Descriptions

C-C motif chemokine 21 (CCL21) is chemokine that inhibits hemopoiesis and stimulates chemotaxis, and may play a role in mediating homing of lymphocytes to secondary lymphoid organ. CCL21 has an unstructured C-terminus that does not adopt a stable fold. This C-terminal tail of CCL21 makes autoinhibitory contacts with and modulates the structure and function of the CCL21 chemokine domain. CCL21's C-terminus transiently interacts with the chemokine domain of CCL21, thereby providing a putative structural correlate of functional autoinhibition.

Autoinhibitory domains (AIDs)

Target domain

1-79 (Chemokine domain)

Relief mechanism

PTM

Assay

Deletion assay, Structural analysis

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

3 structures for O00585

Entry ID Method Resolution Chain Position Source
2L4N NMR - A 24-134 PDB
5EKI X-ray 190 A A/B/C/D/E/F 24-102 PDB
AF-O00585-F1 Predicted AlphaFoldDB

117 variants for O00585

Variant ID(s) Position Change Description Diseaes Association Provenance
CA373273735
COSM1319603
rs1435524206
2 A>V haematopoietic_and_lymphoid_tissue [Cosmic] No ClinGen
cosmic curated
TOPMed
rs376939263
CA5037155
4 S>* No ClinGen
ESP
ExAC
gnomAD
rs1413276539
CA373273656
6 A>V No ClinGen
gnomAD
CA192694192
rs779706400
7 L>P No ClinGen
Ensembl
rs766751281
CA5037154
8 S>G No ClinGen
ExAC
gnomAD
CA192694190
rs901577787
8 S>R No ClinGen
TOPMed
gnomAD
CA373273479
rs1201441537
15 A>T No ClinGen
gnomAD
rs1485651001
CA373273461
16 F>L No ClinGen
gnomAD
CA192694183
rs187539558
16 F>S No ClinGen
1000Genomes
rs372498578
CA192694179
17 G>S No ClinGen
ESP
TOPMed
rs750926648
CA5037152
19 P>H No ClinGen
ExAC
rs1259222173
CA373273358
20 R>S No ClinGen
gnomAD
CA373273350
rs1212746799
21 T>A No ClinGen
gnomAD
rs768165822
CA373273338
21 T>I No ClinGen
ExAC
gnomAD
rs768165822
CA5037151
21 T>N No ClinGen
ExAC
gnomAD
CA373273314
rs1329960763
22 Q>H No ClinGen
gnomAD
rs1332010028
CA373273292
23 G>S No ClinGen
TOPMed
gnomAD
CA373272501
rs1433326878
24 S>R No ClinGen
gnomAD
CA373272480
rs1435356127
25 D>Y No ClinGen
gnomAD
CA373272391
rs1323280490
29 Q>* No ClinGen
gnomAD
rs768083949
CA5037134
29 Q>H No ClinGen
ExAC
gnomAD
CA5037135
rs750836820
29 Q>L No ClinGen
ExAC
gnomAD
rs753133670
CA192693980
30 D>Y No ClinGen
Ensembl
CA373272202
rs1164366610
36 S>G No ClinGen
TOPMed
gnomAD
rs762419173
CA5037133
38 R>K No ClinGen
ExAC
gnomAD
rs1371709137
CA373272121
COSM1314790
39 K>N urinary_tract [Cosmic] No ClinGen
cosmic curated
gnomAD
TCGA novel 39 K>R Variant assessed as Somatic; impact. [NCI-TCGA] No NCI-TCGA
TCGA novel 40 I>F Variant assessed as Somatic; impact. [NCI-TCGA] No NCI-TCGA
rs142482921
CA5037130
42 A>S No ClinGen
ESP
ExAC
TOPMed
gnomAD
rs142482921
CA373272080
42 A>T No ClinGen
ESP
ExAC
TOPMed
gnomAD
CA373272044
rs969995486
43 K>N No ClinGen
TOPMed
gnomAD
rs1435390901
CA373272066
43 K>Q No ClinGen
TOPMed
rs865854292
CA192693934
44 V>I No ClinGen
Ensembl
rs1453433779
CA373271981
46 R>C Variant assessed as Somatic; 0.0 impact. [NCI-TCGA] No ClinGen
NCI-TCGA
gnomAD
rs1453433779
CA373271977
46 R>G No ClinGen
gnomAD
CA5037129
rs776318372
46 R>H No ClinGen
ExAC
TOPMed
gnomAD
rs1195160505
CA373271946
47 S>G No ClinGen
TOPMed
gnomAD
CA5037127
rs760414514
49 R>Q No ClinGen
ExAC
TOPMed
gnomAD
CA5037128
rs765979271
49 R>W No ClinGen
ExAC
TOPMed
gnomAD
rs539376444
CA5037124
53 P>R No ClinGen
1000Genomes
ExAC
TOPMed
gnomAD
rs771921191
CA5037125
53 P>S No ClinGen
ExAC
gnomAD
CA373271768
rs771921191
53 P>T No ClinGen
ExAC
gnomAD
CA5037123
rs774203687
56 G>D No ClinGen
ExAC
gnomAD
rs780269897
CA5037120
59 I>N No ClinGen
ExAC
CA5037121
rs749355595
COSM1108516
59 I>V Variant assessed as Somatic; 0.0 impact. endometrium [NCI-TCGA, Cosmic] No ClinGen
cosmic curated
ExAC
NCI-TCGA
gnomAD
rs1371156951
CA373271610
60 P>L No ClinGen
TOPMed
CA192693815
rs201778181
60 P>S No ClinGen
Ensembl
CA373271554
rs1170851787
62 I>N No ClinGen
gnomAD
CA373271275
rs1283173183
66 P>L No ClinGen
gnomAD
rs753313552
CA5037095
66 P>S No ClinGen
ExAC
TOPMed
gnomAD
rs753313552
CA5037096
66 P>T No ClinGen
ExAC
TOPMed
gnomAD
CA5037092
rs750044894
67 R>C No ClinGen
ExAC
TOPMed
gnomAD
rs34598986
CA5037090
67 R>H No ClinGen
1000Genomes
ESP
ExAC
TOPMed
gnomAD
rs34598986
CA5037091
67 R>L No ClinGen
1000Genomes
ESP
ExAC
TOPMed
gnomAD
rs764022594
CA5037088
68 K>N No ClinGen
ExAC
gnomAD
CA373271198
rs1437686948
68 K>R No ClinGen
TOPMed
gnomAD
CA5037087
rs762798553
69 R>C No ClinGen
ExAC
TOPMed
gnomAD
CA5037086
rs775560130
COSM1247596
69 R>H oesophagus [Cosmic] No ClinGen
cosmic curated
ExAC
TOPMed
gnomAD
rs762798553
CA373271180
69 R>S No ClinGen
ExAC
TOPMed
gnomAD
CA5037085
rs769975656
72 A>E No ClinGen
ExAC
gnomAD
rs1359922266
CA373271097
72 A>T No ClinGen
TOPMed
gnomAD
rs1390934171
CA373271064
74 L>I No ClinGen
gnomAD
rs759733358
CA5037084
75 C>R No ClinGen
ExAC
gnomAD
CA5037083
rs776954599
75 C>S No ClinGen
ExAC
TOPMed
gnomAD
CA373271013
rs1268054875
76 A>T No ClinGen
TOPMed
CA192693454
rs956153540
76 A>V No ClinGen
TOPMed
gnomAD
CA373270965
rs1473024111
78 P>S No ClinGen
gnomAD
rs778006557
CA373270884
80 E>D No ClinGen
ExAC
TOPMed
gnomAD
rs778006557
CA5037080
80 E>D No ClinGen
ExAC
TOPMed
gnomAD
rs1451078274
CA373270854
82 W>* No ClinGen
TOPMed
CA373270829
rs1182863895
83 V>A No ClinGen
TOPMed
TCGA novel 87 M>K Variant assessed as Somatic; impact. [NCI-TCGA] No NCI-TCGA
COSM379761
CA5037079
rs772545076
88 Q>* lung [Cosmic] No ClinGen
cosmic curated
ExAC
TOPMed
CA192693400
rs772545076
88 Q>K No ClinGen
ExAC
TOPMed
CA192693374
rs939141004
89 H>Q No ClinGen
TOPMed
CA5037077
rs748581651
89 H>R No ClinGen
ExAC
TOPMed
gnomAD
CA373270673
rs1334728950
90 L>V No ClinGen
gnomAD
CA5037074
rs755580810
92 K>R No ClinGen
ExAC
gnomAD
CA5037073
rs749954967
93 T>A No ClinGen
ExAC
TOPMed
gnomAD
rs1391448419
CA373270544
95 S>F No ClinGen
TOPMed
rs1161356955
CA373270562
95 S>T No ClinGen
TOPMed
rs1391448419
CA373270558
95 S>Y No ClinGen
TOPMed
CA373270504
rs1408399469
97 Q>R No ClinGen
TOPMed
CA192693334
rs915935603
99 P>L No ClinGen
gnomAD
rs1336150097
CA373270386
101 Q>H No ClinGen
TOPMed
rs751296236
CA5037070
103 C>R No ClinGen
ExAC
gnomAD
rs762857659
CA5037068
104 R>S No ClinGen
ExAC
TOPMed
gnomAD
CA373270274
rs1166542420
105 K>* No ClinGen
gnomAD
CA373270233
rs1450916503
106 D>E No ClinGen
gnomAD
rs752548751
CA5037067
107 R>M No ClinGen
ExAC
TOPMed
gnomAD
rs752548751
CA373270212
107 R>T No ClinGen
ExAC
TOPMed
gnomAD
CA373270198
rs1564116483
108 G>E No ClinGen
Ensembl
rs777471870 109 A>P Variant assessed as Somatic; impact. [NCI-TCGA] No NCI-TCGA
CA5037066
rs759642265
109 A>S No ClinGen
ExAC
TOPMed
gnomAD
CA5037065
rs759642265
109 A>T No ClinGen
ExAC
TOPMed
gnomAD
rs776864576
CA5037063
110 S>F No ClinGen
ExAC
TOPMed
gnomAD
CA373270096
rs1322924992
111 K>N No ClinGen
TOPMed
gnomAD
CA5037062
rs771211630
111 K>R No ClinGen
ExAC
gnomAD
rs760793347
CA5037061
113 G>R No ClinGen
ExAC
gnomAD
CA373270007
rs1257922234
114 K>R No ClinGen
TOPMed
CA373269805
rs772291642
121 G>A No ClinGen
ExAC
TOPMed
gnomAD
COSM1624932
CA5037060
rs773531936
121 G>S liver [Cosmic] No ClinGen
cosmic curated
ExAC
TOPMed
gnomAD
rs772291642
CA5037059
121 G>V No ClinGen
ExAC
TOPMed
gnomAD
CA373269712
rs368229543
124 R>G No ClinGen
ESP
TOPMed
gnomAD
rs779340021
CA5037056
124 R>K No ClinGen
ExAC
TOPMed
gnomAD
CA373269596
rs1219925355
124 R>S No ClinGen
gnomAD
rs754971604
CA5037044
126 E>K No ClinGen
ExAC
TOPMed
gnomAD
rs148496138
CA5037042
COSM1734322
127 R>Q pancreas [Cosmic] No ClinGen
cosmic curated
1000Genomes
ESP
ExAC
TOPMed
gnomAD
rs1370944166
CA373269500
128 S>* Variant assessed as Somatic; 0.0 impact. [NCI-TCGA] No ClinGen
NCI-TCGA
gnomAD
rs576393548
CA5037041
129 Q>E No ClinGen
1000Genomes
ExAC
TOPMed
gnomAD
rs1191474871
CA373269479
129 Q>R No ClinGen
gnomAD
CA5037040
rs374347595
130 T>I No ClinGen
ESP
ExAC
gnomAD
CA373269431
rs1360588383
131 P>S No ClinGen
gnomAD
rs1301405103
CA373269415
132 K>E No ClinGen
TOPMed
rs767802042
CA5037039
132 K>N No ClinGen
ExAC
gnomAD
CA192693140
rs1007358262
133 G>R No ClinGen
Ensembl
rs762022123
CA5037038
134 P>S No ClinGen
ExAC
gnomAD

No associated diseases with O00585

8 regional properties for O00585

Type Name Position InterPro Accession
domain SH3 domain 8 - 69 IPR001452
domain Dedicator of cytokinesis protein 2, DHR2 domain 1200 - 1620 IPR026799
domain C2 DOCK-type domain 419 - 615 IPR027007
domain DOCKER domain 1211 - 1622 IPR027357
domain Dedicator of cytokinesis, N-terminal domain 72 - 414 IPR032376
domain DOCKER, Lobe A 1205 - 1334 IPR046769
domain DOCKER, Lobe B 1395 - 1474 IPR046770
domain DOCKER, Lobe C 1516 - 1615 IPR046773

Functions

Description
EC Number
Subcellular Localization
  • Secreted
PANTHER Family PTHR12015 SMALL INDUCIBLE CYTOKINE A
PANTHER Subfamily PTHR12015:SF72 C-C MOTIF CHEMOKINE 21
PANTHER Protein Class cytokine
PANTHER Pathway Category Inflammation mediated by chemokine and cytokine signaling pathway
CHK

2 GO annotations of cellular component

Name Definition
extracellular region The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
extracellular space That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.

4 GO annotations of molecular function

Name Definition
CCR chemokine receptor binding Binding to a CCR chemokine receptor.
CCR7 chemokine receptor binding Binding to a CCR7 chemokine receptor.
chemokine activity The function of a family of small chemotactic cytokines; their name is derived from their ability to induce directed chemotaxis in nearby responsive cells. All chemokines possess a number of conserved cysteine residues involved in intramolecular disulfide bond formation. Some chemokines are considered pro-inflammatory and can be induced during an immune response to recruit cells of the immune system to a site of infection, while others are considered homeostatic and are involved in controlling the migration of cells during normal processes of tissue maintenance or development. Chemokines are found in all vertebrates, some viruses and some bacteria.
chemokine receptor binding Binding to a chemokine receptor.

51 GO annotations of biological process

Name Definition
activation of GTPase activity Any process that initiates the activity of an inactive GTPase through the replacement of GDP by GTP.
antimicrobial humoral immune response mediated by antimicrobial peptide An immune response against microbes mediated by anti-microbial peptides in body fluid.
cell chemotaxis The directed movement of a motile cell guided by a specific chemical concentration gradient. Movement may be towards a higher concentration (positive chemotaxis) or towards a lower concentration (negative chemotaxis).
cell maturation A developmental process, independent of morphogenetic (shape) change, that is required for a cell to attain its fully functional state.
cell-cell signaling Any process that mediates the transfer of information from one cell to another. This process includes signal transduction in the receiving cell and, where applicable, release of a ligand and any processes that actively facilitate its transport and presentation to the receiving cell. Examples include signaling via soluble ligands, via cell adhesion molecules and via gap junctions.
cellular response to chemokine Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a chemokine stimulus.
cellular response to interleukin-1 Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-1 stimulus.
cellular response to tumor necrosis factor Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tumor necrosis factor stimulus.
cellular response to type II interferon Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interferon-gamma stimulus. Interferon gamma is the only member of the type II interferon found so far.
chemokine (C-C motif) ligand 21 signaling pathway The series of molecular signals initiated by the binding of the C-C chemokine CCL21 to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
chemokine-mediated signaling pathway The series of molecular signals initiated by a chemokine binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
dendritic cell chemotaxis The movement of a dendritic cell in response to an external stimulus.
dendritic cell dendrite assembly Formation of dendrites, branched cellular projections (or cytoplasmic extension) that are extended from the surface of a dendritic immune cell, and which enable the cell to sample luminal pathogens and increase the surface area for antigen presentation to T cells.
eosinophil chemotaxis The movement of an eosinophil in response to an external stimulus.
establishment of T cell polarity The directed orientation of T cell signaling molecules and associated membrane rafts towards a chemokine gradient or a contact point with antigen presenting cell.
G protein-coupled receptor signaling pathway The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane.
immune response Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat.
immunological synapse formation The formation of an area of close contact between a lymphocyte (T-, B-, or natural killer cell) and a target cell through the clustering of particular signaling and adhesion molecules and their associated membrane rafts on both the lymphocyte and target cell, which facilitates activation of the lymphocyte, transfer of membrane from the target cell to the lymphocyte, and in some situations killing of the target cell through release of secretory granules and/or death-pathway ligand-receptor interaction.
inflammatory response The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.
killing of cells of another organism Any process in an organism that results in the killing of cells of another organism, including in some cases the death of the other organism. Killing here refers to the induction of death in one cell by another cell, not cell-autonomous death due to internal or other environmental conditions.
lymphocyte chemotaxis The directed movement of a lymphocyte in response to an external stimulus.
mesangial cell-matrix adhesion The binding of a mesangial cell to the extracellular matrix via adhesion molecules. A mesangial cell is a cell that encapsulates the capillaries and venules in the kidney.
monocyte chemotaxis The movement of a monocyte in response to an external stimulus.
negative regulation of dendritic cell apoptotic process Any process that stops, prevents or reduces the frequency, rate or extent of dendritic cell apoptotic process.
negative regulation of dendritic cell dendrite assembly Any process that stops, prevents or reduces the frequency, rate or extent of dendritic cell dendrite assembly.
negative regulation of leukocyte tethering or rolling Any process that stops, prevents or reduces the frequency, rate or extent of leukocyte tethering or rolling.
neutrophil chemotaxis The directed movement of a neutrophil cell, the most numerous polymorphonuclear leukocyte found in the blood, in response to an external stimulus, usually an infection or wounding.
positive regulation of actin filament polymerization Any process that activates or increases the frequency, rate or extent of actin polymerization.
positive regulation of cell adhesion mediated by integrin Any process that activates or increases the frequency, rate, or extent of cell adhesion mediated by integrin.
positive regulation of cell motility Any process that activates or increases the frequency, rate or extent of cell motility.
positive regulation of cell-matrix adhesion Any process that activates or increases the rate or extent of cell adhesion to an extracellular matrix.
positive regulation of chemotaxis Any process that activates or increases the frequency, rate or extent of the directed movement of a motile cell or organism in response to a specific chemical concentration gradient.
positive regulation of dendritic cell antigen processing and presentation Any process that activates or increases the frequency, rate, or extent of dendritic cell antigen processing and presentation.
positive regulation of ERK1 and ERK2 cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
positive regulation of filopodium assembly Any process that activates or increases the frequency, rate or extent of the assembly of a filopodium, a thin, stiff protrusion extended by the leading edge of a motile cell such as a crawling fibroblast or amoeba, or an axonal growth cone.
positive regulation of glycoprotein biosynthetic process Any process that increases the rate, frequency, or extent of the chemical reactions and pathways resulting in the formation of a glycoprotein, a protein that contains covalently bound glycose (i.e. monosaccharide) residues; the glycose occurs most commonly as oligosaccharide or fairly small polysaccharide but occasionally as monosaccharide.
positive regulation of GTPase activity Any process that activates or increases the activity of a GTPase.
positive regulation of I-kappaB kinase/NF-kappaB signaling Any process that activates or increases the frequency, rate or extent of I-kappaB kinase/NF-kappaB signaling.
positive regulation of JNK cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the JNK cascade.
positive regulation of myeloid dendritic cell chemotaxis Any process that activates or increases the frequency, rate or extent of myeloid dendritic cell chemotaxis.
positive regulation of neutrophil chemotaxis Any process that increases the frequency, rate, or extent of neutrophil chemotaxis. Neutrophil chemotaxis is the directed movement of a neutrophil cell, the most numerous polymorphonuclear leukocyte found in the blood, in response to an external stimulus, usually an infection or wounding.
positive regulation of phosphatidylinositol 3-kinase activity Any process that activates or increases the frequency, rate or extent of phosphatidylinositol 3-kinase activity.
positive regulation of protein kinase activity Any process that activates or increases the frequency, rate or extent of protein kinase activity.
positive regulation of protein kinase B signaling Any process that activates or increases the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B.
positive regulation of pseudopodium assembly Any process that activates or increases the frequency, rate or extent of the assembly of pseudopodia.
positive regulation of receptor-mediated endocytosis Any process that activates or increases the frequency, rate or extent of receptor mediated endocytosis, the uptake of external materials by cells, utilizing receptors to ensure specificity of transport.
positive regulation of T cell chemotaxis Any process that increases the rate, frequency or extent of T cell chemotaxis. T cell chemotaxis is the directed movement of a T cell in response to an external stimulus.
positive regulation of T cell migration Any process that activates or increases the frequency, rate or extent of T cell migration.
release of sequestered calcium ion into cytosol The process in which calcium ions sequestered in the endoplasmic reticulum, Golgi apparatus or mitochondria are released into the cytosolic compartment.
response to prostaglandin E Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a prostagladin E stimulus.
ruffle organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a ruffle, a projection at the leading edge of a crawling cell.

4 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P84444 Ccl21a C-C motif chemokine 21a Mus musculus (Mouse) SS
P86792 Ccl21b C-C motif chemokine 21b Mus musculus (Mouse) SS
P86793 Ccl21c C-C motif chemokine 21c Mus musculus (Mouse) SS
Q8HYP5 CCL21 C-C motif chemokine 21 Macaca mulatta (Rhesus macaque) SS
10 20 30 40 50 60
MAQSLALSLL ILVLAFGIPR TQGSDGGAQD CCLKYSQRKI PAKVVRSYRK QEPSLGCSIP
70 80 90 100 110 120
AILFLPRKRS QAELCADPKE LWVQQLMQHL DKTPSPQKPA QGCRKDRGAS KTGKKGKGSK
130
GCKRTERSQT PKGP