TMEM176B

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.[5]

TMEM176B
Identifiers
AliasesTMEM176B, LR8, MS4B2, transmembrane protein 176B
External IDsOMIM: 610385; MGI: 1916348; HomoloGene: 8521; GeneCards: TMEM176B; OMA:TMEM176B - orthologs
Orthologs
SpeciesHumanMouse
Entrez

28959

65963

Ensembl

ENSG00000106565

ENSMUSG00000029810

UniProt

Q3YBM2

Q9R1Q6

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 7: 150.79 – 150.8 MbChr 6: 48.81 – 48.82 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

Location

TMEM176B is also known as LR8, and MS4B2.[6] The gene is found on the minus end of Chromosome 7, on the long arm at position 7q36.1.[7] 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.[8]

Gene

TMEM176A and LOC105375566 is a neighbor of TMEM176B.[9][10]

Expression

The gene is found to be most expressed in the liver with the kidney being the second most expressed tissue.[6]

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.[11]

Homology

Paralogs

There is one paralog of TMEM176B which is TMEM176A.[12]

Orthologs

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

Common nameAccession numberSequence lengthSequence identitySequence similarity
HumanNP_054739.3270100100
BonoboXP_008966185.12869998
Ugandan red colobusXP_023081229.12689192
Small-eared galagoXP_003792108.12686877
Sunda flying lemurXP_008564209.12717180
House mouseNP_001273581.12635366
Ryukyu mouseXP_021020106.12655367
Przewalski's horseXP_008506799.12707080
CheetahXP_026907001.12716877
Water buffaloXP_006049155.12656676
Wild yakXP_005908946.12656575
Sperm whaleXP_028345261.12666573
Killer whaleXP_012392713.12656473
Pacific walrusXP_004408899.12716475
Giant pandaXP_019651134.12716879
Red foxXP_025849593.12736373
West Indian manateeXP_004372786.12716676
KoalaXP_020833594.12684662
Asian arowanaXP_018595194.12523847
Northern pikeXP_010904195.42512646

There are around 125 orthologs of the gene ranging from primates to mice and to certain species of fish.[13]

Homologs

The homologs of this gene include chimpanzee, rhesus monkey, dog, cow, mouse, and rat.[14]

Protein

The molecular weight of TMEM176B is 29.1 kilodaltons (kDa). The protein is rich in valine and poor in aspartic acid.[15] There are 4 transmembrane regions within TMEM176B isoform a.[16] There is a CD20 domain from 198-687.[17]

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.[18]

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.[19]

Subcellular localization

Mainly localized to the Golgi apparatus but is additionally localized to the plasma membrane and nucleoplasm.[20]

Protein-protein interactions

The protein interacts most commonly with TMEM176A. It also interacts with TMEM47 and CPXM1 (carboxypeptidase 1) but at lower levels.[21]

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.[22]

Protein

There are 4 phosphorylation sites in TMEM176B isoform a.[23]

Clinical significance

There has been research that indicates that TMEM176B is associated with cancer when an abnormal of the gene accumulates.[24]

References
  1. GRCh38: Ensembl release 89: ENSG00000106565 – Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000029810 – Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Picotto G, Morse L, Nguyen N, Saltzman J, Battaglino R (July 2019). "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. doi:10.1089/neu.2019.6498. PMC 6978786. PMID 31354034.
  6. Universal protein resource accession number Q3YBM2 for "Transmembrane Protein 176B" at UniProt.
  7. "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.
  8. "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.
  9. "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.
  10. Genecards.Org, 2019, https://www.genecards.org/cgi-bin/carddisp.pl?gene=LOC105375566.
  11. 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.
  12. "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.
  13. "TMEM176B Orthologs". NCBI, 2019, https://www.ncbi.nlm.nih.gov/gene/28959/ortholog/?scope=117570.
  14. Homologene - NCBI". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/homologene/8521.
  15. "SAPS Results". Ebi.Ac.Uk, 2019, https://www.ebi.ac.uk/Tools/services/web/toolresult.ebi?jobId=saps-I20190730-112615-0877-10414538-p2m.
  16. 2019, https://psort.hgc.jp/cgi-bin/runpsort.pl%5B%5D. Accessed 4 Aug 2019.
  17. "Transmembrane Protein 176B Isoform A [Homo Sapiens] - Protein - NCBI". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/protein/NP_054739.3.
  18. "CDD Conserved Protein Domain Family: CD20". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=309291.
  19. "Phyre 2 Results For Undefined". Sbg.Bio.Ic.Ac.Uk, 2019, http://www.sbg.bio.ic.ac.uk/phyre2/phyre2_output/607daef47ac621bf/summary.html Archived 2019-08-04 at the Wayback Machine.
  20. "Cell Atlas - TMEM176B - The Human Protein Atlas". Proteinatlas.Org, 2019, http://www.proteinatlas.org/ENSG00000106565-TMEM176B/cell.
  21. "TMEM176B Protein (Human) - STRING Interaction Network". String-Db.Org, 2019, https://string-db.org/cgi/network.pl?taskId=YtRoRnnnUnu6.
  22. "Genomatix". Genomatix.De, 2019, https://www.genomatix.de/cgi-bin/eldorado/eldorado.pl?s=31f15c28bad5fbc98bd01817d3f6f82f;SHOW_ANNOTATION=result_1;ELDORADO_VERSION=E34R1811.
  23. Transmembrane Protein 176B Isoform A [Homo Sapiens] - Protein - NCBI". Ncbi.Nlm.Nih.Gov, 2019, https://www.ncbi.nlm.nih.gov/protein/NP_054739.3.
  24. Cuajungco MP, Podevin W, Valluri VK, Bui Q, Nguyen VH, Taylor K (November 2012). "Abnormal accumulation of human transmembrane (TMEM)-176A and 176B proteins is associated with cancer pathology". Acta Histochemica. 114 (7): 705–12. doi:10.1016/j.acthis.2011.12.006. PMC 5419829. PMID 22244448.
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