TMEM176B explained

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.[1]

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.[2] 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.[3]

Gene

TMEM176A and LOC105375566 is a neighbor of TMEM176B.[4] [5]

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.[6]

Homology

Paralogs

There is one paralog of TMEM176B which is TMEM176A.[7]

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
NP_054739.3 270 100 100
XP_008966185.1 286 99 98
XP_023081229.1 268 91 92
XP_003792108.1 268 68 77
XP_008564209.1 271 71 80
NP_001273581.1 263 53 66
XP_021020106.1 265 53 67
XP_008506799.1 270 70 80
XP_026907001.1 271 68 77
XP_006049155.1 265 66 76
XP_005908946.1 265 65 75
XP_028345261.1 266 65 73
XP_012392713.1 265 64 73
XP_004408899.1 271 64 75
XP_019651134.1 271 68 79
XP_025849593.1 273 63 73
XP_004372786.1 271 66 76
XP_020833594.1 268 46 62
XP_018595194.1 252 38 47
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.[8]

Homologs

The homologs of this gene include chimpanzee, rhesus monkey, dog, cow, mouse, and rat.[9]

Protein

The molecular weight of TMEM176B is 29.1 kilodaltons (kDa). The protein is rich in valine and poor in aspartic acid.[10] There are 4 transmembrane regions within TMEM176B isoform a.[11] There is a CD20 domain from 198-687.[12]

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.[13]

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.[14]

Subcellular localization

Mainly localized to the Golgi apparatus but is additionally localized to the plasma membrane and nucleoplasm.[15]

Protein-protein interactions

The protein interacts most commonly with TMEM176A. It also interacts with TMEM47 and CPXM1 (carboxypeptidase 1) but at lower levels.[16]

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.[17]

Protein

There are 4 phosphorylation sites in TMEM176B isoform a.[18]

Clinical significance

There has been research that indicates that TMEM176B is associated with cancer when an abnormal of the gene accumulates.[19]

Notes and References

  1. Picotto G, Morse L, Nguyen N, Saltzman J, Battaglino R . TMEM176A and TMEM176B are candidate regulators of inhibition of dendritic cell maturation and function after chronic spinal cord injury . Journal of Neurotrauma . 37. 3. 528–533. July 2019 . 31354034 . 10.1089/neu.2019.6498 . 6978786 .
  2. "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.
  3. "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.
  4. "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.
  5. Genecards.Org, 2019, https://www.genecards.org/cgi-bin/carddisp.pl?gene=LOC105375566.
  6. 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.
  7. "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.
  8. "TMEM176B Orthologs". NCBI, 2019, https://www.ncbi.nlm.nih.gov/gene/28959/ortholog/?scope=117570.
  9. Homologene - NCBI". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/homologene/8521.
  10. "SAPS Results". Ebi.Ac.Uk, 2019, https://www.ebi.ac.uk/Tools/services/web/toolresult.ebi?jobId=saps-I20190730-112615-0877-10414538-p2m.
  11. 2019, https://psort.hgc.jp/cgi-bin/runpsort.pl. Accessed 4 Aug 2019.
  12. "Transmembrane Protein 176B Isoform A [Homo Sapiens] - Protein - NCBI". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/protein/NP_054739.3.
  13. "CDD Conserved Protein Domain Family: CD20". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=309291.
  14. "Phyre 2 Results For Undefined". Sbg.Bio.Ic.Ac.Uk, 2019, http://www.sbg.bio.ic.ac.uk/phyre2/phyre2_output/607daef47ac621bf/summary.html .
  15. "Cell Atlas - TMEM176B - The Human Protein Atlas". Proteinatlas.Org, 2019, http://www.proteinatlas.org/ENSG00000106565-TMEM176B/cell.
  16. "TMEM176B Protein (Human) - STRING Interaction Network". String-Db.Org, 2019, https://string-db.org/cgi/network.pl?taskId=YtRoRnnnUnu6.
  17. "Genomatix". Genomatix.De, 2019, https://www.genomatix.de/cgi-bin/eldorado/eldorado.pl?s=31f15c28bad5fbc98bd01817d3f6f82f;SHOW_ANNOTATION=result_1;ELDORADO_VERSION=E34R1811.
  18. Transmembrane Protein 176B Isoform A [Homo Sapiens] - Protein - NCBI". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/protein/NP_054739.3.
  19. Cuajungco MP, Podevin W, Valluri VK, Bui Q, Nguyen VH, Taylor K . Abnormal accumulation of human transmembrane (TMEM)-176A and 176B proteins is associated with cancer pathology . Acta Histochemica . 114 . 7 . 705–12 . November 2012 . 22244448 . 5419829 . 10.1016/j.acthis.2011.12.006 .

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