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Protein

Myotubularin-related protein 4

Gene

MTMR4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Dephosphorylates proteins phosphorylated on Ser, Thr, and Tyr residues and low molecular weight phosphatase substrate para-nitrophenylphosphate. Phosphorylates phosphatidylinositol 3,4,5-trisphosphate (PIP3).1 Publication

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei407 – 4071Phosphocysteine intermediatePROSITE-ProRule annotation
Binding sitei453 – 4531SubstrateBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri1114 – 117461FYVE-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. protein serine/threonine phosphatase activity Source: Reactome
  3. protein tyrosine phosphatase activity Source: ProtInc

GO - Biological processi

  1. negative regulation of transforming growth factor beta receptor signaling pathway Source: Reactome
  2. peptidyl-tyrosine dephosphorylation Source: GOC
  3. phosphatidylinositol biosynthetic process Source: Reactome
  4. phospholipid metabolic process Source: Reactome
  5. protein dephosphorylation Source: ProtInc
  6. response to denervation involved in regulation of muscle adaptation Source: Ensembl
  7. small molecule metabolic process Source: Reactome
  8. transforming growth factor beta receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_120727. Downregulation of TGF-beta receptor signaling.
REACT_120756. Synthesis of PIPs at the early endosome membrane.
REACT_120918. Synthesis of PIPs at the late endosome membrane.
SignaLinkiQ9NYA4.

Names & Taxonomyi

Protein namesi
Recommended name:
Myotubularin-related protein 4 (EC:3.1.3.48)
Alternative name(s):
FYVE domain-containing dual specificity protein phosphatase 2
Short name:
FYVE-DSP2
Zinc finger FYVE domain-containing protein 11
Gene namesi
Name:MTMR4
Synonyms:KIAA0647, ZFYVE11
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:7452. MTMR4.

Subcellular locationi

Cytoplasm 1 Publication. Membrane 1 Publication; Peripheral membrane protein 1 Publication
Note: Localized to perinuclear region.

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. early endosome membrane Source: Reactome
  3. extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31255.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11951195Myotubularin-related protein 4PRO_0000304809Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei610 – 6101Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9NYA4.
PaxDbiQ9NYA4.
PRIDEiQ9NYA4.

PTM databases

DEPODiQ9NYA4.
PhosphoSiteiQ9NYA4.

Expressioni

Tissue specificityi

Expressed in brain, heart, kidney, spleen, liver, colon, testis, muscle, placenta, thyroid gland, pancreas, ovary, prostate, skin, peripheral blood, and bone marrow.1 Publication

Developmental stagei

Expressed in fetal brain and fetal liver.1 Publication

Gene expression databases

BgeeiQ9NYA4.
CleanExiHS_MTMR4.
ExpressionAtlasiQ9NYA4. baseline and differential.
GenevestigatoriQ9NYA4.

Organism-specific databases

HPAiHPA043852.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
SMAD2Q157963EBI-1052346,EBI-1040141
SMAD3P840224EBI-1052346,EBI-347161

Protein-protein interaction databases

BioGridi114560. 5 interactions.
IntActiQ9NYA4. 3 interactions.
MINTiMINT-1193708.
STRINGi9606.ENSP00000325285.

Structurei

3D structure databases

ProteinModelPortaliQ9NYA4.
SMRiQ9NYA4. Positions 48-571, 1111-1173.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini153 – 570418Myotubularin phosphatasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni320 – 3234Substrate bindingBy similarity
Regioni345 – 3462Substrate bindingBy similarity
Regioni407 – 4137Substrate bindingBy similarity

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili1023 – 105533Sequence AnalysisAdd
BLAST

Sequence similaritiesi

Contains 1 FYVE-type zinc finger.PROSITE-ProRule annotation
Contains 1 myotubularin phosphatase domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri1114 – 117461FYVE-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiNOG322789.
GeneTreeiENSGT00760000118832.
HOGENOMiHOG000004861.
HOVERGENiHBG052526.
InParanoidiQ9NYA4.
KOiK18082.
OMAiSNGHCTG.
OrthoDBiEOG7PVWNJ.
PhylomeDBiQ9NYA4.
TreeFamiTF315197.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR010569. Myotubularin-like_Pase_dom.
IPR030564. Myotubularin_fam.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERiPTHR10807. PTHR10807. 1 hit.
PfamiPF01363. FYVE. 1 hit.
PF06602. Myotub-related. 1 hit.
[Graphical view]
SMARTiSM00064. FYVE. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 2 hits.
SSF57903. SSF57903. 1 hit.
PROSITEiPS51339. PPASE_MYOTUBULARIN. 1 hit.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9NYA4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGEEGPPSLE YIQAKDLFPP KELVKEEENL QVPFTVLQGE GVEFLGRAAD
60 70 80 90 100
ALIAISNYRL HIKFKDSVIN VPLRMIDSVE SRDMFQLHIS CKDSKVVRCH
110 120 130 140 150
FSTFKQCQEW LSRLSRATAR PAKPEDLFAF AYHAWCLGLT EEDQHTHLCQ
160 170 180 190 200
PGEHIRCRQE AELARMGFDL QNVWRVSHIN SNYKLCPSYP QKLLVPVWIT
210 220 230 240 250
DKELENVASF RSWKRIPVVV YRHLRNGAAI ARCSQPEISW WGWRNADDEY
260 270 280 290 300
LVTSIAKACA LDPGTRATGG SLSTGNNDTS EACDADFDSS LTACSGVEST
310 320 330 340 350
AAPQKLLILD ARSYTAAVAN RAKGGGCECE EYYPNCEVVF MGMANIHAIR
360 370 380 390 400
NSFQYLRAVC SQMPDPSNWL SALESTKWLQ HLSVMLKAAV LVANTVDREG
410 420 430 440 450
RPVLVHCSDG WDRTPQIVAL AKILLDPYYR TLEGFQVLVE SDWLDFGHKF
460 470 480 490 500
GDRCGHQENV EDQNEQCPVF LQWLDSVHQL LKQFPCLFEF NEAFLVKLVQ
510 520 530 540 550
HTYSCLYGTF LANNPCEREK RNIYKRTCSV WALLRAGNKN FHNFLYTPSS
560 570 580 590 600
DMVLHPVCHV RALHLWTAVY LPASSPCTLG EENMDLYLSP VAQSQEFSGR
610 620 630 640 650
SLDRLPKTRS MDDLLSACDT SSPLTRTSSD PNLNNHCQEV RVGLEPWHSN
660 670 680 690 700
PEGSETSFVD SGVGGPQQTV GEVGLPPPLP SSQKDYLSNK PFKSHKSCSP
710 720 730 740 750
SYKLLNTAVP REMKSNTSDP EIKVLEETKG PAPDPSAQDE LGRTLDGIGE
760 770 780 790 800
PPEHCPETEA VSALSKVISN KCDGVCNFPE SSQNSPTGTP QQAQPDSMLG
810 820 830 840 850
VPSKCVLDHS LSTVCNPPSA ACQTPLDPST DFLNQDPSGS VASISHQEQL
860 870 880 890 900
SSVPDLTHGE EDIGKRGNNR NGQLLENPRF GKMPLELVRK PISQSQISEF
910 920 930 940 950
SFLGSNWDSF QGMVTSFPSG EATPRRLLSY GCCSKRPNSK QMRATGPCFG
960 970 980 990 1000
GQWAQREGVK SPVCSSHSNG HCTGPGGKNQ MWLSSHPKQV SSTKPVPLNC
1010 1020 1030 1040 1050
PSPVPPLYLD DDGLPFPTDV IQHRLRQIEA GYKQEVEQLR RQVRELQMRL
1060 1070 1080 1090 1100
DIRHCCAPPA EPPMDYEDDF TCLKESDGSD TEDFGSDHSE DCLSEASWEP
1110 1120 1130 1140 1150
VDKKETEVTR WVPDHMASHC YNCDCEFWLA KRRHHCRNCG NVFCAGCCHL
1160 1170 1180 1190
KLPIPDQQLY DPVLVCNSCY EHIQVSRARE LMSQQLKKPI ATASS
Length:1,195
Mass (Da):133,353
Last modified:May 18, 2010 - v2
Checksum:i936EC3F69335CEB4
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti170 – 1701L → V.2 Publications
Corresponds to variant rs3744108 [ dbSNP | Ensembl ].
VAR_035110
Natural varianti280 – 2801S → G.1 Publication
Corresponds to variant rs2302190 [ dbSNP | Ensembl ].
VAR_035111
Natural varianti297 – 2971V → G.
Corresponds to variant rs2302189 [ dbSNP | Ensembl ].
VAR_035112

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF264717 mRNA. Translation: AAF72539.1.
AB014547 mRNA. Translation: BAA31622.2.
AC005666 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94454.1.
CH471109 Genomic DNA. Translation: EAW94455.1.
BC035609 mRNA. Translation: AAH35609.1.
CCDSiCCDS11608.1.
PIRiT00375.
RefSeqiNP_004678.3. NM_004687.4.
XP_005257843.1. XM_005257786.2.
XP_006722231.1. XM_006722168.1.
UniGeneiHs.514373.

Genome annotation databases

EnsembliENST00000323456; ENSP00000325285; ENSG00000108389.
GeneIDi9110.
KEGGihsa:9110.
UCSCiuc002iwj.2. human.

Polymorphism databases

DMDMi296438298.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF264717 mRNA. Translation: AAF72539.1.
AB014547 mRNA. Translation: BAA31622.2.
AC005666 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94454.1.
CH471109 Genomic DNA. Translation: EAW94455.1.
BC035609 mRNA. Translation: AAH35609.1.
CCDSiCCDS11608.1.
PIRiT00375.
RefSeqiNP_004678.3. NM_004687.4.
XP_005257843.1. XM_005257786.2.
XP_006722231.1. XM_006722168.1.
UniGeneiHs.514373.

3D structure databases

ProteinModelPortaliQ9NYA4.
SMRiQ9NYA4. Positions 48-571, 1111-1173.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114560. 5 interactions.
IntActiQ9NYA4. 3 interactions.
MINTiMINT-1193708.
STRINGi9606.ENSP00000325285.

PTM databases

DEPODiQ9NYA4.
PhosphoSiteiQ9NYA4.

Polymorphism databases

DMDMi296438298.

Proteomic databases

MaxQBiQ9NYA4.
PaxDbiQ9NYA4.
PRIDEiQ9NYA4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000323456; ENSP00000325285; ENSG00000108389.
GeneIDi9110.
KEGGihsa:9110.
UCSCiuc002iwj.2. human.

Organism-specific databases

CTDi9110.
GeneCardsiGC17M056566.
H-InvDBHIX0202387.
HGNCiHGNC:7452. MTMR4.
HPAiHPA043852.
MIMi603559. gene.
neXtProtiNX_Q9NYA4.
PharmGKBiPA31255.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG322789.
GeneTreeiENSGT00760000118832.
HOGENOMiHOG000004861.
HOVERGENiHBG052526.
InParanoidiQ9NYA4.
KOiK18082.
OMAiSNGHCTG.
OrthoDBiEOG7PVWNJ.
PhylomeDBiQ9NYA4.
TreeFamiTF315197.

Enzyme and pathway databases

ReactomeiREACT_120727. Downregulation of TGF-beta receptor signaling.
REACT_120756. Synthesis of PIPs at the early endosome membrane.
REACT_120918. Synthesis of PIPs at the late endosome membrane.
SignaLinkiQ9NYA4.

Miscellaneous databases

ChiTaRSiMTMR4. human.
GenomeRNAii9110.
NextBioi34145.
PROiQ9NYA4.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NYA4.
CleanExiHS_MTMR4.
ExpressionAtlasiQ9NYA4. baseline and differential.
GenevestigatoriQ9NYA4.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR010569. Myotubularin-like_Pase_dom.
IPR030564. Myotubularin_fam.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERiPTHR10807. PTHR10807. 1 hit.
PfamiPF01363. FYVE. 1 hit.
PF06602. Myotub-related. 1 hit.
[Graphical view]
SMARTiSM00064. FYVE. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 2 hits.
SSF57903. SSF57903. 1 hit.
PROSITEiPS51339. PPASE_MYOTUBULARIN. 1 hit.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "FYVE-DSP2, a FYVE domain-containing dual specificity protein phosphatase that dephosphorylates phosphatidylinositol 3-phosphate."
    Zhao R., Qi Y., Chen J., Zhao Z.J.
    Exp. Cell Res. 265:329-338(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, VARIANT VAL-170.
  2. "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
    Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
    DNA Res. 5:169-176(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-170.
    Tissue: Brain.
  3. "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
    Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
    DNA Res. 9:99-106(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SEQUENCE REVISION.
  4. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. 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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-280.
    Tissue: Lung.
  7. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-610, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiMTMR4_HUMAN
AccessioniPrimary (citable) accession number: Q9NYA4
Secondary accession number(s): D3DTZ6, Q8IV27, Q9Y4D5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: May 18, 2010
Last modified: April 1, 2015
This is version 105 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.