Full text data of MYO1E
MYO1E
(MYO1C)
[Confidence: low (only semi-automatic identification from reviews)]
Unconventional myosin-Ie (Myosin-Ic; Unconventional myosin 1E)
Unconventional myosin-Ie (Myosin-Ic; Unconventional myosin 1E)
UniProt
Q12965
ID MYO1E_HUMAN Reviewed; 1108 AA.
AC Q12965; Q14778;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 25-NOV-2008, sequence version 2.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=Unconventional myosin-Ie;
DE AltName: Full=Myosin-Ic;
DE AltName: Full=Unconventional myosin 1E;
GN Name=MYO1E; Synonyms=MYO1C;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7932763; DOI=10.1006/jmbi.1994.1662;
RA Bement W.M., Wirth J.A., Mooseker M.S.;
RT "Cloning and mRNA expression of human unconventional myosin-IC. A
RT homologue of amoeboid myosins-I with a single IQ motif and an SH3
RT domain.";
RL J. Mol. Biol. 243:356-363(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 107-196.
RX PubMed=8022818; DOI=10.1073/pnas.91.14.6549;
RA Bement W.M., Hasson T., Wirth J.A., Cheney R.E., Mooseker M.S.;
RT "Identification and overlapping expression of multiple unconventional
RT myosin genes in vertebrate cell types.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:6549-6553(1994).
RN [4]
RP ERRATUM.
RX PubMed=7972138; DOI=10.1073/pnas.91.24.11767c;
RA Bement W.M., Hasson T., Wirth J.A., Cheney R.E., Mooseker M.S.;
RL Proc. Natl. Acad. Sci. U.S.A. 91:11767-11767(1994).
RN [5]
RP FUNCTION IN ATP HYDROLYSIS, AND INTERACTION WITH F-ACTIN AND CALM.
RX PubMed=11940582; DOI=10.1074/jbc.M200713200;
RA El Mezgueldi M., Tang N., Rosenfeld S.S., Ostap E.M.;
RT "The kinetic mechanism of Myo1e (human myosin-IC).";
RL J. Biol. Chem. 277:21514-21521(2002).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SYNJ1; DNM1 AND
RP DNM2.
RX PubMed=17257598; DOI=10.1016/j.febslet.2007.01.021;
RA Krendel M., Osterweil E.K., Mooseker M.S.;
RT "Myosin 1E interacts with synaptojanin-1 and dynamin and is involved
RT in endocytosis.";
RL FEBS Lett. 581:644-650(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-980 AND SER-1002, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20860408; DOI=10.1021/bi1012657;
RA Feeser E.A., Ignacio C.M., Krendel M., Ostap E.M.;
RT "Myo1e binds anionic phospholipids with high affinity.";
RL Biochemistry 49:9353-9360(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-980, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP INTERACTION WITH ARL14EP, AND TISSUE SPECIFICITY.
RX PubMed=21458045; DOI=10.1016/j.cell.2011.03.023;
RA Paul P., van den Hoorn T., Jongsma M.L., Bakker M.J., Hengeveld R.,
RA Janssen L., Cresswell P., Egan D.A., van Ham M., Ten Brinke A.,
RA Ovaa H., Beijersbergen R.L., Kuijl C., Neefjes J.;
RT "A Genome-wide multidimensional RNAi screen reveals pathways
RT controlling MHC class II antigen presentation.";
RL Cell 145:268-283(2011).
RN [12]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, VARIANT FSGS6 PRO-159,
RP VARIANTS GLY-185; VAL-221; ARG-795 AND HIS-1049, AND CHARACTERIZATION
RP OF VARIANT FSGS6 PRO-159.
RX PubMed=21756023; DOI=10.1056/NEJMoa1101273;
RA Mele C., Iatropoulos P., Donadelli R., Calabria A., Maranta R.,
RA Cassis P., Buelli S., Tomasoni S., Piras R., Krendel M., Bettoni S.,
RA Morigi M., Delledonne M., Pecoraro C., Abbate I., Capobianchi M.R.,
RA Hildebrandt F., Otto E., Schaefer F., Macciardi F., Ozaltin F.,
RA Emre S., Ibsirlioglu T., Benigni A., Remuzzi G., Noris M.;
RT "MYO1E mutations and childhood familial focal segmental
RT glomerulosclerosis.";
RL N. Engl. J. Med. 365:295-306(2011).
RN [13]
RP VARIANT FSGS6 PRO-159.
RX PubMed=21697813; DOI=10.1038/ki.2011.148;
RA Sanna-Cherchi S., Burgess K.E., Nees S.N., Caridi G., Weng P.L.,
RA Dagnino M., Bodria M., Carrea A., Allegretta M.A., Kim H.R.,
RA Perry B.J., Gigante M., Clark L.N., Kisselev S., Cusi D., Gesualdo L.,
RA Allegri L., Scolari F., D'Agati V., Shapiro L.S., Pecoraro C.,
RA Palomero T., Ghiggeri G.M., Gharavi A.G.;
RT "Exome sequencing identified MYO1E and NEIL1 as candidate genes for
RT human autosomal recessive steroid-resistant nephrotic syndrome.";
RL Kidney Int. 80:389-396(2011).
CC -!- FUNCTION: Myosins are actin-based motor molecules with ATPase
CC activity. Unconventional myosins serve in intracellular movements.
CC Their highly divergent tails bind to membranous compartments,
CC which are then moved relative to actin filaments. Binds to
CC membranes containing anionic phospholipids via its tail domain.
CC Required for normal morphology of the glomerular basement
CC membrane, normal development of foot processes by kidney podocytes
CC and normal kidney function. In dendritic cells, may control the
CC movement of class II-containing cytoplasmic vesicles along the
CC actin cytoskeleton by connecting them with the actin network via
CC ARL14EP and ARL14.
CC -!- SUBUNIT: Interacts with CALM and F-actin (By similarity).
CC Interacts (via SH3 domain) with SYNJ1, DNM1 and DNM2. Interacts
CC with ARL14EP.
CC -!- INTERACTION:
CC Q8N8R7:ARL14EP; NbExp=2; IntAct=EBI-4279548, EBI-2807994;
CC P21575:Dnm1 (xeno); NbExp=2; IntAct=EBI-4279548, EBI-80070;
CC P50570:DNM2; NbExp=2; IntAct=EBI-4279548, EBI-346547;
CC Q62910:Synj1 (xeno); NbExp=2; IntAct=EBI-4279548, EBI-1149123;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton.
CC Cytoplasmic vesicle. Cytoplasmic vesicle, clathrin-coated vesicle.
CC Cell junction (By similarity). Note=Colocalizes with F-actin (By
CC similarity). In cultured podocytes, it localizes close to and is
CC associated with the cytoplasmic membrane, with enrichment at the
CC lamellipodia tips. Colocalizes with cytoplasmic vesicles,
CC including endocytic clathrin-coated vesicles. Colocalizes with
CC dynamin at cytoplasmic vesicles.
CC -!- TISSUE SPECIFICITY: Expressed in the immune system. In the kidney,
CC predominantly expressed in the glomerulus, including podocytes.
CC -!- DISEASE: Focal segmental glomerulosclerosis 6 (FSGS6)
CC [MIM:614131]: A renal pathology defined by the presence of
CC segmental sclerosis in glomeruli and resulting in proteinuria,
CC reduced glomerular filtration rate and progressive decline in
CC renal function. Renal insufficiency often progresses to end-stage
CC renal disease, a highly morbid state requiring either dialysis
CC therapy or kidney transplantation. FSGS6 is a childhood-onset
CC disorder resulting in nephrotic syndrome, which includes massive
CC proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Contains 1 IQ domain.
CC -!- SIMILARITY: Contains 1 myosin head-like domain.
CC -!- SIMILARITY: Contains 1 SH3 domain.
CC -!- CAUTION: Represents a unconventional myosin. This protein should
CC not be confused with the conventional myosin-1 (MYH1).
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DR EMBL; U14391; AAA62667.1; -; mRNA.
DR EMBL; AC092756; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L29139; AAA20902.1; -; mRNA.
DR PIR; S53601; S53601.
DR RefSeq; NP_004989.2; NM_004998.3.
DR UniGene; Hs.654506; -.
DR ProteinModelPortal; Q12965; -.
DR SMR; Q12965; 20-692, 1054-1108.
DR DIP; DIP-884N; -.
DR IntAct; Q12965; 7.
DR MINT; MINT-3026848; -.
DR STRING; 9606.ENSP00000288235; -.
DR PhosphoSite; Q12965; -.
DR DMDM; 215274106; -.
DR PaxDb; Q12965; -.
DR PRIDE; Q12965; -.
DR Ensembl; ENST00000288235; ENSP00000288235; ENSG00000157483.
DR GeneID; 4643; -.
DR KEGG; hsa:4643; -.
DR UCSC; uc002aga.4; human.
DR CTD; 4643; -.
DR GeneCards; GC15M059428; -.
DR H-InvDB; HIX0038144; -.
DR HGNC; HGNC:7599; MYO1E.
DR HPA; HPA023886; -.
DR MIM; 601479; gene.
DR MIM; 614131; phenotype.
DR neXtProt; NX_Q12965; -.
DR Orphanet; 93213; Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.
DR PharmGKB; PA31401; -.
DR eggNOG; COG5022; -.
DR HOGENOM; HOG000260265; -.
DR HOVERGEN; HBG100702; -.
DR InParanoid; Q12965; -.
DR KO; K10356; -.
DR OMA; KLKKENW; -.
DR OrthoDB; EOG7V49XQ; -.
DR PhylomeDB; Q12965; -.
DR ChiTaRS; MYO1E; human.
DR GeneWiki; MYO1E; -.
DR GenomeRNAi; 4643; -.
DR NextBio; 17892; -.
DR PRO; PR:Q12965; -.
DR ArrayExpress; Q12965; -.
DR Bgee; Q12965; -.
DR CleanEx; HS_MYO1C; -.
DR CleanEx; HS_MYO1E; -.
DR Genevestigator; Q12965; -.
DR GO; GO:0005912; C:adherens junction; ISS:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016459; C:myosin complex; TAS:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042623; F:ATPase activity, coupled; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0000146; F:microfilament motor activity; TAS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0030048; P:actin filament-based movement; TAS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB.
DR GO; GO:0032836; P:glomerular basement membrane development; ISS:UniProtKB.
DR GO; GO:0003094; P:glomerular filtration; ISS:UniProtKB.
DR GO; GO:0072015; P:glomerular visceral epithelial cell development; ISS:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0035166; P:post-embryonic hemopoiesis; IEA:Ensembl.
DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR001609; Myosin_head_motor_dom.
DR InterPro; IPR010926; Myosin_tail_2.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00063; Myosin_head; 1.
DR Pfam; PF06017; Myosin_TH1; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00193; MYOSINHEAVY.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00242; MYSc; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50096; IQ; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Actin-binding; ATP-binding; Calmodulin-binding; Cell junction;
KW Complete proteome; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton;
KW Disease mutation; Lipid-binding; Motor protein; Myosin;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW SH3 domain.
FT CHAIN 1 1108 Unconventional myosin-Ie.
FT /FTId=PRO_0000123450.
FT DOMAIN 1 679 Myosin head-like.
FT DOMAIN 695 724 IQ.
FT DOMAIN 1051 1108 SH3.
FT NP_BIND 112 119 ATP (Potential).
FT REGION 581 591 Actin-binding (Potential).
FT MOD_RES 980 980 Phosphoserine.
FT MOD_RES 1002 1002 Phosphoserine.
FT VARIANT 159 159 A -> P (in FSGS6; the mutant shows
FT diffuse cytosolic localization with a
FT punctate pattern).
FT /FTId=VAR_065958.
FT VARIANT 185 185 D -> G (in dbSNP:rs141565214).
FT /FTId=VAR_065959.
FT VARIANT 221 221 A -> V.
FT /FTId=VAR_065960.
FT VARIANT 795 795 G -> R (in dbSNP:rs180951130).
FT /FTId=VAR_065961.
FT VARIANT 1049 1049 P -> H (in dbSNP:rs147579391).
FT /FTId=VAR_065962.
FT CONFLICT 889 892 WSAG -> GVQGA (in Ref. 1; AAA62667).
FT CONFLICT 984 984 N -> I (in Ref. 1; AAA62667).
FT CONFLICT 1097 1097 Q -> P (in Ref. 1; AAA62667).
SQ SEQUENCE 1108 AA; 127062 MW; 3073050B9BB4DDC6 CRC64;
MGSKGVYQYH WQSHNVKHSG VDDMVLLSKI TENSIVENLK KRYMDDYIFT YIGSVLISVN
PFKQMPYFGE KEIEMYQGAA QYENPPHIYA LADNMYRNMI IDRENQCVII SGESGAGKTV
AAKYIMSYIS RVSGGGTKVQ HVKDIILQSN PLLEAFGNAK TVRNNNSSRF GKYFEIQFSP
GGEPDGGKIS NFLLEKSRVV MRNPGERSFH IFYQLIEGAS AEQKHSLGIT SMDYYYYLSL
SGSYKVDDID DRREFQETLH AMNVIGIFAE EQTLVLQIVA GILHLGNISF KEVGNYAAVE
SEEFLAFPAY LLGINQDRLK EKLTSRQMDS KWGGKSESIH VTLNVEQACY TRDALAKALH
ARVFDFLVDS INKAMEKDHE EYNIGVLDIY GFEIFQKNGF EQFCINFVNE KLQQIFIELT
LKAEQEEYVQ EGIRWTPIEY FNNKIVCDLI ENKVNPPGIM SILDDVCATM HAVGEGADQT
LLQKLQMQIG SHEHFNSWNQ GFIIHHYAGK VSYDMDGFCE RNRDVLFMDL IELMQSSELP
FIKSLFPENL QADKKGRPTT AGSKIKKQAN DLVSTLMKCT PHYIRCIKPN ETKKPRDWEE
SRVKHQVEYL GLKENIRVRR AGYAYRRIFQ KFLQRYAILT KATWPSWQGE EKQGVLHLLQ
SVNMDSDQFQ LGRSKVFIKA PESLFLLEEM RERKYDGYAR VIQKSWRKFV ARKKYVQMRE
EASDLLLNKK ERRRNSINRN FIGDYIGMEE HPELQQFVGK REKIDFADTV TKYDRRFKGV
KRDLLLTPKC LYLIGREKVK QGPDKGLVKE VLKRKIEIER ILSVSLSTMQ DDIFILHEQE
YDSLLESVFK TEFLSLLAKR YEEKTQKQLP LKFSNTLELK LKKENWGPWS AGGSRQVQFH
QGFGDLAVLK PSNKVLQVSI GPGLPKNSRP TRRNTTQNTG YSSGTQNANY PVRAAPPPPG
YHQNGVIRNQ YVPYPHAPGS QRSNQKSLYT SMARPPLPRQ QSTSSDRVSQ TPESLDFLKV
PDQGAAGVRR QTTSRPPPAG GRPKPQPKPK PQVPQCKALY AYDAQDTDEL SFNANDIIDI
IKEDPSGWWT GRLRGKQGLF PNNYVTKI
//
ID MYO1E_HUMAN Reviewed; 1108 AA.
AC Q12965; Q14778;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 25-NOV-2008, sequence version 2.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=Unconventional myosin-Ie;
DE AltName: Full=Myosin-Ic;
DE AltName: Full=Unconventional myosin 1E;
GN Name=MYO1E; Synonyms=MYO1C;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7932763; DOI=10.1006/jmbi.1994.1662;
RA Bement W.M., Wirth J.A., Mooseker M.S.;
RT "Cloning and mRNA expression of human unconventional myosin-IC. A
RT homologue of amoeboid myosins-I with a single IQ motif and an SH3
RT domain.";
RL J. Mol. Biol. 243:356-363(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 107-196.
RX PubMed=8022818; DOI=10.1073/pnas.91.14.6549;
RA Bement W.M., Hasson T., Wirth J.A., Cheney R.E., Mooseker M.S.;
RT "Identification and overlapping expression of multiple unconventional
RT myosin genes in vertebrate cell types.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:6549-6553(1994).
RN [4]
RP ERRATUM.
RX PubMed=7972138; DOI=10.1073/pnas.91.24.11767c;
RA Bement W.M., Hasson T., Wirth J.A., Cheney R.E., Mooseker M.S.;
RL Proc. Natl. Acad. Sci. U.S.A. 91:11767-11767(1994).
RN [5]
RP FUNCTION IN ATP HYDROLYSIS, AND INTERACTION WITH F-ACTIN AND CALM.
RX PubMed=11940582; DOI=10.1074/jbc.M200713200;
RA El Mezgueldi M., Tang N., Rosenfeld S.S., Ostap E.M.;
RT "The kinetic mechanism of Myo1e (human myosin-IC).";
RL J. Biol. Chem. 277:21514-21521(2002).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SYNJ1; DNM1 AND
RP DNM2.
RX PubMed=17257598; DOI=10.1016/j.febslet.2007.01.021;
RA Krendel M., Osterweil E.K., Mooseker M.S.;
RT "Myosin 1E interacts with synaptojanin-1 and dynamin and is involved
RT in endocytosis.";
RL FEBS Lett. 581:644-650(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-980 AND SER-1002, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20860408; DOI=10.1021/bi1012657;
RA Feeser E.A., Ignacio C.M., Krendel M., Ostap E.M.;
RT "Myo1e binds anionic phospholipids with high affinity.";
RL Biochemistry 49:9353-9360(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-980, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP INTERACTION WITH ARL14EP, AND TISSUE SPECIFICITY.
RX PubMed=21458045; DOI=10.1016/j.cell.2011.03.023;
RA Paul P., van den Hoorn T., Jongsma M.L., Bakker M.J., Hengeveld R.,
RA Janssen L., Cresswell P., Egan D.A., van Ham M., Ten Brinke A.,
RA Ovaa H., Beijersbergen R.L., Kuijl C., Neefjes J.;
RT "A Genome-wide multidimensional RNAi screen reveals pathways
RT controlling MHC class II antigen presentation.";
RL Cell 145:268-283(2011).
RN [12]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, VARIANT FSGS6 PRO-159,
RP VARIANTS GLY-185; VAL-221; ARG-795 AND HIS-1049, AND CHARACTERIZATION
RP OF VARIANT FSGS6 PRO-159.
RX PubMed=21756023; DOI=10.1056/NEJMoa1101273;
RA Mele C., Iatropoulos P., Donadelli R., Calabria A., Maranta R.,
RA Cassis P., Buelli S., Tomasoni S., Piras R., Krendel M., Bettoni S.,
RA Morigi M., Delledonne M., Pecoraro C., Abbate I., Capobianchi M.R.,
RA Hildebrandt F., Otto E., Schaefer F., Macciardi F., Ozaltin F.,
RA Emre S., Ibsirlioglu T., Benigni A., Remuzzi G., Noris M.;
RT "MYO1E mutations and childhood familial focal segmental
RT glomerulosclerosis.";
RL N. Engl. J. Med. 365:295-306(2011).
RN [13]
RP VARIANT FSGS6 PRO-159.
RX PubMed=21697813; DOI=10.1038/ki.2011.148;
RA Sanna-Cherchi S., Burgess K.E., Nees S.N., Caridi G., Weng P.L.,
RA Dagnino M., Bodria M., Carrea A., Allegretta M.A., Kim H.R.,
RA Perry B.J., Gigante M., Clark L.N., Kisselev S., Cusi D., Gesualdo L.,
RA Allegri L., Scolari F., D'Agati V., Shapiro L.S., Pecoraro C.,
RA Palomero T., Ghiggeri G.M., Gharavi A.G.;
RT "Exome sequencing identified MYO1E and NEIL1 as candidate genes for
RT human autosomal recessive steroid-resistant nephrotic syndrome.";
RL Kidney Int. 80:389-396(2011).
CC -!- FUNCTION: Myosins are actin-based motor molecules with ATPase
CC activity. Unconventional myosins serve in intracellular movements.
CC Their highly divergent tails bind to membranous compartments,
CC which are then moved relative to actin filaments. Binds to
CC membranes containing anionic phospholipids via its tail domain.
CC Required for normal morphology of the glomerular basement
CC membrane, normal development of foot processes by kidney podocytes
CC and normal kidney function. In dendritic cells, may control the
CC movement of class II-containing cytoplasmic vesicles along the
CC actin cytoskeleton by connecting them with the actin network via
CC ARL14EP and ARL14.
CC -!- SUBUNIT: Interacts with CALM and F-actin (By similarity).
CC Interacts (via SH3 domain) with SYNJ1, DNM1 and DNM2. Interacts
CC with ARL14EP.
CC -!- INTERACTION:
CC Q8N8R7:ARL14EP; NbExp=2; IntAct=EBI-4279548, EBI-2807994;
CC P21575:Dnm1 (xeno); NbExp=2; IntAct=EBI-4279548, EBI-80070;
CC P50570:DNM2; NbExp=2; IntAct=EBI-4279548, EBI-346547;
CC Q62910:Synj1 (xeno); NbExp=2; IntAct=EBI-4279548, EBI-1149123;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton.
CC Cytoplasmic vesicle. Cytoplasmic vesicle, clathrin-coated vesicle.
CC Cell junction (By similarity). Note=Colocalizes with F-actin (By
CC similarity). In cultured podocytes, it localizes close to and is
CC associated with the cytoplasmic membrane, with enrichment at the
CC lamellipodia tips. Colocalizes with cytoplasmic vesicles,
CC including endocytic clathrin-coated vesicles. Colocalizes with
CC dynamin at cytoplasmic vesicles.
CC -!- TISSUE SPECIFICITY: Expressed in the immune system. In the kidney,
CC predominantly expressed in the glomerulus, including podocytes.
CC -!- DISEASE: Focal segmental glomerulosclerosis 6 (FSGS6)
CC [MIM:614131]: A renal pathology defined by the presence of
CC segmental sclerosis in glomeruli and resulting in proteinuria,
CC reduced glomerular filtration rate and progressive decline in
CC renal function. Renal insufficiency often progresses to end-stage
CC renal disease, a highly morbid state requiring either dialysis
CC therapy or kidney transplantation. FSGS6 is a childhood-onset
CC disorder resulting in nephrotic syndrome, which includes massive
CC proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Contains 1 IQ domain.
CC -!- SIMILARITY: Contains 1 myosin head-like domain.
CC -!- SIMILARITY: Contains 1 SH3 domain.
CC -!- CAUTION: Represents a unconventional myosin. This protein should
CC not be confused with the conventional myosin-1 (MYH1).
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; U14391; AAA62667.1; -; mRNA.
DR EMBL; AC092756; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L29139; AAA20902.1; -; mRNA.
DR PIR; S53601; S53601.
DR RefSeq; NP_004989.2; NM_004998.3.
DR UniGene; Hs.654506; -.
DR ProteinModelPortal; Q12965; -.
DR SMR; Q12965; 20-692, 1054-1108.
DR DIP; DIP-884N; -.
DR IntAct; Q12965; 7.
DR MINT; MINT-3026848; -.
DR STRING; 9606.ENSP00000288235; -.
DR PhosphoSite; Q12965; -.
DR DMDM; 215274106; -.
DR PaxDb; Q12965; -.
DR PRIDE; Q12965; -.
DR Ensembl; ENST00000288235; ENSP00000288235; ENSG00000157483.
DR GeneID; 4643; -.
DR KEGG; hsa:4643; -.
DR UCSC; uc002aga.4; human.
DR CTD; 4643; -.
DR GeneCards; GC15M059428; -.
DR H-InvDB; HIX0038144; -.
DR HGNC; HGNC:7599; MYO1E.
DR HPA; HPA023886; -.
DR MIM; 601479; gene.
DR MIM; 614131; phenotype.
DR neXtProt; NX_Q12965; -.
DR Orphanet; 93213; Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.
DR PharmGKB; PA31401; -.
DR eggNOG; COG5022; -.
DR HOGENOM; HOG000260265; -.
DR HOVERGEN; HBG100702; -.
DR InParanoid; Q12965; -.
DR KO; K10356; -.
DR OMA; KLKKENW; -.
DR OrthoDB; EOG7V49XQ; -.
DR PhylomeDB; Q12965; -.
DR ChiTaRS; MYO1E; human.
DR GeneWiki; MYO1E; -.
DR GenomeRNAi; 4643; -.
DR NextBio; 17892; -.
DR PRO; PR:Q12965; -.
DR ArrayExpress; Q12965; -.
DR Bgee; Q12965; -.
DR CleanEx; HS_MYO1C; -.
DR CleanEx; HS_MYO1E; -.
DR Genevestigator; Q12965; -.
DR GO; GO:0005912; C:adherens junction; ISS:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016459; C:myosin complex; TAS:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042623; F:ATPase activity, coupled; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0000146; F:microfilament motor activity; TAS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0030048; P:actin filament-based movement; TAS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB.
DR GO; GO:0032836; P:glomerular basement membrane development; ISS:UniProtKB.
DR GO; GO:0003094; P:glomerular filtration; ISS:UniProtKB.
DR GO; GO:0072015; P:glomerular visceral epithelial cell development; ISS:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0035166; P:post-embryonic hemopoiesis; IEA:Ensembl.
DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR001609; Myosin_head_motor_dom.
DR InterPro; IPR010926; Myosin_tail_2.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00063; Myosin_head; 1.
DR Pfam; PF06017; Myosin_TH1; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00193; MYOSINHEAVY.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00242; MYSc; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50096; IQ; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Actin-binding; ATP-binding; Calmodulin-binding; Cell junction;
KW Complete proteome; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton;
KW Disease mutation; Lipid-binding; Motor protein; Myosin;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW SH3 domain.
FT CHAIN 1 1108 Unconventional myosin-Ie.
FT /FTId=PRO_0000123450.
FT DOMAIN 1 679 Myosin head-like.
FT DOMAIN 695 724 IQ.
FT DOMAIN 1051 1108 SH3.
FT NP_BIND 112 119 ATP (Potential).
FT REGION 581 591 Actin-binding (Potential).
FT MOD_RES 980 980 Phosphoserine.
FT MOD_RES 1002 1002 Phosphoserine.
FT VARIANT 159 159 A -> P (in FSGS6; the mutant shows
FT diffuse cytosolic localization with a
FT punctate pattern).
FT /FTId=VAR_065958.
FT VARIANT 185 185 D -> G (in dbSNP:rs141565214).
FT /FTId=VAR_065959.
FT VARIANT 221 221 A -> V.
FT /FTId=VAR_065960.
FT VARIANT 795 795 G -> R (in dbSNP:rs180951130).
FT /FTId=VAR_065961.
FT VARIANT 1049 1049 P -> H (in dbSNP:rs147579391).
FT /FTId=VAR_065962.
FT CONFLICT 889 892 WSAG -> GVQGA (in Ref. 1; AAA62667).
FT CONFLICT 984 984 N -> I (in Ref. 1; AAA62667).
FT CONFLICT 1097 1097 Q -> P (in Ref. 1; AAA62667).
SQ SEQUENCE 1108 AA; 127062 MW; 3073050B9BB4DDC6 CRC64;
MGSKGVYQYH WQSHNVKHSG VDDMVLLSKI TENSIVENLK KRYMDDYIFT YIGSVLISVN
PFKQMPYFGE KEIEMYQGAA QYENPPHIYA LADNMYRNMI IDRENQCVII SGESGAGKTV
AAKYIMSYIS RVSGGGTKVQ HVKDIILQSN PLLEAFGNAK TVRNNNSSRF GKYFEIQFSP
GGEPDGGKIS NFLLEKSRVV MRNPGERSFH IFYQLIEGAS AEQKHSLGIT SMDYYYYLSL
SGSYKVDDID DRREFQETLH AMNVIGIFAE EQTLVLQIVA GILHLGNISF KEVGNYAAVE
SEEFLAFPAY LLGINQDRLK EKLTSRQMDS KWGGKSESIH VTLNVEQACY TRDALAKALH
ARVFDFLVDS INKAMEKDHE EYNIGVLDIY GFEIFQKNGF EQFCINFVNE KLQQIFIELT
LKAEQEEYVQ EGIRWTPIEY FNNKIVCDLI ENKVNPPGIM SILDDVCATM HAVGEGADQT
LLQKLQMQIG SHEHFNSWNQ GFIIHHYAGK VSYDMDGFCE RNRDVLFMDL IELMQSSELP
FIKSLFPENL QADKKGRPTT AGSKIKKQAN DLVSTLMKCT PHYIRCIKPN ETKKPRDWEE
SRVKHQVEYL GLKENIRVRR AGYAYRRIFQ KFLQRYAILT KATWPSWQGE EKQGVLHLLQ
SVNMDSDQFQ LGRSKVFIKA PESLFLLEEM RERKYDGYAR VIQKSWRKFV ARKKYVQMRE
EASDLLLNKK ERRRNSINRN FIGDYIGMEE HPELQQFVGK REKIDFADTV TKYDRRFKGV
KRDLLLTPKC LYLIGREKVK QGPDKGLVKE VLKRKIEIER ILSVSLSTMQ DDIFILHEQE
YDSLLESVFK TEFLSLLAKR YEEKTQKQLP LKFSNTLELK LKKENWGPWS AGGSRQVQFH
QGFGDLAVLK PSNKVLQVSI GPGLPKNSRP TRRNTTQNTG YSSGTQNANY PVRAAPPPPG
YHQNGVIRNQ YVPYPHAPGS QRSNQKSLYT SMARPPLPRQ QSTSSDRVSQ TPESLDFLKV
PDQGAAGVRR QTTSRPPPAG GRPKPQPKPK PQVPQCKALY AYDAQDTDEL SFNANDIIDI
IKEDPSGWWT GRLRGKQGLF PNNYVTKI
//
MIM
601479
*RECORD*
*FIELD* NO
601479
*FIELD* TI
*601479 MYOSIN IE; MYO1E
;;MYOSIN IC, FORMERLY; MYO1C, FORMERLY
*FIELD* TX
DESCRIPTION
read more
The MYO1E gene encodes a nonmuscle membrane-associated class I myosin
with a motor-head domain that binds ATP and F-actin, a
calmodulin-binding neck domain, and a tail domain. MYO1E is expressed in
the podocyte membrane in the renal glomerulus (summary by Mele et al.,
2011).
CLONING
Bement et al. (1994) cloned a human unconventional myosin gene, MYO1E,
encoding a predicted 127-kD polypeptide of 1,109 amino acids. The gene,
which they designated myosin IC, contains a characteristic N-terminal
myosin head, a single 'IQ motif' predicted to bind a single myosin light
chain, and a C-terminal tail with a putative membrane-binding site. They
also noted the presence of a C-terminal src-homology domain, reminiscent
of 'long-tailed' myosins I from amoeboid organisms. By Northern
analysis, Bement et al. (1994) detected ubiquitous expression of MYO1E.
MAPPING
Hasson et al. (1996) used fluorescence in situ hybridization to map 4
unconventional myosin loci in humans: MYO1E (formerly MYO1C), MYO1A
(601478), MYO1F (601480), and MYO10 (601481). The MYO1E gene was found
to be located on chromosome 15q21-q22 in the precise location predicted
from its location on chromosome 9 of the mouse.
GENE FUNCTION
Mele et al. (2011) showed that MYO1E localizes to the cytoplasmic side
of the podocyte membrane in glomeruli of human kidney biopsy specimens,
with enrichment at the lamellipodia tips. MYO1E localized at the tips of
F-actin bundles. The findings implicated MYO1E as a key component of the
foot-process cytoskeleton, important for podocyte structure in the
glomerulus. Nonmuscle myosins, such as MYO1E, generate tension that
helps glomerular capillaries resist hydrostatic pressure at the
glomerular filtration barrier.
MOLECULAR GENETICS
By genomewide linkage analysis followed by high-throughput sequencing of
a consanguineous Italian family with focal segmental
glomerulosclerosis-6 (FSGS6; 614131), Mele et al. (2011) identified a
homozygous mutation in the MYO1E gene (A159P; 601479.0001). Sequencing
of the MYO1E gene in 52 additional patients with FSGS or mesangial
sclerosis identified a homozygous truncating mutation (Y695X;
601479.0002) in a Turkish girl with FSGS. Cellular studies showed that
the A159P-mutant protein mislocalized to the cytoplasm, did not
colocalize with F-action, and was unable to promote podocyte migration.
ANIMAL MODEL
In mice, Krendel et al. (2009) showed that Myo1e localizes to kidney
podocytes. Myo1e-knockout mice developed proteinuria and hematuria
associated with chronic renal failure, indicating a defect in the
glomerular filtration barrier. Renal biopsies showed focal segmental
glomerulosclerosis and interstitial fibrosis. Ultrastructural studies
showed changes characteristic of glomerular disease, including a
thickened and disorganized glomerular basement membrane, flattened,
effaced podocyte foot processes, and signs of tubular injury. These
defects were not present at birth but developed in the first weeks of
life. The findings indicated that Myo1e plays an important role in
podocyte function and normal glomerular filtration, and underscored the
importance of the actin cytoskeleton in podocyte biology.
*FIELD* AV
.0001
FOCAL SEGMENTAL GLOMERULOSCLEROSIS 6
MYO1E, ALA159PRO
In 3 sibs, born of consanguineous Italian parents, with focal segmental
glomerulosclerosis-6 (FSGS6; 614131) causing nephrotic syndrome and
various degrees of renal failure, Mele et al. (2011) identified a
homozygous 475G-C transversion in exon 6 of the MYO1E gene, resulting in
an ala159-to-pro (A159P) substitution in a highly conserved residue
within the switch-1 loop of the motor-head domain. This region is in the
ATP-binding pocket close to the actin-binding domain. Each unaffected
parent was heterozygous for the mutation, which was not found in 764
control chromosomes. Human podocytes transfected with the A159P-mutant
protein showed diffuse cytoplasmic localization with a punctate pattern,
whereas wildtype MYO1E localized to the plasma membrane. The mutant
protein did not stain with an anti-MYO1E antibody, suggesting
conformational changes of the mutant protein, did not colocalize with
F-action, and was unable to promote podocyte migration.
.0002
FOCAL SEGMENTAL GLOMERULOSCLEROSIS 6
MYO1E, TYR695TER
In a Turkish girl with focal segmental glomerulosclerosis-6 (614131)
causing nephrotic syndrome, Mele et al. (2011) identified a homozygous
2085T-G transversion in the MYO1E gene, resulting in a tyr695-to-ter
(Y695X) substitution at the start of the calmodulin-binding neck domain.
Each unaffected parent was heterozygous for the mutation, which was not
found in 968 control chromosomes. The mutation was predicted to result
in a nonfunctional protein.
*FIELD* RF
1. Bement, W. M.; Wirth, J. A.; Mooseker, M. S.: Cloning and mRNA
expression of human unconventional myosin-IC: a homologue of amoeboid
myosins-I with a single IQ motif and an SH3 domain. J. Molec. Biol. 243:
356-363, 1994.
2. Hasson, T.; Skowron, J. F.; Gilbert, D. J.; Avraham, K. B.; Perry,
W. L.; Bement, W. M.; Anderson, B. L.; Sherr, E. H.; Chen, Z.-Y.;
Greene, L. A.; Ward, D. C.; Corey, D. P.; Mooseker, M. S.; Copeland,
N. G.; Jenkins, N. A.: Mapping of unconventional myosins in mouse
and human. Genomics 36: 431-439, 1996.
3. Krendel, M.; Kim, S. V.; Willinger, T.; Wang, T.; Kashgarian, M.;
Flavell, R. A.; Mooseker, M. S.: Disruption of myosin 1e promotes
podocyte injury. J. Am. Soc. Nephrol. 20: 86-94, 2009.
4. Mele, C.; Iatropoulos, P.; Donadelli, R.; Calabria, A.; Maranta,
R.; Cassis, P.; Buelli, S.; Tomasoni, S.; Piras, R.; Krendel, M.;
Bettoni, S.; Morigi, M.; and 14 others: MYO1E mutations and childhood
familial focal segmental glomerulosclerosis. New Eng. J. Med. 365:
295-306, 2011.
*FIELD* CN
Cassandra L. Kniffin - updated: 7/28/2011
Mark H. Paalman - updated: 10/23/1996
*FIELD* CD
Victor A. McKusick: 10/22/1996
*FIELD* ED
wwang: 07/29/2011
ckniffin: 7/28/2011
alopez: 6/25/2009
carol: 7/20/2001
mark: 10/23/1996
mark: 10/22/1996
*RECORD*
*FIELD* NO
601479
*FIELD* TI
*601479 MYOSIN IE; MYO1E
;;MYOSIN IC, FORMERLY; MYO1C, FORMERLY
*FIELD* TX
DESCRIPTION
read more
The MYO1E gene encodes a nonmuscle membrane-associated class I myosin
with a motor-head domain that binds ATP and F-actin, a
calmodulin-binding neck domain, and a tail domain. MYO1E is expressed in
the podocyte membrane in the renal glomerulus (summary by Mele et al.,
2011).
CLONING
Bement et al. (1994) cloned a human unconventional myosin gene, MYO1E,
encoding a predicted 127-kD polypeptide of 1,109 amino acids. The gene,
which they designated myosin IC, contains a characteristic N-terminal
myosin head, a single 'IQ motif' predicted to bind a single myosin light
chain, and a C-terminal tail with a putative membrane-binding site. They
also noted the presence of a C-terminal src-homology domain, reminiscent
of 'long-tailed' myosins I from amoeboid organisms. By Northern
analysis, Bement et al. (1994) detected ubiquitous expression of MYO1E.
MAPPING
Hasson et al. (1996) used fluorescence in situ hybridization to map 4
unconventional myosin loci in humans: MYO1E (formerly MYO1C), MYO1A
(601478), MYO1F (601480), and MYO10 (601481). The MYO1E gene was found
to be located on chromosome 15q21-q22 in the precise location predicted
from its location on chromosome 9 of the mouse.
GENE FUNCTION
Mele et al. (2011) showed that MYO1E localizes to the cytoplasmic side
of the podocyte membrane in glomeruli of human kidney biopsy specimens,
with enrichment at the lamellipodia tips. MYO1E localized at the tips of
F-actin bundles. The findings implicated MYO1E as a key component of the
foot-process cytoskeleton, important for podocyte structure in the
glomerulus. Nonmuscle myosins, such as MYO1E, generate tension that
helps glomerular capillaries resist hydrostatic pressure at the
glomerular filtration barrier.
MOLECULAR GENETICS
By genomewide linkage analysis followed by high-throughput sequencing of
a consanguineous Italian family with focal segmental
glomerulosclerosis-6 (FSGS6; 614131), Mele et al. (2011) identified a
homozygous mutation in the MYO1E gene (A159P; 601479.0001). Sequencing
of the MYO1E gene in 52 additional patients with FSGS or mesangial
sclerosis identified a homozygous truncating mutation (Y695X;
601479.0002) in a Turkish girl with FSGS. Cellular studies showed that
the A159P-mutant protein mislocalized to the cytoplasm, did not
colocalize with F-action, and was unable to promote podocyte migration.
ANIMAL MODEL
In mice, Krendel et al. (2009) showed that Myo1e localizes to kidney
podocytes. Myo1e-knockout mice developed proteinuria and hematuria
associated with chronic renal failure, indicating a defect in the
glomerular filtration barrier. Renal biopsies showed focal segmental
glomerulosclerosis and interstitial fibrosis. Ultrastructural studies
showed changes characteristic of glomerular disease, including a
thickened and disorganized glomerular basement membrane, flattened,
effaced podocyte foot processes, and signs of tubular injury. These
defects were not present at birth but developed in the first weeks of
life. The findings indicated that Myo1e plays an important role in
podocyte function and normal glomerular filtration, and underscored the
importance of the actin cytoskeleton in podocyte biology.
*FIELD* AV
.0001
FOCAL SEGMENTAL GLOMERULOSCLEROSIS 6
MYO1E, ALA159PRO
In 3 sibs, born of consanguineous Italian parents, with focal segmental
glomerulosclerosis-6 (FSGS6; 614131) causing nephrotic syndrome and
various degrees of renal failure, Mele et al. (2011) identified a
homozygous 475G-C transversion in exon 6 of the MYO1E gene, resulting in
an ala159-to-pro (A159P) substitution in a highly conserved residue
within the switch-1 loop of the motor-head domain. This region is in the
ATP-binding pocket close to the actin-binding domain. Each unaffected
parent was heterozygous for the mutation, which was not found in 764
control chromosomes. Human podocytes transfected with the A159P-mutant
protein showed diffuse cytoplasmic localization with a punctate pattern,
whereas wildtype MYO1E localized to the plasma membrane. The mutant
protein did not stain with an anti-MYO1E antibody, suggesting
conformational changes of the mutant protein, did not colocalize with
F-action, and was unable to promote podocyte migration.
.0002
FOCAL SEGMENTAL GLOMERULOSCLEROSIS 6
MYO1E, TYR695TER
In a Turkish girl with focal segmental glomerulosclerosis-6 (614131)
causing nephrotic syndrome, Mele et al. (2011) identified a homozygous
2085T-G transversion in the MYO1E gene, resulting in a tyr695-to-ter
(Y695X) substitution at the start of the calmodulin-binding neck domain.
Each unaffected parent was heterozygous for the mutation, which was not
found in 968 control chromosomes. The mutation was predicted to result
in a nonfunctional protein.
*FIELD* RF
1. Bement, W. M.; Wirth, J. A.; Mooseker, M. S.: Cloning and mRNA
expression of human unconventional myosin-IC: a homologue of amoeboid
myosins-I with a single IQ motif and an SH3 domain. J. Molec. Biol. 243:
356-363, 1994.
2. Hasson, T.; Skowron, J. F.; Gilbert, D. J.; Avraham, K. B.; Perry,
W. L.; Bement, W. M.; Anderson, B. L.; Sherr, E. H.; Chen, Z.-Y.;
Greene, L. A.; Ward, D. C.; Corey, D. P.; Mooseker, M. S.; Copeland,
N. G.; Jenkins, N. A.: Mapping of unconventional myosins in mouse
and human. Genomics 36: 431-439, 1996.
3. Krendel, M.; Kim, S. V.; Willinger, T.; Wang, T.; Kashgarian, M.;
Flavell, R. A.; Mooseker, M. S.: Disruption of myosin 1e promotes
podocyte injury. J. Am. Soc. Nephrol. 20: 86-94, 2009.
4. Mele, C.; Iatropoulos, P.; Donadelli, R.; Calabria, A.; Maranta,
R.; Cassis, P.; Buelli, S.; Tomasoni, S.; Piras, R.; Krendel, M.;
Bettoni, S.; Morigi, M.; and 14 others: MYO1E mutations and childhood
familial focal segmental glomerulosclerosis. New Eng. J. Med. 365:
295-306, 2011.
*FIELD* CN
Cassandra L. Kniffin - updated: 7/28/2011
Mark H. Paalman - updated: 10/23/1996
*FIELD* CD
Victor A. McKusick: 10/22/1996
*FIELD* ED
wwang: 07/29/2011
ckniffin: 7/28/2011
alopez: 6/25/2009
carol: 7/20/2001
mark: 10/23/1996
mark: 10/22/1996
MIM
614131
*RECORD*
*FIELD* NO
614131
*FIELD* TI
#614131 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 6; FSGS6
;;GLOMERULOSCLEROSIS, FOCAL SEGMENTAL, 6
read more*FIELD* TX
A number sign (#) is used with this entry because focal segmental
glomerulosclerosis-6 (FSGS6) can be caused by homozygous mutation in the
MYO1E gene (601479) on chromosome 15q21.
DESCRIPTION
Focal segmental glomerulosclerosis-6 is an autosomal recessive
childhood-onset kidney disorder manifest clinically by the nephrotic
syndrome, which is characterized by proteinuria, hematuria,
hypoalbuminemia, and progressive renal failure. It is a disease of the
glomerular podocyte (summary by Mele et al., 2011).
For a general phenotypic description and a discussion of genetic
heterogeneity of focal segmental glomerulosclerosis and nephrotic
syndrome, see FSGS1 (603278).
CLINICAL FEATURES
Mele et al. (2011) reported an 18-year-old Italian girl, born of
consanguineous parents, who presented at age 9 years with
nephrotic-range proteinuria, microhematuria, hypoalbuminemia, and edema.
Renal biopsy showed 30% of glomeruli with segmental sclerohyalinosis
with capsular crescents and 30% of glomeruli with collapse. There was
also focal mesangial hyperplasia and tubular atrophy with tubulitis and
interstitial inflammatory infiltrates. There were diffuse glomerular and
peritubular deposits of Ig antibodies and complement components. Despite
therapy with steroids and cyclosporine, she developed end-stage renal
disease at age 13 years and underwent successful kidney transplant at
age 17. Two younger sibs were similarly affected, but they showed a
partial response to glucocorticoid and cyclosporine therapy. Mele et al.
(2011) also reported a Turkish girl from a consanguineous kindred who
presented at age 1 year with edema, proteinuria, hematuria, and
hypoalbuminemia. Renal biopsy at age 4 years showed segmental or global
sclerosis of 20% glomeruli and focal tubular dilatation and atrophy with
interstitial fibrosis. Electron microscopy showed effacement of the foot
processes, microvillus transformation of podocytes, focal thickening and
disorganization of the glomerular basement membrane, and focal expansion
of the mesangial matrix. She achieved partial remission with medical
treatment. An older sister had died at age 6 years of progressive renal
failure.
MOLECULAR GENETICS
By genomewide linkage analysis followed by high-throughput sequencing of
a consanguineous Italian family with FSGS6, Mele et al. (2011)
identified a homozygous mutation in the MYO1E gene (A159P; 601479.0001)
on chromosome 15q21. Sequencing of the MYO1E gene in 52 additional
patients with FSGS or mesangial sclerosis identified a homozygous
truncating mutation (Y695X; 601479.0002) in a Turkish girl with FSGS.
The MYO1E protein localizes to the plasma membrane of the podocyte and
plays a role in normal glomerular filtration. Cellular studies showed
that the A159P-mutant protein mislocalized to the cytoplasm, did not
colocalize with F-action, and was unable to promote podocyte migration,
indicating a defect in normal MYO1E function.
ANIMAL MODEL
Krendel et al. (2009) showed that Myo1e localizes to kidney podocytes in
mice. Myo1e-knockout mice developed proteinuria and hematuria associated
with chronic renal failure, indicating a defect in the glomerular
filtration barrier. Renal biopsies showed focal segmental
glomerulosclerosis and interstitial fibrosis. Ultrastructural studies
showed changes characteristic of glomerular disease, including a
thickened and disorganized glomerular basement membrane, flattened,
effaced podocyte foot processes, and signs of tubular injury. These
defects were not present at birth, but developed in the first weeks of
life. The findings indicated that Myo1e plays an important role in
podocyte function and normal glomerular filtration, and underscored the
importance of the actin cytoskeleton in podocyte biology.
*FIELD* RF
1. Krendel, M.; Kim, S. V.; Willinger, T.; Wang, T.; Kashgarian, M.;
Flavell, R. A.; Mooseker, M. S.: Disruption of myosin 1e promotes
podocyte injury. J. Am. Soc. Nephrol. 20: 86-94, 2009.
2. Mele, C.; Iatropoulos, P.; Donadelli, R.; Calabria, A.; Maranta,
R.; Cassis, P.; Buelli, S.; Tomasoni, S.; Piras, R.; Krendel, M.;
Bettoni, S.; Morigi, M.; and 14 others: MYO1E mutations and childhood
familial focal segmental glomerulosclerosis. New Eng. J. Med. 365:
295-306, 2011.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GENITOURINARY:
[Kidneys];
Nephrotic syndrome;
Renal failure, progressive;
Focal segmental glomerulosclerosis;
Tubular atrophy;
Mesangial hyperplasia;
Antibody deposits;
Complement component deposits;
Electron microscopy shows foot-process effacement;
Podocytes show microvillous transformation;
Thickening and disorganization of the glomerular basement membrane
MUSCLE, SOFT TISSUE:
Edema
LABORATORY ABNORMALITIES:
Proteinuria;
Hematuria;
Hypoalbuminemia
MISCELLANEOUS:
Onset in childhood (range 1 to 9 years);
Progressive disorder;
Two unrelated families have been reported (as of July 2011);
Poor or no response to glucocorticoid treatment
MOLECULAR BASIS:
Caused by mutation in the myosin IE gene (MYO1E, 601479.0001)
*FIELD* CD
Cassandra L. Kniffin: 7/28/2011
*FIELD* ED
joanna: 12/29/2011
ckniffin: 7/28/2011
*FIELD* CD
Cassandra L. Kniffin: 7/28/2011
*FIELD* ED
carol: 09/07/2011
wwang: 7/29/2011
ckniffin: 7/28/2011
*RECORD*
*FIELD* NO
614131
*FIELD* TI
#614131 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 6; FSGS6
;;GLOMERULOSCLEROSIS, FOCAL SEGMENTAL, 6
read more*FIELD* TX
A number sign (#) is used with this entry because focal segmental
glomerulosclerosis-6 (FSGS6) can be caused by homozygous mutation in the
MYO1E gene (601479) on chromosome 15q21.
DESCRIPTION
Focal segmental glomerulosclerosis-6 is an autosomal recessive
childhood-onset kidney disorder manifest clinically by the nephrotic
syndrome, which is characterized by proteinuria, hematuria,
hypoalbuminemia, and progressive renal failure. It is a disease of the
glomerular podocyte (summary by Mele et al., 2011).
For a general phenotypic description and a discussion of genetic
heterogeneity of focal segmental glomerulosclerosis and nephrotic
syndrome, see FSGS1 (603278).
CLINICAL FEATURES
Mele et al. (2011) reported an 18-year-old Italian girl, born of
consanguineous parents, who presented at age 9 years with
nephrotic-range proteinuria, microhematuria, hypoalbuminemia, and edema.
Renal biopsy showed 30% of glomeruli with segmental sclerohyalinosis
with capsular crescents and 30% of glomeruli with collapse. There was
also focal mesangial hyperplasia and tubular atrophy with tubulitis and
interstitial inflammatory infiltrates. There were diffuse glomerular and
peritubular deposits of Ig antibodies and complement components. Despite
therapy with steroids and cyclosporine, she developed end-stage renal
disease at age 13 years and underwent successful kidney transplant at
age 17. Two younger sibs were similarly affected, but they showed a
partial response to glucocorticoid and cyclosporine therapy. Mele et al.
(2011) also reported a Turkish girl from a consanguineous kindred who
presented at age 1 year with edema, proteinuria, hematuria, and
hypoalbuminemia. Renal biopsy at age 4 years showed segmental or global
sclerosis of 20% glomeruli and focal tubular dilatation and atrophy with
interstitial fibrosis. Electron microscopy showed effacement of the foot
processes, microvillus transformation of podocytes, focal thickening and
disorganization of the glomerular basement membrane, and focal expansion
of the mesangial matrix. She achieved partial remission with medical
treatment. An older sister had died at age 6 years of progressive renal
failure.
MOLECULAR GENETICS
By genomewide linkage analysis followed by high-throughput sequencing of
a consanguineous Italian family with FSGS6, Mele et al. (2011)
identified a homozygous mutation in the MYO1E gene (A159P; 601479.0001)
on chromosome 15q21. Sequencing of the MYO1E gene in 52 additional
patients with FSGS or mesangial sclerosis identified a homozygous
truncating mutation (Y695X; 601479.0002) in a Turkish girl with FSGS.
The MYO1E protein localizes to the plasma membrane of the podocyte and
plays a role in normal glomerular filtration. Cellular studies showed
that the A159P-mutant protein mislocalized to the cytoplasm, did not
colocalize with F-action, and was unable to promote podocyte migration,
indicating a defect in normal MYO1E function.
ANIMAL MODEL
Krendel et al. (2009) showed that Myo1e localizes to kidney podocytes in
mice. Myo1e-knockout mice developed proteinuria and hematuria associated
with chronic renal failure, indicating a defect in the glomerular
filtration barrier. Renal biopsies showed focal segmental
glomerulosclerosis and interstitial fibrosis. Ultrastructural studies
showed changes characteristic of glomerular disease, including a
thickened and disorganized glomerular basement membrane, flattened,
effaced podocyte foot processes, and signs of tubular injury. These
defects were not present at birth, but developed in the first weeks of
life. The findings indicated that Myo1e plays an important role in
podocyte function and normal glomerular filtration, and underscored the
importance of the actin cytoskeleton in podocyte biology.
*FIELD* RF
1. Krendel, M.; Kim, S. V.; Willinger, T.; Wang, T.; Kashgarian, M.;
Flavell, R. A.; Mooseker, M. S.: Disruption of myosin 1e promotes
podocyte injury. J. Am. Soc. Nephrol. 20: 86-94, 2009.
2. Mele, C.; Iatropoulos, P.; Donadelli, R.; Calabria, A.; Maranta,
R.; Cassis, P.; Buelli, S.; Tomasoni, S.; Piras, R.; Krendel, M.;
Bettoni, S.; Morigi, M.; and 14 others: MYO1E mutations and childhood
familial focal segmental glomerulosclerosis. New Eng. J. Med. 365:
295-306, 2011.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GENITOURINARY:
[Kidneys];
Nephrotic syndrome;
Renal failure, progressive;
Focal segmental glomerulosclerosis;
Tubular atrophy;
Mesangial hyperplasia;
Antibody deposits;
Complement component deposits;
Electron microscopy shows foot-process effacement;
Podocytes show microvillous transformation;
Thickening and disorganization of the glomerular basement membrane
MUSCLE, SOFT TISSUE:
Edema
LABORATORY ABNORMALITIES:
Proteinuria;
Hematuria;
Hypoalbuminemia
MISCELLANEOUS:
Onset in childhood (range 1 to 9 years);
Progressive disorder;
Two unrelated families have been reported (as of July 2011);
Poor or no response to glucocorticoid treatment
MOLECULAR BASIS:
Caused by mutation in the myosin IE gene (MYO1E, 601479.0001)
*FIELD* CD
Cassandra L. Kniffin: 7/28/2011
*FIELD* ED
joanna: 12/29/2011
ckniffin: 7/28/2011
*FIELD* CD
Cassandra L. Kniffin: 7/28/2011
*FIELD* ED
carol: 09/07/2011
wwang: 7/29/2011
ckniffin: 7/28/2011