CD5 antigen-like (CD5L)
The protein contains 347 amino acids for an estimated molecular weight of 38088 Da.
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. Able to inhibit lipid droplet size in adipocytes. 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). 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. Regulation of intracellular lipids mediated by CD5L has a direct effect on transcription regulation mediated by nuclear receptors ROR-gamma (RORC). Acts as a key regulator of metabolic switch in T-helper Th17 cells. 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. 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. Participates in obesity-a (updated: May 8, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs11537583 |
No binding partner found
Biological Process
Apoptotic process
Cellular defense response
Immune system process
Inflammatory response
Positive regulation of complement-dependent cytotoxicity
Regulation of complement activation
Zymogen activation
The reference OMIM entry for this protein is 602592
Lymphocyte antigen cd5-like; cd5l
Scavenger receptor cysteine-rich family, member sp-alpha
Sp-alpha
Apoptosis inhibitor 6; api6
Apoptosis inhibitor of macrophages; aim
CLONING
Scavenger receptor cysteine-rich (SRCR) family members are among the proteins that regulate leukocyte function. One group of SRCR proteins includes CD5 (153340) and CD6 (186720), both of which have 3 SRCR-like domains each containing 8 cysteine residues in their extracellular region, a hydrophobic transmembrane domain, and a long cytoplasmic domain. While searching for new SRCR family members in sequence databases, Gebe et al. (1997) identified a gene with extensive homology to CD5 and CD6. The predicted 347-amino acid protein, which they called Sp-alpha, has a 19-amino acid signal sequence followed by 3 cysteine-rich SRCR domains. Northern blot analysis detected 3 mRNAs of 2.4, 2.1, and 1.8 kb in spleen, lymph node, thymus, bone marrow, and fetal liver, but not in nonlymphoid tissues. Some resting myeloid cell lines, as well as peripheral blood monocytes, were capable of binding Sp-alpha.GENE FUNCTION
Arai et al. (2005) found that Aim expression was induced in mouse macrophages in response to loading with highly oxidized low density lipoprotein (oxLDL), and that Aim was expressed in foam cells within atherosclerotic lesions. Both the expression of Aim in lesions and its induction by oxLDL required Lxr (see 602423)/Rxr (see 180245) heterodimers. Aim-null macrophages were highly susceptible to oxLDL-induced apoptosis in vitro and underwent accelerated apoptosis in atherosclerotic lesions in vivo. Double knockout of Aim and Ldlr (606945) reduced atherosclerotic lesions. Arai et al. (2005) concluded that AIM expression protects macrophages from apoptosis within atherosclerotic lesions, promoting early lesion development.MAPPING
Gebe et al. (1997) mapped the Sp-alpha gene to 1q21-q23 by fluorescence in situ hybridization. ... More on the omim web site
May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for CD5L
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602592 was added.