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
Aliases	TMEM176B, LR8, MS4B2, transmembrane protein 176B
External IDs	OMIM: 610385 MGI: 1916348 HomoloGene: 8521 GeneCards: TMEM176B
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q36.1 Start 150,791,285 bp[1] End 150,801,360 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 B2.3|6 23.75 cM Start 48,833,818 bp[2] End 48,841,496 bp[2]
Orthologs
Species	Human	Mouse
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 Mb	Chr 6: 48.83 – 48.84 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/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 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 (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, [email protected]. "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.