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TMEM176B

From Wikipedia, the free encyclopedia
TMEM176B
Identifiers
AliasesTMEM176B, LR8, MS4B2, transmembrane protein 176B
External IDsOMIM: 610385; MGI: 1916348; HomoloGene: 8521; GeneCards: TMEM176B; OMA:TMEM176B - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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

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]

Gene

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Location

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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

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

Expression

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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. [1]

Transcript variants

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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

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Paralogs

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

Orthologs

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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 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_020833863.1 268 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.[13]

Homologs

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

Protein

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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 (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

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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

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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

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

Protein-protein interactions

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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

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Gene

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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

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

Clinical significance

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

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000106565Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029810Ensembl, 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. ^ a b 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[permanent dead link]. 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.