T106B_HUMAN
ID T106B_HUMAN Reviewed; 274 AA.
AC Q9NUM4; A4D108; Q53FL9; Q8N4L0;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Transmembrane protein 106B;
GN Name=TMEM106B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-185.
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Gastric mucosa;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-33, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-183.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [9]
RP INVOLVEMENT IN UP-FTD.
RX PubMed=20154673; DOI=10.1038/ng.536;
RA Van Deerlin V.M., Sleiman P.M., Martinez-Lage M., Chen-Plotkin A.,
RA Wang L.S., Graff-Radford N.R., Dickson D.W., Rademakers R., Boeve B.F.,
RA Grossman M., Arnold S.E., Mann D.M., Pickering-Brown S.M., Seelaar H.,
RA Heutink P., van Swieten J.C., Murrell J.R., Ghetti B., Spina S.,
RA Grafman J., Hodges J., Spillantini M.G., Gilman S., Lieberman A.P.,
RA Kaye J.A., Woltjer R.L., Bigio E.H., Mesulam M., Al-Sarraj S., Troakes C.,
RA Rosenberg R.N., White C.L. III, Ferrer I., Llado A., Neumann M.,
RA Kretzschmar H.A., Hulette C.M., Welsh-Bohmer K.A., Miller B.L.,
RA Alzualde A., de Munain A.L., McKee A.C., Gearing M., Levey A.I., Lah J.J.,
RA Hardy J., Rohrer J.D., Lashley T., Mackenzie I.R., Feldman H.H.,
RA Hamilton R.L., Dekosky S.T., van der Zee J., Kumar-Singh S.,
RA Van Broeckhoven C., Mayeux R., Vonsattel J.P., Troncoso J.C., Kril J.J.,
RA Kwok J.B., Halliday G.M., Bird T.D., Ince P.G., Shaw P.J., Cairns N.J.,
RA Morris J.C., McLean C.A., DeCarli C., Ellis W.G., Freeman S.H.,
RA Frosch M.P., Growdon J.H., Perl D.P., Sano M., Bennett D.A.,
RA Schneider J.A., Beach T.G., Reiman E.M., Woodruff B.K., Cummings J.,
RA Vinters H.V., Miller C.A., Chui H.C., Alafuzoff I., Hartikainen P.,
RA Seilhean D., Galasko D., Masliah E., Cotman C.W., Tunon M.T.,
RA Martinez M.C., Munoz D.G., Carroll S.L., Marson D., Riederer P.F.,
RA Bogdanovic N., Schellenberg G.D., Hakonarson H., Trojanowski J.Q.,
RA Lee V.M.;
RT "Common variants at 7p21 are associated with frontotemporal lobar
RT degeneration with TDP-43 inclusions.";
RL Nat. Genet. 42:234-239(2010).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-33, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP INVOLVEMENT IN UP-FTD.
RX PubMed=21178100; DOI=10.1212/wnl.0b013e31820a0e3b;
RA Finch N., Carrasquillo M.M., Baker M., Rutherford N.J., Coppola G.,
RA Dejesus-Hernandez M., Crook R., Hunter T., Ghidoni R., Benussi L.,
RA Crook J., Finger E., Hantanpaa K.J., Karydas A.M., Sengdy P., Gonzalez J.,
RA Seeley W.W., Johnson N., Beach T.G., Mesulam M., Forloni G., Kertesz A.,
RA Knopman D.S., Uitti R., White C.L. III, Caselli R., Lippa C., Bigio E.H.,
RA Wszolek Z.K., Binetti G., Mackenzie I.R., Miller B.L., Boeve B.F.,
RA Younkin S.G., Dickson D.W., Petersen R.C., Graff-Radford N.R.,
RA Geschwind D.H., Rademakers R.;
RT "TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN
RT mutation carriers.";
RL Neurology 76:467-474(2011).
RN [12]
RP SUBCELLULAR LOCATION, TOPOLOGY, AND GLYCOSYLATION AT ASN-145; ASN-151;
RP ASN-164; ASN-183 AND ASN-256.
RX PubMed=22511793; DOI=10.1074/jbc.m112.365098;
RA Lang C.M., Fellerer K., Schwenk B.M., Kuhn P.H., Kremmer E., Edbauer D.,
RA Capell A., Haass C.;
RT "Membrane orientation and subcellular localization of transmembrane protein
RT 106B (TMEM106B), a major risk factor for frontotemporal lobar
RT degeneration.";
RL J. Biol. Chem. 287:19355-19365(2012).
RN [13]
RP INVOLVEMENT IN UP-FTD.
RX PubMed=22895706; DOI=10.1523/jneurosci.0521-12.2012;
RA Chen-Plotkin A.S., Unger T.L., Gallagher M.D., Bill E., Kwong L.K.,
RA Volpicelli-Daley L., Busch J.I., Akle S., Grossman M., Van Deerlin V.,
RA Trojanowski J.Q., Lee V.M.;
RT "TMEM106B, the risk gene for frontotemporal dementia, is regulated by the
RT microRNA-132/212 cluster and affects progranulin pathways.";
RL J. Neurosci. 32:11213-11227(2012).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23136129; DOI=10.1093/hmg/dds475;
RA Brady O.A., Zheng Y., Murphy K., Huang M., Hu F.;
RT "The frontotemporal lobar degeneration risk factor, TMEM106B, regulates
RT lysosomal morphology and function.";
RL Hum. Mol. Genet. 22:685-695(2013).
RN [15]
RP INVOLVEMENT IN UP-FTD, VARIANT SER-185, SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION AT ASN-183.
RX PubMed=23742080; DOI=10.1111/jnc.12329;
RA Nicholson A.M., Finch N.A., Wojtas A., Baker M.C., Perkerson R.B.,
RA Castanedes-Casey M., Rousseau L., Benussi L., Binetti G., Ghidoni R.,
RA Hsiung G.Y., Mackenzie I.R., Finger E., Boeve B.F., Ertekin-Taner N.,
RA Graff-Radford N.R., Dickson D.W., Rademakers R.;
RT "TMEM106B p.T185S regulates TMEM106B protein levels: implications for
RT frontotemporal dementia.";
RL J. Neurochem. 126:781-791(2013).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-33, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP INVOLVEMENT IN FTDALS1.
RX PubMed=24488309; DOI=10.1007/s00401-014-1249-3;
RA Deming Y., Cruchaga C.;
RT "TMEM106B: a strong FTLD disease modifier.";
RL Acta Neuropathol. 127:419-422(2014).
RN [18]
RP INVOLVEMENT IN FTDALS1.
RX PubMed=24442578; DOI=10.1007/s00401-013-1239-x;
RA Gallagher M.D., Suh E., Grossman M., Elman L., McCluskey L.,
RA Van Swieten J.C., Al-Sarraj S., Neumann M., Gelpi E., Ghetti B.,
RA Rohrer J.D., Halliday G., Van Broeckhoven C., Seilhean D., Shaw P.J.,
RA Frosch M.P., Alafuzoff I., Antonell A., Bogdanovic N., Brooks W.,
RA Cairns N.J., Cooper-Knock J., Cotman C., Cras P., Cruts M., De Deyn P.P.,
RA Decarli C., Dobson-Stone C., Engelborghs S., Fox N., Galasko D.,
RA Gearing M., Gijselinck I., Grafman J., Hartikainen P., Hatanpaa K.J.,
RA Highley J.R., Hodges J., Hulette C., Ince P.G., Jin L.W., Kirby J.,
RA Kofler J., Kril J., Kwok J.B., Levey A., Lieberman A., Llado A.,
RA Martin J.J., Masliah E., McDermott C.J., McKee A., McLean C., Mead S.,
RA Miller C.A., Miller J., Munoz D.G., Murrell J., Paulson H., Piguet O.,
RA Rossor M., Sanchez-Valle R., Sano M., Schneider J., Silbert L.C., Spina S.,
RA van der Zee J., Van Langenhove T., Warren J., Wharton S.B., White Iii C.L.,
RA Woltjer R.L., Trojanowski J.Q., Lee V.M., Van Deerlin V.,
RA Chen-Plotkin A.S.;
RT "TMEM106B is a genetic modifier of frontotemporal lobar degeneration with
RT C9orf72 hexanucleotide repeat expansions.";
RL Acta Neuropathol. 127:407-418(2014).
RN [19]
RP INVOLVEMENT IN FTDALS1.
RX PubMed=24385136; DOI=10.1007/s00401-013-1240-4;
RA van Blitterswijk M., Mullen B., Nicholson A.M., Bieniek K.F., Heckman M.G.,
RA Baker M.C., Dejesus-Hernandez M., Finch N.A., Brown P.H., Murray M.E.,
RA Hsiung G.Y., Stewart H., Karydas A.M., Finger E., Kertesz A., Bigio E.H.,
RA Weintraub S., Mesulam M., Hatanpaa K.J., White Iii C.L., Strong M.J.,
RA Beach T.G., Wszolek Z.K., Lippa C., Caselli R., Petrucelli L.,
RA Josephs K.A., Parisi J.E., Knopman D.S., Petersen R.C., Mackenzie I.R.,
RA Seeley W.W., Grinberg L.T., Miller B.L., Boylan K.B., Graff-Radford N.R.,
RA Boeve B.F., Dickson D.W., Rademakers R.;
RT "TMEM106B protects C9ORF72 expansion carriers against frontotemporal
RT dementia.";
RL Acta Neuropathol. 127:397-406(2014).
RN [20]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MAP6.
RX PubMed=24357581; DOI=10.1002/embj.201385857;
RA Schwenk B.M., Lang C.M., Hogl S., Tahirovic S., Orozco D., Rentzsch K.,
RA Lichtenthaler S.F., Hoogenraad C.C., Capell A., Haass C., Edbauer D.;
RT "The FTLD risk factor TMEM106B and MAP6 control dendritic trafficking of
RT lysosomes.";
RL EMBO J. 33:450-467(2014).
RN [21]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25255805; DOI=10.1038/ncomms5919;
RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT "Global profiling of co- and post-translationally N-myristoylated proteomes
RT in human cells.";
RL Nat. Commun. 5:4919-4919(2014).
RN [22]
RP INVOLVEMENT IN HLD16, AND VARIANT HLD16 ASN-252.
RX PubMed=29186371; DOI=10.1093/brain/awx314;
RA Simons C., Dyment D., Bent S.J., Crawford J., D'Hooghe M.,
RA Kohlschuetter A., Venkateswaran S., Helman G., Poll-The B.T.,
RA Makowski C.C., Ito Y., Kernohan K., Hartley T., Waisfisz Q., Taft R.J.,
RA van der Knaap M.S., Wolf N.I.;
RT "A recurrent de novo mutation in TMEM106B causes hypomyelinating
RT leukodystrophy.";
RL Brain 140:3105-3111(2017).
RN [23]
RP INVOLVEMENT IN HLD16, AND VARIANT HLD16 ASN-252.
RX PubMed=29444210; DOI=10.1093/brain/awy029;
RA Yan H., Kubisiak T., Ji H., Xiao J., Wang J., Burmeister M.;
RT "The recurrent mutation in TMEM106B also causes hypomyelinating
RT leukodystrophy in China and is a CpG hotspot.";
RL Brain 141:E36-E36(2018).
CC -!- FUNCTION: Involved in dendrite morphogenesis and maintenance by
CC regulating lysosomal trafficking via its interaction with MAP6. May act
CC by inhibiting retrograde transport of lysosomes along dendrites.
CC Required for dendrite branching. {ECO:0000269|PubMed:23136129,
CC ECO:0000269|PubMed:24357581}.
CC -!- SUBUNIT: Interacts with MAP6. {ECO:0000269|PubMed:24357581}.
CC -!- INTERACTION:
CC Q9NUM4; P42858: HTT; NbExp=3; IntAct=EBI-10490807, EBI-466029;
CC Q9NUM4; Q9BVX2: TMEM106C; NbExp=3; IntAct=EBI-10490807, EBI-2821497;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane; Single-pass type II
CC membrane protein. Lysosome membrane; Single-pass type II membrane
CC protein. Membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in frontal cortex.
CC -!- DISEASE: Ubiquitin-positive frontotemporal dementia (UP-FTD)
CC [MIM:607485]: Frontotemporal dementia (FTD) is the second most common
CC cause of dementia in people under the age of 65 years. It is an
CC autosomal dominant neurodegenerative disease.
CC {ECO:0000269|PubMed:20154673, ECO:0000269|PubMed:21178100,
CC ECO:0000269|PubMed:22895706, ECO:0000269|PubMed:23742080}. Note=The
CC gene represented in this entry acts as a disease modifier. Risk alleles
CC confer genetic susceptibility by increasing gene expression
CC (PubMed:20154673, PubMed:21178100). Increased expression may be the
CC result of down-regulation of microRNA miR-132 and miR-212, that repress
CC TMEM106B expression (PubMed:22895706). Thr-185 is a risk allele
CC associated with lower GRN protein levels and early age at onset in GRN
CC UP-FTD mutation carriers: it presents slower protein degradation that
CC leads to higher steady-state TMEM106B levels, leading to alterations in
CC the intracellular versus extracellular partitioning of GRN
CC (PubMed:23742080). {ECO:0000269|PubMed:20154673,
CC ECO:0000269|PubMed:21178100, ECO:0000269|PubMed:22895706,
CC ECO:0000269|PubMed:23742080}.
CC -!- DISEASE: Frontotemporal dementia and/or amyotrophic lateral sclerosis 1
CC (FTDALS1) [MIM:105550]: An autosomal dominant neurodegenerative
CC disorder characterized by adult onset of frontotemporal dementia and/or
CC amyotrophic lateral sclerosis in an affected individual. There is high
CC intrafamilial variation. Frontotemporal dementia is characterized by
CC frontal and temporal lobe atrophy associated with neuronal loss,
CC gliosis, and dementia. Patients exhibit progressive changes in social,
CC behavioral, and/or language function. Amyotrophic lateral sclerosis is
CC characterized by the death of motor neurons in the brain, brainstem,
CC and spinal cord, resulting in fatal paralysis.
CC {ECO:0000269|PubMed:24385136, ECO:0000269|PubMed:24442578,
CC ECO:0000303|PubMed:24488309}. Note=The gene represented in this entry
CC acts as a disease modifier.
CC -!- DISEASE: Leukodystrophy, hypomyelinating, 16 (HLD16) [MIM:617964]: An
CC autosomal dominant disorder characterized by hypomyelination,
CC leukodystrophy, and thin corpus callosum observed on brain imaging.
CC Clinical features include hypotonia, nystagmus, and mildly delayed
CC motor development with onset in infancy, ataxic or broad-based gait,
CC hyperreflexia, intention tremor, dysmetria, and a mild pyramidal
CC syndrome. Some patients have cognitive impairment, whereas others may
CC have normal cognition or mild intellectual disability with speech
CC difficulties. {ECO:0000269|PubMed:29186371,
CC ECO:0000269|PubMed:29444210}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TMEM106 family. {ECO:0000305}.
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DR EMBL; AK002135; BAA92099.1; -; mRNA.
DR EMBL; AK223263; BAD96983.1; -; mRNA.
DR EMBL; AC007321; AAQ96840.1; -; Genomic_DNA.
DR EMBL; CH236948; EAL24296.1; -; Genomic_DNA.
DR EMBL; CH471073; EAW93638.1; -; Genomic_DNA.
DR EMBL; BC033901; AAH33901.1; -; mRNA.
DR EMBL; BC039741; AAH39741.1; -; mRNA.
DR CCDS; CCDS5358.1; -.
DR RefSeq; NP_001127704.1; NM_001134232.1.
DR RefSeq; NP_060844.2; NM_018374.3.
DR RefSeq; XP_005249846.1; XM_005249789.1.
DR PDB; 7QVC; EM; 2.64 A; A/B/C=1-274.
DR PDB; 7QVF; EM; 3.64 A; A/B/C/D/E/F=1-274.
DR PDB; 7QWG; EM; 3.38 A; A/B/C=1-274.
DR PDB; 7QWL; EM; 3.47 A; A/B/C=1-274.
DR PDB; 7QWM; EM; 2.76 A; A/B/C=1-274.
DR PDB; 7SAQ; EM; 2.90 A; A/B/C/D/E=1-274.
DR PDB; 7SAR; EM; 3.20 A; A/B/C/D/E/F/G/H/I/J=1-274.
DR PDB; 7SAS; EM; 3.70 A; A/B/C/D/E/F/G/H/I/J=1-274.
DR PDB; 7U10; EM; 3.00 A; A/B/C=120-254.
DR PDB; 7U11; EM; 3.20 A; A/B/C=120-254.
DR PDB; 7U12; EM; 3.50 A; A/B/C=120-254.
DR PDB; 7U13; EM; 2.90 A; A/B/C=120-254.
DR PDB; 7U14; EM; 4.50 A; A/B/C=120-254.
DR PDB; 7U15; EM; 3.00 A; A/B/C=120-254.
DR PDB; 7U16; EM; 2.70 A; A/B/C=120-254.
DR PDB; 7U17; EM; 3.00 A; A/B/C=120-254.
DR PDBsum; 7QVC; -.
DR PDBsum; 7QVF; -.
DR PDBsum; 7QWG; -.
DR PDBsum; 7QWL; -.
DR PDBsum; 7QWM; -.
DR PDBsum; 7SAQ; -.
DR PDBsum; 7SAR; -.
DR PDBsum; 7SAS; -.
DR PDBsum; 7U10; -.
DR PDBsum; 7U11; -.
DR PDBsum; 7U12; -.
DR PDBsum; 7U13; -.
DR PDBsum; 7U14; -.
DR PDBsum; 7U15; -.
DR PDBsum; 7U16; -.
DR PDBsum; 7U17; -.
DR AlphaFoldDB; Q9NUM4; -.
DR BioGRID; 120093; 323.
DR IntAct; Q9NUM4; 10.
DR MINT; Q9NUM4; -.
DR STRING; 9606.ENSP00000379901; -.
DR TCDB; 9.B.23.1.1; the tmem106 (tmem106) family.
DR GlyConnect; 1849; 19 N-Linked glycans (2 sites).
DR GlyGen; Q9NUM4; 8 sites, 21 N-linked glycans (2 sites), 1 O-linked glycan (1 site).
DR iPTMnet; Q9NUM4; -.
DR PhosphoSitePlus; Q9NUM4; -.
DR SwissPalm; Q9NUM4; -.
DR BioMuta; TMEM106B; -.
DR DMDM; 109895058; -.
DR EPD; Q9NUM4; -.
DR jPOST; Q9NUM4; -.
DR MassIVE; Q9NUM4; -.
DR MaxQB; Q9NUM4; -.
DR PaxDb; Q9NUM4; -.
DR PeptideAtlas; Q9NUM4; -.
DR PRIDE; Q9NUM4; -.
DR ProteomicsDB; 82695; -.
DR Antibodypedia; 43908; 130 antibodies from 28 providers.
DR DNASU; 54664; -.
DR Ensembl; ENST00000396667.7; ENSP00000379901.2; ENSG00000106460.19.
DR Ensembl; ENST00000396668.8; ENSP00000379902.3; ENSG00000106460.19.
DR GeneID; 54664; -.
DR KEGG; hsa:54664; -.
DR MANE-Select; ENST00000396668.8; ENSP00000379902.3; NM_001134232.2; NP_001127704.1.
DR UCSC; uc003ssh.4; human.
DR CTD; 54664; -.
DR DisGeNET; 54664; -.
DR GeneCards; TMEM106B; -.
DR HGNC; HGNC:22407; TMEM106B.
DR HPA; ENSG00000106460; Low tissue specificity.
DR MalaCards; TMEM106B; -.
DR MIM; 105550; phenotype.
DR MIM; 607485; phenotype.
DR MIM; 613413; gene.
DR MIM; 617964; phenotype.
DR neXtProt; NX_Q9NUM4; -.
DR OpenTargets; ENSG00000106460; -.
DR Orphanet; 275864; Behavioral variant of frontotemporal dementia.
DR Orphanet; 100070; Progressive non-fluent aphasia.
DR Orphanet; 100069; Semantic dementia.
DR PharmGKB; PA142670756; -.
DR VEuPathDB; HostDB:ENSG00000106460; -.
DR eggNOG; ENOG502QQRZ; Eukaryota.
DR GeneTree; ENSGT00940000158360; -.
DR HOGENOM; CLU_089337_2_0_1; -.
DR InParanoid; Q9NUM4; -.
DR OMA; QTSQERY; -.
DR OrthoDB; 1175832at2759; -.
DR PhylomeDB; Q9NUM4; -.
DR TreeFam; TF328907; -.
DR PathwayCommons; Q9NUM4; -.
DR SignaLink; Q9NUM4; -.
DR BioGRID-ORCS; 54664; 24 hits in 1079 CRISPR screens.
DR ChiTaRS; TMEM106B; human.
DR GeneWiki; TMEM106B; -.
DR GenomeRNAi; 54664; -.
DR Pharos; Q9NUM4; Tbio.
DR PRO; PR:Q9NUM4; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9NUM4; protein.
DR Bgee; ENSG00000106460; Expressed in cauda epididymis and 211 other tissues.
DR ExpressionAtlas; Q9NUM4; baseline and differential.
DR Genevisible; Q9NUM4; HS.
DR GO; GO:0005768; C:endosome; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:HPA.
DR GO; GO:0051117; F:ATPase binding; IPI:MGI.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:UniProtKB.
DR GO; GO:0007042; P:lysosomal lumen acidification; IEA:Ensembl.
DR GO; GO:1905146; P:lysosomal protein catabolic process; IEA:Ensembl.
DR GO; GO:0007041; P:lysosomal transport; IBA:GO_Central.
DR GO; GO:0032418; P:lysosome localization; IMP:UniProtKB.
DR GO; GO:0007040; P:lysosome organization; IBA:GO_Central.
DR GO; GO:0070050; P:neuron cellular homeostasis; IEA:Ensembl.
DR GO; GO:1900006; P:positive regulation of dendrite development; IEA:Ensembl.
DR GO; GO:0051345; P:positive regulation of hydrolase activity; IEA:Ensembl.
DR GO; GO:1905671; P:regulation of lysosome organization; IEA:Ensembl.
DR InterPro; IPR009790; TMEM106.
DR PANTHER; PTHR28556; PTHR28556; 1.
DR Pfam; PF07092; DUF1356; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amyotrophic lateral sclerosis; Disease variant; Endosome;
KW Glycoprotein; Leukodystrophy; Lipoprotein; Lysosome; Membrane; Myristate;
KW Neurodegeneration; Phosphoprotein; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25255805"
FT CHAIN 2..274
FT /note="Transmembrane protein 106B"
FT /id="PRO_0000242650"
FT TOPO_DOM 2..96
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 97..117
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 118..274
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:25255805"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22511793"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22511793"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22511793"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:22511793, ECO:0000269|PubMed:23742080"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22511793"
FT VARIANT 185
FT /note="T -> S (in dbSNP:rs3173615)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:23742080"
FT /id="VAR_026849"
FT VARIANT 252
FT /note="D -> N (in HLD16; dbSNP:rs1554310600)"
FT /evidence="ECO:0000269|PubMed:29186371,
FT ECO:0000269|PubMed:29444210"
FT /id="VAR_081068"
FT CONFLICT 50
FT /note="Y -> C (in Ref. 2; BAD96983)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="L -> P (in Ref. 2; BAD96983)"
FT /evidence="ECO:0000305"
FT CONFLICT 197
FT /note="Y -> N (in Ref. 2; BAD96983)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 274 AA; 31127 MW; 906C923986DC04E6 CRC64;
MGKSLSHLPL HSSKEDAYDG VTSENMRNGL VNSEVHNEDG RNGDVSQFPY VEFTGRDSVT
CPTCQGTGRI PRGQENQLVA LIPYSDQRLR PRRTKLYVMA SVFVCLLLSG LAVFFLFPRS
IDVKYIGVKS AYVSYDVQKR TIYLNITNTL NITNNNYYSV EVENITAQVQ FSKTVIGKAR
LNNITIIGPL DMKQIDYTVP TVIAEEMSYM YDFCTLISIK VHNIVLMMQV TVTTTYFGHS
EQISQERYQY VDCGRNTTYQ LGQSEYLNVL QPQQ
