Q9Z2C5 (MTM1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myotubularin
EC=3.1.3.64

Gene names

Name:

Mtm1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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 By similarity. 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.5 Ref.6
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) By similarity.
Subunit structure	Interacts with MTMR12; the interaction modulates MTM1 intracellular localization. Interacts with MLL (via SET domain) By similarity. Interacts with DES in skeletal muscle but not in cardiac muscle. Ref.6
Subcellular location	Cytoplasm. Cell membrane; Peripheral membrane protein By similarity. Cell projection › filopodium. Cell projection › ruffle. Late endosome By similarity. 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.4
Tissue specificity	Widely expressed with highest levels detected in heart and muscle and low levels in brain (at protein level). Ref.4
Domain	The GRAM domain mediates binding to PI(3,5)P2 and, with lower affinity, to other phosphoinositides By similarity.
Disruption phenotype	Mice are viable although lifespan is severely reduced. An under-representation of mutant males suggests some prenatal lethality. Generalized and progressive myopathy starts at around 4 weeks of age with amyotrophy and accumulation of central nuclei in skeletal muscle fibers, leading to death at 6-14 weeks. Mutants also show mitochondrial disorganization and increased levels of desmin with abnormal desmin intermediate filament formation and architecture. Ref.5 Ref.6
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily. Contains 1 GRAM domain. Contains 1 myotubularin phosphatase domain.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cell membrane Cell projection Cytoplasm Endosome Membrane
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	endosome to lysosome transport Inferred from sequence or structural similarity. Source: UniProtKB intermediate filament organization Inferred from sequence or structural similarity. Source: UniProtKB mitochondrion distribution Inferred from mutant phenotype Ref.6. Source: UniProtKB mitochondrion morphogenesis Inferred from mutant phenotype Ref.6. Source: UniProtKB muscle cell homeostasis Inferred from mutant phenotype Ref.5. Source: MGI peptidyl-tyrosine dephosphorylation Inferred from electronic annotation. Source: GOC phosphatidylinositol dephosphorylation Inferred from sequence or structural similarity. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW regulation of vacuole organization Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	I band Inferred from direct assay PubMed 18434328. Source: MGI filopodium Inferred from sequence or structural similarity. Source: UniProtKB late endosome Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB ruffle Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	intermediate filament binding Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol binding Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol-3-phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB phosphoprotein phosphatase activity Inferred from sequence or structural similarity. 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_0000094931
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 By similarity
	Modified residue	588	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	95	1	K → Y in AAC77821. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9Z2C5 [UniParc]. Last modified June 28, 2011. Version 2. Checksum: 65929312F07FFCC7	FASTA	603	69,559
	10 20 30 40 50 60 MASASASKYN SHSLENESIK KVSQDGVSQD VSETVPRLPG ELLITEKEVI YICPFNGPIK 70 80 90 100 110 120 GRVYITNYRL YLRSLETDSA LILDVPLGVI SRIEKMGGAT SRGENSYGLD ITCKDLRNLR 130 140 150 160 170 180 FALKQEGHSR RDMFEILVKH AFPLAHNLPL FAFVNEEKFN VDGWTVYNPV EEYRRQGLPN 190 200 210 220 230 240 HHWRISFINK CYELCETYPA LLVVPYRTSD DDLRRIATFR SRNRLPVLSW IHPENKMVIM 250 260 270 280 290 300 RCSQPLVGMS GKRNKDDEKY LDVIRETNKQ TSKLMIYDAR PSVNAVANKA TGGGYESDDA 310 320 330 340 350 360 YQNSELSFLD IHNIHVMRES LKKVKDIVYP NIEESHWLSS LESTHWLEHI KLVLTGAIQV 370 380 390 400 410 420 ADQVSSGKSS VLVHCSDGWD RTAQLTSLAM LMLDSFYRTI EGFEILVQKE WISFGHKFAS 430 440 450 460 470 480 RIGHGDKNHA DADRSPIFLQ FIDCVWQMSK QFPTAFEFNE GFLITVLDHL YSCRFGTFLF 490 500 510 520 530 540 NCDSARERQK LTERTVSLWS LINSNKDKFK NPFYTKEINR VLYPVASMRH LELWVNYYIR 550 560 570 580 590 600 WNPRVKQQQP NPVEQRYMEL LALRDDYIKR LEELQLANSA KLADAPASTS SSSQMVPHVQ THF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of the myotubularin dual specificity phosphatase gene family from yeast to human." Laporte J., Blondeau F., Buj-Bello A., Tentler D., Kretz C., Dahl N., Mandel J.-L. Hum. Mol. Genet. 7:1703-1712(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: CD-1. Tissue: Pituitary.
[4]	"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, TISSUE SPECIFICITY.
[5]	"The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice." Buj-Bello A., Laugel V., Messaddeq N., Zahreddine H., Laporte J., Pellissier J.F., Mandel J.L. Proc. Natl. Acad. Sci. U.S.A. 99:15060-15065(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]	"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, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF073996 mRNA. Translation: AAC77821.1. AL731843, AL772294 Genomic DNA. Translation: CAM20185.1. BC090984 mRNA. Translation: AAH90984.1.
IPI	IPI00761919.
RefSeq	NP_001157662.1. NM_001164190.1. NP_001157663.1. NM_001164191.1. NP_001157664.1. NM_001164192.1. NP_064310.2. NM_019926.3.
UniGene	Mm.274981. Mm.423278.
3D structure databases
ProteinModelPortal	Q9Z2C5.
SMR	Q9Z2C5. Positions 33-543.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000099041.
PTM databases
PhosphoSite	Q9Z2C5.
Proteomic databases
PaxDb	Q9Z2C5.
PRIDE	Q9Z2C5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033700; ENSMUSP00000033700; ENSMUSG00000031337. ENSMUST00000061970; ENSMUSP00000057182; ENSMUSG00000031337. ENSMUST00000114617; ENSMUSP00000110264; ENSMUSG00000031337. ENSMUST00000171933; ENSMUSP00000125798; ENSMUSG00000031337.
GeneID	17772.
KEGG	mmu:17772.
Organism-specific databases
CTD	4534.
MGI	MGI:1099452. Mtm1.
Phylogenomic databases
eggNOG	NOG322789.
GeneTree	ENSGT00670000097670.
HOGENOM	HOG000210598.
HOVERGEN	HBG000220.
InParanoid	Q5BKQ5.
KO	K01108.
OrthoDB	EOG4B5P4S.
Gene expression databases
ArrayExpress	Q9Z2C5.
Bgee	Q9Z2C5.
CleanEx	MM_MTM1.
Genevestigator	Q9Z2C5.
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
NextBio	292491.
SOURCE	Search...

Entry information

Entry name

MTM1_MOUSE

Accession

Primary (citable) accession number: Q9Z2C5
Secondary accession number(s): Q5BKQ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	June 28, 2011
Last modified:	May 1, 2013
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program