ID   CCL21_HUMAN             Reviewed;         134 AA.
AC   O00585;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1997, sequence version 1.
DT   11-NOV-2015, entry version 142.
DE   RecName: Full=C-C motif chemokine 21;
DE   AltName: Full=6Ckine;
DE   AltName: Full=Beta-chemokine exodus-2;
DE   AltName: Full=Secondary lymphoid-tissue chemokine;
DE            Short=SLC;
DE   AltName: Full=Small-inducible cytokine A21;
DE   Flags: Precursor;
GN   Name=CCL21; Synonyms=SCYA21; ORFNames=UNQ784/PRO1600;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9235955; DOI=10.1074/jbc.272.31.19518;
RA   Nagira M., Imai T., Hieshima K., Kusuda J., Ridanpaeae M., Takagi S.,
RA   Nishimura M., Kakizaki M., Nomiyama H., Yoshie O.;
RT   "Molecular cloning of a novel human CC chemokine secondary lymphoid-
RT   tissue chemokine that is a potent chemoattractant for lymphocytes and
RT   mapped to chromosome 9p13.";
RL   J. Biol. Chem. 272:19518-19524(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9257816;
RA   Hedrick J.A., Zlotnik A.;
RT   "Identification and characterization of a novel beta chemokine
RT   containing six conserved cysteines.";
RL   J. Immunol. 159:1589-1593(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 24-33.
RX   PubMed=9300671;
RA   Hromas R., Kim C.H., Klemsz M., Krathwohl M., Fife K., Cooper S.,
RA   Schnizlein-Bick C., Broxmeyer H.E.;
RT   "Isolation and characterization of Exodus-2, a novel C-C chemokine
RT   with a unique 37-amino acid carboxyl-terminal extension.";
RL   J. Immunol. 159:2554-2558(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RX   PubMed=9419363; DOI=10.1073/pnas.95.1.258;
RA   Gunn M.D., Tangemann K., Tam C., Cyster J.G., Rosen S.D.,
RA   Williams L.T.;
RT   "A chemokine expressed in lymphoid high endothelial venules promotes
RT   the adhesion and chemotaxis of naive T lymphocytes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:258-263(1998).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Reiterer P., Bernhardt G., Lipp M.;
RT   "Genomic organisation of human SLC.";
RL   Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN   [6]
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.,
RA   Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA   Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA   Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA   Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA   Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA   Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale
RT   effort to identify novel human secreted and transmembrane proteins: a
RT   bioinformatics assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pancreas, and Spleen;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   RECEPTOR INTERACTION.
RX   PubMed=9507024; DOI=10.1074/jbc.273.12.7118;
RA   Yoshida R., Nagira M., Kitaura M., Imagawa N., Imai T., Yoshie O.;
RT   "Secondary lymphoid-tissue chemokine is a functional ligand for the CC
RT   chemokine receptor CCR7.";
RL   J. Biol. Chem. 273:7118-7122(1998).
RN   [9]
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
RT   human chemokine decoy receptor CCX-CKR.";
RL   J. Biol. Chem. 288:7169-7181(2013).
RN   [10]
RP   STRUCTURE BY NMR OF 24-134, SUBUNIT, AND DISULFIDE BONDS.
RX   PubMed=22221265; DOI=10.1021/bi201601k;
RA   Love M., Sandberg J.L., Ziarek J.J., Gerarden K.P., Rode R.R.,
RA   Jensen D.R., McCaslin D.R., Peterson F.C., Veldkamp C.T.;
RT   "Solution structure of CCL21 and identification of a putative CCR7
RT   binding site.";
RL   Biochemistry 51:733-735(2012).
CC   -!- FUNCTION: Inhibits hemopoiesis and stimulates chemotaxis.
CC       Chemotactic in vitro for thymocytes and activated T-cells, but not
CC       for B-cells, macrophages, or neutrophils. Shows preferential
CC       activity towards naive T-cells. May play a role in mediating
CC       homing of lymphocytes to secondary lymphoid organs. Binds to
CC       atypical chemokine receptor ACKR4 and mediates the recruitment of
CC       beta-arrestin (ARRB1/2) to ACKR4.
CC   -!- SUBUNIT: Monomer. Binds to CCR7. {ECO:0000269|PubMed:22221265}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Highly expressed in high endothelial venules
CC       of lymph nodes, spleen and appendix. Intermediate levels found in
CC       small intestine, thyroid gland and trachea. Low level expression
CC       in thymus, bone marrow, liver, and pancreas. Also found in tonsil,
CC       fetal heart and fetal spleen.
CC   -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=CCL21 entry;
CC       URL="https://en.wikipedia.org/wiki/CCL21";
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DR   EMBL; AB002409; BAA21817.1; -; mRNA.
DR   EMBL; AF001979; AAB86594.1; -; mRNA.
DR   EMBL; U88320; AAB91454.1; -; mRNA.
DR   EMBL; AJ005654; CAA06653.1; -; Genomic_DNA.
DR   EMBL; AY358887; AAQ89246.1; -; mRNA.
DR   EMBL; BC027918; AAH27918.1; -; mRNA.
DR   CCDS; CCDS6571.1; -.
DR   RefSeq; NP_002980.1; NM_002989.3.
DR   UniGene; Hs.57907; -.
DR   PDB; 2L4N; NMR; -; A=24-134.
DR   PDBsum; 2L4N; -.
DR   ProteinModelPortal; O00585; -.
DR   SMR; O00585; 24-93.
DR   BioGrid; 112269; 9.
DR   DIP; DIP-5854N; -.
DR   IntAct; O00585; 7.
DR   MINT; MINT-123964; -.
DR   STRING; 9606.ENSP00000259607; -.
DR   PhosphoSite; O00585; -.
DR   PaxDb; O00585; -.
DR   PRIDE; O00585; -.
DR   DNASU; 6366; -.
DR   Ensembl; ENST00000259607; ENSP00000259607; ENSG00000137077.
DR   GeneID; 6366; -.
DR   KEGG; hsa:6366; -.
DR   UCSC; uc003zvo.4; human.
DR   CTD; 6366; -.
DR   GeneCards; CCL21; -.
DR   HGNC; HGNC:10620; CCL21.
DR   HPA; CAB005067; -.
DR   HPA; HPA051210; -.
DR   MIM; 602737; gene.
DR   neXtProt; NX_O00585; -.
DR   PharmGKB; PA35552; -.
DR   eggNOG; ENOG410J3QM; Eukaryota.
DR   eggNOG; ENOG410Z7F2; LUCA.
DR   HOGENOM; HOG000036685; -.
DR   HOVERGEN; HBG017871; -.
DR   InParanoid; O00585; -.
DR   KO; K16062; -.
DR   OMA; CCLKYSL; -.
DR   OrthoDB; EOG7GXPDG; -.
DR   PhylomeDB; O00585; -.
DR   TreeFam; TF338224; -.
DR   Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   ChiTaRS; CCL21; human.
DR   GeneWiki; CCL21; -.
DR   GenomeRNAi; 6366; -.
DR   NextBio; 24734; -.
DR   PMAP-CutDB; O00585; -.
DR   PRO; PR:O00585; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   Bgee; O00585; -.
DR   CleanEx; HS_CCL21; -.
DR   ExpressionAtlas; O00585; baseline and differential.
DR   Genevisible; O00585; HS.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005622; C:intracellular; IDA:GOC.
DR   GO; GO:0048020; F:CCR chemokine receptor binding; IBA:GO_Central.
DR   GO; GO:0031732; F:CCR7 chemokine receptor binding; ISS:BHF-UCL.
DR   GO; GO:0008009; F:chemokine activity; IDA:UniProtKB.
DR   GO; GO:0042379; F:chemokine receptor binding; IDA:UniProtKB.
DR   GO; GO:0090630; P:activation of GTPase activity; IDA:BHF-UCL.
DR   GO; GO:0060326; P:cell chemotaxis; IDA:UniProtKB.
DR   GO; GO:0048469; P:cell maturation; ISS:BHF-UCL.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR   GO; GO:0071346; P:cellular response to interferon-gamma; IBA:GO_Central.
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:0070098; P:chemokine-mediated signaling pathway; IBA:GO_Central.
DR   GO; GO:0002407; P:dendritic cell chemotaxis; IDA:BHF-UCL.
DR   GO; GO:0097026; P:dendritic cell dendrite assembly; ISS:BHF-UCL.
DR   GO; GO:0001768; P:establishment of T cell polarity; IDA:BHF-UCL.
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:0001771; P:immunological synapse formation; ISS:BHF-UCL.
DR   GO; GO:0006954; P:inflammatory response; NAS:BHF-UCL.
DR   GO; GO:0048247; P:lymphocyte chemotaxis; IBA:GO_Central.
DR   GO; GO:0035759; P:mesangial cell-matrix adhesion; IDA:BHF-UCL.
DR   GO; GO:0002548; P:monocyte chemotaxis; IBA:GO_Central.
DR   GO; GO:2000548; P:negative regulation of dendritic cell dendrite assembly; ISS:BHF-UCL.
DR   GO; GO:2000107; P:negative regulation of leukocyte apoptotic process; IDA:BHF-UCL.
DR   GO; GO:1903237; P:negative regulation of leukocyte tethering or rolling; IDA:UniProtKB.
DR   GO; GO:0030838; P:positive regulation of actin filament polymerization; IDA:BHF-UCL.
DR   GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; IDA:BHF-UCL.
DR   GO; GO:2000147; P:positive regulation of cell motility; IDA:BHF-UCL.
DR   GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IDA:UniProtKB.
DR   GO; GO:0050921; P:positive regulation of chemotaxis; ISS:BHF-UCL.
DR   GO; GO:0002606; P:positive regulation of dendritic cell antigen processing and presentation; ISS:BHF-UCL.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL.
DR   GO; GO:0051491; P:positive regulation of filopodium assembly; IDA:BHF-UCL.
DR   GO; GO:0010560; P:positive regulation of glycoprotein biosynthetic process; ISS:BHF-UCL.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:BHF-UCL.
DR   GO; GO:0046330; P:positive regulation of JNK cascade; IDA:BHF-UCL.
DR   GO; GO:2000529; P:positive regulation of myeloid dendritic cell chemotaxis; IDA:BHF-UCL.
DR   GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IDA:BHF-UCL.
DR   GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IDA:BHF-UCL.
DR   GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:BHF-UCL.
DR   GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:BHF-UCL.
DR   GO; GO:0031274; P:positive regulation of pseudopodium assembly; IDA:BHF-UCL.
DR   GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; ISS:BHF-UCL.
DR   GO; GO:2000406; P:positive regulation of T cell migration; IDA:MGI.
DR   GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:BHF-UCL.
DR   GO; GO:0034695; P:response to prostaglandin E; IDA:BHF-UCL.
DR   GO; GO:0031529; P:ruffle organization; IDA:BHF-UCL.
DR   GO; GO:0031295; P:T cell costimulation; ISS:BHF-UCL.
DR   InterPro; IPR030593; CCL21.
DR   InterPro; IPR001811; Chemokine_IL8-like_dom.
DR   PANTHER; PTHR12015:SF72; PTHR12015:SF72; 1.
DR   Pfam; PF00048; IL8; 1.
DR   SMART; SM00199; SCY; 1.
DR   SUPFAM; SSF54117; SSF54117; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Chemotaxis; Complete proteome; Cytokine;
KW   Direct protein sequencing; Disulfide bond; Inflammatory response;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL        1     23       {ECO:0000269|PubMed:9300671}.
FT   CHAIN        24    134       C-C motif chemokine 21.
FT                                /FTId=PRO_0000005220.
FT   REGION       98    134       C-terminal basic extension.
FT   DISULFID     31     57       {ECO:0000269|PubMed:22221265}.
FT   DISULFID     32     75       {ECO:0000269|PubMed:22221265}.
FT   DISULFID    103    122       {ECO:0000255}.
FT   TURN         42     44       {ECO:0000244|PDB:2L4N}.
FT   STRAND       45     50       {ECO:0000244|PDB:2L4N}.
FT   TURN         53     56       {ECO:0000244|PDB:2L4N}.
FT   STRAND       62     68       {ECO:0000244|PDB:2L4N}.
FT   STRAND       74     76       {ECO:0000244|PDB:2L4N}.
FT   HELIX        81     91       {ECO:0000244|PDB:2L4N}.
SQ   SEQUENCE   134 AA;  14646 MW;  FB48C2F71CB4A9D2 CRC64;
     MAQSLALSLL ILVLAFGIPR TQGSDGGAQD CCLKYSQRKI PAKVVRSYRK QEPSLGCSIP
     AILFLPRKRS QAELCADPKE LWVQQLMQHL DKTPSPQKPA QGCRKDRGAS KTGKKGKGSK
     GCKRTERSQT PKGP
//