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Protein

CD5 antigen-like

Gene

CD5L

Organism
Homo sapiens (Human)
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. 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 Publications

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cellular defense response Source: ProtInc
  • immune system process Source: UniProtKB-KW
  • inflammatory response Source: UniProtKB-KW

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:
hAIM1 Publication
CT-21 Publication
IgM-associated peptide1 Publication
SP-alpha1 Publication
Gene namesi
Name:CD5L
Synonyms:API6
ORF Names:UNQ203/PRO2291 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000073754.5
HGNCiHGNC:1690 CD5L
MIMi602592 gene
neXtProtiNX_O43866

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi123S → A: No effect; when associated with 129-A--A-132. 1 Publication1
Mutagenesisi129 – 132SSFS → AAFA: No effect; when associated with A-123. 1 Publication4

Organism-specific databases

DisGeNETi922
OpenTargetsiENSG00000073754
PharmGKBiPA26229

Polymorphism and mutation databases

BioMutaiCD5L

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 193 PublicationsAdd BLAST19
ChainiPRO_000003322520 – 347CD5 antigen-likeAdd BLAST328

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi33 ↔ 67PROSITE-ProRule annotation
Disulfide bondi49 ↔ 114PROSITE-ProRule annotation
Disulfide bondi62 ↔ 124PROSITE-ProRule annotation
Disulfide bondi96 ↔ 106PROSITE-ProRule annotation
Disulfide bondi163 ↔ 228PROSITE-ProRule annotation
Disulfide bondi176 ↔ 238PROSITE-ProRule annotation
Disulfide bondi208 ↔ 218PROSITE-ProRule annotation
Disulfide bondi253 ↔ 287PROSITE-ProRule annotation
Disulfide bondi269 ↔ 335PROSITE-ProRule annotation
Disulfide bondi282 ↔ 345PROSITE-ProRule annotation
Disulfide bondi315 ↔ 325PROSITE-ProRule annotation

Post-translational modificationi

Not N-glycosylated (PubMed:23236605). Probably not O-glycosylated (PubMed:23236605).1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO43866
PeptideAtlasiO43866
PRIDEiO43866
ProteomicsDBi49213

PTM databases

iPTMnetiO43866
PhosphoSitePlusiO43866

Expressioni

Tissue specificityi

Expressed in spleen, lymph node, thymus, bone marrow, and fetal liver, but not in non-lymphoid tissues.1 Publication

Gene expression databases

BgeeiENSG00000073754 Expressed in 61 organ(s), highest expression level in spleen
CleanExiHS_CD5L
GenevisibleiO43866 HS

Organism-specific databases

HPAiHPA065686
HPA068384

Interactioni

Subunit structurei

Interacts with FASN; the interaction is direct (By similarity). Interacts with IgM; protecting CD5L from renal excretion and leading to increased CD5L levels in circulating blood (PubMed:8034987, PubMed:24804991).By similarity2 Publications

Protein-protein interaction databases

IntActiO43866, 7 interactors
STRINGi9606.ENSP00000357156

Structurei

3D structure databases

ProteinModelPortaliO43866
SMRiO43866
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 125SRCR 1PROSITE-ProRule annotationAdd BLAST102
Domaini138 – 239SRCR 2PROSITE-ProRule annotationAdd BLAST102
Domaini244 – 346SRCR 3PROSITE-ProRule annotationAdd BLAST103

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IKHN Eukaryota
ENOG4110209 LUCA
GeneTreeiENSGT00900000140803
HOGENOMiHOG000290652
HOVERGENiHBG031373
InParanoidiO43866
OMAiYHGEDAS
OrthoDBiEOG091G0DF7
PhylomeDBiO43866
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, 2 hits
PS50287 SRCR_2, 3 hits

Sequencei

Sequence statusi: Complete.

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

O43866-1 [UniParc]FASTAAdd to basket
« Hide
        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
Length:347
Mass (Da):38,088
Last modified:June 1, 1998 - v1
Checksum:i40A8BE08F9495D83
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti347G → V in AAQ88858 (PubMed:12975309).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_033728117D → 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
CCDSiCCDS1171.1
RefSeqiNP_001334627.1, NM_001347698.1
NP_005885.1, NM_005894.2
UniGeneiHs.134035

Genome annotation databases

EnsembliENST00000368174; ENSP00000357156; ENSG00000073754
GeneIDi922
KEGGihsa:922
UCSCiuc001frk.5 human

Keywords - Coding sequence diversityi

Polymorphism

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
CCDSiCCDS1171.1
RefSeqiNP_001334627.1, NM_001347698.1
NP_005885.1, NM_005894.2
UniGeneiHs.134035

3D structure databases

ProteinModelPortaliO43866
SMRiO43866
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO43866, 7 interactors
STRINGi9606.ENSP00000357156

PTM databases

iPTMnetiO43866
PhosphoSitePlusiO43866

Polymorphism and mutation databases

BioMutaiCD5L

Proteomic databases

PaxDbiO43866
PeptideAtlasiO43866
PRIDEiO43866
ProteomicsDBi49213

Protocols and materials databases

DNASUi922
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368174; ENSP00000357156; ENSG00000073754
GeneIDi922
KEGGihsa:922
UCSCiuc001frk.5 human

Organism-specific databases

CTDi922
DisGeNETi922
EuPathDBiHostDB:ENSG00000073754.5
GeneCardsiCD5L
HGNCiHGNC:1690 CD5L
HPAiHPA065686
HPA068384
MIMi602592 gene
neXtProtiNX_O43866
OpenTargetsiENSG00000073754
PharmGKBiPA26229
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKHN Eukaryota
ENOG4110209 LUCA
GeneTreeiENSGT00900000140803
HOGENOMiHOG000290652
HOVERGENiHBG031373
InParanoidiO43866
OMAiYHGEDAS
OrthoDBiEOG091G0DF7
PhylomeDBiO43866
TreeFamiTF329295

Miscellaneous databases

ChiTaRSiCD5L human
GeneWikiiCD5L
GenomeRNAii922
PROiPR:O43866
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000073754 Expressed in 61 organ(s), highest expression level in spleen
CleanExiHS_CD5L
GenevisibleiO43866 HS

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, 2 hits
PS50287 SRCR_2, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiCD5L_HUMAN
AccessioniPrimary (citable) accession number: O43866
Secondary accession number(s): A8K7M5, Q6UX63
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: June 1, 1998
Last modified: September 12, 2018
This is version 143 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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