Transmembrane Protein 176B, or TMEM176B is a transmembrane protein that in humans is encoded by the TMEM176B gene. It is thought to play a role in the process of maturation of dendritic cells.

Gene

Location TMEM176B is also known as LR8, and MS4B2. The gene is found on the minus end of Chromosome 7, on the long arm at position 7q36.1."TMEM176B Transmembrane Protein 176B [Homo Sapiens (Human)] - Gene - NCBI". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=full_report&list_uids=28959. The starting position of the gene is at 150,791,287 and goes to 150,801,360. It has 10,074 base pairs and has a total of 11 exons."Homo Sapiens Chromosome 7, Grch38.P13 Primary Assembly - Nucleotide - NCBI". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/nuccore/NC_000007.14?report=fasta&from=150791287&to=150801360&strand=true.

Gene TMEM176A and LOC105375566 is a neighbor of TMEM176B."Geneloc Integrated Map For Chromosome 7: Search Results". Genecards.Weizmann.Ac.Il, 2019, https://genecards.weizmann.ac.il/geneloc-bin/display_map.pl?chr_nr=7&range_type=gc_id&gc_id=GC07M150791#GC07M150791.Genecards.Org, 2019, https://www.genecards.org/cgi-bin/carddisp.pl?gene=LOC105375566.

Expression The gene is found to be most expressed in the liver with the kidney being the second most expressed tissue.

Transcript variants There are 3 isoforms (A, B, C) of this gene with variants of isoform A and C. Isoform A variant 1 has 1444 nucleotides that encode 270 amino acids. There are 17 alternatively spliced variants with 1 unspliced transcript variant.Danielle Thierry-Mieg and Jean Thierry-Mieg, . "Aceview: Geneid:TMEM176B, A Comprehensive Annotation Of Human, Mouse And Worm Genes With Mrnas Or Estsaceview.". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?c=geneid&org=9606&l=28959.

Homology

Paralogs There is one paralog of TMEM176B which is TMEM176A."Gene: TMEM176A (ENSG00000002933) - Paralogues - Homo Sapiens - Ensembl Genome Browser 97". Useast.Ensembl.Org, 2019, http://useast.ensembl.org/Homo_sapiens/Gene/Compara_Paralog?g=ENSG00000002933;r=7:150800403-150805118.

Orthologs

Below is a table of orthologs of TMEM176B, these include close and somewhat distant orthologs.

Common name Accession number Sequence length Sequence identity Sequence similarity Human NP_054739.3 270 100 100 Bonobo XP_008966185.1 286 99 98 Ugandan red colobus XP_023081229.1 268 91 92 Small-eared galago XP_003792108.1 268 68 77 Sunda flying lemur XP_008564209.1 271 71 80 House mouse NP_001273581.1 263 53 66 Ryukyu mouse XP_021020106.1 265 53 67 Przewalski's horse XP_008506799.1 270 70 80 Cheetah XP_026907001.1 271 68 77 Water buffalo XP_006049155.1 265 66 76 Wild yak XP_005908946.1 265 65 75 Sperm whale XP_028345261.1 266 65 73 Killer whale XP_012392713.1 265 64 73 Pacific walrus XP_004408899.1 271 64 75 Giant panda XP_019651134.1 271 68 79 Red fox XP_025849593.1 273 63 73 West Indian manatee XP_004372786.1 271 66 76 Koala XP_020833594.1 268 46 62 Asian arowana XP_018595194.1 252 38 47 Northern pike XP_010904195.4 251 26 46

There are around 125 orthologs of the gene ranging from primates to mice and to certain species of fish."TMEM176B Orthologs". NCBI, 2019, https://www.ncbi.nlm.nih.gov/gene/28959/ortholog/?scope=117570.

Homologs The homologs of this gene include chimpanzee, rhesus monkey, dog, cow, mouse, and rat.Homologene - NCBI". Ncbi.Nlm.Nih.Gov, 2019, .

Protein

The molecular weight of TMEM176B is 29.1 kilodaltons (kDa). The protein is rich in valine and poor in aspartic acid."SAPS Results". Ebi.Ac.Uk, 2019, https://www.ebi.ac.uk/Tools/services/web/toolresult.ebi?jobId=saps-I20190730-112615-0877-10414538-p2m. There are 4 transmembrane regions within TMEM176B isoform a.2019, https://psort.hgc.jp/cgi-bin/runpsort.pl. Accessed 4 Aug 2019. There is a CD20 domain from 198 to 687."Transmembrane Protein 176B Isoform A [Homo Sapiens] - Protein - NCBI". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/protein/NP_054739.3.

Domains The CD20-like family includes the CD20 gene but is part of the family pfam04103 which is part of superfamily cl04401. This specific domain region is 489 bp."CDD Conserved Protein Domain Family: CD20". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=309291.

Secondary structure TMEM176B is composed of alpha helices, beta strands and TM helices. The Alpha helices make up most of the secondary structure followed by TM helices."Phyre 2 Results For Undefined". Sbg.Bio.Ic.Ac.Uk, 2019, http://www.sbg.bio.ic.ac.uk/phyre2/phyre2_output/607daef47ac621bf/summary.html .

Subcellular localization Mainly localized to the Golgi apparatus but is additionally localized to the plasma membrane and nucleoplasm."Cell Atlas - TMEM176B - The Human Protein Atlas". Proteinatlas.Org, 2019, http://www.proteinatlas.org/ENSG00000106565-TMEM176B/cell.

Protein-protein interactions The protein interacts most commonly with TMEM176A. It also interacts with TMEM47 and CPXM1 (carboxypeptidase 1) but at lower levels."TMEM176B Protein (Human) - STRING Interaction Network". String-Db.Org, 2019, https://string-db.org/cgi/network.pl?taskId=YtRoRnnnUnu6.

Regulation

Gene There are 11 promoters in TMEM176B. The promoter region before isoform a is 1101 bp and covers 150,799,077-150,800,177."Genomatix". Genomatix.De, 2019, https://www.genomatix.de/cgi-bin/eldorado/eldorado.pl?s=31f15c28bad5fbc98bd01817d3f6f82f;SHOW_ANNOTATION=result_1;ELDORADO_VERSION=E34R1811.

Protein There are 4 phosphorylation sites in TMEM176B isoform a.Transmembrane Protein 176B Isoform A [Homo Sapiens] - Protein - NCBI". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/protein/NP_054739.3.

Clinical significance

There has been research that indicates that TMEM176B is associated with cancer when an abnormal of the gene accumulates.

References