Q9Y217 (MTMR6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myotubularin-related protein 6
EC=3.1.3.-

Gene names

Name:

MTMR6

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	621 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Phosphatase that acts on lipids with a phosphoinositol headgroup. Acts as a negative regulator of KCNN4/KCa3.1 channel activity in CD4+ T-cells possibly by decreasing intracellular levels of phosphatidylinositol 3 phosphatase. Negatively regulates proliferation of reactivated CD4+ T-cells. Ref.8 Ref.10
Subunit structure	Interacts with KCNN4, MTMR7, MTMR8 and MTMR9. Ref.1 Ref.8 Ref.9
Subcellular location	Nucleus envelope Ref.9.
Tissue specificity	Expressed in CD4+ T-cells. Ref.10
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily. Contains 1 myotubularin phosphatase domain.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	phosphatidylinositol biosynthetic process Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome nuclear envelope Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium-activated potassium channel activity Inferred from direct assay Ref.8. Source: UniProtKB protein serine/threonine phosphatase activity Non-traceable author statement Ref.7. Source: UniProtKB protein tyrosine phosphatase activity Non-traceable author statement Ref.7. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y217-1)

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.

Isoform 2 (identifier: Q9Y217-2)

The sequence of this isoform differs from the canonical sequence as follows:
     536-548: KIKQRKNKQTDGI → LTSYSSFKIIVGQ
     549-621: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 621

621

Myotubularin-related protein 6

PRO_0000094939

Regions

Domain

124 – 499

376

Myotubularin phosphatase

Region

248 – 251

4

Substrate binding By similarity

Region

273 – 274

2

Substrate binding By similarity

Region

336 – 342

7

Substrate binding By similarity

Sites

Active site

336

1

Phosphocysteine intermediate By similarity

Binding site

382

1

Substrate By similarity

Amino acid modifications

Modified residue

108

1

Phosphotyrosine By similarity

Modified residue

561

1

Phosphoserine Ref.11

Modified residue

589

1

Phosphoserine Ref.11

Natural variations

Alternative sequence

536 – 548

13

KIKQR…QTDGI → LTSYSSFKIIVGQ in isoform 2.

VSP_036614

Alternative sequence

549 – 621

73

Missing in isoform 2.

VSP_036615

Natural variant

131

1

A → T.
Corresponds to variant rs34885345 [ dbSNP | Ensembl ].

VAR_057143

Natural variant

319

1

I → V. Ref.2 Ref.3 Ref.4 Ref.6 Ref.7
Corresponds to variant rs7995033 [ dbSNP | Ensembl ].

VAR_024583

Experimental info

Sequence conflict

89

1

H → R in CAD89918. Ref.4

Sequence conflict

114

1

P → S in BAG37162. Ref.3

Sequence conflict

125

1

W → R in CAD89918. Ref.4

Sequence conflict

333

1

L → S in AAL01037. Ref.2

Sequence conflict

333

1

L → S in AAC78841. Ref.7

Sequence conflict

368

1

I → T in BAG37162. Ref.3

Sequence conflict

430

1

H → D in BAG52676. Ref.3

Sequence conflict

442

1

Q → P in AAL01037. Ref.2

Sequence conflict

442

1

Q → P in AAC78841. Ref.7

Secondary structure

1

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621

Helix Strand Turn

Details...

Beta strand

5 – 11

7

Beta strand

26 – 31

6

Beta strand

33 – 43

11

Beta strand

45 – 49

5

Helix

50 – 52

3

Beta strand

53 – 58

6

Beta strand

65 – 72

8

Beta strand

77 – 83

7

Helix

85 – 98

14

Helix

108 – 110

3

Helix

119 – 125

7

Helix

130 – 136

7

Beta strand

140 – 147

8

Helix

148 – 150

3

Beta strand

157 – 159

3

Beta strand

161 – 169

9

Helix

171 – 180

10

Helix

182 – 184

3

Beta strand

188 – 192

5

Turn

194 – 196

3

Beta strand

199 – 202

4

Helix

215 – 227

13

Beta strand

234 – 238

5

Turn

258 – 260

3

Beta strand

264 – 268

5

Helix

274 – 288

15

Helix

295 – 304

10

Helix

307 – 326

20

Beta strand

332 – 334

3

Turn

336 – 338

3

Beta strand

339 – 341

3

Helix

342 – 354

13

Helix

357 – 359

3

Helix

361 – 371

11

Turn

372 – 376

5

Helix

379 – 383

5

Beta strand

385 – 387

3

Helix

390 – 392

3

Helix

396 – 410

15

Turn

412 – 414

3

Helix

419 – 429

11

Turn

430 – 432

3

Beta strand

439 – 441

3

Helix

442 – 447

6

Helix

450 – 453

4

Helix

458 – 461

4

Helix

465 – 468

4

Beta strand

488 – 491

4

Helix

496 – 502

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 11, 2011. Version 3. Checksum: 1F34608F99DCEA39	FASTA	621	71,968
	10 20 30 40 50 60 MEHIRTTKVE QVKLLDRFST SNKSLTGTLY LTATHLLFID SHQKETWILH HHIASVEKLA 70 80 90 100 110 120 LTTSGCPLVI QCKNFRTVHF IVPRERDCHD IYNSLLQLSK QAKYEDLYAF SYNPKQNDSE 130 140 150 160 170 180 RLQGWQLIDL AEEYKRMGVP NSHWQLSDAN RDYKICETYP RELYVPRIAS KPIIVGSSKF 190 200 210 220 230 240 RSKGRFPVLS YYHQDKEAAI CRCSQPLSGF SARCLEDEHL LQAISKANPV NRYMYVMDTR 250 260 270 280 290 300 PKLNAMANRA AGKGYENEDN YSNIRFQFVG IENIHVMRSS LQKLLEVNGT KGLSVNDFYS 310 320 330 340 350 360 GLESSGWLRH IKAVMDAAIF LAKAITVENA SVLVHCSDGW DRTSQVCSLG SLLLDSYYRT 370 380 390 400 410 420 IKGFMVLIEK DWISFGHKFS ERCGQLDGDP KEVSPVFTQF LECVWHLTEQ FPQAFEFSEA 430 440 450 460 470 480 FLLQIHEHIH SCQFGNFLGN CQKEREELKL KEKTYSLWPF LLEDQKKYLN PLYSSESHRF 490 500 510 520 530 540 TVLEPNTVSF NFKFWRNMYH QFDRTLHPRQ SVFNIIMNMN EQNKQLEKDI KDLESKIKQR 550 560 570 580 590 600 KNKQTDGILT KELLHSVHPE SPNLKTSLCF KEQTLLPVND ALRTIEGSSP ADNRYSEYAE 610 620 EFSKSEPAVV SLEYGVARMT C
	Isoform 2 [UniParc]. Checksum: 161703C7D46CBD88	FASTA	548	63,743
	10 20 30 40 50 60 MEHIRTTKVE QVKLLDRFST SNKSLTGTLY LTATHLLFID SHQKETWILH HHIASVEKLA 70 80 90 100 110 120 LTTSGCPLVI QCKNFRTVHF IVPRERDCHD IYNSLLQLSK QAKYEDLYAF SYNPKQNDSE 130 140 150 160 170 180 RLQGWQLIDL AEEYKRMGVP NSHWQLSDAN RDYKICETYP RELYVPRIAS KPIIVGSSKF 190 200 210 220 230 240 RSKGRFPVLS YYHQDKEAAI CRCSQPLSGF SARCLEDEHL LQAISKANPV NRYMYVMDTR 250 260 270 280 290 300 PKLNAMANRA AGKGYENEDN YSNIRFQFVG IENIHVMRSS LQKLLEVNGT KGLSVNDFYS 310 320 330 340 350 360 GLESSGWLRH IKAVMDAAIF LAKAITVENA SVLVHCSDGW DRTSQVCSLG SLLLDSYYRT 370 380 390 400 410 420 IKGFMVLIEK DWISFGHKFS ERCGQLDGDP KEVSPVFTQF LECVWHLTEQ FPQAFEFSEA 430 440 450 460 470 480 FLLQIHEHIH SCQFGNFLGN CQKEREELKL KEKTYSLWPF LLEDQKKYLN PLYSSESHRF 490 500 510 520 530 540 TVLEPNTVSF NFKFWRNMYH QFDRTLHPRQ SVFNIIMNMN EQNKQLEKDI KDLESLTSYS SFKIIVGQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of myotubularin-related protein 7 and its binding partner, myotubularin-related protein 9." Mochizuki Y., Majerus P.W. Proc. Natl. Acad. Sci. U.S.A. 100:9768-9773(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH MTMR9.
[2]	Hong W. Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT VAL-319.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT VAL-319. Tissue: Testis and Trachea.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-319. Tissue: Skeletal muscle.
[5]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM 1), VARIANT VAL-319. Tissue: Eye.
[7]	"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] OF 157-621 (ISOFORM 1), VARIANT VAL-319.
[8]	"The phosphatidylinositol 3-phosphate phosphatase myotubularin-related protein 6 (MTMR6) is a negative regulator of the Ca2+-activated K+ channel KCa3.1." Srivastava S., Li Z., Lin L., Liu G., Ko K., Coetzee W.A., Skolnik E.Y. Mol. Cell. Biol. 25:3630-3638(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH KCNN4.
[9]	"Systematic analysis of myotubularins: heteromeric interactions, subcellular localisation and endosome related functions." Lorenzo O., Urbe S., Clague M.J. J. Cell Sci. 119:2953-2959(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH MTMR7; MTMR8 AND MTMR9.
[10]	"Phosphatidylinositol-3 phosphatase myotubularin-related protein 6 negatively regulates CD4 T cells." Srivastava S., Ko K., Choudhury P., Li Z., Johnson A.K., Nadkarni V., Unutmaz D., Coetzee W.A., Skolnik E.Y. Mol. Cell. Biol. 26:5595-5602(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[11]	"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-561 AND SER-589, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF406619 mRNA. Translation: AAL01037.1.
AK093237 mRNA. Translation: BAG52676.1.
AK314587 mRNA. Translation: BAG37162.1.
AL832017 mRNA. Translation: CAD89918.1.
AL590787 Genomic DNA. Translation: CAI39897.1.
BC040012 mRNA. Translation: AAH40012.1.
AF072928 mRNA. Translation: AAC78841.1.

IPI

IPI00329385.
IPI00923409.

RefSeq

NP_004676.3. NM_004685.3.

UniGene

Hs.643702.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YF0	X-ray	2.65	A	1-505	[»]

ProteinModelPortal

Q9Y217.

SMR

Q9Y217. Positions 4-505.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y217. 2 interactions.

STRING

9606.ENSP00000371221.

PTM databases

PhosphoSite

Q9Y217.

Polymorphism databases

DMDM

33112672.

Proteomic databases

PaxDb

Q9Y217.

PRIDE

Q9Y217.

Protocols and materials databases

DNASU

9107.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000381801; ENSP00000371221; ENSG00000139505.
ENST00000540661; ENSP00000443161; ENSG00000139505.

GeneID

9107.

KEGG

hsa:9107.

UCSC

uc001uqe.1. human.
uc001uqf.4. human.

Organism-specific databases

CTD

9107.

GeneCards

GC13M025820.

H-InvDB

HIX0011183.
HIX0171878.

HGNC

HGNC:7453. MTMR6.

HPA

HPA034778.

MIM

603561. gene.

neXtProt

NX_Q9Y217.

PharmGKB

PA31256.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG322789.

HOVERGEN

HBG000220.

InParanoid

Q9Y217.

KO

K01112.

OMA

VFNIIMN.

OrthoDB

EOG49P9Z0.

PhylomeDB

Q9Y217.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q9Y217.

Bgee

Q9Y217.

CleanEx

HS_MTMR6.

Genevestigator

Q9Y217.

GermOnline

ENSG00000139505. Homo sapiens.

Family and domain databases

Gene3D

2.30.29.30. 1 hit.

InterPro

IPR010569. Myotub-related.
IPR017906. Myotubularin_phosphatase_dom.
IPR011993. PH_like_dom.
IPR016130. Tyr_Pase_AS.
[Graphical view]

Pfam

PF06602. Myotub-related. 1 hit.
[Graphical view]

PROSITE

PS51339. PPASE_MYOTUBULARIN. 1 hit.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

9107.

NextBio

34137.

SOURCE

Search...

Entry information

Entry name

MTMR6_HUMAN

Accession

Primary (citable) accession number: Q9Y217
Secondary accession number(s): B2RBB5 , B3KSB4, Q5JRG6, Q86TB7, Q86YH4, Q96P80

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	January 11, 2011
Last modified:	April 3, 2013
This is version 119 of the entry and version 3 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.