TMEM176B

Protein-coding gene in the species Homo sapiens
TMEM176B
Identifiers
AliasesTMEM176B, LR8, MS4B2, transmembrane protein 176B
External IDsOMIM: 610385; MGI: 1916348; HomoloGene: 8521; GeneCards: TMEM176B; OMA:TMEM176B - orthologs
Gene location (Human)
Chromosome 7 (human)
Chr.Chromosome 7 (human)[1]
Chromosome 7 (human)
Genomic location for TMEM176B
Genomic location for TMEM176B
Band7q36.1Start150,791,285 bp[1]
End150,801,360 bp[1]
Gene location (Mouse)
Chromosome 6 (mouse)
Chr.Chromosome 6 (mouse)[2]
Chromosome 6 (mouse)
Genomic location for TMEM176B
Genomic location for TMEM176B
Band6 B2.3|6 23.75 cMStart48,810,752 bp[2]
End48,818,430 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • right lobe of liver

  • granulocyte

  • mucosa of transverse colon

  • gallbladder

  • rectum

  • human kidney

  • mucosa of ileum

  • cecum

  • appendix

  • decidua
Top expressed in
  • right kidney

  • human kidney

  • median eminence

  • proximal tubule

  • vestibular membrane of cochlear duct

  • adrenal gland

  • right lung

  • vestibular sensory epithelium

  • lactiferous gland

  • right lung lobe
More reference expression data
BioGPS
n/a
Orthologs
SpeciesHumanMouse
Entrez

28959

65963

Ensembl

ENSG00000106565

ENSMUSG00000029810

UniProt

Q3YBM2

Q9R1Q6

RefSeq (mRNA)
NM_001101311
NM_001101312
NM_001101313
NM_001101314
NM_014020

NM_001362691
NM_001362692

NM_001164207
NM_001164208
NM_001164209
NM_001286651
NM_001286652

NM_023056

RefSeq (protein)
NP_001094781
NP_001094782
NP_001094784
NP_054739
NP_001349620

NP_001349621

NP_001157679
NP_001157680
NP_001157681
NP_001273580
NP_001273581

NP_075543

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

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. [1]

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 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_020833594.1 268 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

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 (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]

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. ^ a b c GRCh38: Ensembl release 89: ENSG00000106565 – Ensembl, May 2017
  2. ^ a b c 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. ^ 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.