Q9QWK4 · CD5L_MOUSE
- ProteinCD5 antigen-like
- GeneCd5l
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids352 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection or atherosclerosis (PubMed:26048980).
Able to inhibit lipid droplet size in adipocytes (PubMed:20519120, PubMed:22579686).
Following incorporation into mature adipocytes via CD36-mediated endocytosis, associates with cytosolic FASN, inhibiting fatty acid synthase activity and leading to lipolysis, the degradation of triacylglycerols into glycerol and free fatty acids (FFA) (PubMed:20519120).
CD5L-induced lipolysis occurs with progression of obesity: participates in obesity-associated inflammation following recruitment of inflammatory macrophages into adipose tissues, a cause of insulin resistance and obesity-related metabolic disease (PubMed:21730133).
Regulation of intracellular lipids mediated by CD5L has a direct effect on transcription regulation mediated by nuclear receptors ROR-gamma (RORC) (PubMed:22579686, PubMed:26607793).
Acts as a key regulator of metabolic switch in T-helper Th17 cells (PubMed:26607793, PubMed:26607794).
Regulates the expression of pro-inflammatory genes in Th17 cells by altering the lipid content and limiting synthesis of cholesterol ligand of RORC, the master transcription factor of Th17-cell differentiation (PubMed:26607793).
CD5L is mainly present in non-pathogenic Th17 cells, where it decreases the content of polyunsaturated fatty acyls (PUFA), affecting two metabolic proteins MSMO1 and CYP51A1, which synthesize ligands of RORC, limiting RORC activity and expression of pro-inflammatory genes (PubMed:26607793).
Participates in obesity-associated autoimmunity via its association with IgM, interfering with the binding of IgM to Fcalpha/mu receptor and enhancing the development of long-lived plasma cells that produce high-affinity IgG autoantibodies (PubMed:23562157).
Also acts as an inhibitor of apoptosis in macrophages: promotes macrophage survival from the apoptotic effects of oxidized lipids in case of atherosclerosis (PubMed:16054063, PubMed:9892623).
Involved in early response to microbial infection against various pathogens by acting as a pattern recognition receptor and by promoting autophagy (By similarity).
Able to inhibit lipid droplet size in adipocytes (PubMed:20519120, PubMed:22579686).
Following incorporation into mature adipocytes via CD36-mediated endocytosis, associates with cytosolic FASN, inhibiting fatty acid synthase activity and leading to lipolysis, the degradation of triacylglycerols into glycerol and free fatty acids (FFA) (PubMed:20519120).
CD5L-induced lipolysis occurs with progression of obesity: participates in obesity-associated inflammation following recruitment of inflammatory macrophages into adipose tissues, a cause of insulin resistance and obesity-related metabolic disease (PubMed:21730133).
Regulation of intracellular lipids mediated by CD5L has a direct effect on transcription regulation mediated by nuclear receptors ROR-gamma (RORC) (PubMed:22579686, PubMed:26607793).
Acts as a key regulator of metabolic switch in T-helper Th17 cells (PubMed:26607793, PubMed:26607794).
Regulates the expression of pro-inflammatory genes in Th17 cells by altering the lipid content and limiting synthesis of cholesterol ligand of RORC, the master transcription factor of Th17-cell differentiation (PubMed:26607793).
CD5L is mainly present in non-pathogenic Th17 cells, where it decreases the content of polyunsaturated fatty acyls (PUFA), affecting two metabolic proteins MSMO1 and CYP51A1, which synthesize ligands of RORC, limiting RORC activity and expression of pro-inflammatory genes (PubMed:26607793).
Participates in obesity-associated autoimmunity via its association with IgM, interfering with the binding of IgM to Fcalpha/mu receptor and enhancing the development of long-lived plasma cells that produce high-affinity IgG autoantibodies (PubMed:23562157).
Also acts as an inhibitor of apoptosis in macrophages: promotes macrophage survival from the apoptotic effects of oxidized lipids in case of atherosclerosis (PubMed:16054063, PubMed:9892623).
Involved in early response to microbial infection against various pathogens by acting as a pattern recognition receptor and by promoting autophagy (By similarity).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 316 | Not glycosylated | ||||
Sequence: N |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cell surface | |
Cellular Component | cytoplasm | |
Cellular Component | extracellular region | |
Cellular Component | plasma membrane | |
Molecular Function | serine-type endopeptidase activity | |
Biological Process | apoptotic process | |
Biological Process | immune system process | |
Biological Process | inflammatory response | |
Biological Process | positive regulation of complement-dependent cytotoxicity | |
Biological Process | regulation of complement activation | |
Biological Process | zymogen activation |
Keywords
- Biological process
Names & Taxonomy
Protein names
- Recommended nameCD5 antigen-like
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9QWK4
- Secondary accessions
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
Mice are apparently healthy under specific pathogen-free conditions. However, thymus of mice display much fewer thymocytes and CD4/CD8 double-positive (DP) thymocytes are more susceptible to apoptosis (PubMed:9892623).
Increased adipocyte size and adipose tissue mass (PubMed:20519120).
Higher level of free cholesterol in Th17 cells (PubMed:26607793).
Increased adipocyte size and adipose tissue mass (PubMed:20519120).
Higher level of free cholesterol in Th17 cells (PubMed:26607793).
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | 61 | |||||
Sequence: V → M | ||||||
Mutagenesis | 99 | Decreased glycosylation. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 194 | Abolishes interaction with IgM. | ||||
Sequence: C → S | ||||||
Natural variant | 197 | |||||
Sequence: N → S | ||||||
Natural variant | 205 | |||||
Sequence: W → R | ||||||
Mutagenesis | 229 | Decreased glycosylation. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 316 | Does not affect glycosylation. | ||||
Sequence: N → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 21 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-21 | |||||
Sequence: MAPLFNLMLAILSIFVGSCFS | ||||||
Chain | PRO_0000033226 | 22-352 | CD5 antigen-like | |||
Sequence: ESPTKVQLVGGAHRCEGRVEVEHNGQWGTVCDDGWDRRDVAVVCRELNCGAVIQTPRGASYQPPASEQRVLIQGVDCNGTEDTLAQCELNYDVFDCSHEEDAGAQCENPDSDLLFIPEDVRLVDGPGHCQGRVEVLHQSQWSTVCKAGWNLQVSKVVCRQLGCGRALLTYGSCNKNTQGKGPIWMGKMSCSGQEANLRSCLLSRLENNCTHGEDTWMECEDPFELKLVGGDTPCSGRLEVLHKGSWGSVCDDNWGEKEDQVVCKQLGCGKSLHPSPKTRKIYGPGAGRIWLDDVNCSGKEQSLEFCRHRLWGYHDCTHKEDVEVICTDFDV | ||||||
Disulfide bond | 36↔70 | |||||
Sequence: CEGRVEVEHNGQWGTVCDDGWDRRDVAVVCRELNC | ||||||
Disulfide bond | 52↔117 | |||||
Sequence: CDDGWDRRDVAVVCRELNCGAVIQTPRGASYQPPASEQRVLIQGVDCNGTEDTLAQCELNYDVFDC | ||||||
Disulfide bond | 65↔127 | |||||
Sequence: CRELNCGAVIQTPRGASYQPPASEQRVLIQGVDCNGTEDTLAQCELNYDVFDCSHEEDAGAQC | ||||||
Disulfide bond | 98↔108 | |||||
Sequence: CNGTEDTLAQC | ||||||
Glycosylation | 99 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 166↔230 | |||||
Sequence: CKAGWNLQVSKVVCRQLGCGRALLTYGSCNKNTQGKGPIWMGKMSCSGQEANLRSCLLSRLENNC | ||||||
Disulfide bond | 179↔240 | |||||
Sequence: CRQLGCGRALLTYGSCNKNTQGKGPIWMGKMSCSGQEANLRSCLLSRLENNCTHGEDTWMEC | ||||||
Disulfide bond | 194 | Interchain (with C-414 of IGHM) | ||||
Sequence: C | ||||||
Disulfide bond | 211↔221 | |||||
Sequence: CSGQEANLRSC | ||||||
Glycosylation | 229 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 255↔289 | |||||
Sequence: CSGRLEVLHKGSWGSVCDDNWGEKEDQVVCKQLGC | ||||||
Disulfide bond | 271↔337 | |||||
Sequence: CDDNWGEKEDQVVCKQLGCGKSLHPSPKTRKIYGPGAGRIWLDDVNCSGKEQSLEFCRHRLWGYHDC | ||||||
Disulfide bond | 284↔347 | |||||
Sequence: CKQLGCGKSLHPSPKTRKIYGPGAGRIWLDDVNCSGKEQSLEFCRHRLWGYHDCTHKEDVEVIC | ||||||
Disulfide bond | 317↔327 | |||||
Sequence: CSGKEQSLEFC |
Post-translational modification
N-glycosylated (PubMed:10651944, PubMed:23236605).
N-glycan at Asn-99 possesses only alpha2,6-sialylated terminals, while Asn-229 possesses both alpha2,6-sialylated and non-sialylated terminals (PubMed:23236605).
N-glycosylation increases secretion
N-glycan at Asn-99 possesses only alpha2,6-sialylated terminals, while Asn-229 possesses both alpha2,6-sialylated and non-sialylated terminals (PubMed:23236605).
N-glycosylation increases secretion
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Specifically expressed in tissue macrophages (PubMed:9892623).
Expressed in thymus, liver, spleen and lymph nodes (PubMed:10651944).
Present in Th17 cells; mainly present in non-pathogenic Th17 cells (PubMed:26607793).
Expressed in thymus, liver, spleen and lymph nodes (PubMed:10651944).
Present in Th17 cells; mainly present in non-pathogenic Th17 cells (PubMed:26607793).
Induction
Transcription is activated by nuclear receptor liver X /retinoid X (RXR/LXR).
Gene expression databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 27-128 | SRCR 1 | ||||
Sequence: VQLVGGAHRCEGRVEVEHNGQWGTVCDDGWDRRDVAVVCRELNCGAVIQTPRGASYQPPASEQRVLIQGVDCNGTEDTLAQCELNYDVFDCSHEEDAGAQCE | ||||||
Domain | 141-241 | SRCR 2 | ||||
Sequence: VRLVDGPGHCQGRVEVLHQSQWSTVCKAGWNLQVSKVVCRQLGCGRALLTYGSCNKNTQGKGPIWMGKMSCSGQEANLRSCLLSRLENNCTHGEDTWMECE | ||||||
Domain | 246-348 | SRCR 3 | ||||
Sequence: LKLVGGDTPCSGRLEVLHKGSWGSVCDDNWGEKEDQVVCKQLGCGKSLHPSPKTRKIYGPGAGRIWLDDVNCSGKEQSLEFCRHRLWGYHDCTHKEDVEVICT |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length352
- Mass (Da)38,863
- Last updated2011-07-27 v3
- Checksum41596AA8012E1AEE
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 13 | in Ref. 1; AAB70571 | ||||
Sequence: S → N | ||||||
Sequence conflict | 113 | in Ref. 2; AAD01445 | ||||
Sequence: D → Y |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF018268 EMBL· GenBank· DDBJ | AAB70571.1 EMBL· GenBank· DDBJ | mRNA | ||
AF018269 EMBL· GenBank· DDBJ | AAB70572.1 EMBL· GenBank· DDBJ | mRNA | ||
AF011428 EMBL· GenBank· DDBJ | AAD01445.1 EMBL· GenBank· DDBJ | mRNA | ||
AK159132 EMBL· GenBank· DDBJ | BAE34844.1 EMBL· GenBank· DDBJ | mRNA | ||
AK159181 EMBL· GenBank· DDBJ | BAE34880.1 EMBL· GenBank· DDBJ | mRNA | ||
AK159823 EMBL· GenBank· DDBJ | BAE35403.1 EMBL· GenBank· DDBJ | mRNA | ||
BC006799 EMBL· GenBank· DDBJ | AAH06799.1 EMBL· GenBank· DDBJ | mRNA | ||
BC094459 EMBL· GenBank· DDBJ | AAH94459.1 EMBL· GenBank· DDBJ | mRNA |