UniProtKB - O43866 (CD5L_HUMAN)
CD5 antigen-like
CD5L
Functioni
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-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 (By similarity).
Also acts as an inhibitor of apoptosis in macrophages: promotes macrophage survival from the apoptotic effects of oxidized lipids in case of atherosclerosis (PubMed:24295828).
Involved in early response to microbial infection against various pathogens by acting as a pattern recognition receptor and by promoting autophagy (PubMed:16030018, PubMed:24223991, PubMed:24583716, PubMed:25713983).
By similarity5 PublicationsGO - Molecular functioni
- scavenger receptor activity Source: InterPro
- serine-type endopeptidase activity Source: GO_Central
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- cellular defense response Source: ProtInc
- immune system process Source: UniProtKB-KW
- inflammatory response Source: UniProtKB-KW
- positive regulation of complement-dependent cytotoxicity Source: Ensembl
- regulation of complement activation Source: Ensembl
- zymogen activation Source: GO_Central
Keywordsi
Biological process | Apoptosis, Immunity, Inflammatory response |
Enzyme and pathway databases
PathwayCommonsi | O43866 |
SignaLinki | O43866 |
Names & Taxonomyi
Protein namesi | Recommended name: CD5 antigen-likeAlternative name(s): Apoptosis inhibitor expressed by macrophages1 Publication Short name: hAIM1 Publication CT-21 Publication IgM-associated peptide1 Publication SP-alpha1 Publication |
Gene namesi | Name:CD5L Synonyms:API6 ORF Names:UNQ203/PRO2291 Publication |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:1690, CD5L |
MIMi | 602592, gene |
neXtProti | NX_O43866 |
VEuPathDBi | HostDB:ENSG00000073754 |
Subcellular locationi
Extracellular region or secreted
- blood microparticle Source: UniProtKB
- extracellular region Source: UniProtKB
- extracellular space Source: ProtInc
Plasma Membrane
- plasma membrane Source: GO_Central
Other locations
- cell surface Source: MGI
- cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cytoplasm, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 123 | S → A: No effect; when associated with 129-A--A-132. 1 Publication | 1 | |
Mutagenesisi | 129 – 132 | SSFS → AAFA: No effect; when associated with A-123. 1 Publication | 4 |
Organism-specific databases
DisGeNETi | 922 |
OpenTargetsi | ENSG00000073754 |
PharmGKBi | PA26229 |
Miscellaneous databases
Pharosi | O43866, Tbio |
Genetic variation databases
BioMutai | CD5L |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | 3 PublicationsAdd BLAST | 19 | |
ChainiPRO_0000033225 | 20 – 347 | CD5 antigen-likeAdd BLAST | 328 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 33 ↔ 67 | PROSITE-ProRule annotation | ||
Disulfide bondi | 49 ↔ 114 | PROSITE-ProRule annotation | ||
Disulfide bondi | 62 ↔ 124 | PROSITE-ProRule annotation | ||
Disulfide bondi | 96 ↔ 106 | PROSITE-ProRule annotation | ||
Disulfide bondi | 163 ↔ 228 | PROSITE-ProRule annotation | ||
Disulfide bondi | 176 ↔ 238 | PROSITE-ProRule annotation | ||
Disulfide bondi | 208 ↔ 218 | PROSITE-ProRule annotation | ||
Disulfide bondi | 253 ↔ 287 | PROSITE-ProRule annotation | ||
Disulfide bondi | 269 ↔ 335 | PROSITE-ProRule annotation | ||
Disulfide bondi | 282 ↔ 345 | PROSITE-ProRule annotation | ||
Disulfide bondi | 315 ↔ 325 | PROSITE-ProRule annotation |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
CPTACi | non-CPTAC-1092 |
jPOSTi | O43866 |
MassIVEi | O43866 |
PaxDbi | O43866 |
PeptideAtlasi | O43866 |
PRIDEi | O43866 |
ProteomicsDBi | 49213 |
PTM databases
GlyGeni | O43866, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | O43866 |
PhosphoSitePlusi | O43866 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000073754, Expressed in spleen and 91 other tissues |
Genevisiblei | O43866, HS |
Organism-specific databases
HPAi | ENSG00000073754, Tissue enriched (lymphoid) |
Interactioni
Subunit structurei
Protein-protein interaction databases
IntActi | O43866, 7 interactors |
STRINGi | 9606.ENSP00000357156 |
Miscellaneous databases
RNActi | O43866, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 24 – 125 | SRCR 1PROSITE-ProRule annotationAdd BLAST | 102 | |
Domaini | 138 – 239 | SRCR 2PROSITE-ProRule annotationAdd BLAST | 102 | |
Domaini | 244 – 346 | SRCR 3PROSITE-ProRule annotationAdd BLAST | 103 |
Keywords - Domaini
Repeat, SignalPhylogenomic databases
eggNOGi | ENOG502SHID, Eukaryota |
GeneTreei | ENSGT00940000161974 |
HOGENOMi | CLU_002555_11_0_1 |
InParanoidi | O43866 |
OMAi | LHKGVWG |
OrthoDBi | 158600at2759 |
PhylomeDBi | O43866 |
TreeFami | TF329295 |
Family and domain databases
Gene3Di | 3.10.250.10, 3 hits |
InterProi | View protein in InterPro IPR001190, SRCR IPR017448, SRCR-like_dom IPR036772, SRCR-like_dom_sf |
Pfami | View protein in Pfam PF00530, SRCR, 3 hits |
PRINTSi | PR00258, SPERACTRCPTR |
SMARTi | View protein in SMART SM00202, SR, 3 hits |
SUPFAMi | SSF56487, SSF56487, 3 hits |
PROSITEi | View protein in PROSITE PS00420, SRCR_1, 2 hits PS50287, SRCR_2, 3 hits |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MALLFSLILA ICTRPGFLAS PSGVRLVGGL HRCEGRVEVE QKGQWGTVCD
60 70 80 90 100
DGWDIKDVAV LCRELGCGAA SGTPSGILYE PPAEKEQKVL IQSVSCTGTE
110 120 130 140 150
DTLAQCEQEE VYDCSHDEDA GASCENPESS FSPVPEGVRL ADGPGHCKGR
160 170 180 190 200
VEVKHQNQWY TVCQTGWSLR AAKVVCRQLG CGRAVLTQKR CNKHAYGRKP
210 220 230 240 250
IWLSQMSCSG REATLQDCPS GPWGKNTCNH DEDTWVECED PFDLRLVGGD
260 270 280 290 300
NLCSGRLEVL HKGVWGSVCD DNWGEKEDQV VCKQLGCGKS LSPSFRDRKC
310 320 330 340
YGPGVGRIWL DNVRCSGEEQ SLEQCQHRFW GFHDCTHQED VAVICSG
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 347 | G → V in AAQ88858 (PubMed:12975309).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_033728 | 117 | D → E. Corresponds to variant dbSNP:rs11537583Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U82812 mRNA Translation: AAB91989.1 AF011429 mRNA Translation: AAD01446.1 AY358494 mRNA Translation: AAQ88858.1 AK292040 mRNA Translation: BAF84729.1 AL139409 Genomic DNA No translation available. CH471121 Genomic DNA Translation: EAW52859.1 BC033586 mRNA Translation: AAH33586.1 |
CCDSi | CCDS1171.1 |
RefSeqi | NP_001334627.1, NM_001347698.1 NP_005885.1, NM_005894.2 |
Genome annotation databases
Ensembli | ENST00000368174.5; ENSP00000357156.4; ENSG00000073754.6 |
GeneIDi | 922 |
KEGGi | hsa:922 |
MANE-Selecti | ENST00000368174.5; ENSP00000357156.4; NM_005894.3; NP_005885.1 |
UCSCi | uc001frk.5, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U82812 mRNA Translation: AAB91989.1 AF011429 mRNA Translation: AAD01446.1 AY358494 mRNA Translation: AAQ88858.1 AK292040 mRNA Translation: BAF84729.1 AL139409 Genomic DNA No translation available. CH471121 Genomic DNA Translation: EAW52859.1 BC033586 mRNA Translation: AAH33586.1 |
CCDSi | CCDS1171.1 |
RefSeqi | NP_001334627.1, NM_001347698.1 NP_005885.1, NM_005894.2 |
3D structure databases
AlphaFoldDBi | O43866 |
SMRi | O43866 |
ModBasei | Search... |
Protein-protein interaction databases
IntActi | O43866, 7 interactors |
STRINGi | 9606.ENSP00000357156 |
PTM databases
GlyGeni | O43866, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | O43866 |
PhosphoSitePlusi | O43866 |
Genetic variation databases
BioMutai | CD5L |
Proteomic databases
CPTACi | non-CPTAC-1092 |
jPOSTi | O43866 |
MassIVEi | O43866 |
PaxDbi | O43866 |
PeptideAtlasi | O43866 |
PRIDEi | O43866 |
ProteomicsDBi | 49213 |
Protocols and materials databases
Antibodypediai | 20452, 504 antibodies from 36 providers |
DNASUi | 922 |
Genome annotation databases
Ensembli | ENST00000368174.5; ENSP00000357156.4; ENSG00000073754.6 |
GeneIDi | 922 |
KEGGi | hsa:922 |
MANE-Selecti | ENST00000368174.5; ENSP00000357156.4; NM_005894.3; NP_005885.1 |
UCSCi | uc001frk.5, human |
Organism-specific databases
CTDi | 922 |
DisGeNETi | 922 |
GeneCardsi | CD5L |
HGNCi | HGNC:1690, CD5L |
HPAi | ENSG00000073754, Tissue enriched (lymphoid) |
MIMi | 602592, gene |
neXtProti | NX_O43866 |
OpenTargetsi | ENSG00000073754 |
PharmGKBi | PA26229 |
VEuPathDBi | HostDB:ENSG00000073754 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502SHID, Eukaryota |
GeneTreei | ENSGT00940000161974 |
HOGENOMi | CLU_002555_11_0_1 |
InParanoidi | O43866 |
OMAi | LHKGVWG |
OrthoDBi | 158600at2759 |
PhylomeDBi | O43866 |
TreeFami | TF329295 |
Enzyme and pathway databases
PathwayCommonsi | O43866 |
SignaLinki | O43866 |
Miscellaneous databases
BioGRID-ORCSi | 922, 8 hits in 1063 CRISPR screens |
ChiTaRSi | CD5L, human |
GeneWikii | CD5L |
GenomeRNAii | 922 |
Pharosi | O43866, Tbio |
PROi | PR:O43866 |
RNActi | O43866, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000073754, Expressed in spleen and 91 other tissues |
Genevisiblei | O43866, HS |
Family and domain databases
Gene3Di | 3.10.250.10, 3 hits |
InterProi | View protein in InterPro IPR001190, SRCR IPR017448, SRCR-like_dom IPR036772, SRCR-like_dom_sf |
Pfami | View protein in Pfam PF00530, SRCR, 3 hits |
PRINTSi | PR00258, SPERACTRCPTR |
SMARTi | View protein in SMART SM00202, SR, 3 hits |
SUPFAMi | SSF56487, SSF56487, 3 hits |
PROSITEi | View protein in PROSITE PS00420, SRCR_1, 2 hits PS50287, SRCR_2, 3 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | CD5L_HUMAN | |
Accessioni | O43866Primary (citable) accession number: O43866 Secondary accession number(s): A8K7M5, Q6UX63 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 16, 2002 |
Last sequence update: | June 1, 1998 | |
Last modified: | May 25, 2022 | |
This is version 163 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot