MTMR4_HUMAN
ID MTMR4_HUMAN Reviewed; 1195 AA.
AC Q9NYA4; D3DTZ6; Q8IV27; Q9Y4D5;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Myotubularin-related protein 4;
DE EC=3.1.3.48;
DE AltName: Full=FYVE domain-containing dual specificity protein phosphatase 2;
DE Short=FYVE-DSP2;
DE AltName: Full=Zinc finger FYVE domain-containing protein 11;
GN Name=MTMR4; Synonyms=KIAA0647, ZFYVE11;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND VARIANT VAL-170.
RX PubMed=11302699; DOI=10.1006/excr.2001.5185;
RA Zhao R., Qi Y., Chen J., Zhao Z.J.;
RT "FYVE-DSP2, a FYVE domain-containing dual specificity protein phosphatase
RT that dephosphorylates phosphatidylinositol 3-phosphate.";
RL Exp. Cell Res. 265:329-338(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-170.
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-280.
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8; SER-610 AND SER-629, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-610, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Dephosphorylates proteins phosphorylated on Ser, Thr, and Tyr
CC residues and low molecular weight phosphatase substrate para-
CC nitrophenylphosphate. Phosphorylates phosphatidylinositol 3,4,5-
CC trisphosphate (PIP3). {ECO:0000269|PubMed:11302699}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10044};
CC -!- INTERACTION:
CC Q9NYA4; Q15796: SMAD2; NbExp=2; IntAct=EBI-1052346, EBI-1040141;
CC Q9NYA4; P84022: SMAD3; NbExp=2; IntAct=EBI-1052346, EBI-347161;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11302699}. Membrane
CC {ECO:0000269|PubMed:11302699}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11302699}. Note=Localized to perinuclear region.
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, kidney, spleen, liver,
CC colon, testis, muscle, placenta, thyroid gland, pancreas, ovary,
CC prostate, skin, peripheral blood, and bone marrow.
CC {ECO:0000269|PubMed:11302699}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal brain and fetal liver.
CC {ECO:0000269|PubMed:11302699}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class myotubularin subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF264717; AAF72539.1; -; mRNA.
DR EMBL; AB014547; BAA31622.2; -; mRNA.
DR EMBL; AC005666; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471109; EAW94454.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94455.1; -; Genomic_DNA.
DR EMBL; BC035609; AAH35609.1; -; mRNA.
DR CCDS; CCDS11608.1; -.
DR PIR; T00375; T00375.
DR RefSeq; NP_004678.3; NM_004687.4.
DR RefSeq; XP_005257843.1; XM_005257786.4.
DR RefSeq; XP_006722231.1; XM_006722168.3.
DR AlphaFoldDB; Q9NYA4; -.
DR SMR; Q9NYA4; -.
DR BioGRID; 114560; 180.
DR IntAct; Q9NYA4; 35.
DR MINT; Q9NYA4; -.
DR STRING; 9606.ENSP00000325285; -.
DR DEPOD; MTMR4; -.
DR GlyGen; Q9NYA4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NYA4; -.
DR PhosphoSitePlus; Q9NYA4; -.
DR BioMuta; MTMR4; -.
DR DMDM; 296438298; -.
DR EPD; Q9NYA4; -.
DR jPOST; Q9NYA4; -.
DR MassIVE; Q9NYA4; -.
DR MaxQB; Q9NYA4; -.
DR PaxDb; Q9NYA4; -.
DR PeptideAtlas; Q9NYA4; -.
DR PRIDE; Q9NYA4; -.
DR ProteomicsDB; 83205; -.
DR Antibodypedia; 30984; 190 antibodies from 26 providers.
DR DNASU; 9110; -.
DR Ensembl; ENST00000323456.9; ENSP00000325285.5; ENSG00000108389.10.
DR GeneID; 9110; -.
DR KEGG; hsa:9110; -.
DR UCSC; uc002iwj.3; human.
DR CTD; 9110; -.
DR DisGeNET; 9110; -.
DR GeneCards; MTMR4; -.
DR HGNC; HGNC:7452; MTMR4.
DR HPA; ENSG00000108389; Low tissue specificity.
DR MIM; 603559; gene.
DR neXtProt; NX_Q9NYA4; -.
DR OpenTargets; ENSG00000108389; -.
DR PharmGKB; PA31255; -.
DR VEuPathDB; HostDB:ENSG00000108389; -.
DR eggNOG; KOG4471; Eukaryota.
DR GeneTree; ENSGT00940000158976; -.
DR HOGENOM; CLU_001839_2_2_1; -.
DR InParanoid; Q9NYA4; -.
DR OMA; TRWLQHM; -.
DR OrthoDB; 824298at2759; -.
DR PhylomeDB; Q9NYA4; -.
DR TreeFam; TF315197; -.
DR PathwayCommons; Q9NYA4; -.
DR Reactome; R-HSA-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-HSA-1660517; Synthesis of PIPs at the late endosome membrane.
DR Reactome; R-HSA-2173788; Downregulation of TGF-beta receptor signaling.
DR SignaLink; Q9NYA4; -.
DR SIGNOR; Q9NYA4; -.
DR BioGRID-ORCS; 9110; 18 hits in 1079 CRISPR screens.
DR ChiTaRS; MTMR4; human.
DR GenomeRNAi; 9110; -.
DR Pharos; Q9NYA4; Tbio.
DR PRO; PR:Q9NYA4; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9NYA4; protein.
DR Bgee; ENSG00000108389; Expressed in middle temporal gyrus and 207 other tissues.
DR ExpressionAtlas; Q9NYA4; baseline and differential.
DR Genevisible; Q9NYA4; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0052629; F:phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity; IBA:GO_Central.
DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; IBA:GO_Central.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; TAS:Reactome.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; TAS:ProtInc.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; TAS:ProtInc.
DR GO; GO:0010506; P:regulation of autophagy; IBA:GO_Central.
DR GO; GO:0060304; P:regulation of phosphatidylinositol dephosphorylation; IDA:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:InterPro.
DR CDD; cd13342; PH-GRAM_MTMR4; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR030590; MTMR4.
DR InterPro; IPR035997; MTMR4_PH-GRAM.
DR InterPro; IPR010569; Myotubularin-like_Pase_dom.
DR InterPro; IPR030564; Myotubularin_fam.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR000306; Znf_FYVE.
DR InterPro; IPR017455; Znf_FYVE-rel.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR10807; PTHR10807; 1.
DR PANTHER; PTHR10807:SF64; PTHR10807:SF64; 1.
DR Pfam; PF01363; FYVE; 1.
DR Pfam; PF06602; Myotub-related; 1.
DR SMART; SM00064; FYVE; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS51339; PPASE_MYOTUBULARIN; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50178; ZF_FYVE; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; Hydrolase; Membrane; Metal-binding; Phosphoprotein;
KW Protein phosphatase; Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..1195
FT /note="Myotubularin-related protein 4"
FT /id="PRO_0000304809"
FT DOMAIN 153..570
FT /note="Myotubularin phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT ZN_FING 1114..1174
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 645..756
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 780..800
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 827..877
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1023..1055
FT /evidence="ECO:0000255"
FT COMPBIAS 650..664
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 682..714
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 780..798
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 827..854
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 407
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 320..323
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 345..346
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 407..413
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 453
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 1120
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1123
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1136
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1139
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1147
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1166
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1169
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 610
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 629
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 170
FT /note="L -> V (in dbSNP:rs3744108)"
FT /evidence="ECO:0000269|PubMed:11302699,
FT ECO:0000269|PubMed:9734811"
FT /id="VAR_035110"
FT VARIANT 280
FT /note="S -> G (in dbSNP:rs2302190)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_035111"
FT VARIANT 297
FT /note="V -> G (in dbSNP:rs2302189)"
FT /id="VAR_035112"
SQ SEQUENCE 1195 AA; 133353 MW; 936EC3F69335CEB4 CRC64;
MGEEGPPSLE YIQAKDLFPP KELVKEEENL QVPFTVLQGE GVEFLGRAAD ALIAISNYRL
HIKFKDSVIN VPLRMIDSVE SRDMFQLHIS CKDSKVVRCH FSTFKQCQEW LSRLSRATAR
PAKPEDLFAF AYHAWCLGLT EEDQHTHLCQ PGEHIRCRQE AELARMGFDL QNVWRVSHIN
SNYKLCPSYP QKLLVPVWIT DKELENVASF RSWKRIPVVV YRHLRNGAAI ARCSQPEISW
WGWRNADDEY LVTSIAKACA LDPGTRATGG SLSTGNNDTS EACDADFDSS LTACSGVEST
AAPQKLLILD ARSYTAAVAN RAKGGGCECE EYYPNCEVVF MGMANIHAIR NSFQYLRAVC
SQMPDPSNWL SALESTKWLQ HLSVMLKAAV LVANTVDREG RPVLVHCSDG WDRTPQIVAL
AKILLDPYYR TLEGFQVLVE SDWLDFGHKF GDRCGHQENV EDQNEQCPVF LQWLDSVHQL
LKQFPCLFEF NEAFLVKLVQ HTYSCLYGTF LANNPCEREK RNIYKRTCSV WALLRAGNKN
FHNFLYTPSS DMVLHPVCHV RALHLWTAVY LPASSPCTLG EENMDLYLSP VAQSQEFSGR
SLDRLPKTRS MDDLLSACDT SSPLTRTSSD PNLNNHCQEV RVGLEPWHSN PEGSETSFVD
SGVGGPQQTV GEVGLPPPLP SSQKDYLSNK PFKSHKSCSP SYKLLNTAVP REMKSNTSDP
EIKVLEETKG PAPDPSAQDE LGRTLDGIGE PPEHCPETEA VSALSKVISN KCDGVCNFPE
SSQNSPTGTP QQAQPDSMLG VPSKCVLDHS LSTVCNPPSA ACQTPLDPST DFLNQDPSGS
VASISHQEQL SSVPDLTHGE EDIGKRGNNR NGQLLENPRF GKMPLELVRK PISQSQISEF
SFLGSNWDSF QGMVTSFPSG EATPRRLLSY GCCSKRPNSK QMRATGPCFG GQWAQREGVK
SPVCSSHSNG HCTGPGGKNQ MWLSSHPKQV SSTKPVPLNC PSPVPPLYLD DDGLPFPTDV
IQHRLRQIEA GYKQEVEQLR RQVRELQMRL DIRHCCAPPA EPPMDYEDDF TCLKESDGSD
TEDFGSDHSE DCLSEASWEP VDKKETEVTR WVPDHMASHC YNCDCEFWLA KRRHHCRNCG
NVFCAGCCHL KLPIPDQQLY DPVLVCNSCY EHIQVSRARE LMSQQLKKPI ATASS