Galectin-8 (LGALS8)

The protein contains 317 amino acids for an estimated molecular weight of 35808 Da.

 

Beta-galactoside-binding lectin that acts as a sensor of membrane damage caused by infection and restricts the proliferation of infecting pathogens by targeting them for autophagy (PubMed:22246324, PubMed:28077878). Detects membrane rupture by binding beta-galactoside ligands located on the lumenal side of the endosome membrane; these ligands becoming exposed to the cytoplasm following rupture (PubMed:22246324, PubMed:28077878). Restricts infection by initiating autophagy via interaction with CALCOCO2/NDP52 (PubMed:22246324, PubMed:28077878). Required to restrict infection of bacterial invasion such as S.typhimurium (PubMed:22246324). Also required to restrict infection of Picornaviridae viruses (PubMed:28077878). Has a marked preference for 3'-O-sialylated and 3'-O-sulfated glycans (PubMed:21288902). (updated: Jan. 31, 2018)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 94%
Model score: 99

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VariantDescription
dbSNP:rs1126407
dbSNP:rs1041935
dbSNP:rs1041937
dbSNP:rs2243525

The reference OMIM entry for this protein is 606099

Lectin, galactoside-binding, soluble, 8; lgals8
Galectin 8
Prostate carcinoma tumor antigen 1; pcta1

DESCRIPTION

Galectins, such as LGALS8, are beta-galactoside-binding animal lectins with conserved carbohydrate recognition domains (CRDs). Galectins are involved in various biologic processes, including cell signaling, proliferative control, cell adhesion, and cell migration (summary by Su et al. (1996) and Gopalkrishnan et al. (2000)).

CLONING

By surface-epitope masking and expression cloning using a prostate cancer cDNA library, Su et al. (1996) isolated a cDNA encoding LGALS8, which they called PCTA1. The deduced 317-amino acid protein is 81% homologous to rat galectin-8 (Hadari et al., 1995), which contains 2 CRDs. By Northern blot analysis, Gopalkrishnan et al. (2000) detected wide but variable expression of 3 major LGALS8 transcripts of 1.6, 2.6, and 6.0 kb in normal tissue. Fluorescence microscopy demonstrated cytoplasmic expression.

GENE FUNCTION

Using RT-PCR analysis, Su et al. (1996) detected expression of LGALS8 in all 7 prostate carcinomas tested, but in only in 1 of 4 benign prostatic hypertrophy samples tested. By screening for innate proteins that could recognize human blood group antigens, Stowell et al. (2010) identified GAL4 (LGALS4; 602518) and GAL8, both of which are expressed in the intestinal tract, as proteins that recognized and killed E. coli expressing blood group antigen, but not bacteria that did not express such antigens. Video, fluorescence, and electron microscopy showed that bacterial cells lost motility and membrane integrity upon treatment with these lectins. Mutation analysis indicated that the killing activity was mediated by the C-terminal domains of GAL4 and GAL8 in a rapid, complement-independent manner. Stowell et al. (2010) concluded that innate defense lectins provide immunity against pathogens expressing blood group-like antigens on their surface. Thurston et al. (2012) demonstrated in human cells that galectin-8, a cytosolic lectin also known as LGALS8, is a danger receptor that restricts Salmonella proliferation. Galectin-8 monitors endosomal and lysosomal integrity and detects bacterial invasion by binding host glycans exposed on damaged Salmonella-containing vacuoles. By recruiting NDP52 (CALCOCO2; 604587), galectin-8 activates antibacterial autophagy. Galectin-8-dependent recruitment of NDP52 to Salmonella-containing vesicles is transient and followed by ubiquitin-dependent NDP52 recruitment. Because galectin-8 also detects sterile damage to endosomes or lysosomes, as well as invasion by Listeria or Shigella, Thurston et al. (2012) suggested that galectin-8 serves as a versatile receptor for vesicle-damaging pathogens. The results of Thurston et al. (2012) also illustrated how cells deploy the danger receptor galectin-8 to combat infection by monitoring endosomal and lysosomal integrity on the basis of the specific lack of complex carbohydrates in the cytosol.

GENE STRUCTURE

By genomic sequence analysis, Gopalkrishnan et al. (2000) determined that the LGALS8 gene contains a TATA box and 10 exons, 8 of which are expressed constitutively. The additional exons, 7-prime and 7-double-prime, are present in splice variants.

MAPPING

By radiation hybrid analysis, Gopalkrishnan et al. (2000) mapped the LGALS8 gene to chromosome 1q42-q43, a region that contains a gene predisposing to early-onset prostate cancer (PCAP; 602759). ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 606099 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed