Immunoglobulin lambda variable 6-57 is a protein which is encoded by the IGLV6-57 gene in humans.
This gene is primarily expressed in the lymphatic system. IGLV6-57 is an extracellular protein that has been predicted to reside within the cytoplasm of cells. The function of IGLV6-57 is predicted to be involved in the immune response and enabling antigen binding activity. This prediction also matches with pathogen recognition from antibodies utilizing IGLV6-57 light chains.
Gene
Aliases Known aliases of IGLV6-57 include V1-22 or IGLV657.
Locus Human IGLV6-57 gene is found on the forward (+) strand at the locus NC_000022.11. The gene ranges from position 22026076 to position 22922913 on chromosome 22. mRNA IGLV6-57's transcript is reported to be around 478 nucleotides long. It has two exons separated between one intron.
Expression pattern IGLV6-57 is moderately expressed in spleen, lymph node, and tonsil tissue.
Transcript IGLV6-57 gene contains no alternatively spliced forms because it is an immunoglobulin variable-region gene segment, not a complete antibody gene.
Protein
Protein characteristics The predicted molecular weight of IGLV6-57 is 12.566 kDa, and it has a predicted isoelectric point (pI) of pH 4.59. In terms of amino acid composition, IGLV6-57 has a relatively proportion of polar amino acids serine, glycine, and threonine. It also is relatively poor in histidine, methionine, and tryptophan.
Isoforms Immunoglobulin Lambda Variable 6-57 primarily expresses a single protein isoform. Secondary structure The predicted secondary structure of IGLV6-57 is composed primarily of β strands.
Teritiary structure The predicted teritiary structure of IGLV6-57 consists of two antiparallel β sheets stabilized by conserved intradomain disulfide bond.
Post-translational modifications
Disulfide bond formation Conceptual translation of human IGLV6-57 mRNA revealed two conserved cysteine residues at position 20 and 89 and are predicted to form an intradomain disulfide bond.
Cellular localization Computational prediction have identifies the IGLV6-57 protein in the extracellular and cytoplasm location. IGLV6-57 is predicted to be a soluble protein.
Regulation and expression
Promoters No promoter was identified in the analyzed upstream sequence of IGLV6-57 using computational promoter prediction methods.
Transcription factors The following table summarizes transcription factors predicted to bind highly conserved regions of the IGLV6-57 sequence. +Selected transcription factors predicted to bind to highly conserved regions of IGLV6-57Transcription FactorDescriptionMAFGbZip Maf transcription factor proteinMAFKbZip Maf transcription factor proteinMAFAβ cell-specific activator
Expression
Tissue specificity According to RNA-seq data, IGLV6-57 is expressed most highly in lymph node, spleen, and appendix tissue.
Embryonic development IGLV6-57 expression is highest in the fetal adrenal gland during mid-gestation (16–18 weeks), with lower expression in several other fetal tissues. No specific role in embryonic development has been established.
Differential expression IGLV6-57 has been observed to be expressed at higher levels in beta-catenin-depleted cells than in untreated control cells.
IGLV6-57 has been observed to be expressed at higher levels in tumor tissue than in adjacent normal tissue.
Interacting proteins The StringNetwork database indicates that the following proteins have been found to interact with the IGLV6-57 protein. +ProteinDescriptionFCARbinds the heavy-chain constant region of Immunoglobulin A (IgA) antibodiesCD5cluster of differentiation expressed on the surface of T cellsTFPIsingle-chain polypeptide which can reversibly inhibit factor Xa (Xa)
Homology and evolution
Orthologs IGLV6-57 has orthologs in Mammalia, Aves, Reptillia, and Amphibia. A table of selected orthologs is listed below.
Selected orthologs of the homo sapiens IGLV6-57 protein Genus and SpeciesCommon NameTaxonomic GroupDate of Divergence from Humans (MYA)Accession Number #Sequence LengthSequence IdentityHomo sapiensHumanPrimates0NP_037510.1116 aa43%Mus musculusHouse mousePlacental87NP_001415808.1130 aa68%Saccopteryx bilineataGreater sac-winged batChiroptera94XP_066116077.1121 aa86%Phascolarctos cinereusKoalaMarsupials Mammal160XP_020833304.1123 aa69%Ornithorhynchus anatinusPlatypusMonotremes180XP_028904584.1123 aa63%Athene noctuaLittle owlAves319XP_074777375.1272 aa58%Centrocercus urophasianusGreater sage-grouseAves319XP_042685107.1125 aa56%Pseudonaja textilisEastern brown snakeSquamata319XP_026574391.1110 aa61%Crocodylus porosusSaltwater crocodileCrocodilia319XP_019394969.1125 aa59%Pelodiscus sinensisChinese softshell turtleTestudines319XP_075753974.1137 aa59%Bufo bufoCommon toadAnura352XP_040275605.1239 aa53%Ambystoma mexicanumAxolotlCaudata352XP_069476393.1144 aa48%Hyla sardaSardinian tree frogAnura352XP_056387603.1130 aa46%Rhinatrema bivittatumTwo-lined caecilianGymnophiona352XP_029426890.1127 aa51%
Evolutionary history IGLV6-57 is not a highly conserved gene due to evolutionary divergence driven by the adaptive immune system. The most evolutionary distant ortholog of IGLV6-57 is in the Sardinian tree frog (Hyla sarda); and it is conserved from Amphibia to Mammalia, with no detectable orthologs in invertebrates. Paralogs IGLV6-57 contains numerous paralogous genes located within the immunoglobulin lambda locus on chromosome 22. +Paralog genes located within the immunoglobulin lambda locus on chromosome 22ParalogDescriptionIGLVV-58antigen recognitionIGLV11-55non-functional immunoglobulin lambda variable geneIGLV1-56antigen recognitionBMP6P1pseudogene
Clinical significance IGLV6-57 has been a linked site for an amyloid-associated residue change associated with AL amyloidosis. Additionally, proteins from this specific lambda light chain class is likely to unfold, exposing the hydrophobic core of the protein. Due to structural instability, the IGLV6-57 gene segment frequently misfolds.
References