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Protein

CD5 antigen-like

Gene

CD5L

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
Complete GO annotation...

Keywords - Biological processi

Apoptosis, Immunity, Inflammatory response

Enzyme and pathway databases

BioCyciZFISH:ENSG00000073754-MONOMER.

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

HGNCiHGNC:1690. CD5L.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • cytoplasm Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: ProtInc
  • membrane Source: InterPro
Complete GO annotation...

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.

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.
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.
MINTiMINT-6769012.
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

Sequence similaritiesi

Contains 3 SRCR domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IKHN. Eukaryota.
ENOG4110209. LUCA.
GeneTreeiENSGT00840000129699.
HOGENOMiHOG000290652.
HOVERGENiHBG031373.
InParanoidiO43866.
OMAiYHGEDAS.
OrthoDBiEOG091G0DF7.
PhylomeDBiO43866.
TreeFamiTF329295.

Family and domain databases

Gene3Di3.10.250.10. 3 hits.
InterProiIPR001190. SRCR.
IPR017448. SRCR-like_dom.
[Graphical view]
PfamiPF00530. SRCR. 3 hits.
[Graphical view]
PRINTSiPR00258. SPERACTRCPTR.
SMARTiSM00202. SR. 3 hits.
[Graphical view]
SUPFAMiSSF56487. SSF56487. 3 hits.
PROSITEiPS00420. SRCR_1. 2 hits.
PS50287. SRCR_2. 3 hits.
[Graphical view]

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 rs11537583dbSNPEnsembl.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. Translation: CAC19458.1.
CH471121 Genomic DNA. Translation: EAW52859.1.
BC033586 mRNA. Translation: AAH33586.1.
CCDSiCCDS1171.1.
RefSeqiNP_005885.1. NM_005894.2.
XP_005245659.1. XM_005245602.1.
UniGeneiHs.134035.

Genome annotation databases

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

Keywords - Coding sequence diversityi

Polymorphism

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. Translation: CAC19458.1.
CH471121 Genomic DNA. Translation: EAW52859.1.
BC033586 mRNA. Translation: AAH33586.1.
CCDSiCCDS1171.1.
RefSeqiNP_005885.1. NM_005894.2.
XP_005245659.1. XM_005245602.1.
UniGeneiHs.134035.

3D structure databases

ProteinModelPortaliO43866.
SMRiO43866.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO43866. 7 interactors.
MINTiMINT-6769012.
STRINGi9606.ENSP00000357156.

PTM databases

iPTMnetiO43866.
PhosphoSitePlusiO43866.

Polymorphism and mutation databases

BioMutaiCD5L.

Proteomic databases

PaxDbiO43866.
PeptideAtlasiO43866.
PRIDEiO43866.

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.
GeneCardsiCD5L.
HGNCiHGNC:1690. CD5L.
HPAiHPA065686.
HPA068384.
MIMi602592. gene.
neXtProtiNX_O43866.
OpenTargetsiENSG00000073754.
PharmGKBiPA26229.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKHN. Eukaryota.
ENOG4110209. LUCA.
GeneTreeiENSGT00840000129699.
HOGENOMiHOG000290652.
HOVERGENiHBG031373.
InParanoidiO43866.
OMAiYHGEDAS.
OrthoDBiEOG091G0DF7.
PhylomeDBiO43866.
TreeFamiTF329295.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000073754-MONOMER.

Miscellaneous databases

GeneWikiiCD5L.
GenomeRNAii922.
PROiO43866.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000073754.
CleanExiHS_CD5L.
GenevisibleiO43866. HS.

Family and domain databases

Gene3Di3.10.250.10. 3 hits.
InterProiIPR001190. SRCR.
IPR017448. SRCR-like_dom.
[Graphical view]
PfamiPF00530. SRCR. 3 hits.
[Graphical view]
PRINTSiPR00258. SPERACTRCPTR.
SMARTiSM00202. SR. 3 hits.
[Graphical view]
SUPFAMiSSF56487. SSF56487. 3 hits.
PROSITEiPS00420. SRCR_1. 2 hits.
PS50287. SRCR_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCD5L_HUMAN
AccessioniPrimary (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: November 2, 2016
This is version 133 of the entry and version 1 of the sequence. [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
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.