TMEM106A

TMEM106A is a gene that encodes the transmembrane protein 106A (TMEM106A) in Homo sapiens.^[5] It is located at 17q21.31 on the plus strand next to cancer-related genes NBR1 and BRCA1.^[5][6] The TMEM106A gene contains a domain of unknown function, DUF1356.^[5]

TMEM106A
Identifiers
Aliases	TMEM106A, transmembrane protein 106A
External IDs	MGI: 1922056; HomoloGene: 16996; GeneCards: TMEM106A; OMA:TMEM106A - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q21.31 Start 43,211,835 bp[1] End 43,220,041 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 D Start 101,473,068 bp[2] End 101,482,614 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell renal medulla pylorus synovial membrane monocyte tibia bone marrow cell gonad appendix parietal pleura Top expressed in right kidney lumbar spinal ganglion human kidney epithelium of small intestine ileum intestinal villus stroma of bone marrow proximal tubule jejunum duodenum More reference expression data BioGPS n/a
Gene ontology Molecular function molecular function Cellular component integral component of membrane membrane plasma membrane Biological process biological process CD80 biosynthetic process CD86 biosynthetic process macrophage activation positive regulation of I-kappaB kinase/NF-kappaB signaling positive regulation of MAPK cascade positive regulation of MHC class II biosynthetic process positive regulation of nitric oxide metabolic process immune system process innate immune response Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 113277 217203 Ensembl ENSG00000184988 ENSMUSG00000034947 UniProt Q96A25 Q8VC04 RefSeq (mRNA) NM_001291586 NM_001291587 NM_001291588 NM_145041 NM_144830 NM_001359325 NM_001359326 NM_001359327 RefSeq (protein) NP_001278515 NP_001278516 NP_001278517 NP_659478 NP_659079 NP_001346254 NP_001346255 NP_001346256 Location (UCSC) Chr 17: 43.21 – 43.22 Mb Chr 11: 101.47 – 101.48 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Protein structure

The TMEM106A protein has a molecular weight of 28.9 kDa. It has 262 amino acids, 240 of which are in the domain of function.^[5] The protein has a transmembrane region.^[7] There is evidence for a secondary transmembrane region in humans but this region is not conserved in related orthologs.^[8] The protein does not contain a signal peptide.^[9] The protein structure contains a similar proportion of alpha-helix and beta-strand secondary structures (this does not include transmembrane structures).^[10][11]

TMEM106A protein with beta-sheets (red), alpha-helices (blue), and transmembrane region (grey)

There are several areas for post-translational modification for TMEM106A including:

• Phosphorylation,^[12]
• N-glycosylation^[13]
• Lysine glycosylation^[14]

Homology

Paralogs

The TMEM106A gene has two paralogs: TMEM106B and TMEM106C. These paralogs belong to the gene family pfam07092, which belongs to the DUF1356 superfamily. This family consists of several mammalian proteins that are around 250 amino acids in length.^[15] TMEM106B and TMEM106C are conserved in invertebrates to mammals.

Protein	Accession Number	Amino Acids	Identity Percent	Highest Expression
TMEM106A	AAI46977	262	100	Kidney [16]
TMEM106B	NP_001127704	274	43	Ubiquitous [17]
TMEM106C	AAI07793	231	36	Ubiquitous [18]

Orthologs

Expression of TMEM106A in human tissues^[19]

The TMEM106A gene has been found in only the Chordate phylum.^[20] Of the three subphyla, TMEM106A is most commonly found in Vertebrata and has also been found in select members of Tunicata, which are invertebrate marine filter feeders. This phylum split occurred 722.5 million years ago.^[21] TMEM106A has not been seen in bacteria, plants, or fungi.

Organism	Common Name	Accession Number	Amino Acids	Identity Percent	Notes
Homo sapiens	Human	AAI46977.1	262	100	Mammal
Pan troglodytes	Chimpanzee	XP_001154896.2	262	99.2	Mammal
Pongo abelii	Orangutan	XP_002827523.1	262	96.2	Mammal
Callithrix jacchus	Marmoset	XP_002748067.1	262	90.5	Mammal
Canis lupus familiaris	Dog	XP_548074.2	262	84.8	Mammal
Mus musculus	Mouse	AAH22145.1	261	66.4	Mammal
Xenopus borealis	Marsabit Clawed Frog	ACC55056.1	262	59.5	Reptile
Danio rerio	Zebrafish	AAH50177.1	282	34.5	Fish
Oikopleura dioica	Sea-squirt	CBY08060.1	249	27.8	Invertebrate

Expression

TMEM106A is expressed in several human tissues. The tissues with highest expression are uterus, kidneys, small intestine, and stomach.^[16][22] EST profiles for orthologs show expression is conserved with greatest expression in kidneys and lesser expression in several other areas.^[23] Some tissues never show expression including: muscle, adipose tissue, and bone.

Gene neighborhood

In Homo sapiens, TMEM106A is located next to NBR1, a gene identified as an ovarian tumor antigen monitored in ovarian cancer.^[24] It is also located near BRCA1, a breast cancer tumor suppressor gene.^[25] The first 140 amino acids of the TMEM106A protein, including portions of DUF1356 and a transmembrane region, are deleted along with BRCA1 during early-onset breast cancer.^[26]

Gene neighborhood of TMEM106A