Full text data of EPB41L3
EPB41L3
(DAL1, KIAA0987)
[Confidence: low (only semi-automatic identification from reviews)]
Band 4.1-like protein 3 (4.1B; Differentially expressed in adenocarcinoma of the lung protein 1; DAL-1; Band 4.1-like protein 3, N-terminally processed)
Band 4.1-like protein 3 (4.1B; Differentially expressed in adenocarcinoma of the lung protein 1; DAL-1; Band 4.1-like protein 3, N-terminally processed)
UniProt
Q9Y2J2
ID E41L3_HUMAN Reviewed; 1087 AA.
AC Q9Y2J2; O95713; Q9BRP5;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-DEC-2001, sequence version 2.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=Band 4.1-like protein 3;
DE AltName: Full=4.1B;
DE AltName: Full=Differentially expressed in adenocarcinoma of the lung protein 1;
DE Short=DAL-1;
DE Contains:
DE RecName: Full=Band 4.1-like protein 3, N-terminally processed;
GN Name=EPB41L3; Synonyms=DAL1, KIAA0987;
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] (ISOFORM C), FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=9892180;
RA Tran Y.K., Boegler O., Gorse K.M., Wieland I., Green M.R.,
RA Newsham I.F.;
RT "A novel member of the NF2/ERM/4.1 superfamily with growth suppressing
RT properties in lung cancer.";
RL Cancer Res. 59:35-43(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH CADM1.
RX PubMed=12234973;
RA Yageta M., Kuramochi M., Masuda M., Fukami T., Fukuhara H.,
RA Maruyama T., Shibuya M., Murakami Y.;
RT "Direct association of TSLC1 and DAL-1, two distinct tumor suppressor
RT proteins in lung cancer.";
RL Cancer Res. 62:5129-5133(2002).
RN [5]
RP FUNCTION, AND INTERACTION WITH PRMT3; PRMT5 AND PRMT6.
RX PubMed=15334060; DOI=10.1038/sj.onc.1208057;
RA Singh V., Miranda T.B., Jiang W., Frankel A., Roemer M.E., Robb V.A.,
RA Gutmann D.H., Herschman H.R., Clarke S., Newsham I.F.;
RT "DAL-1/4.1B tumor suppressor interacts with protein arginine N-
RT methyltransferase 3 (PRMT3) and inhibits its ability to methylate
RT substrates in vitro and in vivo.";
RL Oncogene 23:7761-7771(2004).
RN [6]
RP FUNCTION, AND INTERACTION WITH PRMT5.
RX PubMed=15737618; DOI=10.1016/j.bbrc.2005.01.153;
RA Jiang W., Roemer M.E., Newsham I.F.;
RT "The tumor suppressor DAL-1/4.1B modulates protein arginine N-
RT methyltransferase 5 activity in a substrate-specific manner.";
RL Biochem. Biophys. Res. Commun. 329:522-530(2005).
RN [7]
RP FUNCTION.
RX PubMed=16420693; DOI=10.1186/1476-4598-5-4;
RA Jiang W., Newsham I.F.;
RT "The tumor suppressor DAL-1/4.1B and protein methylation cooperate in
RT inducing apoptosis in MCF-7 breast cancer cells.";
RL Mol. Cancer 5:4-4(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-962, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND THR-2, MASS
RP SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-460 AND THR-469,
RP AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 108-390 IN COMPLEX WITH
RP CADM1, AND INTERACTION WITH CADM1.
RX PubMed=21131357; DOI=10.1074/jbc.M110.174011;
RA Busam R.D., Thorsell A.G., Flores A., Hammarstrom M., Persson C.,
RA Obrink B., Hallberg B.M.;
RT "Structural basis of tumor suppressor in lung cancer 1 (TSLC1) binding
RT to differentially expressed in adenocarcinoma of the lung (DAL-
RT 1/4.1B).";
RL J. Biol. Chem. 286:4511-4516(2011).
CC -!- FUNCTION: Tumor suppressor that inhibits cell proliferation and
CC promotes apoptosis. Modulates the activity of protein arginine N-
CC methyltransferases, including PRMT3 and PRMT5.
CC -!- SUBUNIT: Interacts (via FERM domain) with CADM1. Interacts with
CC PRMT3, PRMT5 and PRMT6.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton (By similarity).
CC Cell junction. Cell membrane; Peripheral membrane protein;
CC Cytoplasmic side. Cytoplasm. Note=Detected in the cytoplasm of
CC actively dividing cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist;
CC Name=A;
CC IsoId=Q9Y2J2-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q9Y2J2-2; Sequence=VSP_000482, VSP_000483, VSP_000484,
CC VSP_000485;
CC Name=C;
CC IsoId=Q9Y2J2-3; Sequence=VSP_000482, VSP_000483, VSP_000484,
CC VSP_000485, VSP_000486;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in brain, with lower
CC levels in kidney, intestine, and testis. Detected in lung.
CC -!- SIMILARITY: Contains 1 FERM domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC79806.1; Type=Frameshift; Positions=29, 59;
CC Sequence=BAA76831.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org//Genes/EPB41L3ID40458ch18p11.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF069072; AAC79806.1; ALT_FRAME; mRNA.
DR EMBL; AB023204; BAA76831.1; ALT_INIT; mRNA.
DR EMBL; BC006141; AAH06141.1; -; mRNA.
DR RefSeq; NP_001268462.1; NM_001281533.1.
DR RefSeq; NP_001268463.1; NM_001281534.1.
DR RefSeq; NP_001268464.1; NM_001281535.1.
DR RefSeq; NP_036439.2; NM_012307.3.
DR UniGene; Hs.213394; -.
DR PDB; 2HE7; X-ray; 2.00 A; A=108-390.
DR PDB; 3BIN; X-ray; 2.30 A; A=109-390.
DR PDBsum; 2HE7; -.
DR PDBsum; 3BIN; -.
DR ProteinModelPortal; Q9Y2J2; -.
DR SMR; Q9Y2J2; 108-390.
DR DIP; DIP-17035N; -.
DR IntAct; Q9Y2J2; 20.
DR MINT; MINT-1630957; -.
DR STRING; 9606.ENSP00000341138; -.
DR PhosphoSite; Q9Y2J2; -.
DR DMDM; 17433099; -.
DR PaxDb; Q9Y2J2; -.
DR PRIDE; Q9Y2J2; -.
DR Ensembl; ENST00000341928; ENSP00000343158; ENSG00000082397.
DR Ensembl; ENST00000342933; ENSP00000341138; ENSG00000082397.
DR Ensembl; ENST00000400111; ENSP00000382981; ENSG00000082397.
DR Ensembl; ENST00000540638; ENSP00000442091; ENSG00000082397.
DR GeneID; 23136; -.
DR KEGG; hsa:23136; -.
DR UCSC; uc002kmt.1; human.
DR CTD; 23136; -.
DR GeneCards; GC18M005382; -.
DR HGNC; HGNC:3380; EPB41L3.
DR HPA; HPA028605; -.
DR MIM; 605331; gene.
DR neXtProt; NX_Q9Y2J2; -.
DR PharmGKB; PA27813; -.
DR eggNOG; NOG242913; -.
DR HOGENOM; HOG000228840; -.
DR HOVERGEN; HBG007777; -.
DR InParanoid; Q9Y2J2; -.
DR KO; K06107; -.
DR OMA; STDTAIT; -.
DR OrthoDB; EOG7Z69BP; -.
DR PhylomeDB; Q9Y2J2; -.
DR EvolutionaryTrace; Q9Y2J2; -.
DR GeneWiki; EPB41L3; -.
DR GenomeRNAi; 23136; -.
DR NextBio; 44399; -.
DR PRO; PR:Q9Y2J2; -.
DR ArrayExpress; Q9Y2J2; -.
DR Bgee; Q9Y2J2; -.
DR CleanEx; HS_EPB41L3; -.
DR Genevestigator; Q9Y2J2; -.
DR GO; GO:0030673; C:axolemma; IEA:Ensembl.
DR GO; GO:0005911; C:cell-cell junction; IDA:HGNC.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0019898; C:extrinsic to membrane; IEA:InterPro.
DR GO; GO:0044224; C:juxtaparanode region of axon; ISS:BHF-UCL.
DR GO; GO:0033270; C:paranode region of axon; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; NAS:UniProtKB.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:BHF-UCL.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IEA:InterPro.
DR GO; GO:0030865; P:cortical cytoskeleton organization; TAS:BHF-UCL.
DR GO; GO:0007016; P:cytoskeletal anchoring at plasma membrane; TAS:BHF-UCL.
DR GO; GO:0043217; P:myelin maintenance; ISS:BHF-UCL.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:BHF-UCL.
DR GO; GO:0030913; P:paranodal junction assembly; ISS:BHF-UCL.
DR GO; GO:0071205; P:protein localization to juxtaparanode region of axon; ISS:BHF-UCL.
DR GO; GO:0002175; P:protein localization to paranode region of axon; ISS:BHF-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:BHF-UCL.
DR GO; GO:0008360; P:regulation of cell shape; ISS:BHF-UCL.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR008379; Band_4.1_C.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR019750; Band_41_fam.
DR InterPro; IPR021187; Band_41_protein.
DR InterPro; IPR000798; Ez/rad/moesin_like.
DR InterPro; IPR014847; FERM-adjacent.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_3-hlx.
DR InterPro; IPR019748; FERM_central.
DR InterPro; IPR019747; FERM_CS.
DR InterPro; IPR000299; FERM_domain.
DR InterPro; IPR018979; FERM_N.
DR InterPro; IPR018980; FERM_PH-like_C.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR007477; SAB_dom.
DR Pfam; PF05902; 4_1_CTD; 1.
DR Pfam; PF08736; FA; 1.
DR Pfam; PF09380; FERM_C; 1.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF09379; FERM_N; 1.
DR Pfam; PF04382; SAB; 1.
DR PIRSF; PIRSF002304; Membrane_skeletal_4_1; 1.
DR PRINTS; PR00935; BAND41.
DR PRINTS; PR00661; ERMFAMILY.
DR SMART; SM00295; B41; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR PROSITE; PS00660; FERM_1; 1.
DR PROSITE; PS00661; FERM_2; 1.
DR PROSITE; PS50057; FERM_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Alternative splicing;
KW Apoptosis; Cell junction; Cell membrane; Complete proteome; Cytoplasm;
KW Cytoskeleton; Membrane; Phosphoprotein; Polymorphism;
KW Reference proteome; Tumor suppressor.
FT CHAIN 1 1087 Band 4.1-like protein 3.
FT /FTId=PRO_0000219399.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 1087 Band 4.1-like protein 3, N-terminally
FT processed.
FT /FTId=PRO_0000423194.
FT DOMAIN 110 391 FERM.
FT REGION 394 513 Hydrophilic.
FT REGION 514 860 Spectrin--actin-binding (Potential).
FT REGION 861 1083 C-terminal (CTD).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylthreonine; in Band 4.1-like
FT protein 3, N-terminally processed.
FT MOD_RES 88 88 Phosphoserine.
FT MOD_RES 460 460 Phosphoserine.
FT MOD_RES 469 469 Phosphothreonine.
FT MOD_RES 962 962 Phosphoserine.
FT MOD_RES 1081 1081 Phosphothreonine (By similarity).
FT VAR_SEQ 446 446 G -> GASVNENHEIYMKDSMSAA (in isoform B
FT and isoform C).
FT /FTId=VSP_000482.
FT VAR_SEQ 503 689 Missing (in isoform B and isoform C).
FT /FTId=VSP_000483.
FT VAR_SEQ 708 719 Missing (in isoform B and isoform C).
FT /FTId=VSP_000484.
FT VAR_SEQ 784 824 Missing (in isoform B and isoform C).
FT /FTId=VSP_000485.
FT VAR_SEQ 835 1087 Missing (in isoform C).
FT /FTId=VSP_000486.
FT VARIANT 555 555 A -> T (in dbSNP:rs9966357).
FT /FTId=VAR_048353.
FT VARIANT 575 575 Y -> C (in dbSNP:rs8082898).
FT /FTId=VAR_048354.
FT VARIANT 859 859 E -> Q (in dbSNP:rs8096452).
FT /FTId=VAR_048355.
FT CONFLICT 32 32 Missing (in Ref. 1; AAC79806).
FT CONFLICT 498 498 R -> Q (in Ref. 1; AAC79806).
FT STRAND 109 115
FT STRAND 121 127
FT HELIX 132 142
FT HELIX 148 150
FT STRAND 151 156
FT STRAND 162 164
FT HELIX 171 174
FT STRAND 180 188
FT HELIX 193 195
FT HELIX 199 214
FT HELIX 222 237
FT TURN 242 244
FT TURN 247 252
FT STRAND 256 258
FT HELIX 261 273
FT TURN 274 276
FT HELIX 279 290
FT TURN 294 297
FT STRAND 299 304
FT STRAND 310 315
FT STRAND 317 324
FT STRAND 327 333
FT HELIX 334 336
FT STRAND 339 343
FT STRAND 346 351
FT TURN 354 357
FT STRAND 361 366
FT HELIX 370 388
SQ SEQUENCE 1087 AA; 120678 MW; 0A33CA4A43F12620 CRC64;
MTTESGSDSE SKPDQEAEPQ EAAGAQGRAG APVPEPPKEE QQQALEQFAA AAAHSTPVRR
EVTDKEQEFA ARAAKQLEYQ QLEDDKLSQK SSSSKLSRSP LKIVKKPKSM QCKVILLDGS
EYTCDVEKRS RGQVLFDKVC EHLNLLEKDY FGLTYRDAEN QKNWLDPAKE IKKQVRSGAW
HFSFNVKFYP PDPAQLSEDI TRYYLCLQLR DDIVSGRLPC SFVTLALLGS YTVQSELGDY
DPDECGSDYI SEFRFAPNHT KELEDKVIEL HKSHRGMTPA EAEMHFLENA KKLSMYGVDL
HHAKDSEGVE IMLGVCASGL LIYRDRLRIN RFAWPKVLKI SYKRNNFYIK IRPGEFEQFE
STIGFKLPNH RAAKRLWKVC VEHHTFFRLL LPEAPPKKFL TLGSKFRYSG RTQAQTRRAS
ALIDRPAPYF ERSSSKRYTM SRSLDGEVGT GQYATTKGIS QTNLITTVTP EKKAEEERDE
EEDKRRKGEE VTPISAIRHE GKSPGLGTDS CPLSPPSTHC APTSPTELRR RCKENDCKLP
GYEPSRAEHL PGEPALDSDG PGRPYLGDQD VAFSYRQQTG KGTTLFSFSL QLPESFPSLL
DDDGYLSFPN LSETNLLPQS LQHYLPIRSP SLVPCFLFIF FFLLSASFSV PYALTLSFPL
ALCLCYLEPK AASLSASLDN DPSDSSEEET DSERTDTAAD GETTATESDQ EEDAELKAQE
LEKTQDDLMK HQTNISELKR TFLETSTDTA VTNEWEKRLS TSPVRLAARQ EDAPMIEPLV
PEETKQSSGE KLMDGSEIFS LLESARKPTE FIGGVTSTSQ SWVQKMETKT ESSGIETEPT
VHHLPLSTEK VVQETVLVEE RRVVHASGDA SYSAGDSGDA AAQPAFTGIK GKEGSALTEG
AKEEGGEEVA KAVLEQEETA AASRERQEEQ SAAIHISETL EQKPHFESST VKTETISFGS
VSPGGVKLEI STKEVPVVHT ETKTITYESS QVDPGTDLEP GVLMSAQTIT SETTSTTTTT
HITKTVKGGI SETRIEKRIV ITGDADIDHD QALAQAIKEA KEQHPDMSVT KVVVHKETEI
TPEDGED
//
ID E41L3_HUMAN Reviewed; 1087 AA.
AC Q9Y2J2; O95713; Q9BRP5;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-DEC-2001, sequence version 2.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=Band 4.1-like protein 3;
DE AltName: Full=4.1B;
DE AltName: Full=Differentially expressed in adenocarcinoma of the lung protein 1;
DE Short=DAL-1;
DE Contains:
DE RecName: Full=Band 4.1-like protein 3, N-terminally processed;
GN Name=EPB41L3; Synonyms=DAL1, KIAA0987;
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] (ISOFORM C), FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=9892180;
RA Tran Y.K., Boegler O., Gorse K.M., Wieland I., Green M.R.,
RA Newsham I.F.;
RT "A novel member of the NF2/ERM/4.1 superfamily with growth suppressing
RT properties in lung cancer.";
RL Cancer Res. 59:35-43(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH CADM1.
RX PubMed=12234973;
RA Yageta M., Kuramochi M., Masuda M., Fukami T., Fukuhara H.,
RA Maruyama T., Shibuya M., Murakami Y.;
RT "Direct association of TSLC1 and DAL-1, two distinct tumor suppressor
RT proteins in lung cancer.";
RL Cancer Res. 62:5129-5133(2002).
RN [5]
RP FUNCTION, AND INTERACTION WITH PRMT3; PRMT5 AND PRMT6.
RX PubMed=15334060; DOI=10.1038/sj.onc.1208057;
RA Singh V., Miranda T.B., Jiang W., Frankel A., Roemer M.E., Robb V.A.,
RA Gutmann D.H., Herschman H.R., Clarke S., Newsham I.F.;
RT "DAL-1/4.1B tumor suppressor interacts with protein arginine N-
RT methyltransferase 3 (PRMT3) and inhibits its ability to methylate
RT substrates in vitro and in vivo.";
RL Oncogene 23:7761-7771(2004).
RN [6]
RP FUNCTION, AND INTERACTION WITH PRMT5.
RX PubMed=15737618; DOI=10.1016/j.bbrc.2005.01.153;
RA Jiang W., Roemer M.E., Newsham I.F.;
RT "The tumor suppressor DAL-1/4.1B modulates protein arginine N-
RT methyltransferase 5 activity in a substrate-specific manner.";
RL Biochem. Biophys. Res. Commun. 329:522-530(2005).
RN [7]
RP FUNCTION.
RX PubMed=16420693; DOI=10.1186/1476-4598-5-4;
RA Jiang W., Newsham I.F.;
RT "The tumor suppressor DAL-1/4.1B and protein methylation cooperate in
RT inducing apoptosis in MCF-7 breast cancer cells.";
RL Mol. Cancer 5:4-4(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-962, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND THR-2, MASS
RP SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-460 AND THR-469,
RP AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 108-390 IN COMPLEX WITH
RP CADM1, AND INTERACTION WITH CADM1.
RX PubMed=21131357; DOI=10.1074/jbc.M110.174011;
RA Busam R.D., Thorsell A.G., Flores A., Hammarstrom M., Persson C.,
RA Obrink B., Hallberg B.M.;
RT "Structural basis of tumor suppressor in lung cancer 1 (TSLC1) binding
RT to differentially expressed in adenocarcinoma of the lung (DAL-
RT 1/4.1B).";
RL J. Biol. Chem. 286:4511-4516(2011).
CC -!- FUNCTION: Tumor suppressor that inhibits cell proliferation and
CC promotes apoptosis. Modulates the activity of protein arginine N-
CC methyltransferases, including PRMT3 and PRMT5.
CC -!- SUBUNIT: Interacts (via FERM domain) with CADM1. Interacts with
CC PRMT3, PRMT5 and PRMT6.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton (By similarity).
CC Cell junction. Cell membrane; Peripheral membrane protein;
CC Cytoplasmic side. Cytoplasm. Note=Detected in the cytoplasm of
CC actively dividing cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist;
CC Name=A;
CC IsoId=Q9Y2J2-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q9Y2J2-2; Sequence=VSP_000482, VSP_000483, VSP_000484,
CC VSP_000485;
CC Name=C;
CC IsoId=Q9Y2J2-3; Sequence=VSP_000482, VSP_000483, VSP_000484,
CC VSP_000485, VSP_000486;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in brain, with lower
CC levels in kidney, intestine, and testis. Detected in lung.
CC -!- SIMILARITY: Contains 1 FERM domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC79806.1; Type=Frameshift; Positions=29, 59;
CC Sequence=BAA76831.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org//Genes/EPB41L3ID40458ch18p11.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF069072; AAC79806.1; ALT_FRAME; mRNA.
DR EMBL; AB023204; BAA76831.1; ALT_INIT; mRNA.
DR EMBL; BC006141; AAH06141.1; -; mRNA.
DR RefSeq; NP_001268462.1; NM_001281533.1.
DR RefSeq; NP_001268463.1; NM_001281534.1.
DR RefSeq; NP_001268464.1; NM_001281535.1.
DR RefSeq; NP_036439.2; NM_012307.3.
DR UniGene; Hs.213394; -.
DR PDB; 2HE7; X-ray; 2.00 A; A=108-390.
DR PDB; 3BIN; X-ray; 2.30 A; A=109-390.
DR PDBsum; 2HE7; -.
DR PDBsum; 3BIN; -.
DR ProteinModelPortal; Q9Y2J2; -.
DR SMR; Q9Y2J2; 108-390.
DR DIP; DIP-17035N; -.
DR IntAct; Q9Y2J2; 20.
DR MINT; MINT-1630957; -.
DR STRING; 9606.ENSP00000341138; -.
DR PhosphoSite; Q9Y2J2; -.
DR DMDM; 17433099; -.
DR PaxDb; Q9Y2J2; -.
DR PRIDE; Q9Y2J2; -.
DR Ensembl; ENST00000341928; ENSP00000343158; ENSG00000082397.
DR Ensembl; ENST00000342933; ENSP00000341138; ENSG00000082397.
DR Ensembl; ENST00000400111; ENSP00000382981; ENSG00000082397.
DR Ensembl; ENST00000540638; ENSP00000442091; ENSG00000082397.
DR GeneID; 23136; -.
DR KEGG; hsa:23136; -.
DR UCSC; uc002kmt.1; human.
DR CTD; 23136; -.
DR GeneCards; GC18M005382; -.
DR HGNC; HGNC:3380; EPB41L3.
DR HPA; HPA028605; -.
DR MIM; 605331; gene.
DR neXtProt; NX_Q9Y2J2; -.
DR PharmGKB; PA27813; -.
DR eggNOG; NOG242913; -.
DR HOGENOM; HOG000228840; -.
DR HOVERGEN; HBG007777; -.
DR InParanoid; Q9Y2J2; -.
DR KO; K06107; -.
DR OMA; STDTAIT; -.
DR OrthoDB; EOG7Z69BP; -.
DR PhylomeDB; Q9Y2J2; -.
DR EvolutionaryTrace; Q9Y2J2; -.
DR GeneWiki; EPB41L3; -.
DR GenomeRNAi; 23136; -.
DR NextBio; 44399; -.
DR PRO; PR:Q9Y2J2; -.
DR ArrayExpress; Q9Y2J2; -.
DR Bgee; Q9Y2J2; -.
DR CleanEx; HS_EPB41L3; -.
DR Genevestigator; Q9Y2J2; -.
DR GO; GO:0030673; C:axolemma; IEA:Ensembl.
DR GO; GO:0005911; C:cell-cell junction; IDA:HGNC.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0019898; C:extrinsic to membrane; IEA:InterPro.
DR GO; GO:0044224; C:juxtaparanode region of axon; ISS:BHF-UCL.
DR GO; GO:0033270; C:paranode region of axon; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; NAS:UniProtKB.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:BHF-UCL.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IEA:InterPro.
DR GO; GO:0030865; P:cortical cytoskeleton organization; TAS:BHF-UCL.
DR GO; GO:0007016; P:cytoskeletal anchoring at plasma membrane; TAS:BHF-UCL.
DR GO; GO:0043217; P:myelin maintenance; ISS:BHF-UCL.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:BHF-UCL.
DR GO; GO:0030913; P:paranodal junction assembly; ISS:BHF-UCL.
DR GO; GO:0071205; P:protein localization to juxtaparanode region of axon; ISS:BHF-UCL.
DR GO; GO:0002175; P:protein localization to paranode region of axon; ISS:BHF-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:BHF-UCL.
DR GO; GO:0008360; P:regulation of cell shape; ISS:BHF-UCL.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR008379; Band_4.1_C.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR019750; Band_41_fam.
DR InterPro; IPR021187; Band_41_protein.
DR InterPro; IPR000798; Ez/rad/moesin_like.
DR InterPro; IPR014847; FERM-adjacent.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_3-hlx.
DR InterPro; IPR019748; FERM_central.
DR InterPro; IPR019747; FERM_CS.
DR InterPro; IPR000299; FERM_domain.
DR InterPro; IPR018979; FERM_N.
DR InterPro; IPR018980; FERM_PH-like_C.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR007477; SAB_dom.
DR Pfam; PF05902; 4_1_CTD; 1.
DR Pfam; PF08736; FA; 1.
DR Pfam; PF09380; FERM_C; 1.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF09379; FERM_N; 1.
DR Pfam; PF04382; SAB; 1.
DR PIRSF; PIRSF002304; Membrane_skeletal_4_1; 1.
DR PRINTS; PR00935; BAND41.
DR PRINTS; PR00661; ERMFAMILY.
DR SMART; SM00295; B41; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR PROSITE; PS00660; FERM_1; 1.
DR PROSITE; PS00661; FERM_2; 1.
DR PROSITE; PS50057; FERM_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Alternative splicing;
KW Apoptosis; Cell junction; Cell membrane; Complete proteome; Cytoplasm;
KW Cytoskeleton; Membrane; Phosphoprotein; Polymorphism;
KW Reference proteome; Tumor suppressor.
FT CHAIN 1 1087 Band 4.1-like protein 3.
FT /FTId=PRO_0000219399.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 1087 Band 4.1-like protein 3, N-terminally
FT processed.
FT /FTId=PRO_0000423194.
FT DOMAIN 110 391 FERM.
FT REGION 394 513 Hydrophilic.
FT REGION 514 860 Spectrin--actin-binding (Potential).
FT REGION 861 1083 C-terminal (CTD).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylthreonine; in Band 4.1-like
FT protein 3, N-terminally processed.
FT MOD_RES 88 88 Phosphoserine.
FT MOD_RES 460 460 Phosphoserine.
FT MOD_RES 469 469 Phosphothreonine.
FT MOD_RES 962 962 Phosphoserine.
FT MOD_RES 1081 1081 Phosphothreonine (By similarity).
FT VAR_SEQ 446 446 G -> GASVNENHEIYMKDSMSAA (in isoform B
FT and isoform C).
FT /FTId=VSP_000482.
FT VAR_SEQ 503 689 Missing (in isoform B and isoform C).
FT /FTId=VSP_000483.
FT VAR_SEQ 708 719 Missing (in isoform B and isoform C).
FT /FTId=VSP_000484.
FT VAR_SEQ 784 824 Missing (in isoform B and isoform C).
FT /FTId=VSP_000485.
FT VAR_SEQ 835 1087 Missing (in isoform C).
FT /FTId=VSP_000486.
FT VARIANT 555 555 A -> T (in dbSNP:rs9966357).
FT /FTId=VAR_048353.
FT VARIANT 575 575 Y -> C (in dbSNP:rs8082898).
FT /FTId=VAR_048354.
FT VARIANT 859 859 E -> Q (in dbSNP:rs8096452).
FT /FTId=VAR_048355.
FT CONFLICT 32 32 Missing (in Ref. 1; AAC79806).
FT CONFLICT 498 498 R -> Q (in Ref. 1; AAC79806).
FT STRAND 109 115
FT STRAND 121 127
FT HELIX 132 142
FT HELIX 148 150
FT STRAND 151 156
FT STRAND 162 164
FT HELIX 171 174
FT STRAND 180 188
FT HELIX 193 195
FT HELIX 199 214
FT HELIX 222 237
FT TURN 242 244
FT TURN 247 252
FT STRAND 256 258
FT HELIX 261 273
FT TURN 274 276
FT HELIX 279 290
FT TURN 294 297
FT STRAND 299 304
FT STRAND 310 315
FT STRAND 317 324
FT STRAND 327 333
FT HELIX 334 336
FT STRAND 339 343
FT STRAND 346 351
FT TURN 354 357
FT STRAND 361 366
FT HELIX 370 388
SQ SEQUENCE 1087 AA; 120678 MW; 0A33CA4A43F12620 CRC64;
MTTESGSDSE SKPDQEAEPQ EAAGAQGRAG APVPEPPKEE QQQALEQFAA AAAHSTPVRR
EVTDKEQEFA ARAAKQLEYQ QLEDDKLSQK SSSSKLSRSP LKIVKKPKSM QCKVILLDGS
EYTCDVEKRS RGQVLFDKVC EHLNLLEKDY FGLTYRDAEN QKNWLDPAKE IKKQVRSGAW
HFSFNVKFYP PDPAQLSEDI TRYYLCLQLR DDIVSGRLPC SFVTLALLGS YTVQSELGDY
DPDECGSDYI SEFRFAPNHT KELEDKVIEL HKSHRGMTPA EAEMHFLENA KKLSMYGVDL
HHAKDSEGVE IMLGVCASGL LIYRDRLRIN RFAWPKVLKI SYKRNNFYIK IRPGEFEQFE
STIGFKLPNH RAAKRLWKVC VEHHTFFRLL LPEAPPKKFL TLGSKFRYSG RTQAQTRRAS
ALIDRPAPYF ERSSSKRYTM SRSLDGEVGT GQYATTKGIS QTNLITTVTP EKKAEEERDE
EEDKRRKGEE VTPISAIRHE GKSPGLGTDS CPLSPPSTHC APTSPTELRR RCKENDCKLP
GYEPSRAEHL PGEPALDSDG PGRPYLGDQD VAFSYRQQTG KGTTLFSFSL QLPESFPSLL
DDDGYLSFPN LSETNLLPQS LQHYLPIRSP SLVPCFLFIF FFLLSASFSV PYALTLSFPL
ALCLCYLEPK AASLSASLDN DPSDSSEEET DSERTDTAAD GETTATESDQ EEDAELKAQE
LEKTQDDLMK HQTNISELKR TFLETSTDTA VTNEWEKRLS TSPVRLAARQ EDAPMIEPLV
PEETKQSSGE KLMDGSEIFS LLESARKPTE FIGGVTSTSQ SWVQKMETKT ESSGIETEPT
VHHLPLSTEK VVQETVLVEE RRVVHASGDA SYSAGDSGDA AAQPAFTGIK GKEGSALTEG
AKEEGGEEVA KAVLEQEETA AASRERQEEQ SAAIHISETL EQKPHFESST VKTETISFGS
VSPGGVKLEI STKEVPVVHT ETKTITYESS QVDPGTDLEP GVLMSAQTIT SETTSTTTTT
HITKTVKGGI SETRIEKRIV ITGDADIDHD QALAQAIKEA KEQHPDMSVT KVVVHKETEI
TPEDGED
//
MIM
605331
*RECORD*
*FIELD* NO
605331
*FIELD* TI
*605331 ERYTHROCYTE MEMBRANE PROTEIN BAND 4.1-LIKE 3; EPB41L3
;;DIFFERENTIALLY EXPRESSED IN ADENOCARCINOMA OF THE LUNG; DAL1;;
read moreNONERYTHROID PROTEIN 4.1, BRAIN TYPE; 4.1B
*FIELD* TX
Meningiomas are common nervous system tumors. The most frequent genetic
alteration detected in these tumors is loss of heterozygosity (LOH) on
chromosome 22q. This finding led to the identification of the NF2 tumor
suppressor gene (607379) on 22q12, which is inactivated in 40% of
sporadic meningiomas. The NF2 gene product, merlin (or schwannomin), is
a member of the protein 4.1 (EPB41; 130500) family of
membrane-associated proteins, which also includes ezrin (123900),
radixin (179410), and moesin (309845). Tran et al. (1999) identified
another protein-4.1 gene, DAL1 (differentially expressed in
adenocarcinoma of the lung) located on chromosome 18p11.3, which is lost
in approximately 60% of non-small cell lung carcinomas, and exhibits
growth-suppressing properties in lung cancer cell lines. DAL1 is 73%
identical in its N-terminal domain to members of the protein 4.1 family
and shares structural similarity to the Drosophila 4.1 homolog
'coracle.' DAL1 is normally expressed at high levels in brain, with
lower levels in kidney, intestine, and testis. Using LOH, RT-PCR,
western blot, and immunohistochemistry analyses, Gutmann et al. (2000)
demonstrated DAL1 loss in 60% of sporadic meningiomas. Analogous to
merlin, the authors showed that DAL1 loss is an early event in
meningioma tumorigenesis, suggesting that these 2 protein-4.1 family
members are critical growth regulators in the pathogenesis of
meningiomas. The authors hypothesized that membrane-associated
alterations may be important in the early stages of neoplastic
transformation.
EVOLUTION
Tan et al. (2005) found that the EPB41 and EPB41L3 genes from fish,
bird, amphibian, and mammalian genomes exhibit shared features,
including alternative first exons and differential splicing acceptors in
exon 2. In all cases, the most 5-prime exon, exon 1A, splices
exclusively to a weaker internal acceptor site in exon 2, skipping a
fragment designated exon 2-prime. Conversely, alternative first exons 1B
and 1C always splice to the stronger first acceptor site, retaining exon
2-prime. These correlations were independent of cell type or species of
origin. Since exon 2-prime contains a translation initiation site,
splice variants generate protein isoforms with distinct N termini. Tan
et al. (2005) calculated that coupling between upstream promoters and
downstream splicing in EPB41 and EBP41L3 has been conserved for at least
500 million years.
*FIELD* RF
1. Gutmann, D. H.; Donahoe, J.; Perry, A.; Lemke, N.; Gorse, K.; Kittiniyom,
K.; Rempel, S. A.; Gutierrez, J. A.; Newsham, I. F.: Loss of DAL-1,
a protein 4.1-related tumor suppressor, is an important early event
in the pathogenesis of meningiomas. Hum. Molec. Genet. 9: 1495-1500,
2000.
2. Tan, J. S.; Mohandas, N.; Conboy, J. G.: Evolutionarily conserved
coupling of transcription and alternative splicing in the EPB41 (protein
4.1R) and EPB41L3 (protein 4.1B) genes. Genomics 86: 701-707, 2005.
3. Tran, Y. K.; Bogler, O.; Gorse, K. M.; Wieland, I.; Green, M. R.;
Newsham, I. F.: A novel member of the NF2/ERM/4.1 superfamily with
growth suppressing properties in lung cancer. Cancer Res. 59: 35-43,
1999.
*FIELD* CN
Patricia A. Hartz - updated: 2/7/2008
*FIELD* CD
George E. Tiller: 10/12/2000
*FIELD* ED
mgross: 02/20/2008
terry: 2/7/2008
mgross: 3/10/2003
carol: 1/28/2003
alopez: 4/2/2001
terry: 3/20/2001
alopez: 10/13/2000
alopez: 10/12/2000
*RECORD*
*FIELD* NO
605331
*FIELD* TI
*605331 ERYTHROCYTE MEMBRANE PROTEIN BAND 4.1-LIKE 3; EPB41L3
;;DIFFERENTIALLY EXPRESSED IN ADENOCARCINOMA OF THE LUNG; DAL1;;
read moreNONERYTHROID PROTEIN 4.1, BRAIN TYPE; 4.1B
*FIELD* TX
Meningiomas are common nervous system tumors. The most frequent genetic
alteration detected in these tumors is loss of heterozygosity (LOH) on
chromosome 22q. This finding led to the identification of the NF2 tumor
suppressor gene (607379) on 22q12, which is inactivated in 40% of
sporadic meningiomas. The NF2 gene product, merlin (or schwannomin), is
a member of the protein 4.1 (EPB41; 130500) family of
membrane-associated proteins, which also includes ezrin (123900),
radixin (179410), and moesin (309845). Tran et al. (1999) identified
another protein-4.1 gene, DAL1 (differentially expressed in
adenocarcinoma of the lung) located on chromosome 18p11.3, which is lost
in approximately 60% of non-small cell lung carcinomas, and exhibits
growth-suppressing properties in lung cancer cell lines. DAL1 is 73%
identical in its N-terminal domain to members of the protein 4.1 family
and shares structural similarity to the Drosophila 4.1 homolog
'coracle.' DAL1 is normally expressed at high levels in brain, with
lower levels in kidney, intestine, and testis. Using LOH, RT-PCR,
western blot, and immunohistochemistry analyses, Gutmann et al. (2000)
demonstrated DAL1 loss in 60% of sporadic meningiomas. Analogous to
merlin, the authors showed that DAL1 loss is an early event in
meningioma tumorigenesis, suggesting that these 2 protein-4.1 family
members are critical growth regulators in the pathogenesis of
meningiomas. The authors hypothesized that membrane-associated
alterations may be important in the early stages of neoplastic
transformation.
EVOLUTION
Tan et al. (2005) found that the EPB41 and EPB41L3 genes from fish,
bird, amphibian, and mammalian genomes exhibit shared features,
including alternative first exons and differential splicing acceptors in
exon 2. In all cases, the most 5-prime exon, exon 1A, splices
exclusively to a weaker internal acceptor site in exon 2, skipping a
fragment designated exon 2-prime. Conversely, alternative first exons 1B
and 1C always splice to the stronger first acceptor site, retaining exon
2-prime. These correlations were independent of cell type or species of
origin. Since exon 2-prime contains a translation initiation site,
splice variants generate protein isoforms with distinct N termini. Tan
et al. (2005) calculated that coupling between upstream promoters and
downstream splicing in EPB41 and EBP41L3 has been conserved for at least
500 million years.
*FIELD* RF
1. Gutmann, D. H.; Donahoe, J.; Perry, A.; Lemke, N.; Gorse, K.; Kittiniyom,
K.; Rempel, S. A.; Gutierrez, J. A.; Newsham, I. F.: Loss of DAL-1,
a protein 4.1-related tumor suppressor, is an important early event
in the pathogenesis of meningiomas. Hum. Molec. Genet. 9: 1495-1500,
2000.
2. Tan, J. S.; Mohandas, N.; Conboy, J. G.: Evolutionarily conserved
coupling of transcription and alternative splicing in the EPB41 (protein
4.1R) and EPB41L3 (protein 4.1B) genes. Genomics 86: 701-707, 2005.
3. Tran, Y. K.; Bogler, O.; Gorse, K. M.; Wieland, I.; Green, M. R.;
Newsham, I. F.: A novel member of the NF2/ERM/4.1 superfamily with
growth suppressing properties in lung cancer. Cancer Res. 59: 35-43,
1999.
*FIELD* CN
Patricia A. Hartz - updated: 2/7/2008
*FIELD* CD
George E. Tiller: 10/12/2000
*FIELD* ED
mgross: 02/20/2008
terry: 2/7/2008
mgross: 3/10/2003
carol: 1/28/2003
alopez: 4/2/2001
terry: 3/20/2001
alopez: 10/13/2000
alopez: 10/12/2000