CCL21 C-C motif chemokine ligand 21 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CCL21provided by HGNC
Official Full Name: C-C motif chemokine ligand 21provided by HGNC
Primary source: HGNC:HGNC:10620
See related: Ensembl:ENSG00000137077 MIM:602737; AllianceGenome:HGNC:10620
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ECL; SLC; CKb9; TCA4; 6Ckine; SCYA21
Summary: This antimicrobial gene is one of several CC cytokine genes clustered on the p-arm of chromosome 9. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. Similar to other chemokines the protein encoded by this gene inhibits hemopoiesis and stimulates chemotaxis. This protein is chemotactic in vitro for thymocytes and activated T cells, but not for B cells, macrophages, or neutrophils. The cytokine encoded by this gene may also play a role in mediating homing of lymphocytes to secondary lymphoid organs. It is a high affinity functional ligand for chemokine receptor 7 that is expressed on T and B lymphocytes and a known receptor for another member of the cytokine family (small inducible cytokine A19). [provided by RefSeq, Sep 2014]
Expression: Biased expression in lymph node (RPKM 1020.3), spleen (RPKM 170.8) and 2 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9p13.3

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (34709005..34710136, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (34728031..34729162, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (34709002..34710133, complement)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CCL21 and CLDN11 Are Key Driving Factors of Lymph Node Metastasis in Gastric Cancer.
Title: CCL21 and CLDN11 Are Key Driving Factors of Lymph Node Metastasis in Gastric Cancer.
Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy.
Title: Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy.
CCL19 (rs3136658) and CCL21 (rs2812377) Variants Are Associated With Susceptibility and Related Mortality of SARS-CoV-2 Infection.
Title: CCL19 (rs3136658) and CCL21 (rs2812377) Variants Are Associated With Susceptibility and Related Mortality of SARS-CoV-2 Infection.
CCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma.
Title: CCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma.
Plasma levels of CCL21, but not CCL19, independently predict future coronary events in a prospective population-based cohort.
Title: Plasma levels of CCL21, but not CCL19, independently predict future coronary events in a prospective population-based cohort.
Heparin Specifically Interacts with Basic BBXB Motifs of the Chemokine CCL21 to Define CCR7 Signaling.
Title: Heparin Specifically Interacts with Basic BBXB Motifs of the Chemokine CCL21 to Define CCR7 Signaling.
Target organ expression and biomarker characterization of chemokine CCL21 in systemic sclerosis associated pulmonary arterial hypertension.
Title: Target organ expression and biomarker characterization of chemokine CCL21 in systemic sclerosis associated pulmonary arterial hypertension.
Plasminogen and plasmin can bind to human T cells and generate truncated CCL21 that increases dendritic cell chemotactic responses.
Title: Plasminogen and plasmin can bind to human T cells and generate truncated CCL21 that increases dendritic cell chemotactic responses.
CCL21 and IP10 as serum biomarkers for pulmonary involvement in systemic lupus erythematosus.
Title: CCL21 and IP10 as serum biomarkers for pulmonary involvement in systemic lupus erythematosus.
Crosstalk between Heart Failure and Cognitive Impairment via hsa-miR-933/RELB/CCL21 Pathway.
Title: Crosstalk between Heart Failure and Cognitive Impairment via hsa-miR-933/RELB/CCL21 Pathway.

Submit: New GeneRIF Correction See all GeneRIFs (137)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Common variants at CD40 and other loci confer risk of rheumatoid arthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetics of rheumatoid arthritis contributes to biology and drug discovery. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 enhances CCL-21-induced CD4+ T cell chemotaxis in a CXCR4- and CD4-dependent manner	PubMed
	env	CXCR4-tropic and CXCR4/CCR5 dual-tropic HIV-1 gp120 proteins inhibit B cell chemotaxis toward CXCL12, CCL20, and CCL21, and gp120-induced p38 MAPK activation is triggered by CCL21 and CCL20	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables CCR chemokine receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables CCR7 chemokine receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables chemokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables chemokine activity	IDA Inferred from Direct Assay more info	PubMed
enables chemokine activity	ISS Inferred from Sequence or Structural Similarity more info
enables chemokine receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in T cell costimulation	ISS Inferred from Sequence or Structural Similarity more info
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell chemotaxis	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in cell maturation	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to chemokine	ISS Inferred from Sequence or Structural Similarity more info
involved_in chemokine (C-C motif) ligand 21 signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in chemokine-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in dendritic cell chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in dendritic cell dendrite assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in establishment of T cell polarity	IDA Inferred from Direct Assay more info	PubMed
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in immunological synapse formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in inflammatory response	NAS Non-traceable Author Statement more info	PubMed
involved_in mesangial cell-matrix adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of dendritic cell apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of dendritic cell dendrite assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of leukocyte tethering or rolling	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of GTPase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of JNK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of T cell chemotaxis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of T cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of actin filament polymerization	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell adhesion mediated by integrin	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cell motility	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell-matrix adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of chemotaxis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of dendritic cell antigen processing and presentation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of filopodium assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of glycoprotein biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of myeloid dendritic cell chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neutrophil chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of pseudopodium assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of receptor-mediated endocytosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in release of sequestered calcium ion into cytosol	IDA Inferred from Direct Assay more info	PubMed
involved_in response to prostaglandin E	IDA Inferred from Direct Assay more info	PubMed
involved_in ruffle organization	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: C-C motif chemokine 21

Names: Efficient Chemoattractant for Lymphocytes; beta chemokine exodus-2; chemokine (C-C motif) ligand 21; secondary lymphoid tissue chemokine; small inducible cytokine subfamily A (Cys-Cys), member 21

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_002989.4 → NP_002980.1 C-C motif chemokine 21 precursor

See identical proteins and their annotated locations for NP_002980.1

Status: REVIEWED

Source sequence(s)

BC027918, BI833188

Consensus CDS

CCDS6571.1

UniProtKB/Swiss-Prot

O00585, Q6ICR7

UniProtKB/TrEMBL

Q5VZ73

Related

ENSP00000259607.2, ENST00000259607.7

Conserved Domains (1) summary

cd01119
Location:29 → 91

Chemokine_CC_DCCL; Chemokine_CC_DCCL: subgroup of the Chemokine_CC subgroup based on the presence of a DCCL motif involving the two N-terminal cysteine residues; includes a number of small inducible cytokines capable of reversibly inhibiting normal hematopoietic ...