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
Gene location (Human)
Chr.Chromosome 7 (human)[1]
Band7q36.1Start150,791,285 bp[1]
End150,801,360 bp[1]
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: 48.83 – 48.84 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]

This figure shows the level of expression of TMEM176B in different tissues throughout the body.

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
This is an unrooted phylogenetic tree based on the table of orthologs. The black group are fish, the red group are Carnivora, the blue group is Artiodactyla and Sirenia, the green group is Rodentia, and the orange group is Primates

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
Model of TMEM176B secondary structure. This structure is a membrane protein and is a voltage-dependent calcium channel gamma-8.

The molecular weight of TMEM176B is 29.1 kiloDaltons (kdal). 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 interactaions

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

Diagram of the TMEM176B interacting proteins.

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, mieg@ncbi.nlm.nih.gov. "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. 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.
  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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