ID   CCL25_HUMAN             Reviewed;         150 AA.
AC   O15444; A1L4J4; A6NI52; A8K9E7; B5MCA5; Q96KJ7;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   22-JUL-2008, sequence version 2.
DT   27-MAR-2024, entry version 175.
DE   RecName: Full=C-C motif chemokine 25;
DE   AltName: Full=Chemokine TECK;
DE   AltName: Full=Small-inducible cytokine A25;
DE   AltName: Full=Thymus-expressed chemokine;
DE   Flags: Precursor;
GN   Name=CCL25; Synonyms=SCYA25, TECK;
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] (ISOFORM 1), AND VARIANT MET-104.
RC   TISSUE=Thymus;
RX   PubMed=9285413; DOI=10.1016/s1074-7613(00)80531-2;
RA   Vicari A.P., Figueroa D.J., Hedrick J.A., Foster J.S., Singh K.P.,
RA   Menon S., Copeland N.G., Gilbert D.J., Jenkins N.A., Bacon K.B.,
RA   Zlotnik A.;
RT   "TECK: a novel CC chemokine specifically expressed by thymic dendritic
RT   cells and potentially involved in T cell development.";
RL   Immunity 7:291-301(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   TISSUE=Thymus;
RA   Hieshima K., Nakayama T., Fujisawa R., Izawa D., Yoshie O.;
RT   "Molecular cloning and characterization of a splicing variant of chemokine
RT   TECK: a natural antagonist of human TECK.";
RL   Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Thymus;
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 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
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   [7]
RP   RECEPTOR INTERACTION.
RX   PubMed=10229797;
RA   Zaballos A., Gutierrez J., Varona R., Ardavin C., Marquez G.;
RT   "Identification of the orphan chemokine receptor GPR-9-6 as CCR9, the
RT   receptor for the chemokine TECK.";
RL   J. Immunol. 162:5671-5675(1999).
RN   [8]
RP   RECEPTOR INTERACTION.
RX   PubMed=23341447; DOI=10.1074/jbc.m112.406108;
RA   Watts A.O., Verkaar F., van der Lee M.M., Timmerman C.A., Kuijer M.,
RA   van Offenbeek J., van Lith L.H., Smit M.J., Leurs R., Zaman G.J.,
RA   Vischer H.F.;
RT   "Beta-arrestin recruitment and G protein signaling by the atypical human
RT   chemokine decoy receptor CCX-CKR.";
RL   J. Biol. Chem. 288:7169-7181(2013).
CC   -!- FUNCTION: Potentially involved in T-cell development. Recombinant
CC       protein shows chemotactic activity on thymocytes, macrophages, THP-1
CC       cells, and dendritics cells but is inactive on peripheral blood
CC       lymphocytes and neutrophils. Binds to CCR9. Isoform 2 is an antagonist
CC       of isoform 1. Binds to atypical chemokine receptor ACKR4 and mediates
CC       the recruitment of beta-arrestin (ARRB1/2) to ACKR4.
CC   -!- INTERACTION:
CC       O15444; Q92583: CCL17; NbExp=2; IntAct=EBI-7783341, EBI-16640146;
CC       O15444; P13501: CCL5; NbExp=2; IntAct=EBI-7783341, EBI-2848366;
CC       O15444; P48061: CXCL12; NbExp=2; IntAct=EBI-7783341, EBI-3913254;
CC       O15444; P02776: PF4; NbExp=3; IntAct=EBI-7783341, EBI-2565740;
CC       O15444; P10720: PF4V1; NbExp=2; IntAct=EBI-7783341, EBI-1223944;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=O15444-1; Sequence=Displayed;
CC       Name=2; Synonyms=TECKvar;
CC         IsoId=O15444-2; Sequence=VSP_001064;
CC       Name=3;
CC         IsoId=O15444-3; Sequence=VSP_043199;
CC   -!- TISSUE SPECIFICITY: Specifically expressed by thymic dendritic cells.
CC       High levels in thymus and small intestine.
CC   -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=CCL25 entry;
CC       URL="https://en.wikipedia.org/wiki/CCL25";
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DR   EMBL; U86358; AAB69981.1; -; mRNA.
DR   EMBL; AB046579; BAB62257.1; -; mRNA.
DR   EMBL; AK292662; BAF85351.1; -; mRNA.
DR   EMBL; AC008946; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471139; EAW68952.1; -; Genomic_DNA.
DR   EMBL; BC130561; AAI30562.1; -; mRNA.
DR   EMBL; BC144463; AAI44464.1; -; mRNA.
DR   CCDS; CCDS12194.1; -. [O15444-1]
DR   CCDS; CCDS56080.1; -. [O15444-3]
DR   RefSeq; NP_001188288.1; NM_001201359.1. [O15444-3]
DR   RefSeq; NP_005615.2; NM_005624.3. [O15444-1]
DR   RefSeq; XP_011526479.1; XM_011528177.2.
DR   RefSeq; XP_016882609.1; XM_017027120.1.
DR   RefSeq; XP_016882610.1; XM_017027121.1.
DR   RefSeq; XP_016882611.1; XM_017027122.1.
DR   AlphaFoldDB; O15444; -.
DR   SMR; O15444; -.
DR   BioGRID; 112273; 11.
DR   DIP; DIP-5883N; -.
DR   IntAct; O15444; 11.
DR   MINT; O15444; -.
DR   STRING; 9606.ENSP00000375086; -.
DR   iPTMnet; O15444; -.
DR   PhosphoSitePlus; O15444; -.
DR   BioMuta; CCL25; -.
DR   MassIVE; O15444; -.
DR   PaxDb; 9606-ENSP00000375086; -.
DR   PeptideAtlas; O15444; -.
DR   ProteomicsDB; 48672; -. [O15444-1]
DR   ProteomicsDB; 48673; -. [O15444-2]
DR   ProteomicsDB; 48674; -. [O15444-3]
DR   Antibodypedia; 24738; 439 antibodies from 30 providers.
DR   DNASU; 6370; -.
DR   Ensembl; ENST00000253451.9; ENSP00000253451.4; ENSG00000131142.14. [O15444-3]
DR   Ensembl; ENST00000315626.6; ENSP00000324756.6; ENSG00000131142.14. [O15444-1]
DR   Ensembl; ENST00000390669.7; ENSP00000375086.3; ENSG00000131142.14. [O15444-1]
DR   Ensembl; ENST00000680450.1; ENSP00000506202.1; ENSG00000131142.14. [O15444-3]
DR   Ensembl; ENST00000680506.1; ENSP00000505422.1; ENSG00000131142.14. [O15444-1]
DR   Ensembl; ENST00000680646.1; ENSP00000504875.1; ENSG00000131142.14. [O15444-1]
DR   Ensembl; ENST00000681526.1; ENSP00000505387.1; ENSG00000131142.14. [O15444-3]
DR   GeneID; 6370; -.
DR   KEGG; hsa:6370; -.
DR   MANE-Select; ENST00000315626.6; ENSP00000324756.6; NM_005624.4; NP_005615.2.
DR   UCSC; uc002mjc.5; human. [O15444-1]
DR   AGR; HGNC:10624; -.
DR   CTD; 6370; -.
DR   DisGeNET; 6370; -.
DR   GeneCards; CCL25; -.
DR   HGNC; HGNC:10624; CCL25.
DR   HPA; ENSG00000131142; Group enriched (intestine, lymphoid tissue).
DR   MIM; 602565; gene.
DR   neXtProt; NX_O15444; -.
DR   OpenTargets; ENSG00000131142; -.
DR   PharmGKB; PA35556; -.
DR   VEuPathDB; HostDB:ENSG00000131142; -.
DR   eggNOG; ENOG502S8D1; Eukaryota.
DR   GeneTree; ENSGT01100000263557; -.
DR   HOGENOM; CLU_113773_0_0_1; -.
DR   InParanoid; O15444; -.
DR   OMA; RAWAYRI; -.
DR   OrthoDB; 5355241at2759; -.
DR   PhylomeDB; O15444; -.
DR   TreeFam; TF353160; -.
DR   PathwayCommons; O15444; -.
DR   Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   SignaLink; O15444; -.
DR   SIGNOR; O15444; -.
DR   BioGRID-ORCS; 6370; 11 hits in 1141 CRISPR screens.
DR   GenomeRNAi; 6370; -.
DR   Pharos; O15444; Tbio.
DR   PRO; PR:O15444; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; O15444; Protein.
DR   Bgee; ENSG00000131142; Expressed in duodenum and 76 other cell types or tissues.
DR   ExpressionAtlas; O15444; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0048020; F:CCR chemokine receptor binding; IBA:GO_Central.
DR   GO; GO:0031735; F:CCR10 chemokine receptor binding; IDA:BHF-UCL.
DR   GO; GO:0008009; F:chemokine activity; IDA:UniProtKB.
DR   GO; GO:0042379; F:chemokine receptor binding; IDA:UniProtKB.
DR   GO; GO:0005179; F:hormone activity; TAS:ProtInc.
DR   GO; GO:0060326; P:cell chemotaxis; IDA:UniProtKB.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0071347; P:cellular response to interleukin-1; IBA:GO_Central.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IBA:GO_Central.
DR   GO; GO:0071346; P:cellular response to type II interferon; IBA:GO_Central.
DR   GO; GO:0070098; P:chemokine-mediated signaling pathway; IBA:GO_Central.
DR   GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR   GO; GO:0048245; P:eosinophil chemotaxis; IBA:GO_Central.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0006955; P:immune response; TAS:ProtInc.
DR   GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR   GO; GO:0048247; P:lymphocyte chemotaxis; IBA:GO_Central.
DR   GO; GO:0002548; P:monocyte chemotaxis; IBA:GO_Central.
DR   GO; GO:1903237; P:negative regulation of leukocyte tethering or rolling; IDA:UniProtKB.
DR   GO; GO:0030593; P:neutrophil chemotaxis; IBA:GO_Central.
DR   GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IDA:UniProtKB.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR   CDD; cd01119; Chemokine_CC_DCCL; 1.
DR   Gene3D; 2.40.50.40; -; 1.
DR   InterPro; IPR039809; Chemokine_b/g/d.
DR   InterPro; IPR034133; Chemokine_CC_DCCL.
DR   InterPro; IPR001811; Chemokine_IL8-like_dom.
DR   InterPro; IPR036048; Interleukin_8-like_sf.
DR   PANTHER; PTHR12015:SF70; C-C MOTIF CHEMOKINE 25; 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   Genevisible; O15444; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Chemotaxis; Cytokine; Disulfide bond;
KW   Inflammatory response; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..150
FT                   /note="C-C motif chemokine 25"
FT                   /id="PRO_0000005235"
FT   DISULFID        30..58
FT                   /evidence="ECO:0000250"
FT   DISULFID        31..75
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         65..150
FT                   /note="FYLPKRHRKVCGNPKSREVQRAMKLLDARNKVFAKLHHNTQTFQAGPHAVKK
FT                   LSSGNSKLSSSKFSNPISSSKRNVSLLISANSGL -> RPSCCKEVEFWKLQVIIIQV
FT                   (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_001064"
FT   VAR_SEQ         109
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039,
FT                   ECO:0000303|PubMed:15489334"
FT                   /id="VSP_043199"
FT   VARIANT         23
FT                   /note="T -> A (in dbSNP:rs960173)"
FT                   /id="VAR_044519"
FT   VARIANT         101
FT                   /note="H -> R (in dbSNP:rs2032887)"
FT                   /id="VAR_044520"
FT   VARIANT         104
FT                   /note="T -> M (in dbSNP:rs1129763)"
FT                   /evidence="ECO:0000269|PubMed:9285413"
FT                   /id="VAR_044521"
SQ   SEQUENCE   150 AA;  16609 MW;  91D0810F137FBC7B CRC64;
     MNLWLLACLV AGFLGAWAPA VHTQGVFEDC CLAYHYPIGW AVLRRAWTYR IQEVSGSCNL
     PAAIFYLPKR HRKVCGNPKS REVQRAMKLL DARNKVFAKL HHNTQTFQAG PHAVKKLSSG
     NSKLSSSKFS NPISSSKRNV SLLISANSGL
//