Myotubularin - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot Q13496 (MTM1_HUMAN)

Last modified June 16, 2009. Version 83. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
Myotubularin
EC=3.1.3.48

Gene names

Name:	MTM1
Synonyms:	CG2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	603 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Dual-specificity phosphatase that acts on both phosphotyrosine and phosphoserine. Could be involved in a signal transduction pathway necessary for late myogenesis, although its ubiquitous expression suggests a wider function.
Catalytic activity	Protein tyrosine phosphate + H₂O = protein tyrosine + phosphate.
Involvement in disease	Defects in MTM1 are the cause of X-linked centronuclear myopathy X-linked (XCNM) [MIM:310400]; also known as X-linked myotubular myopathy (XLMTM) or myotubular myopathy type 1 (MTM1). Centronuclear myopathies are congenital muscle disorders 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. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily. Contains 1 GRAM domain. Contains 1 myotubularin phosphatase domain.

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Ontologies

Keywords
Disease	Disease mutation
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	muscle organ development Ref.1 Traceable author statement. Source: ProtInc protein amino acid dephosphorylation Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: HPA extracellular matrix Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular function	protein serine/threonine phosphatase activity Non-traceable author statement. Source: UniProtKB protein tyrosine phosphatase activity Ref.1 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

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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

GRAM

Domain

163 – 538

376

Myotubularin phosphatase

Sites

Active site

375

Phosphocysteine intermediate By similarity

Amino acid modifications

Modified residue

Phosphoserine Ref.6

Modified residue

495

Phosphothreonine Ref.5

Modified residue

588

Phosphoserine Ref.7

Modified residue

591

Phosphoserine Ref.7

Natural variations

Natural variant

Missing in XCNM. Ref.17

VAR_006386

Natural variant

V → F in XCNM. Ref.14

VAR_018227

Natural variant

Y → D in XCNM. Ref.17

VAR_018228

Natural variant

R → C in XCNM; mild. Ref.8 Ref.9 Ref.14 Ref.17

VAR_006387

Natural variant

R → P in XCNM. Ref.8 Ref.9 Ref.14 Ref.17

VAR_018229

Natural variant

R → S in XCNM; severe. Ref.8 Ref.9 Ref.14 Ref.17

VAR_018230

Natural variant

L → F in XCNM; mild. Ref.9 Ref.17

VAR_006388

Natural variant

L → P in XCNM; mild. Ref.9

VAR_006389

Natural variant

157

E → K in XCNM. Ref.16

VAR_018231

Natural variant

179

P → S in XCNM; mild. Ref.12 Ref.14

VAR_009217

Natural variant

180

N → K in XCNM; very mild. Ref.17

VAR_018232

Natural variant

184

R → G in XCNM; severe. Ref.8 Ref.17

VAR_006390

Natural variant

184

R → L in XCNM. Ref.8 Ref.17

VAR_018233

Natural variant

186

T → I in XCNM. Ref.14

VAR_018234

Natural variant

189

N → S in XCNM. Ref.9

VAR_006391

Natural variant

197

T → I in XCNM. Ref.15

VAR_018235

Natural variant

198

Y → N in XCNM; severe. Ref.8

VAR_006392

Natural variant

199

P → S in XCNM. Ref.15

VAR_018236

Natural variant

202

L → S in XCNM; severe. Ref.17

VAR_018237

Natural variant

205

P → L in XCNM; severe. Ref.9 Ref.13 Ref.14 Ref.17

VAR_006393

Natural variant

225

I → T in XCNM; mild. Ref.12 Ref.13

VAR_009218

Natural variant

226

P → T in XCNM. Ref.17

VAR_018238

Natural variant

227

V → M in XCNM. Ref.14

VAR_018239

Natural variant

228

L → P in XCNM. Ref.14

VAR_018240

Natural variant

229

S → P in XCNM; mild. Ref.9

VAR_006394

Natural variant

230

W → C in XCNM. Ref.13 Ref.17

VAR_018241

Natural variant

232

H → R in XCNM. Ref.13

VAR_018242

Natural variant

241

R → C in XCNM; mild to moderate. Ref.8 Ref.9 Ref.12 Ref.13 Ref.14 Ref.17

VAR_006395

Natural variant

241

R → L in XCNM; severe. Ref.8 Ref.9 Ref.12 Ref.13 Ref.14 Ref.17

VAR_006396

Natural variant

264

I → S in XCNM; severe. Ref.12

VAR_009219

Natural variant

279

A → G in XCNM. Ref.14

VAR_018243

Natural variant

294

Missing in XCNM; mild. Ref.12

VAR_009220

Natural variant

317

M → R in XCNM; mild. Ref.8

VAR_006397

Natural variant

346

W → C in XCNM; mild. Ref.17

VAR_018244

Natural variant

346

W → S in XCNM. Ref.17

VAR_018245

Natural variant

364

V → G in XCNM. Ref.17

VAR_018246

Natural variant

374

H → D in XCNM.

VAR_018247

Natural variant

376

S → N in XCNM. Ref.9

VAR_006398

Natural variant

378

G → E in XCNM. Ref.9 Ref.11 Ref.12 Ref.14 Ref.15

VAR_018248

Natural variant

378

G → R in XCNM; severe. Ref.9 Ref.11 Ref.12 Ref.14 Ref.15

VAR_006399

Natural variant

389

A → D in XCNM; severe. Ref.17

VAR_018249

Natural variant

391

L → P in XCNM. Ref.14

VAR_018250

Natural variant

397

Y → C in XCNM; severe. Ref.8 Ref.9 Ref.14 Ref.17

VAR_006400

Natural variant

402

G → A in XCNM; mild. Ref.9 Ref.10 Ref.13 Ref.14 Ref.15

VAR_006401

Natural variant

402

G → R in XCNM. Ref.9 Ref.10 Ref.13 Ref.14 Ref.15

VAR_018251

Natural variant

402

G → V in XCNM. Ref.9 Ref.10 Ref.13 Ref.14 Ref.15

VAR_018252

Natural variant

404

E → K in XCNM; mild. Ref.8

VAR_006402

Natural variant

406

L → P in XCNM; severe. Ref.8

VAR_006403

Natural variant

411

W → C in XCNM.

VAR_018253

Natural variant

420

S → SFIQ in XCNM; severe.

VAR_009221

Natural variant

421

R → Q in XCNM; severe. Ref.8 Ref.9 Ref.14 Ref.17

VAR_006404

Natural variant

421

R → RFIQ in XCNM; severe. Ref.8 Ref.9 Ref.14 Ref.17

VAR_006405

Natural variant

431

D → N in XCNM. Ref.9

VAR_006406

Natural variant

433

D → N in XCNM. Ref.9

VAR_006407

Natural variant

444

C → Y in XCNM. Ref.13

VAR_018254

Natural variant

469

H → P in XCNM. Ref.9 Ref.17

VAR_006408

Natural variant

470

L → P in XCNM; severe. Ref.17

VAR_018255

Natural variant

481

N → Y in XCNM; mild. Ref.17

VAR_018256

Natural variant

499

W → R in XCNM; mild. Ref.8

VAR_006409

Natural variant

510

K → N in XCNM; severe. Ref.12

VAR_009222

Experimental info

Sequence conflict

410

E → K in AAH30779. Ref.3

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Sequences

Sequence

Length

Mass (Da)

Tools

Q13496-1 [UniParc].

Last modified July 15, 1998. Version 2.
Checksum: BE9770F2471957C0
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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

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 8640223] [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: 9781038] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[4]	"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: 10790201] [Abstract] Cited for: REVIEW ON XCNM VARIANTS.
[5]	"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: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-495, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, MASS SPECTROMETRY. Tissue: Platelet.
[7]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588 AND SER-591, MASS SPECTROMETRY.
[8]	"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: 9285787] [Abstract] Cited for: VARIANTS XCNM CYS-69; GLY-184; ASN-198; LEU-241; ARG-317; CYS-397; LYS-404; PRO-406; GLN-421 AND ARG-499.
[9]	"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: 9305655] [Abstract] Cited for: VARIANTS XCNM 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.
[10]	"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: 9829274] [Abstract] Cited for: VARIANT XCNM VAL-402.
[11]	"Germline mosaicism in X-linked myotubular myopathy." Haene B.G., Rogers R.C., Schwartz C.E. Clin. Genet. 56:77-81(1999) [PubMed: 10466421] [Abstract] Cited for: VARIANT XCNM GLU-378.
[12]	"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: 10502779] [Abstract] Cited for: VARIANTS XCNM SER-179; THR-225; CYS-241; SER-264; GLY-294 DEL; ARG-378 AND ASN-510.
[13]	"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: 10063835] [Abstract] Cited for: VARIANTS XCNM LEU-205; THR-225; CYS-230; ARG-232; CYS-241; ARG-402 AND TYR-444.
[14]	"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: 11793470] [Abstract] Cited for: VARIANTS XCNM 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.
[15]	"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: 12031625] [Abstract] Cited for: VARIANTS XCNM ILE-197; SER-199; ARG-378 AND ARG-402.
[16]	"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: 12859411] [Abstract] Cited for: VARIANT XCNM LYS-157.
[17]	"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: 12522554] [Abstract] Cited for: VARIANTS XCNM 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.
+	Additional computationally mapped references.

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Web resources

GeneReviews

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Cross-references

Sequence databases
	U46024 mRNA. Translation: AAC51682.1. AF020676 AF020675 Genomic DNA. Translation: AAC12865.1. BC030779 mRNA. Translation: AAH30779.1.
IPI	IPI00748788.
RefSeq	NP_000243.1.
UniGene	Hs.655056
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	Q13496.
Proteomic databases
PRIDE	Q13496.
Genome annotation databases
Ensembl	ENSG00000171100. Homo sapiens. [Contig view]
GeneID	4534.
KEGG	hsa:4534.
Organism-specific databases
GeneCards	GC0XP149487.
H-InvDB	HIX0017108.
HGNC	HGNC:7448. MTM1.
HPA	HPA010008. HPA010665.
MIM	300415. gene. 310400. phenotype.
Orphanet	595. Centronuclear myopathy. 596. X-linked centronuclear myopathy.
PharmGKB	PA38811.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q13496.
OMA	Q13496. HIKLVLT.
Enzyme and pathway databases
BRENDA	3.1.3.48. 247. 3.1.3.64. 247.
Gene expression databases
ArrayExpress	Q13496.
Bgee	Q13496.
CleanEx	HS_MTM1.
GermOnline	ENSG00000171100. Homo sapiens.
Family and domain databases
InterPro	IPR004182. GRAM. IPR010569. Myotub-related. IPR017906. Myotubularin_phosphatase. IPR000387. Tyr_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 Resources
NextBio	17492.
SOURCE	Search...

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Entry information

Entry name

MTM1_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 15, 1998
Last modified:	June 16, 2009
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents