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Protein

Myotubularin-related protein 2

Gene

MTMR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Phosphatase that acts on lipids with a phosphoinositol headgroup. Has phosphatase activity towards phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate.3 Publications

Catalytic activityi

1-phosphatidyl-1D-myo-inositol 3-phosphate + H2O = 1-phosphatidyl-1D-myo-inositol + phosphate.2 Publications
1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 5-phosphate + phosphate.1 Publication

Enzyme regulationi

Interaction with SBF1 increases phosphatase activity.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei417Phosphocysteine intermediate1
Binding sitei463Substrate1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processLipid metabolism

Enzyme and pathway databases

BRENDAi3.1.3.64 2681
3.1.3.95 2681
ReactomeiR-HSA-1483248 Synthesis of PIPs at the ER membrane
R-HSA-1660499 Synthesis of PIPs at the plasma membrane
R-HSA-1660516 Synthesis of PIPs at the early endosome membrane
R-HSA-1660517 Synthesis of PIPs at the late endosome membrane

Chemistry databases

SwissLipidsiSLP:000001135

Names & Taxonomyi

Protein namesi
Recommended name:
Myotubularin-related protein 2
Alternative name(s):
Phosphatidylinositol-3,5-bisphosphate 3-phosphatase (EC:3.1.3.951 Publication)
Phosphatidylinositol-3-phosphate phosphatase (EC:3.1.3.642 Publications)
Gene namesi
Name:MTMR2
Synonyms:KIAA1073
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000087053.18
HGNCiHGNC:7450 MTMR2
MIMi603557 gene
neXtProtiNX_Q13614

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Charcot-Marie-Tooth disease 4B1 (CMT4B1)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4.
See also OMIM:601382
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_047947283R → W in CMT4B1. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi417C → S: Loss of activity. 2 Publications1
Mutagenesisi419D → A: No effect. 1 Publication1
Mutagenesisi422D → A: Loss of activity. 1 Publication1
Mutagenesisi607L → Y: Reduces homodimerization and interaction with SBF1. 1 Publication1

Keywords - Diseasei

Charcot-Marie-Tooth disease, Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi8898
GeneReviewsiMTMR2
MalaCardsiMTMR2
MIMi601382 phenotype
OpenTargetsiENSG00000087053
Orphaneti99955 Charcot-Marie-Tooth disease type 4B1
PharmGKBiPA31253

Polymorphism and mutation databases

BioMutaiMTMR2
DMDMi212276520

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000949341 – 643Myotubularin-related protein 2Add BLAST643

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei6PhosphoserineBy similarity1
Modified residuei9PhosphoserineBy similarity1
Modified residuei58PhosphoserineCombined sources1 Publication1

Post-translational modificationi

Phosphorylation at Ser-58 decreases MTMR2 localization to endocytic vesicular structures.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ13614
MaxQBiQ13614
PaxDbiQ13614
PeptideAtlasiQ13614
PRIDEiQ13614
ProteomicsDBi59600

PTM databases

DEPODiQ13614
iPTMnetiQ13614
PhosphoSitePlusiQ13614
SwissPalmiQ13614

Expressioni

Gene expression databases

BgeeiENSG00000087053
CleanExiHS_MTMR2
ExpressionAtlasiQ13614 baseline and differential
GenevisibleiQ13614 HS

Organism-specific databases

HPAiHPA049831

Interactioni

Subunit structurei

Homooligomer and heterooligomer. Interacts with SBF1 and SBF2.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
NEFLP071962EBI-475631,EBI-475646

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114415, 34 interactors
IntActiQ13614, 5 interactors
MINTiQ13614
STRINGi9606.ENSP00000345752

Structurei

Secondary structure

1643
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi84 – 95Combined sources12
Turni96 – 98Combined sources3
Beta strandi99 – 121Combined sources23
Beta strandi123 – 128Combined sources6
Helixi129 – 131Combined sources3
Beta strandi132 – 138Combined sources7
Beta strandi145 – 147Combined sources3
Beta strandi149 – 155Combined sources7
Turni156 – 158Combined sources3
Beta strandi159 – 164Combined sources6
Helixi167 – 169Combined sources3
Helixi172 – 182Combined sources11
Turni185 – 189Combined sources5
Helixi193 – 195Combined sources3
Helixi205 – 207Combined sources3
Helixi211 – 217Combined sources7
Beta strandi223 – 228Combined sources6
Turni230 – 233Combined sources4
Beta strandi234 – 236Combined sources3
Beta strandi242 – 247Combined sources6
Helixi252 – 261Combined sources10
Helixi263 – 265Combined sources3
Beta strandi269 – 273Combined sources5
Turni275 – 277Combined sources3
Beta strandi280 – 284Combined sources5
Turni290 – 293Combined sources4
Helixi297 – 309Combined sources13
Beta strandi310 – 312Combined sources3
Beta strandi314 – 320Combined sources7
Helixi324 – 333Combined sources10
Turni340 – 342Combined sources3
Beta strandi346 – 350Combined sources5
Helixi356 – 370Combined sources15
Helixi376 – 378Combined sources3
Helixi379 – 386Combined sources8
Helixi388 – 407Combined sources20
Beta strandi413 – 416Combined sources4
Beta strandi418 – 422Combined sources5
Helixi423 – 435Combined sources13
Helixi437 – 440Combined sources4
Helixi442 – 452Combined sources11
Turni453 – 457Combined sources5
Helixi460 – 464Combined sources5
Turni465 – 467Combined sources3
Helixi479 – 493Combined sources15
Turni495 – 497Combined sources3
Helixi502 – 514Combined sources13
Beta strandi516 – 518Combined sources3
Beta strandi522 – 524Combined sources3
Helixi525 – 530Combined sources6
Helixi533 – 536Combined sources4
Helixi540 – 545Combined sources6
Helixi548 – 551Combined sources4
Turni554 – 557Combined sources4
Beta strandi560 – 562Combined sources3
Turni570 – 572Combined sources3
Helixi577 – 580Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LW3X-ray2.30A1-643[»]
1M7RX-ray2.60A/B1-643[»]
1ZSQX-ray1.82A73-586[»]
1ZVRX-ray1.98A73-586[»]
5GNHX-ray2.60A/B73-643[»]
ProteinModelPortaliQ13614
SMRiQ13614
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13614

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini68 – 139GRAMAdd BLAST72
Domaini205 – 580Myotubularin phosphatasePROSITE-ProRule annotationAdd BLAST376

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni330 – 333Substrate binding1 Publication4
Regioni355 – 356Substrate binding1 Publication2
Regioni417 – 423Substrate binding1 Publication7

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili593 – 6271 PublicationAdd BLAST35

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi4 – 53Ser-richAdd BLAST50

Domaini

The coiled-coil domain mediates interaction with SBF2.

Sequence similaritiesi

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG1089 Eukaryota
ENOG410XPTU LUCA
GeneTreeiENSGT00760000118832
HOGENOMiHOG000210598
HOVERGENiHBG000220
InParanoidiQ13614
KOiK18081
OMAiPENGWKV
OrthoDBiEOG091G04DS
PhylomeDBiQ13614
TreeFamiTF315197

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR004182 GRAM
IPR010569 Myotubularin-like_Pase_dom
IPR030564 Myotubularin_fam
IPR011993 PH-like_dom_sf
IPR029021 Prot-tyrosine_phosphatase-like
IPR016130 Tyr_Pase_AS
IPR003595 Tyr_Pase_cat
IPR000387 TYR_PHOSPHATASE_dom
PANTHERiPTHR10807 PTHR10807, 1 hit
PfamiView protein in Pfam
PF02893 GRAM, 1 hit
PF06602 Myotub-related, 1 hit
SMARTiView protein in SMART
SM00568 GRAM, 1 hit
SM00404 PTPc_motif, 1 hit
SUPFAMiSSF52799 SSF52799, 1 hit
PROSITEiView protein in PROSITE
PS51339 PPASE_MYOTUBULARIN, 1 hit
PS00383 TYR_PHOSPHATASE_1, 1 hit
PS50056 TYR_PHOSPHATASE_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13614-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEKSSSCESL GSQPAAARPP SVDSLSSAST SHSENSVHTK SASVVSSDSI
60 70 80 90 100
STSADNFSPD LRVLRESNKL AEMEEPPLLP GENIKDMAKD VTYICPFTGA
110 120 130 140 150
VRGTLTVTNY RLYFKSMERD PPFVLDASLG VINRVEKIGG ASSRGENSYG
160 170 180 190 200
LETVCKDIRN LRFAHKPEGR TRRSIFENLM KYAFPVSNNL PLFAFEYKEV
210 220 230 240 250
FPENGWKLYD PLLEYRRQGI PNESWRITKI NERYELCDTY PALLVVPANI
260 270 280 290 300
PDEELKRVAS FRSRGRIPVL SWIHPESQAT ITRCSQPMVG VSGKRSKEDE
310 320 330 340 350
KYLQAIMDSN AQSHKIFIFD ARPSVNAVAN KAKGGGYESE DAYQNAELVF
360 370 380 390 400
LDIHNIHVMR ESLRKLKEIV YPNIEETHWL SNLESTHWLE HIKLILAGAL
410 420 430 440 450
RIADKVESGK TSVVVHCSDG WDRTAQLTSL AMLMLDGYYR TIRGFEVLVE
460 470 480 490 500
KEWLSFGHRF QLRVGHGDKN HADADRSPVF LQFIDCVWQM TRQFPTAFEF
510 520 530 540 550
NEYFLITILD HLYSCLFGTF LCNSEQQRGK ENLPKRTVSL WSYINSQLED
560 570 580 590 600
FTNPLYGSYS NHVLYPVASM RHLELWVGYY IRWNPRMKPQ EPIHNRYKEL
610 620 630 640
LAKRAELQKK VEELQREISN RSTSSSERAS SPAQCVTPVQ TVV
Length:643
Mass (Da):73,381
Last modified:November 4, 2008 - v4
Checksum:i10FD6508D0CDA719
GO
Isoform 2 (identifier: Q13614-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: Missing.

Note: No experimental confirmation available.
Show »
Length:571
Mass (Da):65,959
Checksum:iDBC304269CEFC843
GO

Sequence cautioni

The sequence BAA83025 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0472553K → T2 PublicationsCorresponds to variant dbSNP:rs3824874EnsemblClinVar.1
Natural variantiVAR_047947283R → W in CMT4B1. 1 Publication1
Natural variantiVAR_047256545N → S. Corresponds to variant dbSNP:rs558018EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0449331 – 72Missing in isoform 2. 1 PublicationAdd BLAST72

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB028996 mRNA Translation: BAA83025.2 Different initiation.
AK302940 mRNA Translation: BAG64098.1
AP000870 Genomic DNA No translation available.
AP001877 Genomic DNA No translation available.
CH471065 Genomic DNA Translation: EAW66971.1
BC052990 mRNA Translation: AAH52990.1
U58033 mRNA Translation: AAC79118.1
CCDSiCCDS8305.1 [Q13614-1]
CCDS8306.1 [Q13614-2]
PIRiT09497
RefSeqiNP_001230500.1, NM_001243571.1 [Q13614-2]
NP_057240.3, NM_016156.5 [Q13614-1]
NP_958435.1, NM_201278.2 [Q13614-2]
NP_958438.1, NM_201281.2 [Q13614-2]
XP_005274431.1, XM_005274374.2 [Q13614-2]
XP_005274432.1, XM_005274375.2 [Q13614-2]
XP_006718997.1, XM_006718934.2 [Q13614-2]
XP_006718998.1, XM_006718935.2 [Q13614-2]
XP_006718999.1, XM_006718936.3 [Q13614-2]
XP_016874006.1, XM_017018517.1 [Q13614-2]
XP_016874007.1, XM_017018518.1 [Q13614-2]
UniGeneiHs.181326

Genome annotation databases

EnsembliENST00000346299; ENSP00000345752; ENSG00000087053 [Q13614-1]
ENST00000352297; ENSP00000343737; ENSG00000087053 [Q13614-2]
ENST00000393223; ENSP00000376915; ENSG00000087053 [Q13614-2]
ENST00000409459; ENSP00000386882; ENSG00000087053 [Q13614-2]
GeneIDi8898
KEGGihsa:8898
UCSCiuc001pft.4 human [Q13614-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMTMR2_HUMAN
AccessioniPrimary (citable) accession number: Q13614
Secondary accession number(s): A6NN98, Q9UPS9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 4, 2008
Last modified: June 20, 2018
This is version 187 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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