TMEM106B
entrez
54664
canonical
uniprot
Q9NUM4
canonical
ensembl
ENSG00000106460
resolver
ensp
ENSP00000379901
resolver
ensp
ENSP00000379902
resolver
ensp
ENSP00000401302
resolver
ensp
ENSP00000515905
resolver
ensp
ENSP00000573810
resolver
ensp
ENSP00000635754
resolver
ensp
ENSP00000635755
resolver
ensp
ENSP00000635756
resolver
enst
ENST00000396667
resolver
enst
ENST00000396668
resolver
enst
ENST00000444443
resolver
enst
ENST00000704455
resolver
enst
ENST00000903751
resolver
enst
ENST00000965695
resolver
enst
ENST00000965696
resolver
enst
ENST00000965697
resolver
genesymbol
TMEM106B
resolver
hgnc
HGNC:22407
resolver
uniprot
A4D108
resolver
uniprot
Q53FL9
resolver
uniprot
Q8N4L0
resolver
uniprot_entry
T106B_HUMAN
resolver
uniprot_sec
A4D108
resolver
uniprot_sec
Q53FL9
resolver
uniprot_sec
Q8N4L0
resolver
amino_acid_sequence
MGKSLSHLPLHSSKEDAYDGVTSENMRNGLVNSEVHNEDGRNGDVSQFPYVEFTGRDSVTCPTCQGTGRIPRGQENQLVALIPYSDQRLRPRRTKLYVMASVFVCLLLSGLAVFFLFPRSIDVKYIGVKSAYVSYDVQKRTIYLNITNTLNITNNNYYSVEVENITAQVQFSKTVIGKARLNNITIIGPLDMKQIDYTVPTVIAEEMSYMYDFCTLISIKVHNIVLMMQVTVTTTYFGHSEQISQERYQYVDCGRNTTYQLGQSEYLNVLQPQQ
uniprot
proteins
disease_involvement
DISEASE: Frontotemporal dementia 2 (FTD2) [MIM:607485]: A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. Gestural apraxia, parkinsonism, visual loss, and visual hallucinations are present in 25 to 40% of patients. {ECO:0000269|PubMed:20154673, ECO:0000269|PubMed:21178100, ECO:0000269|PubMed:22895706, ECO:0000269|PubMed:23742080}. Note=The gene represented in this entry may act as a disease modifier. Risk alleles confer genetic susceptibility by increasing gene expression (PubMed:20154673, PubMed:21178100). Increased expression may be the result of down-regulation of microRNA miR-132 and miR-212, that repress TMEM106B expression (PubMed:22895706). Thr-185 is a risk allele associated with lower GRN protein levels and early age at onset in GRN FTD2 mutation carriers: it presents slower protein degradation that leads to higher steady-state TMEM106B levels, leading to alterations in the intracellular versus extracellular partitioning of GRN (PubMed:23742080). {ECO:0000269|PubMed:20154673, ECO:0000269|PubMed:21178100, ECO:0000269|PubMed:22895706, ECO:0000269|PubMed:23742080}.; DISEASE: Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (FTDALS1) [MIM:105550]: An autosomal dominant neurodegenerative disorder characterized by adult onset of frontotemporal dementia and/or amyotrophic lateral sclerosis in an affected individual. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. {ECO:0000269|PubMed:24385136, ECO:0000269|PubMed:24442578, ECO:0000303|PubMed:24488309}. Note=The gene represented in this entry acts as a disease modifier.; DISEASE: Leukodystrophy, hypomyelinating, 16 (HLD16) [MIM:617964]: An autosomal dominant disorder characterized by hypomyelination, leukodystrophy, and thin corpus callosum observed on brain imaging. Clinical features include hypotonia, nystagmus, and mildly delayed motor development with onset in infancy, ataxic or broad-based gait, hyperreflexia, intention tremor, dysmetria, and a mild pyramidal syndrome. Some patients have cognitive impairment, whereas others may have normal cognition or mild intellectual disability with speech difficulties. {ECO:0000269|PubMed:29186371, ECO:0000269|PubMed:29444210}. Note=The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Note=A TMEM106B truncated C-terminal fragment (residues 120 through 254) was found to aggregate into stable amyloid fibrils in the brain of patients suffering from diverse genetic and sporadic tauopathies, amyloid-beta amyloidoses, synucleinopathies and TDP-43 proteinopathies. It is currently unclear whether TMEM106B fibrils are associated with a pathogenic process or represents a non-specific secondary phenomenon, a general downstream marker of lysosomal stress for instance (PubMed:35247328, PubMed:35344984, PubMed:35344985). TMEM106B amyloid filaments form in an age-dependent manner in human brains, however fibrillization of TMEM106B seems substantially greater in patients with known neurodegeneration compared to age-matched unaffected individuals (PubMed:35344985). {ECO:0000269|PubMed:35247328, ECO:0000269|PubMed:35344984, ECO:0000269|PubMed:35344985}.
uniprot
proteins
function
FUNCTION: In neurons, involved in the transport of late endosomes/lysosomes (PubMed:25066864). May be involved in dendrite morphogenesis and maintenance by regulating lysosomal trafficking (PubMed:25066864). May act as a molecular brake for retrograde transport of late endosomes/lysosomes, possibly via its interaction with MAP6 (By similarity). In motoneurons, may mediate the axonal transport of lysosomes and axonal sorting at the initial segment (By similarity). It remains unclear whether TMEM106B affects the transport of moving lysosomes in the anterograde or retrograde direction in neurites and whether it is important in the sorting of lysosomes in axons or in dendrites (By similarity). In neurons, may also play a role in the regulation of lysosomal size and responsiveness to stress (PubMed:25066864). Required for proper lysosomal acidification (By similarity). {ECO:0000250|UniProtKB:Q6AYA5, ECO:0000250|UniProtKB:Q80X71, ECO:0000269|PubMed:25066864}.; FUNCTION: (Microbial infection) Plays a role in human coronavirus SARS-CoV-2 infection, but not in common cold coronaviruses HCoV-229E and HCoV-OC43 infections. Involved in ACE2-independent SARS-CoV-2 cell entry. Required for post-endocytic stage of virus entry, facilitates spike-mediated membrane fusion. Virus attachment and endocytosis can also be mediated by other cell surface receptors. {ECO:0000269|PubMed:33333024, ECO:0000269|PubMed:33686287, ECO:0000269|PubMed:37421949}.
uniprot
proteins
mass_dalton
31127
uniprot
proteins
mutagenesis
MUTAGEN 210..213; /note="MYDF->AYDA: Highly decreased number of infected cells by SARS-CoV-2. No effect on infection with HCoV-229E."; /evidence="ECO:0000269|PubMed:37421949"; MUTAGEN 210; /note="M->A: Decreased number of infected cells by SARS-CoV-2. No effect on infection with HCoV-229E."; /evidence="ECO:0000269|PubMed:37421949"; MUTAGEN 213; /note="F->A: Decreased number of infected cells by SARS-CoV-2. No effect on infection with HCoV-229E."; /evidence="ECO:0000269|PubMed:37421949
uniprot
proteins
protein_family
TMEM106 family
uniprot
proteins
pubmed
12690205
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20154673
uniprot
proteins
pubmed
21178100
uniprot
proteins
pubmed
22511793
uniprot
proteins
pubmed
22895706
uniprot
proteins
pubmed
23136129
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23742080
uniprot
proteins
pubmed
24357581
uniprot
proteins
pubmed
24385136
uniprot
proteins
pubmed
24442578
uniprot
proteins
pubmed
24488309
uniprot
proteins
pubmed
25066864
uniprot
proteins
pubmed
25255805
uniprot
proteins
pubmed
28728022
uniprot
proteins
pubmed
29186371
uniprot
proteins
pubmed
29444210
uniprot
proteins
pubmed
33333024
uniprot
proteins
pubmed
33686287
uniprot
proteins
pubmed
35247328
uniprot
proteins
pubmed
35344984
uniprot
proteins
pubmed
35344985
uniprot
proteins
pubmed
37421949
uniprot
proteins
sequence_length
274
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Late endosome membrane {ECO:0000269|PubMed:22511793, ECO:0000269|PubMed:23136129, ECO:0000269|PubMed:25066864}; Single-pass type II membrane protein {ECO:0000269|PubMed:22511793, ECO:0000269|PubMed:23136129, ECO:0000269|PubMed:25066864}. Lysosome membrane {ECO:0000269|PubMed:22511793, ECO:0000269|PubMed:25066864, ECO:0000269|PubMed:37421949}; Single-pass type II membrane protein {ECO:0000269|PubMed:22511793, ECO:0000269|PubMed:23136129, ECO:0000269|PubMed:25066864}. Cell membrane {ECO:0000269|PubMed:37421949}; Single-pass type II membrane protein {ECO:0000255}. Note=Colocalizes with LAMP1. A small fraction resides on the cell surface (PubMed:37421949). {ECO:0000269|PubMed:22511793, ECO:0000269|PubMed:25066864, ECO:0000269|PubMed:37421949}.
uniprot
proteins
transmembrane_region
TRANSMEM 97..117; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins