TMEM176B

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox_gene}}

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.{{cite journal | vauthors = Picotto G, Morse L, Nguyen N, Saltzman J, Battaglino R | title = TMEM176A and TMEM176B are candidate regulators of inhibition of dendritic cell maturation and function after chronic spinal cord injury | journal = Journal of Neurotrauma | volume = 37| issue = 3| pages = 528–533| date = July 2019 | pmid = 31354034 | doi = 10.1089/neu.2019.6498 | pmc = 6978786 }}

Gene

= Location =

TMEM176B is also known as LR8, and MS4B2.{{UniProt Full|Q3YBM2|Transmembrane Protein 176B}} 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.

File:TMEM176B Tissue Expression.jpg]

= 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 =

File:TMEM176B Unrooted Phylogenetic Tree.jpg, 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.

class="wikitable sortable"
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."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, https://www.ncbi.nlm.nih.gov/homologene/8521.

Protein

File:TMEM176B Secondary Structure.jpg

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{{Dead link|date=October 2022 |bot=InternetArchiveBot |fix-attempted=yes }}. Accessed 4 Aug 2019. There is a CD20 domain from 198-687."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 {{Webarchive|url=https://web.archive.org/web/20190804180458/http://www.sbg.bio.ic.ac.uk/phyre2/phyre2_output/607daef47ac621bf/summary.html |date=2019-08-04 }}.

=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.

File:TMEM176B Interacting Proteins.jpg

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.{{cite journal | vauthors = Cuajungco MP, Podevin W, Valluri VK, Bui Q, Nguyen VH, Taylor K | title = Abnormal accumulation of human transmembrane (TMEM)-176A and 176B proteins is associated with cancer pathology | journal = Acta Histochemica | volume = 114 | issue = 7 | pages = 705–12 | date = November 2012 | pmid = 22244448 | pmc = 5419829 | doi = 10.1016/j.acthis.2011.12.006 }}

References

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