UniProtKB - Q9QWK4 (CD5L_MOUSE)
Protein
CD5 antigen-like
Gene
Cd5l
Organism
Mus musculus (Mouse)
Status
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 (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:26607794, PubMed:26607793). 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:9892623, PubMed:16054063). Involved in early response to microbial infection against various pathogens by acting as a pattern recognition receptor and by promoting autophagy (By similarity).1 PublicationBy similarity8 Publications
GO - Molecular functioni
- scavenger receptor activity Source: InterPro
- serine-type endopeptidase activity Source: GO_Central
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- immune system process Source: UniProtKB-KW
- inflammatory response Source: UniProtKB-KW
- positive regulation of complement-dependent cytotoxicity Source: MGI
- regulation of complement activation Source: MGI
- zymogen activation Source: GO_Central
Keywordsi
Biological process | Apoptosis, Immunity, Inflammatory response |
Names & Taxonomyi
Protein namesi | Recommended name: CD5 antigen-likeAlternative name(s): Apoptosis inhibitor expressed by macrophages1 Publication Short name: mAIM1 Publication Apoptosis inhibitory 6 SP-alpha1 Publication |
Gene namesi | Name:Cd5l Synonyms:Aim1 Publication, Api6 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1334419, Cd5l |
Subcellular locationi
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: MGI
Other locations
- cell surface Source: MGI
- cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cytoplasm, SecretedPathology & Biotechi
Disruption phenotypei
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).3 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 99 | N → Q: Decreased glycosylation. 1 Publication | 1 | |
Mutagenesisi | 229 | N → Q: Decreased glycosylation. 1 Publication | 1 | |
Mutagenesisi | 316 | N → Q: Does not affect glycosylation. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | Sequence analysisAdd BLAST | 21 | |
ChainiPRO_0000033226 | 22 – 352 | CD5 antigen-likeAdd BLAST | 331 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 36 ↔ 70 | PROSITE-ProRule annotation | ||
Disulfide bondi | 52 ↔ 117 | PROSITE-ProRule annotation | ||
Disulfide bondi | 65 ↔ 127 | PROSITE-ProRule annotation | ||
Disulfide bondi | 98 ↔ 108 | PROSITE-ProRule annotation | ||
Glycosylationi | 99 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 166 ↔ 230 | PROSITE-ProRule annotation | ||
Disulfide bondi | 179 ↔ 240 | PROSITE-ProRule annotation | ||
Disulfide bondi | 211 ↔ 221 | PROSITE-ProRule annotation | ||
Glycosylationi | 229 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 255 ↔ 289 | PROSITE-ProRule annotation | ||
Disulfide bondi | 271 ↔ 337 | PROSITE-ProRule annotation | ||
Disulfide bondi | 284 ↔ 347 | PROSITE-ProRule annotation | ||
Disulfide bondi | 317 ↔ 327 | PROSITE-ProRule annotation |
Post-translational modificationi
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.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 316 | Not glycosylated1 Publication | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
CPTACi | non-CPTAC-5585 non-CPTAC-5586 |
MaxQBi | Q9QWK4 |
PaxDbi | Q9QWK4 |
PeptideAtlasi | Q9QWK4 |
PRIDEi | Q9QWK4 |
PTM databases
GlyGeni | Q9QWK4, 2 sites |
iPTMneti | Q9QWK4 |
PhosphoSitePlusi | Q9QWK4 |
Expressioni
Tissue specificityi
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).3 Publications
Inductioni
Transcription is activated by nuclear receptor liver X /retinoid X (RXR/LXR).
Gene expression databases
Bgeei | ENSMUSG00000015854, Expressed in liver and 88 other tissues |
Genevisiblei | Q9QWK4, MM |
Interactioni
Subunit structurei
Protein-protein interaction databases
BioGRIDi | 198152, 1 interactor |
IntActi | Q9QWK4, 1 interactor |
MINTi | Q9QWK4 |
STRINGi | 10090.ENSMUSP00000015998 |
Miscellaneous databases
RNActi | Q9QWK4, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 27 – 128 | SRCR 1PROSITE-ProRule annotationAdd BLAST | 102 | |
Domaini | 141 – 241 | SRCR 2PROSITE-ProRule annotationAdd BLAST | 101 | |
Domaini | 246 – 348 | SRCR 3PROSITE-ProRule annotationAdd BLAST | 103 |
Keywords - Domaini
Repeat, SignalPhylogenomic databases
eggNOGi | ENOG502SHID, Eukaryota |
GeneTreei | ENSGT00940000161974 |
HOGENOMi | CLU_002555_11_0_1 |
InParanoidi | Q9QWK4 |
OMAi | SQCERED |
OrthoDBi | 158600at2759 |
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, 1 hit PS50287, SRCR_2, 3 hits |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q9QWK4-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAPLFNLMLA ILSIFVGSCF SESPTKVQLV GGAHRCEGRV EVEHNGQWGT
60 70 80 90 100
VCDDGWDRRD VAVVCRELNC GAVIQTPRGA SYQPPASEQR VLIQGVDCNG
110 120 130 140 150
TEDTLAQCEL NYDVFDCSHE EDAGAQCENP DSDLLFIPED VRLVDGPGHC
160 170 180 190 200
QGRVEVLHQS QWSTVCKAGW NLQVSKVVCR QLGCGRALLT YGSCNKNTQG
210 220 230 240 250
KGPIWMGKMS CSGQEANLRS CLLSRLENNC THGEDTWMEC EDPFELKLVG
260 270 280 290 300
GDTPCSGRLE VLHKGSWGSV CDDNWGEKED QVVCKQLGCG KSLHPSPKTR
310 320 330 340 350
KIYGPGAGRI WLDDVNCSGK EQSLEFCRHR LWGYHDCTHK EDVEVICTDF
DV
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 13 | S → N in AAB70571 (PubMed:10651944).Curated | 1 | |
Sequence conflicti | 113 | D → Y in AAD01445 (PubMed:9892623).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 61 | V → M1 Publication | 1 | |
Natural varianti | 197 | N → S2 Publications | 1 | |
Natural varianti | 205 | W → R1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF018268 mRNA Translation: AAB70571.1 AF018269 mRNA Translation: AAB70572.1 AF011428 mRNA Translation: AAD01445.1 AK159132 mRNA Translation: BAE34844.1 AK159181 mRNA Translation: BAE34880.1 AK159823 mRNA Translation: BAE35403.1 BC006799 mRNA Translation: AAH06799.1 BC094459 mRNA Translation: AAH94459.1 |
CCDSi | CCDS17451.1 |
RefSeqi | NP_033820.2, NM_009690.2 |
Genome annotation databases
Ensembli | ENSMUST00000015998; ENSMUSP00000015998; ENSMUSG00000015854 |
GeneIDi | 11801 |
KEGGi | mmu:11801 |
UCSCi | uc008psa.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF018268 mRNA Translation: AAB70571.1 AF018269 mRNA Translation: AAB70572.1 AF011428 mRNA Translation: AAD01445.1 AK159132 mRNA Translation: BAE34844.1 AK159181 mRNA Translation: BAE34880.1 AK159823 mRNA Translation: BAE35403.1 BC006799 mRNA Translation: AAH06799.1 BC094459 mRNA Translation: AAH94459.1 |
CCDSi | CCDS17451.1 |
RefSeqi | NP_033820.2, NM_009690.2 |
3D structure databases
SMRi | Q9QWK4 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 198152, 1 interactor |
IntActi | Q9QWK4, 1 interactor |
MINTi | Q9QWK4 |
STRINGi | 10090.ENSMUSP00000015998 |
PTM databases
GlyGeni | Q9QWK4, 2 sites |
iPTMneti | Q9QWK4 |
PhosphoSitePlusi | Q9QWK4 |
Proteomic databases
CPTACi | non-CPTAC-5585 non-CPTAC-5586 |
MaxQBi | Q9QWK4 |
PaxDbi | Q9QWK4 |
PeptideAtlasi | Q9QWK4 |
PRIDEi | Q9QWK4 |
Protocols and materials databases
Antibodypediai | 20452, 487 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000015998; ENSMUSP00000015998; ENSMUSG00000015854 |
GeneIDi | 11801 |
KEGGi | mmu:11801 |
UCSCi | uc008psa.2, mouse |
Organism-specific databases
CTDi | 922 |
MGIi | MGI:1334419, Cd5l |
Phylogenomic databases
eggNOGi | ENOG502SHID, Eukaryota |
GeneTreei | ENSGT00940000161974 |
HOGENOMi | CLU_002555_11_0_1 |
InParanoidi | Q9QWK4 |
OMAi | SQCERED |
OrthoDBi | 158600at2759 |
TreeFami | TF329295 |
Miscellaneous databases
BioGRID-ORCSi | 11801, 0 hits in 17 CRISPR screens |
PROi | PR:Q9QWK4 |
RNActi | Q9QWK4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000015854, Expressed in liver and 88 other tissues |
Genevisiblei | Q9QWK4, MM |
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, 1 hit PS50287, SRCR_2, 3 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CD5L_MOUSE | |
Accessioni | Q9QWK4Primary (citable) accession number: Q9QWK4 Secondary accession number(s): O35300 Q91W05 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 16, 2002 |
Last sequence update: | July 27, 2011 | |
Last modified: | February 10, 2021 | |
This is version 149 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot