITE 63 64 Cleavage. {ECO:0000250|UniProtKB:D4A875}.
DISULFID 75 103 {ECO:0000305|PubMed:23115081}.
DISULFID 77 110 {ECO:0000305|PubMed:23115081}.
MUTAGEN 50 50 C->S: Inhibits migration of nonactivated
dendritic cells and monocytes; when
associated with S-52; S-75; S-77; S-103
and S-110. {ECO:0000269|PubMed:16455961}.
MUTAGEN 52 52 C->S: Inhibits migration of nonactivated
dendritic cells and monocytes; when
associated with S-50; S-75; S-77; S-103
and S-110. {ECO:0000269|PubMed:16455961}.
MUTAGEN 75 75 C->S: Inhibits migration of nonactivated
dendritic cells and monocytes; when
associated with S-50; S-52; S-77; S-103
and S-110. {ECO:0000269|PubMed:16455961}.
MUTAGEN 77 77 C->S: Inhibits migration of nonactivated
dendritic cells and monocytes; when
associated with S-50; S-52; S-75; S-103
and S-110. {ECO:0000269|PubMed:16455961}.
MUTAGEN 103 103 C->S: Inhibits migration of nonactivated
dendritic cells and monocytes; when
associated with S-50; S-52; S-75; S-77
and S-110. {ECO:0000269|PubMed:16455961}.
MUTAGEN 110 110 C->S: Inhibits migration of nonactivated
dendritic cells and monocytes; when
associated with S-50; S-52; S-75; S-77
and S-103. {ECO:0000269|PubMed:16455961}.
SEQUENCE 119 AA; 13819 MW; F2D2FD686E47CC9B CRC64;
MKVLISSLLL LLPLMLMSMV SSSLNPGVAR GHRDRGQASR RWLQEGGQEC ECKDWFLRAP
RRKFMTVSGL PKKQCPCDHF KGNVKKTRHQ RHHRKPNKHS RACQQFLKQC QLRSFALPL


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