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Protein

CD5 antigen-like

Gene

Cd5l

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflammed 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

GO - Biological processi

Keywordsi

Biological processApoptosis, Immunity, Inflammatory response

Names & Taxonomyi

Protein namesi
Recommended name:
CD5 antigen-like
Alternative 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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1334419 Cd5l

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Secreted

Pathology & 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 keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi99N → Q: Decreased glycosylation. 1 Publication1
Mutagenesisi229N → Q: Decreased glycosylation. 1 Publication1
Mutagenesisi316N → Q: Does not affect glycosylation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000003322622 – 352CD5 antigen-likeAdd BLAST331

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi36 ↔ 70PROSITE-ProRule annotation
Disulfide bondi52 ↔ 117PROSITE-ProRule annotation
Disulfide bondi65 ↔ 127PROSITE-ProRule annotation
Disulfide bondi98 ↔ 108PROSITE-ProRule annotation
Glycosylationi99N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi166 ↔ 230PROSITE-ProRule annotation
Disulfide bondi179 ↔ 240PROSITE-ProRule annotation
Disulfide bondi211 ↔ 221PROSITE-ProRule annotation
Glycosylationi229N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi255 ↔ 289PROSITE-ProRule annotation
Disulfide bondi271 ↔ 337PROSITE-ProRule annotation
Disulfide bondi284 ↔ 347PROSITE-ProRule annotation
Disulfide bondi317 ↔ 327PROSITE-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 keyPosition(s)DescriptionActionsGraphical viewLength
Sitei316Not glycosylated1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9QWK4
PaxDbiQ9QWK4
PeptideAtlasiQ9QWK4
PRIDEiQ9QWK4

PTM databases

iPTMnetiQ9QWK4
PhosphoSitePlusiQ9QWK4

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

BgeeiENSMUSG00000015854 Expressed in 75 organ(s), highest expression level in liver
CleanExiMM_CD5L
GenevisibleiQ9QWK4 MM

Interactioni

Subunit structurei

Interacts with FASN; the interaction is direct (PubMed:20519120). Interacts with IgM; protecting CD5L from renal excretion and leading to increased CD5L levels in circulating blood (PubMed:23562157).2 Publications

Protein-protein interaction databases

BioGridi198152, 1 interactor
IntActiQ9QWK4, 1 interactor
MINTiQ9QWK4
STRINGi10090.ENSMUSP00000015998

Structurei

3D structure databases

ProteinModelPortaliQ9QWK4
SMRiQ9QWK4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 128SRCR 1PROSITE-ProRule annotationAdd BLAST102
Domaini141 – 241SRCR 2PROSITE-ProRule annotationAdd BLAST101
Domaini246 – 348SRCR 3PROSITE-ProRule annotationAdd BLAST103

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IKHN Eukaryota
ENOG4110209 LUCA
GeneTreeiENSGT00900000140803
HOGENOMiHOG000290652
HOVERGENiHBG031373
InParanoidiQ9QWK4
OMAiYHGEDAS
OrthoDBiEOG091G0DF7
TreeFamiTF329295

Family and domain databases

Gene3Di3.10.250.10, 3 hits
InterProiView protein in InterPro
IPR001190 SRCR
IPR017448 SRCR-like_dom
IPR036772 SRCR-like_dom_sf
PfamiView protein in Pfam
PF00530 SRCR, 3 hits
PRINTSiPR00258 SPERACTRCPTR
SMARTiView protein in SMART
SM00202 SR, 3 hits
SUPFAMiSSF56487 SSF56487, 3 hits
PROSITEiView protein in PROSITE
PS00420 SRCR_1, 1 hit
PS50287 SRCR_2, 3 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9QWK4-1 [UniParc]FASTAAdd to basket
« Hide
        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
Length:352
Mass (Da):38,863
Last modified:July 27, 2011 - v3
Checksum:i41596AA8012E1AEE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti13S → N in AAB70571 (PubMed:10651944).Curated1
Sequence conflicti113D → Y in AAD01445 (PubMed:9892623).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti61V → M1 Publication1
Natural varianti197N → S2 Publications1
Natural varianti205W → R1 Publication1

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
CCDSiCCDS17451.1
RefSeqiNP_033820.2, NM_009690.2
UniGeneiMm.6676

Genome annotation databases

EnsembliENSMUST00000015998; ENSMUSP00000015998; ENSMUSG00000015854
GeneIDi11801
KEGGimmu:11801
UCSCiuc008psa.2 mouse

Keywords - Coding sequence diversityi

Polymorphism

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
CCDSiCCDS17451.1
RefSeqiNP_033820.2, NM_009690.2
UniGeneiMm.6676

3D structure databases

ProteinModelPortaliQ9QWK4
SMRiQ9QWK4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198152, 1 interactor
IntActiQ9QWK4, 1 interactor
MINTiQ9QWK4
STRINGi10090.ENSMUSP00000015998

PTM databases

iPTMnetiQ9QWK4
PhosphoSitePlusiQ9QWK4

Proteomic databases

MaxQBiQ9QWK4
PaxDbiQ9QWK4
PeptideAtlasiQ9QWK4
PRIDEiQ9QWK4

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000015998; ENSMUSP00000015998; ENSMUSG00000015854
GeneIDi11801
KEGGimmu:11801
UCSCiuc008psa.2 mouse

Organism-specific databases

CTDi922
MGIiMGI:1334419 Cd5l

Phylogenomic databases

eggNOGiENOG410IKHN Eukaryota
ENOG4110209 LUCA
GeneTreeiENSGT00900000140803
HOGENOMiHOG000290652
HOVERGENiHBG031373
InParanoidiQ9QWK4
OMAiYHGEDAS
OrthoDBiEOG091G0DF7
TreeFamiTF329295

Miscellaneous databases

PROiPR:Q9QWK4
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000015854 Expressed in 75 organ(s), highest expression level in liver
CleanExiMM_CD5L
GenevisibleiQ9QWK4 MM

Family and domain databases

Gene3Di3.10.250.10, 3 hits
InterProiView protein in InterPro
IPR001190 SRCR
IPR017448 SRCR-like_dom
IPR036772 SRCR-like_dom_sf
PfamiView protein in Pfam
PF00530 SRCR, 3 hits
PRINTSiPR00258 SPERACTRCPTR
SMARTiView protein in SMART
SM00202 SR, 3 hits
SUPFAMiSSF56487 SSF56487, 3 hits
PROSITEiView protein in PROSITE
PS00420 SRCR_1, 1 hit
PS50287 SRCR_2, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiCD5L_MOUSE
AccessioniPrimary (citable) accession number: Q9QWK4
Secondary accession number(s): O35300
, O35301, Q3TXN5, Q505P6, Q91W05
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: July 27, 2011
Last modified: October 10, 2018
This is version 135 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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