Q13496 (MTM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myotubularin
EC=3.1.3.64

Gene names

Name:	MTM1
Synonyms:	CG2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	603 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Lipid phosphatase which dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). Has also been shown to dephosphorylate phosphotyrosine- and phosphoserine-containing peptides. Negatively regulates EGFR degradation through regulation of EGFR trafficking from the late endosome to the lysosome. Plays a role in vacuolar formation and morphology. Regulates desmin intermediate filament assembly and architecture. Plays a role in mitochondrial morphology and positioning. Required for skeletal muscle maintenance but not for myogenesis. Ref.6 Ref.8 Ref.9 Ref.11 Ref.13 Ref.18
Catalytic activity	1-phosphatidyl-1D-myo-inositol 3-phosphate + H2O = 1-phosphatidyl-1D-myo-inositol + phosphate.
Enzyme regulation	Allosterically activated by phosphatidylinositol 5-phosphate (PI5P). Ref.11
Subunit structure	Interacts with MTMR12; the interaction modulates MTM1 intracellular localization. Interacts with MLL (via SET domain). Interacts with DES in skeletal muscle but not in cardiac muscle. Ref.6 Ref.12 Ref.18
Subcellular location	Cytoplasm. Cell membrane; Peripheral membrane protein. Cell projection › filopodium. Cell projection › ruffle. Late endosome. Note: Localizes as a dense cytoplasmic network. Also localizes to the plasma membrane, including plasma membrane extensions such as filopodia and ruffles. Predominantly located in the cytoplasm following interaction with MTMR12. Recruited to the late endosome following EGF stimulation. Ref.8 Ref.9 Ref.10 Ref.12 Ref.13
Domain	The GRAM domain mediates binding to PI(3,5)P2 and, with lower affinity, to other phosphoinositides. Ref.13
Involvement in disease	Myopathy, centronuclear, X-linked (CNMX) [MIM:310400]: A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily. Contains 1 GRAM domain. Contains 1 myotubularin phosphatase domain.
Biophysicochemical properties	Kinetic parameters: KM=39 µM for PI3P Ref.13 KM=17 µM for PI(3,5)P2

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cell membrane Cell projection Cytoplasm Endosome Membrane
Disease	Disease mutation
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	endosome to lysosome transport Inferred from direct assay Ref.13. Source: UniProtKB intermediate filament organization Inferred from mutant phenotype Ref.18. Source: UniProtKB mitochondrion distribution Inferred from mutant phenotype Ref.18. Source: UniProtKB mitochondrion morphogenesis Inferred from direct assay Ref.18. Source: UniProtKB muscle cell homeostasis Inferred from electronic annotation. Source: Compara peptidyl-tyrosine dephosphorylation Inferred from electronic annotation. Source: GOC phosphatidylinositol biosynthetic process Traceable author statement. Source: Reactome phosphatidylinositol dephosphorylation Inferred from direct assay Ref.9Ref.11. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW regulation of vacuole organization Inferred from direct assay Ref.13. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	I band Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome filopodium Inferred from direct assay Ref.10. Source: UniProtKB late endosome Inferred from direct assay Ref.13. Source: UniProtKB plasma membrane Inferred from direct assay Ref.10PubMed 12217958Ref.12. Source: UniProtKB ruffle Inferred from direct assay Ref.10. Source: UniProtKB
Molecular_function	intermediate filament binding Inferred from direct assay Ref.18. Source: UniProtKB phosphatidylinositol binding Inferred from direct assay Ref.13. Source: UniProtKB phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity Inferred from direct assay Ref.11. Source: UniProtKB phosphatidylinositol-3-phosphatase activity Inferred from direct assay Ref.9. Source: UniProtKB phosphoprotein phosphatase activity Inferred from direct assay Ref.6. Source: UniProtKB protein tyrosine phosphatase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 603	603	Myotubularin		PRO_0000094930
Regions
	Domain	29 – 97	69	GRAM
	Domain	163 – 538	376	Myotubularin phosphatase
Sites
	Active site	375	1	Phosphocysteine intermediate By similarity
Amino acid modifications
	Modified residue	495	1	Phosphothreonine Ref.14
	Modified residue	588	1	Phosphoserine Ref.15 Ref.16
Natural variations
	Natural variant	47	1	Missing in CNMX. Ref.28		VAR_006386
	Natural variant	49	1	V → F in CNMX; greatly reduced binding to PI(3,5)P2; does not translocate to the late endosome following EGF stimulation; shows normal EGFR degradation. Ref.13 Ref.25		VAR_018227
	Natural variant	68	1	Y → D in CNMX. Ref.28		VAR_018228
	Natural variant	69	1	R → C in CNMX; mild; reduced response to PI5P and reduced binding to PI(3,5)P2. Ref.11 Ref.13 Ref.19 Ref.20 Ref.25		VAR_006387
	Natural variant	69	1	R → P in CNMX. Ref.28		VAR_018229
	Natural variant	69	1	R → S in CNMX; severe. Ref.28		VAR_018230
	Natural variant	70	1	L → F in CNMX; mild; reduced binding to PI(3,5)P2. Ref.13 Ref.20 Ref.28		VAR_006388
	Natural variant	87	1	L → P in CNMX; mild; reduced binding to PI(3,5)P2. Ref.13 Ref.20		VAR_006389
	Natural variant	157	1	E → K in CNMX. Ref.27		VAR_018231
	Natural variant	179	1	P → S in CNMX; mild. Ref.23 Ref.25		VAR_009217
	Natural variant	180	1	N → K in CNMX; very mild. Ref.28		VAR_018232
	Natural variant	184	1	R → G in CNMX; severe; loss of activity; abolishes interaction with DES. Ref.11 Ref.18 Ref.19		VAR_006390
	Natural variant	184	1	R → L in CNMX; reduced activity and response to PI5P. Ref.28		VAR_018233
	Natural variant	186	1	T → I in CNMX. Ref.25		VAR_018234
	Natural variant	189	1	N → S in CNMX. Ref.20		VAR_006391
	Natural variant	197	1	T → I in CNMX. Ref.26		VAR_018235
	Natural variant	198	1	Y → N in CNMX; severe. Ref.19		VAR_006392
	Natural variant	199	1	P → S in CNMX. Ref.26		VAR_018236
	Natural variant	202	1	L → S in CNMX; severe. Ref.28		VAR_018237
	Natural variant	205	1	P → L in CNMX; severe; dramatic decrease in phosphatase activity; abolishes interaction with DES. Ref.9 Ref.18 Ref.20 Ref.24 Ref.25 Ref.28		VAR_006393
	Natural variant	225	1	I → T in CNMX; mild. Ref.23 Ref.24		VAR_009218
	Natural variant	226	1	P → T in CNMX. Ref.28		VAR_018238
	Natural variant	227	1	V → M in CNMX. Ref.25		VAR_018239
	Natural variant	228	1	L → P in CNMX. Ref.25		VAR_018240
	Natural variant	229	1	S → P in CNMX; mild. Ref.20		VAR_006394
	Natural variant	230	1	W → C in CNMX. Ref.24 Ref.28		VAR_018241
	Natural variant	232	1	H → R in CNMX. Ref.24		VAR_018242
	Natural variant	241	1	R → C in CNMX; mild to moderate; abolishes interaction with DES. Ref.18 Ref.20 Ref.23 Ref.24 Ref.25 Ref.28		VAR_006395
	Natural variant	241	1	R → L in CNMX; severe; loss of activity. Ref.9 Ref.11 Ref.19		VAR_006396
	Natural variant	264	1	I → S in CNMX; severe. Ref.23		VAR_009219
	Natural variant	279	1	A → G in CNMX. Ref.25		VAR_018243
	Natural variant	294	1	Missing in CNMX; mild. Ref.23		VAR_009220
	Natural variant	317	1	M → R in CNMX; mild. Ref.19		VAR_006397
	Natural variant	346	1	W → C in CNMX; mild. Ref.28		VAR_018244
	Natural variant	346	1	W → S in CNMX.		VAR_018245
	Natural variant	364	1	V → G in CNMX. Ref.28		VAR_018246
	Natural variant	374	1	H → D in CNMX.		VAR_018247
	Natural variant	376	1	S → N in CNMX; dramatic decrease in phosphatase activity. Ref.9 Ref.20		VAR_006398
	Natural variant	378	1	G → E in CNMX. Ref.22		VAR_018248
	Natural variant	378	1	G → R in CNMX; severe; dramatic decrease in phosphatase activity; does not affect EGFR degradation. Ref.9 Ref.20 Ref.23 Ref.25 Ref.26		VAR_006399
	Natural variant	387	1	S → Y in CNMX. Ref.30		VAR_068846
	Natural variant	389	1	A → D in CNMX; severe. Ref.28		VAR_018249
	Natural variant	391	1	L → P in CNMX. Ref.25		VAR_018250
	Natural variant	397	1	Y → C in CNMX; severe; dramatic decrease in phosphatase activity. Ref.9 Ref.19 Ref.20 Ref.25 Ref.28		VAR_006400
	Natural variant	402	1	G → A in CNMX; mild. Ref.20		VAR_006401
	Natural variant	402	1	G → R in CNMX. Ref.24 Ref.25 Ref.26		VAR_018251
	Natural variant	402	1	G → V in CNMX. Ref.21		VAR_018252
	Natural variant	404	1	E → K in CNMX; mild. Ref.19 Ref.29		VAR_006402
	Natural variant	406	1	L → P in CNMX; severe. Ref.19		VAR_006403
	Natural variant	411	1	W → C in CNMX.		VAR_018253
	Natural variant	420	1	S → SFIQ in CNMX; severe.		VAR_009221
	Natural variant	421	1	R → Q in CNMX; severe; reduced activity and response to PI5P; does not affect interaction with DES. Ref.11 Ref.18 Ref.19 Ref.20 Ref.25 Ref.28		VAR_006404
	Natural variant	421	1	R → RFIQ in CNMX; severe.		VAR_006405
	Natural variant	431	1	D → N in CNMX. Ref.20		VAR_006406
	Natural variant	433	1	D → N in CNMX. Ref.20		VAR_006407
	Natural variant	444	1	C → Y in CNMX. Ref.24		VAR_018254
	Natural variant	469	1	H → P in CNMX; loss of activity. Ref.11 Ref.20 Ref.28		VAR_006408
	Natural variant	470	1	L → P in CNMX; severe. Ref.28		VAR_018255
	Natural variant	481	1	N → Y in CNMX; mild. Ref.28		VAR_018256
	Natural variant	499	1	W → R in CNMX; mild. Ref.19		VAR_006409
	Natural variant	510	1	K → N in CNMX; severe. Ref.23		VAR_009222
Experimental info
	Mutagenesis	114	1	K → A: Reduced response to PI5P. Ref.11
	Mutagenesis	181	1	H → A: Disrupts interaction with DES. Does not affect lipid phosphatase activity. Ref.18
	Mutagenesis	206	1	Y → A: Disrupts interaction with DES. Does not affect lipid phosphatase activity. Ref.18
	Mutagenesis	209	1	S → A: Disrupts interaction with DES. Does not affect lipid phosphatase activity. Ref.18
	Mutagenesis	220	1	R → A: Loss of activity. Ref.11
	Mutagenesis	255	1	K → A: Disrupts interaction with DES. Ref.18
	Mutagenesis	257	1	D → A: No effect on subcellular location. Ref.10
	Mutagenesis	269	1	K → A: Disrupts interaction with DES. Does not affect lipid phosphatase activity. Ref.18
	Mutagenesis	278	1	D → A: Localizes to plasma membrane extensions. Does not affect interaction with DES. Ref.8 Ref.10 Ref.18
	Mutagenesis	375	1	C → A: No effect on subcellular location. Ref.8 Ref.9 Ref.10 Ref.11 Ref.18
	Mutagenesis	375	1	C → S: Lacks activity toward PI3P. Does not affect interaction with DES. Ref.8 Ref.9 Ref.10 Ref.11 Ref.18
	Mutagenesis	377	1	D → A: No effect on subcellular location. Ref.8 Ref.10
	Mutagenesis	380	1	D → A: Does not affect interaction with DES. Ref.8 Ref.10 Ref.18
	Mutagenesis	394	1	D → A: Produces an unstable protein. Ref.8
	Mutagenesis	410	1	E → A: Produces an unstable protein. Ref.8
	Mutagenesis	420	1	S → D: Does not affect interaction with DES. Ref.18
	Mutagenesis	443	1	D → A: Produces an unstable protein. Ref.8
	Sequence conflict	410	1	E → K in AAH30779. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q13496 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: BE9770F2471957C0	FASTA	603	69,932
	10 20 30 40 50 60 MASASTSKYN SHSLENESIK RTSRDGVNRD LTEAVPRLPG ETLITDKEVI YICPFNGPIK 70 80 90 100 110 120 GRVYITNYRL YLRSLETDSS LILDVPLGVI SRIEKMGGAT SRGENSYGLD ITCKDMRNLR 130 140 150 160 170 180 FALKQEGHSR RDMFEILTRY AFPLAHSLPL FAFLNEEKFN VDGWTVYNPV EEYRRQGLPN 190 200 210 220 230 240 HHWRITFINK CYELCDTYPA LLVVPYRASD DDLRRVATFR SRNRIPVLSW IHPENKTVIV 250 260 270 280 290 300 RCSQPLVGMS GKRNKDDEKY LDVIRETNKQ ISKLTIYDAR PSVNAVANKA TGGGYESDDA 310 320 330 340 350 360 YHNAELFFLD IHNIHVMRES LKKVKDIVYP NVEESHWLSS LESTHWLEHI KLVLTGAIQV 370 380 390 400 410 420 ADKVSSGKSS VLVHCSDGWD RTAQLTSLAM LMLDSFYRSI EGFEILVQKE WISFGHKFAS 430 440 450 460 470 480 RIGHGDKNHT DADRSPIFLQ FIDCVWQMSK QFPTAFEFNE QFLIIILDHL YSCRFGTFLF 490 500 510 520 530 540 NCESARERQK VTERTVSLWS LINSNKEKFK NPFYTKEINR VLYPVASMRH LELWVNYYIR 550 560 570 580 590 600 WNPRIKQQQP NPVEQRYMEL LALRDEYIKR LEELQLANSA KLSDPPTSPS SPSQMMPHVQ THF

References

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[1]	"A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast." Laporte J., Hu L.-J., Kretz C., Mandel J.-L., Kioschis P., Coy J., Klauck S.M., Poutska A., Dahl N. Nat. Genet. 13:175-182(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Genomic organization of the MTM1 gene implicated in X-linked myotubular myopathy." Laporte J., Guiraud-Chaumeil C., Tanner S.M., Blondeau F., Hu L.J., Vicaire S., Liechti-Gallati S., Mandel J.-L. Eur. J. Hum. Genet. 6:325-330(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[6]	"Association of SET domain and myotubularin-related proteins modulates growth control." Cui X., De Vivo I., Slany R., Miyamoto A., Firestein R., Cleary M.L. Nat. Genet. 18:331-337(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MLL.
[7]	"MTM1 mutations in X-linked myotubular myopathy." Laporte J., Biancalana V., Tanner S.M., Kress W., Schneider V., Wallgren-Pettersson C., Herger F., Buj-Bello A., Blondeau F., Liechti-Gallati S., Mandel J.-L. Hum. Mutat. 15:393-409(2000) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS CNMX.
[8]	"Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway." Blondeau F., Laporte J., Bodin S., Superti-Furga G., Payrastre B., Mandel J.L. Hum. Mol. Genet. 9:2223-2229(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-278; CYS-375; ASP-377; ASP-380; ASP-394; GLU-410 AND ASP-443.
[9]	"Myotubularin, a protein tyrosine phosphatase mutated in myotubular myopathy, dephosphorylates the lipid second messenger, phosphatidylinositol 3-phosphate." Taylor G.S., Maehama T., Dixon J.E. Proc. Natl. Acad. Sci. U.S.A. 97:8910-8915(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS LEU-205; LEU-241; ASN-376; ARG-378 AND CYS-397, MUTAGENESIS OF CYS-375.
[10]	"The PtdIns3P phosphatase myotubularin is a cytoplasmic protein that also localizes to Rac1-inducible plasma membrane ruffles." Laporte J., Blondeau F., Gansmuller A., Lutz Y., Vonesch J.L., Mandel J.L. J. Cell Sci. 115:3105-3117(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-257; ASP-278; CYS-375; ASP-377 AND ASP-380.
[11]	"Phosphatidylinositol-5-phosphate activation and conserved substrate specificity of the myotubularin phosphatidylinositol 3-phosphatases." Schaletzky J., Dove S.K., Short B., Lorenzo O., Clague M.J., Barr F.A. Curr. Biol. 13:504-509(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, CHARACTERIZATION OF VARIANTS CYS-69; GLY-184; LEU-241; GLN-421 AND PRO-469, MUTAGENESIS OF LYS-114; ARG-220 AND CYS-375.
[12]	"Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter protein, 3-PAP." Nandurkar H.H., Layton M., Laporte J., Selan C., Corcoran L., Caldwell K.K., Mochizuki Y., Majerus P.W., Mitchell C.A. Proc. Natl. Acad. Sci. U.S.A. 100:8660-8665(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MTMR12, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
[13]	"Myotubularin regulates the function of the late endosome through the gram domain-phosphatidylinositol 3,5-bisphosphate interaction." Tsujita K., Itoh T., Ijuin T., Yamamoto A., Shisheva A., Laporte J., Takenawa T. J. Biol. Chem. 279:13817-13824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, ROLE OF GRAM DOMAIN, CHARACTERIZATION OF VARIANTS PHE-49; CYS-69; PHE-70 AND PRO-87.
[14]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-495, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]	"Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle." Hnia K., Tronchere H., Tomczak K.K., Amoasii L., Schultz P., Beggs A.H., Payrastre B., Mandel J.L., Laporte J. J. Clin. Invest. 121:70-85(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DES, CHARACTERIZATION OF VARIANTS GLY-184; LEU-205; CYS-241 AND GLN-421, MUTAGENESIS OF HIS-181; TYR-206; SER-209; LYS-255; LYS-269; ASP-278; CYS-375; ASP-380 AND SER-420.
[19]	"Characterization of mutations in the myotubularin gene in twenty six patients with X-linked myotubular myopathy." de Gouyon B.M., Zhao W., Laporte J., Mandel J.-L., Metzenberg A., Herman G.E. Hum. Mol. Genet. 6:1499-1504(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CNMX CYS-69; GLY-184; ASN-198; LEU-241; ARG-317; CYS-397; LYS-404; PRO-406; GLN-421 AND ARG-499.
[20]	"Mutations in the MTM1 gene implicated in X-linked myotubular myopathy." Laporte J., Guiraud-Chaumeil C., Vincent M.-C., Mandel J.-L., Tanner S.M., Liechti-Gallati S., Wallgren-Pettersson C., Dahl N., Kress W., Bolhuis P.A., Fardeau M., Samson F., Bertini E. Hum. Mol. Genet. 6:1505-1511(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CNMX CYS-69; PHE-70; PRO-87; SER-189; LEU-205; PRO-229; CYS-241; ASN-376; ARG-378; CYS-397; ALA-402; GLN-421; ASN-431; ASN-433 AND PRO-469.
[21]	"MTM1 gene mutations in Japanese patients with the severe infantile form of myotubular myopathy." Nishino I., Minami N., Kobayashi O., Ikezawa M., Goto Y., Arahata K., Nonaka I. Neuromuscul. Disord. 8:453-458(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CNMX VAL-402.
[22]	"Germline mosaicism in X-linked myotubular myopathy." Haene B.G., Rogers R.C., Schwartz C.E. Clin. Genet. 56:77-81(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CNMX GLU-378.
[23]	"Identification of novel mutations in the MTM1 gene causing severe and mild forms of X-linked myotubular myopathy." Buj-Bello A., Biancalana V., Moutou C., Laporte J., Mandel J.-L. Hum. Mutat. 14:320-325(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CNMX SER-179; THR-225; CYS-241; SER-264; GLY-294 DEL; ARG-378 AND ASN-510.
[24]	"Characterization of 34 novel and six known MTM1 gene mutations in 47 unrelated X-linked myotubular myopathy patients." Tanner S.M., Schneider V., Thomas N.S.T., Clarke A., Lazarou L., Liechti-Gallati S. Neuromuscul. Disord. 9:41-49(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CNMX LEU-205; THR-225; CYS-230; ARG-232; CYS-241; ARG-402 AND TYR-444.
[25]	"Characterization of mutations in fifty North American patients with X-linked myotubular myopathy." Herman G.E., Kopacz K., Zhao W., Mills P.L., Metzenberg A., Das S. Hum. Mutat. 19:114-121(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CNMX PHE-49; CYS-69; SER-179; ILE-186; LEU-205; MET-227; PRO-228; CYS-241; GLY-279; ARG-378; PRO-391; CYS-397; ARG-402 AND GLN-421.
[26]	"Rapid scanning of myotubularin (MTM1) gene by denaturing high-performance liquid chromatography (DHPLC)." Flex E., De Luca A., D'Apice M.R., Buccino A., Dallapiccola B., Novelli G. Neuromuscul. Disord. 12:501-505(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CNMX ILE-197; SER-199; ARG-378 AND ARG-402.
[27]	"X-linked myotubular myopathy in a family with three adult survivors." Yu S., Manson J., White S., Bourne A., Waddy H., Davis M., Haan E. Clin. Genet. 64:148-152(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CNMX LYS-157.
[28]	"Characterisation of mutations in 77 patients with X-linked myotubular myopathy, including a family with a very mild phenotype." Biancalana V., Caron O., Gallati S., Baas F., Kress W., Novelli G., D'Apice M.R., Lagier-Tourenne C., Buj-Bello A., Romero N.B., Mandel J.-L. Hum. Genet. 112:135-142(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CNMX LYS-47 DEL; ASP-68; PRO-69; SER-69; PHE-70; LYS-180; LEU-184; SER-202; LEU-205; THR-226; CYS-230; CYS-241; CYS-346; GLY-364; ASP-389; CYS-397; GLN-421; PRO-469; PRO-470 AND TYR-481.
[29]	"Extreme phenotypic variability in a German family with X-linked myotubular myopathy associated with E404K mutation in MTM1." Hoffjan S., Thiels C., Vorgerd M., Neuen-Jacob E., Epplen J.T., Kress W. Neuromuscul. Disord. 16:749-753(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CNMX LYS-404.
[30]	"X-linked myotubular myopathy with a novel MTM1 mutation in a Taiwanese child." Chang C.Y., Lin S.P., Lin H.Y., Chuang C.K., Ho C.S., Su Y.N. J. Formos. Med. Assoc. 107:965-970(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CNMX TYR-387.
+	Additional computationally mapped references.

Web resources

GeneReviews

Leiden Muscular Dystrophy pages, Myotubularin 1 (MTM1)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases
EMBL GenBank DDBJ	U46024 mRNA. Translation: AAC51682.1. AF020676 , AF020664, AF020665, AF020666, AF020667, AF020668, AF020669, AF020670, AF020671, AF020672, AF020673, AF020674, AF020675 Genomic DNA. Translation: AAC12865.1. AC109994 Genomic DNA. No translation available. AF002223 Genomic DNA. No translation available. CH471169 Genomic DNA. Translation: EAW99377.1. BC030779 mRNA. Translation: AAH30779.1.
IPI	IPI00748788.
RefSeq	NP_000243.1. NM_000252.2.
UniGene	Hs.655056.
3D structure databases
ProteinModelPortal	Q13496.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13496. 2 interactions.
STRING	9606.ENSP00000359423.
PTM databases
PhosphoSite	Q13496.
Polymorphism databases
DMDM	2851537.
Proteomic databases
PaxDb	Q13496.
PRIDE	Q13496.
Protocols and materials databases
DNASU	4534.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000370396; ENSP00000359423; ENSG00000171100. ENST00000598147; ENSP00000472211; ENSG00000269031.
GeneID	4534.
KEGG	hsa:4534.
UCSC	uc004fef.4. human.
Organism-specific databases
CTD	4534.
GeneCards	GC0XP149738.
HGNC	HGNC:7448. MTM1.
HPA	HPA010008. HPA010665.
MIM	300415. gene. 310400. phenotype.
neXtProt	NX_Q13496.
Orphanet	596. X-linked centronuclear myopathy.
PharmGKB	PA31251.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG322789.
HOGENOM	HOG000210598.
HOVERGEN	HBG000220.
InParanoid	Q13496.
KO	K01108.
OMA	TDKEVIY.
OrthoDB	EOG4B5P4S.
PhylomeDB	Q13496.
Enzyme and pathway databases
BRENDA	3.1.3.64. 2681.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q13496.
Bgee	Q13496.
CleanEx	HS_MTM1.
Genevestigator	Q13496.
GermOnline	ENSG00000171100. Homo sapiens.
Family and domain databases
Gene3D	2.30.29.30. 1 hit.
InterPro	IPR004182. GRAM. IPR010569. Myotub-related. IPR017906. Myotubularin_phosphatase_dom. IPR011993. PH_like_dom. IPR000387. Tyr/Dual-sp_Pase. IPR016130. Tyr_Pase_AS. [Graphical view]
Pfam	PF02893. GRAM. 1 hit. PF06602. Myotub-related. 1 hit. [Graphical view]
SMART	SM00568. GRAM. 1 hit. [Graphical view]
PROSITE	PS51339. PPASE_MYOTUBULARIN. 1 hit. PS00383. TYR_PHOSPHATASE_1. 1 hit. PS50056. TYR_PHOSPHATASE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MTM1. human.
GenomeRNAi	4534.
NextBio	17492.
SOURCE	Search...

Entry information

Entry name

MTM1_HUMAN

Accession

Primary (citable) accession number: Q13496
Secondary accession number(s): A6NDB1, Q8NEL1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 15, 1998
Last modified:	May 1, 2013
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.