ID CCL22_HUMAN Reviewed; 93 AA. AC O00626; A0N0Q6; B2R4W2; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 02-NOV-2010, sequence version 2. DT 24-JAN-2024, entry version 189. DE RecName: Full=C-C motif chemokine 22; DE AltName: Full=CC chemokine STCP-1; DE AltName: Full=MDC(1-69); DE AltName: Full=Macrophage-derived chemokine; DE AltName: Full=Small-inducible cytokine A22; DE AltName: Full=Stimulated T-cell chemotactic protein 1; DE Contains: DE RecName: Full=MDC(3-69); DE Contains: DE RecName: Full=MDC(5-69); DE Contains: DE RecName: Full=MDC(7-69); DE Flags: Precursor; GN Name=CCL22; Synonyms=MDC, SCYA22; ORFNames=A-152E5.1; 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], AND VARIANT ALA-2. RC TISSUE=Macrophage; RX PubMed=9312138; DOI=10.1074/jbc.272.40.25229; RA Chang M.-S., McNinch J., Elias C. III, Manthey C.L., Grosshans D., Meng T., RA Boone T., Andrew D.P.; RT "Molecular cloning and functional characterization of a novel CC chemokine, RT stimulated T cell chemotactic protein (STCP-1) that specifically acts on RT activated T lymphocytes."; RL J. Biol. Chem. 272:25229-25237(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 25-35, AND VARIANT ALA-2. RC TISSUE=Macrophage; RX PubMed=9151897; DOI=10.1084/jem.185.9.1595; RA Godiska R., Chantry D., Raport C.J., Sozzani S., Allavena P., Leviten D., RA Mantovani A., Gray P.W.; RT "Human macrophage-derived chemokine (MDC), a novel chemoattractant for RT monocytes, monocyte-derived dendritic cells, and natural killer cells."; RL J. Exp. Med. 185:1595-1604(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-2. RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., RA Nickerson D.A.; RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Peripheral blood; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-2. RX PubMed=10493829; DOI=10.1006/geno.1999.5927; RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., RA Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., RA Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., RA Adams M.D.; RT "Genome duplications and other features in 12 Mb of DNA sequence from human RT chromosome 16p and 16q."; RL Genomics 60:295-308(1999). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-2. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-2. 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP RECEPTOR INTERACTION. RX PubMed=9430724; DOI=10.1074/jbc.273.3.1764; RA Imai T., Chantry D., Raport C.J., Wood C.L., Nishimura M., Godiska R., RA Yoshie O., Gray P.W.; RT "Macrophage-derived chemokine is a functional ligand for the CC chemokine RT receptor 4."; RL J. Biol. Chem. 273:1764-1768(1998). RN [10] RP TISSUE SPECIFICITY, PROTEOLYTIC PROCESSING OF N-TERMINUS, AND RP IDENTIFICATION OF MDC(3-69); MDC(5-69) AND MDC(7-69). RC TISSUE=Dendritic cell; RX PubMed=11241286; RX DOI=10.1002/1521-4141(200103)31:3<812::aid-immu812>3.0.co;2-l; RA Vulcano M., Albanesi C., Stoppacciaro A., Bagnati R., D'Amico G., RA Struyf S., Transidico P., Bonecchi R., Del Prete A., Allavena P., RA Ruco L.P., Chiabrando C., Girolomoni G., Mantovani A., Sozzani S.; RT "Dendritic cells as a major source of macrophage-derived chemokine/CCL22 in RT vitro and in vivo."; RL Eur. J. Immunol. 31:812-822(2001). CC -!- FUNCTION: May play a role in the trafficking of activated/effector T- CC lymphocytes to inflammatory sites and other aspects of activated T- CC lymphocyte physiology. Chemotactic for monocytes, dendritic cells and CC natural killer cells. Mild chemoattractant for primary activated T- CC lymphocytes and a potent chemoattractant for chronically activated T- CC lymphocytes but has no chemoattractant activity for neutrophils, CC eosinophils, and resting T-lymphocytes. Binds to CCR4. Processed forms CC MDC(3-69), MDC(5-69) and MDC(7-69) seem not be active. CC -!- INTERACTION: CC O00626; Q13520: AQP6; NbExp=3; IntAct=EBI-3907871, EBI-13059134; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Highly expressed in macrophage and in monocyte- CC derived dendritic cells, and thymus. Also found in lymph node, CC appendix, activated monocytes, resting and activated macrophages. Lower CC expression in lung and spleen. Very weak expression in small intestine. CC In lymph node expressed in a mature subset of Langerhans' cells (CD1a+ CC and CD83+). Expressed in Langerhans' cell histiocytosis but not in CC dermatopathic lymphadenopathy. Expressed in atopic dermatitis, allergic CC contact dermatitis skin, and psoriasis, in both the epidermis and CC dermis. {ECO:0000269|PubMed:11241286}. CC -!- PTM: The N-terminal processed forms MDC(3-69), MDC(5-69) and MDC(7-69) CC are produced by proteolytic cleavage after secretion from monocyte CC derived dendrocytes. {ECO:0000269|PubMed:11241286}. CC -!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=CCL22 entry; CC URL="https://en.wikipedia.org/wiki/CCL22"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U83239; AAB53372.1; -; mRNA. DR EMBL; U83171; AAB58360.1; -; mRNA. DR EMBL; EF064764; ABK41947.1; -; Genomic_DNA. DR EMBL; AK311970; BAG34909.1; -; mRNA. DR EMBL; AC004382; AAC24306.1; -; Genomic_DNA. DR EMBL; AC009052; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471092; EAW82918.1; -; Genomic_DNA. DR EMBL; BC027952; AAH27952.1; -; mRNA. DR CCDS; CCDS10778.1; -. DR RefSeq; NP_002981.2; NM_002990.4. DR RefSeq; XP_016879020.1; XM_017023531.1. DR AlphaFoldDB; O00626; -. DR SMR; O00626; -. DR BioGRID; 112270; 53. DR DIP; DIP-5849N; -. DR IntAct; O00626; 34. DR MINT; O00626; -. DR STRING; 9606.ENSP00000219235; -. DR ChEMBL; CHEMBL4295649; -. DR iPTMnet; O00626; -. DR PhosphoSitePlus; O00626; -. DR BioMuta; CCL22; -. DR MassIVE; O00626; -. DR PaxDb; 9606-ENSP00000219235; -. DR PeptideAtlas; O00626; -. DR Antibodypedia; 15019; 575 antibodies from 33 providers. DR DNASU; 6367; -. DR Ensembl; ENST00000219235.5; ENSP00000219235.4; ENSG00000102962.5. DR GeneID; 6367; -. DR KEGG; hsa:6367; -. DR MANE-Select; ENST00000219235.5; ENSP00000219235.4; NM_002990.5; NP_002981.2. DR UCSC; uc002elh.4; human. DR AGR; HGNC:10621; -. DR CTD; 6367; -. DR DisGeNET; 6367; -. DR GeneCards; CCL22; -. DR HGNC; HGNC:10621; CCL22. DR HPA; ENSG00000102962; Tissue enhanced (lymphoid tissue, skin). DR MIM; 602957; gene. DR neXtProt; NX_O00626; -. DR OpenTargets; ENSG00000102962; -. DR PharmGKB; PA35553; -. DR VEuPathDB; HostDB:ENSG00000102962; -. DR eggNOG; ENOG502SWZ0; Eukaryota. DR GeneTree; ENSGT01100000263482; -. DR HOGENOM; CLU_141716_4_2_1; -. DR InParanoid; O00626; -. DR OMA; RDYIRHP; -. DR OrthoDB; 4265193at2759; -. DR PhylomeDB; O00626; -. DR TreeFam; TF334888; -. DR PathwayCommons; O00626; -. DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines. DR Reactome; R-HSA-6783783; Interleukin-10 signaling. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR SignaLink; O00626; -. DR BioGRID-ORCS; 6367; 5 hits in 1144 CRISPR screens. DR ChiTaRS; CCL22; human. DR GeneWiki; CCL22; -. DR GenomeRNAi; 6367; -. DR Pharos; O00626; Tbio. DR PRO; PR:O00626; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; O00626; Protein. DR Bgee; ENSG00000102962; Expressed in vermiform appendix and 111 other cell types or tissues. 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:0008009; F:chemokine activity; IBA:GO_Central. DR GO; GO:0007267; P:cell-cell signaling; 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; IBA:GO_Central. 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:0030593; P:neutrophil chemotaxis; IBA:GO_Central. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central. DR GO; GO:0009615; P:response to virus; TAS:ProtInc. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd00272; Chemokine_CC; 1. DR Gene3D; 2.40.50.40; -; 1. DR InterPro; IPR039809; Chemokine_b/g/d. DR InterPro; IPR000827; Chemokine_CC_CS. DR InterPro; IPR001811; Chemokine_IL8-like_dom. DR InterPro; IPR036048; Interleukin_8-like_sf. DR PANTHER; PTHR12015:SF102; C-C MOTIF CHEMOKINE 22; 1. DR PANTHER; PTHR12015; SMALL INDUCIBLE CYTOKINE A; 1. DR Pfam; PF00048; IL8; 1. DR PRINTS; PR00436; INTERLEUKIN8. DR SMART; SM00199; SCY; 1. DR SUPFAM; SSF54117; Interleukin 8-like chemokines; 1. DR PROSITE; PS00472; SMALL_CYTOKINES_CC; 1. DR Genevisible; O00626; HS. PE 1: Evidence at protein level; KW Chemotaxis; Cytokine; Direct protein sequencing; Disulfide bond; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..24 FT /evidence="ECO:0000269|PubMed:9151897" FT CHAIN 25..93 FT /note="C-C motif chemokine 22" FT /id="PRO_0000005224" FT CHAIN 27..93 FT /note="MDC(3-69)" FT /id="PRO_0000005225" FT CHAIN 29..93 FT /note="MDC(5-69)" FT /id="PRO_0000005226" FT CHAIN 31..93 FT /note="MDC(7-69)" FT /id="PRO_0000005227" FT DISULFID 36..60 FT /evidence="ECO:0000250" FT DISULFID 37..76 FT /evidence="ECO:0000250" FT VARIANT 2 FT /note="D -> A (in dbSNP:rs4359426)" FT /evidence="ECO:0000269|PubMed:10493829, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9151897, FT ECO:0000269|PubMed:9312138, ECO:0000269|Ref.3, FT ECO:0000269|Ref.7" FT /id="VAR_055117" SQ SEQUENCE 93 AA; 10625 MW; 641FCE999586A7D2 CRC64; MDRLQTALLV VLVLLAVALQ ATEAGPYGAN MEDSVCCRDY VRYRLPLRVV KHFYWTSDSC PRPGVVLLTF RDKEICADPR VPWVKMILNK LSQ //