Full text data of RDX
RDX
[Confidence: high (present in two of the MS resources)]
Radixin
Radixin
hRBCD
IPI00017367
IPI00017367 Radixin crucial role in the binding of the barbed end of actin filaments to the plasma membrane soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00017367 Radixin crucial role in the binding of the barbed end of actin filaments to the plasma membrane soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P35241
ID RADI_HUMAN Reviewed; 583 AA.
AC P35241; A7YIJ8; A7YIK0; A7YIK3; B7Z9U6; F5H1A7; Q86Y61;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1994, sequence version 1.
DT 22-JAN-2014, entry version 129.
DE RecName: Full=Radixin;
GN Name=RDX;
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 1).
RC TISSUE=Liver;
RX PubMed=8486357; DOI=10.1006/geno.1993.1159;
RA Wilgenbus K.K., Milatovich A., Francke U., Furthmayr H.;
RT "Molecular cloning, cDNA sequence, and chromosomal assignment of the
RT human radixin gene and two dispersed pseudogenes.";
RL Genomics 16:199-206(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 5), AND VARIANT DFNB24
RP ASN-578.
RC TISSUE=Retina;
RX PubMed=17226784; DOI=10.1002/humu.20469;
RA Khan S.Y., Ahmed Z.M., Shabbir M.I., Kitajiri S., Kalsoom S.,
RA Tasneem S., Shayiq S., Ramesh A., Srisailpathy S., Khan S.N.,
RA Smith R.J.H., Riazuddin S., Friedman T.B., Riazuddin S.;
RT "Mutations of the RDX gene cause nonsyndromic hearing loss at the
RT DFNB24 locus.";
RL Hum. Mutat. 28:417-423(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP GLU-328.
RC TISSUE=Brain;
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 [7]
RP INTERACTION WITH SLC9A3R1.
RX PubMed=9430655; DOI=10.1074/jbc.273.3.1273;
RA Murthy A., Gonzalez-Agosti C., Cordero E., Pinney D., Candia C.,
RA Solomon F., Gusella J., Ramesh V.;
RT "NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common
RT interactor for merlin and ERM (MERM) proteins.";
RL J. Biol. Chem. 273:1273-1276(1998).
RN [8]
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).
CC -!- FUNCTION: Probably plays a crucial role in the binding of the
CC barbed end of actin filaments to the plasma membrane.
CC -!- ENZYME REGULATION: A head-to-tail association, of the N-terminal
CC and C-terminal halves results in a closed conformation (inactive
CC form) which is incapable of actin or membrane-binding (By
CC similarity).
CC -!- SUBUNIT: Binds SLC9A3R1. Interacts with NHERF1, NHERF2, LAYN,
CC MME/NEP and ICAM2 (By similarity).
CC -!- INTERACTION:
CC P05107:ITGB2; NbExp=2; IntAct=EBI-2514878, EBI-300173;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein;
CC Cytoplasmic side. Cytoplasm, cytoskeleton. Cleavage furrow.
CC Note=Highly concentrated in the undercoat of the cell-to-cell
CC adherens junction and the cleavage furrow in the interphase and
CC mitotic phase, respectively.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=P35241-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P35241-2; Sequence=VSP_045315, VSP_045318;
CC Name=3;
CC IsoId=P35241-3; Sequence=VSP_045316, VSP_045317, VSP_045318;
CC Name=4;
CC IsoId=P35241-4; Sequence=VSP_047276;
CC Name=5;
CC IsoId=P35241-5; Sequence=VSP_045318;
CC -!- DOMAIN: The N-terminal domain interacts with the C-terminal domain
CC of LAYN. An interdomain interaction between its N-terminal and C-
CC terminal domains inhibits its ability to bind LAYN. In the
CC presence of acidic phospholipids, the interdomain interaction is
CC inhibited and this enhances binding to LAYN (By similarity).
CC -!- PTM: Phosphorylated by tyrosine-protein kinases. Phosphorylation
CC by ROCK2 suppresses the head-to-tail association of the N-terminal
CC and C-terminal halves resulting in an opened conformation which is
CC capable of actin and membrane-binding (By similarity).
CC -!- DISEASE: Deafness, autosomal recessive, 24 (DFNB24) [MIM:611022]:
CC A form of non-syndromic sensorineural hearing loss. Sensorineural
CC deafness results from damage to the neural receptors of the inner
CC ear, the nerve pathways to the brain, or the area of the brain
CC that receives sound information. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 1 FERM domain.
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DR EMBL; L02320; AAA36541.1; -; mRNA.
DR EMBL; AK316061; BAH14432.1; -; mRNA.
DR EMBL; DQ916738; ABI34710.1; -; mRNA.
DR EMBL; DQ916739; ABI34711.1; -; mRNA.
DR EMBL; DQ916741; ABI34713.1; -; mRNA.
DR EMBL; DQ916742; ABI34714.1; -; mRNA.
DR EMBL; DQ916740; ABI34712.1; -; mRNA.
DR EMBL; AP000901; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002788; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471065; EAW67129.1; -; Genomic_DNA.
DR EMBL; BC047109; AAH47109.1; -; mRNA.
DR PIR; A46127; A46127.
DR RefSeq; NP_001247421.1; NM_001260492.1.
DR RefSeq; NP_001247422.1; NM_001260493.1.
DR RefSeq; NP_001247423.1; NM_001260494.1.
DR RefSeq; NP_001247424.1; NM_001260495.1.
DR RefSeq; NP_001247425.1; NM_001260496.1.
DR RefSeq; NP_002897.1; NM_002906.3.
DR UniGene; Hs.263671; -.
DR UniGene; Hs.584560; -.
DR UniGene; Hs.741211; -.
DR ProteinModelPortal; P35241; -.
DR SMR; P35241; 1-583.
DR IntAct; P35241; 9.
DR MINT; MINT-1536950; -.
DR STRING; 9606.ENSP00000342830; -.
DR PhosphoSite; P35241; -.
DR DMDM; 464541; -.
DR PaxDb; P35241; -.
DR PeptideAtlas; P35241; -.
DR PRIDE; P35241; -.
DR Ensembl; ENST00000343115; ENSP00000342830; ENSG00000137710.
DR Ensembl; ENST00000405097; ENSP00000384136; ENSG00000137710.
DR Ensembl; ENST00000528498; ENSP00000432112; ENSG00000137710.
DR Ensembl; ENST00000528900; ENSP00000433580; ENSG00000137710.
DR Ensembl; ENST00000530301; ENSP00000436277; ENSG00000137710.
DR Ensembl; ENST00000530749; ENSP00000437301; ENSG00000137710.
DR Ensembl; ENST00000544551; ENSP00000445826; ENSG00000137710.
DR GeneID; 5962; -.
DR KEGG; hsa:5962; -.
DR UCSC; uc009yxy.3; human.
DR CTD; 5962; -.
DR GeneCards; GC11M110045; -.
DR HGNC; HGNC:9944; RDX.
DR HPA; HPA000263; -.
DR HPA; HPA000763; -.
DR MIM; 179410; gene.
DR MIM; 611022; phenotype.
DR neXtProt; NX_P35241; -.
DR Orphanet; 90636; Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
DR PharmGKB; PA34311; -.
DR eggNOG; NOG236035; -.
DR HOGENOM; HOG000007113; -.
DR HOVERGEN; HBG002185; -.
DR InParanoid; P35241; -.
DR KO; K05762; -.
DR OMA; SDGVMNH; -.
DR OrthoDB; EOG7BGHK6; -.
DR PhylomeDB; P35241; -.
DR Reactome; REACT_111045; Developmental Biology.
DR ChiTaRS; RDX; human.
DR GeneWiki; Radixin; -.
DR GenomeRNAi; 5962; -.
DR NextBio; 23212; -.
DR PRO; PR:P35241; -.
DR ArrayExpress; P35241; -.
DR Bgee; P35241; -.
DR CleanEx; HS_RDX; -.
DR Genevestigator; P35241; -.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0032154; C:cleavage furrow; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0019898; C:extrinsic to membrane; IEA:InterPro.
DR GO; GO:0030175; C:filopodium; IEA:Ensembl.
DR GO; GO:0030027; C:lamellipodium; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001726; C:ruffle; IEA:Ensembl.
DR GO; GO:0032420; C:stereocilium; IEA:Ensembl.
DR GO; GO:0051693; P:actin filament capping; IEA:UniProtKB-KW.
DR GO; GO:0045176; P:apical protein localization; IEA:Ensembl.
DR GO; GO:0030033; P:microvillus assembly; IEA:Ensembl.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR019750; Band_41_fam.
DR InterPro; IPR011174; ERM.
DR InterPro; IPR011259; ERM_C_dom.
DR InterPro; IPR000798; Ez/rad/moesin_like.
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; IPR008954; Moesin_tail.
DR InterPro; IPR011993; PH_like_dom.
DR Pfam; PF00769; ERM; 1.
DR Pfam; PF09380; FERM_C; 1.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF09379; FERM_N; 1.
DR PIRSF; PIRSF002305; ERM; 1.
DR PRINTS; PR00935; BAND41.
DR PRINTS; PR00661; ERMFAMILY.
DR SMART; SM00295; B41; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR SUPFAM; SSF48678; SSF48678; 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 Actin capping; Actin-binding; Alternative splicing; Cell membrane;
KW Complete proteome; Cytoplasm; Cytoskeleton; Deafness;
KW Disease mutation; Membrane; Non-syndromic deafness; Phosphoprotein;
KW Polymorphism; Reference proteome.
FT CHAIN 1 583 Radixin.
FT /FTId=PRO_0000219421.
FT DOMAIN 5 295 FERM.
FT REGION 60 63 Phosphatidylinositol binding (By
FT similarity).
FT COMPBIAS 311 522 Glu-rich.
FT COMPBIAS 470 477 Poly-Pro.
FT BINDING 278 278 Phosphatidylinositol (By similarity).
FT MOD_RES 564 564 Phosphothreonine; by ROCK2 (By
FT similarity).
FT VAR_SEQ 1 347 Missing (in isoform 2).
FT /FTId=VSP_045315.
FT VAR_SEQ 1 156 MPKPINVRVTTMDAELEFAIQPNTTGKQLFDQVVKTVGLRE
FT VWFFGLQYVDSKGYSTWLKLNKKVTQQDVKKENPLQFKFRA
FT KFFPEDVSEELIQEITQRLFFLQVKEAILNDEIYCPPETAV
FT LLASYAVQAKYGDYNKEIHKPGYLANDRLLPQR -> MLSW
FT NLPFSPIQLANNFLTS (in isoform 4).
FT /FTId=VSP_047276.
FT VAR_SEQ 33 64 Missing (in isoform 3).
FT /FTId=VSP_045316.
FT VAR_SEQ 168 539 Missing (in isoform 3).
FT /FTId=VSP_045317.
FT VAR_SEQ 583 583 M -> MWGPKLYALFQMRSCQSSIKQM (in isoform
FT 2, isoform 3 and isoform 5).
FT /FTId=VSP_045318.
FT VARIANT 328 328 K -> E (in dbSNP:rs17854427).
FT /FTId=VAR_036857.
FT VARIANT 490 490 D -> N (in dbSNP:rs34471100).
FT /FTId=VAR_036858.
FT VARIANT 578 578 D -> N (in DFNB24).
FT /FTId=VAR_036859.
FT CONFLICT 435 435 K -> R (in Ref. 2; BAH14432).
SQ SEQUENCE 583 AA; 68564 MW; 889687E1D675FFE7 CRC64;
MPKPINVRVT TMDAELEFAI QPNTTGKQLF DQVVKTVGLR EVWFFGLQYV DSKGYSTWLK
LNKKVTQQDV KKENPLQFKF RAKFFPEDVS EELIQEITQR LFFLQVKEAI LNDEIYCPPE
TAVLLASYAV QAKYGDYNKE IHKPGYLAND RLLPQRVLEQ HKLTKEQWEE RIQNWHEEHR
GMLREDSMME YLKIAQDLEM YGVNYFEIKN KKGTELWLGV DALGLNIYEH DDKLTPKIGF
PWSEIRNISF NDKKFVIKPI DKKAPDFVFY APRLRINKRI LALCMGNHEL YMRRRKPDTI
EVQQMKAQAR EEKHQKQLER AQLENEKKKR EIAEKEKERI EREKEELMER LKQIEEQTIK
AQKELEEQTR KALELDQERK RAKEEAERLE KERRAAEEAK SAIAKQAADQ MKNQEQLAAE
LAEFTAKIAL LEEAKKKKEE EATEWQHKAF AAQEDLEKTK EELKTVMSAP PPPPPPPVIP
PTENEHDEHD ENNAEASAEL SNEGVMNHRS EEERVTETQK NERVKKQLQA LSSELAQARD
ETKKTQNDVL HAENVKAGRD KYKTLRQIRQ GNTKQRIDEF EAM
//
ID RADI_HUMAN Reviewed; 583 AA.
AC P35241; A7YIJ8; A7YIK0; A7YIK3; B7Z9U6; F5H1A7; Q86Y61;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1994, sequence version 1.
DT 22-JAN-2014, entry version 129.
DE RecName: Full=Radixin;
GN Name=RDX;
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 1).
RC TISSUE=Liver;
RX PubMed=8486357; DOI=10.1006/geno.1993.1159;
RA Wilgenbus K.K., Milatovich A., Francke U., Furthmayr H.;
RT "Molecular cloning, cDNA sequence, and chromosomal assignment of the
RT human radixin gene and two dispersed pseudogenes.";
RL Genomics 16:199-206(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 5), AND VARIANT DFNB24
RP ASN-578.
RC TISSUE=Retina;
RX PubMed=17226784; DOI=10.1002/humu.20469;
RA Khan S.Y., Ahmed Z.M., Shabbir M.I., Kitajiri S., Kalsoom S.,
RA Tasneem S., Shayiq S., Ramesh A., Srisailpathy S., Khan S.N.,
RA Smith R.J.H., Riazuddin S., Friedman T.B., Riazuddin S.;
RT "Mutations of the RDX gene cause nonsyndromic hearing loss at the
RT DFNB24 locus.";
RL Hum. Mutat. 28:417-423(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP GLU-328.
RC TISSUE=Brain;
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 [7]
RP INTERACTION WITH SLC9A3R1.
RX PubMed=9430655; DOI=10.1074/jbc.273.3.1273;
RA Murthy A., Gonzalez-Agosti C., Cordero E., Pinney D., Candia C.,
RA Solomon F., Gusella J., Ramesh V.;
RT "NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common
RT interactor for merlin and ERM (MERM) proteins.";
RL J. Biol. Chem. 273:1273-1276(1998).
RN [8]
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).
CC -!- FUNCTION: Probably plays a crucial role in the binding of the
CC barbed end of actin filaments to the plasma membrane.
CC -!- ENZYME REGULATION: A head-to-tail association, of the N-terminal
CC and C-terminal halves results in a closed conformation (inactive
CC form) which is incapable of actin or membrane-binding (By
CC similarity).
CC -!- SUBUNIT: Binds SLC9A3R1. Interacts with NHERF1, NHERF2, LAYN,
CC MME/NEP and ICAM2 (By similarity).
CC -!- INTERACTION:
CC P05107:ITGB2; NbExp=2; IntAct=EBI-2514878, EBI-300173;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein;
CC Cytoplasmic side. Cytoplasm, cytoskeleton. Cleavage furrow.
CC Note=Highly concentrated in the undercoat of the cell-to-cell
CC adherens junction and the cleavage furrow in the interphase and
CC mitotic phase, respectively.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=P35241-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P35241-2; Sequence=VSP_045315, VSP_045318;
CC Name=3;
CC IsoId=P35241-3; Sequence=VSP_045316, VSP_045317, VSP_045318;
CC Name=4;
CC IsoId=P35241-4; Sequence=VSP_047276;
CC Name=5;
CC IsoId=P35241-5; Sequence=VSP_045318;
CC -!- DOMAIN: The N-terminal domain interacts with the C-terminal domain
CC of LAYN. An interdomain interaction between its N-terminal and C-
CC terminal domains inhibits its ability to bind LAYN. In the
CC presence of acidic phospholipids, the interdomain interaction is
CC inhibited and this enhances binding to LAYN (By similarity).
CC -!- PTM: Phosphorylated by tyrosine-protein kinases. Phosphorylation
CC by ROCK2 suppresses the head-to-tail association of the N-terminal
CC and C-terminal halves resulting in an opened conformation which is
CC capable of actin and membrane-binding (By similarity).
CC -!- DISEASE: Deafness, autosomal recessive, 24 (DFNB24) [MIM:611022]:
CC A form of non-syndromic sensorineural hearing loss. Sensorineural
CC deafness results from damage to the neural receptors of the inner
CC ear, the nerve pathways to the brain, or the area of the brain
CC that receives sound information. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 1 FERM domain.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; L02320; AAA36541.1; -; mRNA.
DR EMBL; AK316061; BAH14432.1; -; mRNA.
DR EMBL; DQ916738; ABI34710.1; -; mRNA.
DR EMBL; DQ916739; ABI34711.1; -; mRNA.
DR EMBL; DQ916741; ABI34713.1; -; mRNA.
DR EMBL; DQ916742; ABI34714.1; -; mRNA.
DR EMBL; DQ916740; ABI34712.1; -; mRNA.
DR EMBL; AP000901; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002788; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471065; EAW67129.1; -; Genomic_DNA.
DR EMBL; BC047109; AAH47109.1; -; mRNA.
DR PIR; A46127; A46127.
DR RefSeq; NP_001247421.1; NM_001260492.1.
DR RefSeq; NP_001247422.1; NM_001260493.1.
DR RefSeq; NP_001247423.1; NM_001260494.1.
DR RefSeq; NP_001247424.1; NM_001260495.1.
DR RefSeq; NP_001247425.1; NM_001260496.1.
DR RefSeq; NP_002897.1; NM_002906.3.
DR UniGene; Hs.263671; -.
DR UniGene; Hs.584560; -.
DR UniGene; Hs.741211; -.
DR ProteinModelPortal; P35241; -.
DR SMR; P35241; 1-583.
DR IntAct; P35241; 9.
DR MINT; MINT-1536950; -.
DR STRING; 9606.ENSP00000342830; -.
DR PhosphoSite; P35241; -.
DR DMDM; 464541; -.
DR PaxDb; P35241; -.
DR PeptideAtlas; P35241; -.
DR PRIDE; P35241; -.
DR Ensembl; ENST00000343115; ENSP00000342830; ENSG00000137710.
DR Ensembl; ENST00000405097; ENSP00000384136; ENSG00000137710.
DR Ensembl; ENST00000528498; ENSP00000432112; ENSG00000137710.
DR Ensembl; ENST00000528900; ENSP00000433580; ENSG00000137710.
DR Ensembl; ENST00000530301; ENSP00000436277; ENSG00000137710.
DR Ensembl; ENST00000530749; ENSP00000437301; ENSG00000137710.
DR Ensembl; ENST00000544551; ENSP00000445826; ENSG00000137710.
DR GeneID; 5962; -.
DR KEGG; hsa:5962; -.
DR UCSC; uc009yxy.3; human.
DR CTD; 5962; -.
DR GeneCards; GC11M110045; -.
DR HGNC; HGNC:9944; RDX.
DR HPA; HPA000263; -.
DR HPA; HPA000763; -.
DR MIM; 179410; gene.
DR MIM; 611022; phenotype.
DR neXtProt; NX_P35241; -.
DR Orphanet; 90636; Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
DR PharmGKB; PA34311; -.
DR eggNOG; NOG236035; -.
DR HOGENOM; HOG000007113; -.
DR HOVERGEN; HBG002185; -.
DR InParanoid; P35241; -.
DR KO; K05762; -.
DR OMA; SDGVMNH; -.
DR OrthoDB; EOG7BGHK6; -.
DR PhylomeDB; P35241; -.
DR Reactome; REACT_111045; Developmental Biology.
DR ChiTaRS; RDX; human.
DR GeneWiki; Radixin; -.
DR GenomeRNAi; 5962; -.
DR NextBio; 23212; -.
DR PRO; PR:P35241; -.
DR ArrayExpress; P35241; -.
DR Bgee; P35241; -.
DR CleanEx; HS_RDX; -.
DR Genevestigator; P35241; -.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0032154; C:cleavage furrow; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0019898; C:extrinsic to membrane; IEA:InterPro.
DR GO; GO:0030175; C:filopodium; IEA:Ensembl.
DR GO; GO:0030027; C:lamellipodium; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001726; C:ruffle; IEA:Ensembl.
DR GO; GO:0032420; C:stereocilium; IEA:Ensembl.
DR GO; GO:0051693; P:actin filament capping; IEA:UniProtKB-KW.
DR GO; GO:0045176; P:apical protein localization; IEA:Ensembl.
DR GO; GO:0030033; P:microvillus assembly; IEA:Ensembl.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR019750; Band_41_fam.
DR InterPro; IPR011174; ERM.
DR InterPro; IPR011259; ERM_C_dom.
DR InterPro; IPR000798; Ez/rad/moesin_like.
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; IPR008954; Moesin_tail.
DR InterPro; IPR011993; PH_like_dom.
DR Pfam; PF00769; ERM; 1.
DR Pfam; PF09380; FERM_C; 1.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF09379; FERM_N; 1.
DR PIRSF; PIRSF002305; ERM; 1.
DR PRINTS; PR00935; BAND41.
DR PRINTS; PR00661; ERMFAMILY.
DR SMART; SM00295; B41; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR SUPFAM; SSF48678; SSF48678; 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 Actin capping; Actin-binding; Alternative splicing; Cell membrane;
KW Complete proteome; Cytoplasm; Cytoskeleton; Deafness;
KW Disease mutation; Membrane; Non-syndromic deafness; Phosphoprotein;
KW Polymorphism; Reference proteome.
FT CHAIN 1 583 Radixin.
FT /FTId=PRO_0000219421.
FT DOMAIN 5 295 FERM.
FT REGION 60 63 Phosphatidylinositol binding (By
FT similarity).
FT COMPBIAS 311 522 Glu-rich.
FT COMPBIAS 470 477 Poly-Pro.
FT BINDING 278 278 Phosphatidylinositol (By similarity).
FT MOD_RES 564 564 Phosphothreonine; by ROCK2 (By
FT similarity).
FT VAR_SEQ 1 347 Missing (in isoform 2).
FT /FTId=VSP_045315.
FT VAR_SEQ 1 156 MPKPINVRVTTMDAELEFAIQPNTTGKQLFDQVVKTVGLRE
FT VWFFGLQYVDSKGYSTWLKLNKKVTQQDVKKENPLQFKFRA
FT KFFPEDVSEELIQEITQRLFFLQVKEAILNDEIYCPPETAV
FT LLASYAVQAKYGDYNKEIHKPGYLANDRLLPQR -> MLSW
FT NLPFSPIQLANNFLTS (in isoform 4).
FT /FTId=VSP_047276.
FT VAR_SEQ 33 64 Missing (in isoform 3).
FT /FTId=VSP_045316.
FT VAR_SEQ 168 539 Missing (in isoform 3).
FT /FTId=VSP_045317.
FT VAR_SEQ 583 583 M -> MWGPKLYALFQMRSCQSSIKQM (in isoform
FT 2, isoform 3 and isoform 5).
FT /FTId=VSP_045318.
FT VARIANT 328 328 K -> E (in dbSNP:rs17854427).
FT /FTId=VAR_036857.
FT VARIANT 490 490 D -> N (in dbSNP:rs34471100).
FT /FTId=VAR_036858.
FT VARIANT 578 578 D -> N (in DFNB24).
FT /FTId=VAR_036859.
FT CONFLICT 435 435 K -> R (in Ref. 2; BAH14432).
SQ SEQUENCE 583 AA; 68564 MW; 889687E1D675FFE7 CRC64;
MPKPINVRVT TMDAELEFAI QPNTTGKQLF DQVVKTVGLR EVWFFGLQYV DSKGYSTWLK
LNKKVTQQDV KKENPLQFKF RAKFFPEDVS EELIQEITQR LFFLQVKEAI LNDEIYCPPE
TAVLLASYAV QAKYGDYNKE IHKPGYLAND RLLPQRVLEQ HKLTKEQWEE RIQNWHEEHR
GMLREDSMME YLKIAQDLEM YGVNYFEIKN KKGTELWLGV DALGLNIYEH DDKLTPKIGF
PWSEIRNISF NDKKFVIKPI DKKAPDFVFY APRLRINKRI LALCMGNHEL YMRRRKPDTI
EVQQMKAQAR EEKHQKQLER AQLENEKKKR EIAEKEKERI EREKEELMER LKQIEEQTIK
AQKELEEQTR KALELDQERK RAKEEAERLE KERRAAEEAK SAIAKQAADQ MKNQEQLAAE
LAEFTAKIAL LEEAKKKKEE EATEWQHKAF AAQEDLEKTK EELKTVMSAP PPPPPPPVIP
PTENEHDEHD ENNAEASAEL SNEGVMNHRS EEERVTETQK NERVKKQLQA LSSELAQARD
ETKKTQNDVL HAENVKAGRD KYKTLRQIRQ GNTKQRIDEF EAM
//
MIM
179410
*RECORD*
*FIELD* NO
179410
*FIELD* TI
*179410 RADIXIN; RDX
*FIELD* TX
CLONING
Radixin is a cytoskeletal protein that may be important in linking actin
read moreto the plasma membrane. Cloning of the murine and porcine radixin cDNAs
demonstrated a protein highly homologous to ezrin (123900) and moesin
(309845). Wilgenbus et al. (1993) cloned and sequenced the human radixin
cDNA and found the predicted amino acid sequence for the human protein
to be nearly identical to those predicted for radixin in the two other
species.
By immunocytochemical analysis of isolated inner ear hair cells, Pataky
et al. (2004) demonstrated that radixin is expressed at the base of hair
bundles in chicken, frog, mouse, and zebrafish. Electron microscopic
analysis found labeling in the stereociliary taper and the lower
stereociliary shaft, with progressively less labeling toward the top of
the hair bundle. Pataky et al. (2004) concluded that radixin may
participate in anchoring the 'pointed' ends of actin filaments to the
membrane in stereocilia.
Khan et al. (2007) identified 6 alternatively spliced RDX isoforms in
human retina and inner eye. The major full-length protein contains 627
amino acids forming 3 known functional domains: an N-terminal FERM
domain that localizes the protein to the plasma membrane, a central
helical alpha-domain, and a C-terminal actin-binding domain. By
immunohistochemical analysis of mouse inner ear, Khan et al. (2007)
confirmed the localization of radixin along the length of cochlear hair
cell stereocilia and in hair cells of the crista ampullaris at postnatal
day 30.
GENE FUNCTION
Using antigen-activated T cells, Faure et al. (2004) showed that the
ezrin-radixin-moesin (ERM) proteins are rapidly inactivated through a
VAV1 (164875)-RAC1 (602048) pathway. The resulting disanchoring of the
cortical actin cytoskeleton from the plasma membrane decreased cellular
rigidity, leading to more efficient T cell-APC (antigen-presenting cell)
conjugate formation. The authors concluded that this pathway favors
immunologic synapse formation and the development of an effective immune
response.
MAPPING
Wilgenbus et al. (1993) used PCR of Chinese hamster/human somatic cell
hybrid DNAs, as well as standard Southern analysis of somatic cell
hybrids, to assign the RDX gene to 11q. By fluorescence in situ
hybridization, they further localized the gene to 11q23.
- Pseudogenes
Wilgenbus et al. (1993) assigned a truncated version of the RDX gene
representing a pseudogene (RDXP2) was assigned to Xp21.3. Another
pseudogene that seemed to lack introns (RDXP1) was mapped to 11p by
Southern and PCR analyses.
MOLECULAR GENETICS
Khan et al. (2007) identified 3 respective pathogenic mutations in the
RDX gene (179410.0001-179410.0003) in affected members of 3 Pakistani
families with autosomal recessive deafness-24 (DFNB24; 611022). The
mutations were predicted to disrupt or delete the actin-binding domain
of the protein. None of the affected individuals had vestibular
dysfunction or hyperbilirubinemia.
ANIMAL MODEL
The ERM family of proteins crosslink actin filaments and integral
membrane proteins. Radixin is the dominant ERM protein in the liver of
wildtype mice and is concentrated at bile canalicular membranes (BCM).
Kikuchi et al. (2002) showed that Rdx -/- mice are normal at birth, but
their serum concentrations of conjugated bilirubin begin to increase
gradually around 4 weeks of age, and they show mild liver injury after 8
weeks. This phenotype is similar to human conjugated hyperbilirubinemia
in Dubin-Johnson syndrome (237500), which is caused by mutations in the
ABCC2 gene (601107), although Dubin-Johnson syndrome is not associated
with overt liver injury. In wildtype mice, the protein product of the
ABCC2 gene, multidrug resistance protein-2, or MRP2, concentrates at
BCMs to secrete conjugated bilirubin into bile. In the BCMs of Rdx -/-
mice, Mrp2 is decreased compared with other BCM proteins such as
dipeptidyl peptidase IV (CD26; 102720) and P-glycoproteins. In vitro
binding studies showed that radixin associates directly with the
C-terminal cytoplasmic domain of human MRP2. These findings indicated
that radixin is required for secretion of conjugated bilirubin through
its support of Mrp2 localization at BCMs.
In the adult mouse, Kitajiri et al. (2004) demonstrated that radixin was
enriched in stereocilia of cochlear and vestibular sensory hair cells.
Rdx-null mice adult mice were deaf but had no obvious vestibular
dysfunction. As the Rdx-null mice grew, ezrin-based cochlear stereocilia
progressively degenerated, whereas ezrin-based vestibular stereocilia
were maintained normally. Kitajiri et al. (2004) concluded that radixin
is indispensable for hearing ability in mice through the maintenance of
cochlear stereocilia, but that ezrin can compensate for radixin
deficiency in vestibular stereocilia.
*FIELD* AV
.0001
DEAFNESS, AUTOSOMAL RECESSIVE, 24
RDX, ASP578ASN
In 2 affected sisters from a consanguineous Pakistani family with
autosomal recessive deafness-24 (DFNB24; 611022), Khan et al. (2007)
identified a homozygous 1732G-A transition in exon 14 of the RDX gene,
resulting in an asp578-to-asn (D578N) substitution predicted to disrupt
the actin binding domain of radixin. The mutation was not identified in
200 ethnically matched chromosomes.
.0002
DEAFNESS, AUTOSOMAL RECESSIVE, 24
RDX, 1-BP INS, 1404G
In 4 affected members of a consanguineous Pakistani family with DFNB24
(611022), Khan et al. (2007) identified a homozygous 1-bp insertion
(1404insG) in exon 13 of the RDX gene, resulting in a frameshift and a
truncated protein of 486 amino acids that would lack the actin-binding
domain. The mutation was not identified in 200 ethnically matched
chromosomes.
.0003
DEAFNESS, AUTOSOMAL RECESSIVE, 24
RDX, GLN155TER
In affected members of a family with DFNB24 (611022), Khan et al. (2007)
identified a homozygous 463C-T transition in exon 5 of the RDX gene,
resulting in a gln155-to-ter (Q155X) substitution in the FERM domain.
The mutation was not identified in 200 ethnically matched chromosomes.
.0004
DEAFNESS, AUTOSOMAL RECESSIVE, 24
RDX, IVS7DS, G-A, +1
In 4 affected members of a consanguineous Iranian family with DFNB24
(611022), Shearer et al. (2009) identified a homozygous G-to-A
transition in intron 7 of the RDX gene (689+1G-A), predicted to result
in premature termination following exon 7 or nonsense-mediated mRNA
decay. Affected individuals had congenital onset of severe to profound
hearing loss. The mutation was not identified in 53 Iranian and 133
European controls.
*FIELD* RF
1. Faure, S.; Salazar-Fontana, L. I.; Semichon, M.; Tybulewicz, V.
L. J.; Bismuth, G.; Trautmann, A.; Germain, R. N.; Delon, J.: ERM
proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation. Nature
Immun. 5: 272-279, 2004.
2. Khan, S. Y.; Ahmed, Z. M.; Shabbir, M. I.; Kitajiri, S.; Kalsoom,
S.; Tasneem, S.; Shayiq, S.; Ramesh, A.; Srisailpathy, S.; Khan, S.
N.; Smith, R. J. H.; Riazuddin, S.; Friedman, T. B.; Riazuddin, S.
: Mutations of the RDX gene cause nonsyndromic hearing loss at the
DFNB24 locus. Hum. Mutat. 28: 417-423, 2007.
3. Kikuchi, S.; Hata, M.; Fukumoto, K.; Yamane, Y.; Matsui, T.; Tamura,
A.; Yonemura, S.; Yamagishi, H.; Keppler, D.; Tsukita, S.; Tsukita,
S.: Radixin deficiency causes conjugated hyperbilirubinemia with
loss of Mrp2 from bile canalicular membranes. Nature Genet. 31:
320-325, 2002.
4. Kitajiri, S.; Fukumoto, K.; Hata, M.; Sasaki, H.; Katsuno, T.;
Nakagawa, T.; Ito, J.; Tsukita, S.; Tsukita, S.: Radixin deficiency
causes deafness associated with progressive degeneration of cochlear
stereocilia. J. Cell Biol. 166: 559-570, 2004.
5. Pataky, F.; Pironkova, R.; Hudspeth, A. J.: Radixin is a constituent
of stereocilia in hair cells. Proc. Nat. Acad. Sci. 101: 2601-2606,
2004.
6. Shearer, A. E.; Hildebrand, M. S.; Bromhead, C. J.; Kahrizi, K.;
Webster, J. A.; Azadeh, B.; Kimberling, W. J.; Anousheh, A.; Nazeri,
A.; Stephan, D.; Najmabadi, H.; Smith, R. J. H.; Bahlo, M.: A novel
splice site mutation in the RDX gene causes DFNB24 hearing loss in
an Iranian family. (Letter) Am. J. Med. Genet. 149A: 555-558, 2009.
7. Wilgenbus, K. K.; Milatovich, A.; Francke, U.; Furthmayr, H.:
Molecular cloning, cDNA sequence, and chromosomal assignment of the
human radixin gene and two dispersed pseudogenes. Genomics 16: 199-206,
1993.
*FIELD* CN
Cassandra L. Kniffin - updated: 5/14/2007
Patricia A. Hartz - updated: 3/16/2004
Paul J. Converse - updated: 2/13/2004
Victor A. McKusick - updated: 6/18/2002
*FIELD* CD
Victor A. McKusick: 5/4/1993
*FIELD* ED
carol: 09/17/2013
wwang: 2/18/2010
ckniffin: 2/8/2010
wwang: 6/7/2007
ckniffin: 5/14/2007
mgross: 3/24/2004
terry: 3/16/2004
alopez: 3/1/2004
mgross: 2/13/2004
alopez: 7/25/2002
alopez: 6/20/2002
terry: 6/18/2002
carol: 4/15/1994
carol: 5/4/1993
*RECORD*
*FIELD* NO
179410
*FIELD* TI
*179410 RADIXIN; RDX
*FIELD* TX
CLONING
Radixin is a cytoskeletal protein that may be important in linking actin
read moreto the plasma membrane. Cloning of the murine and porcine radixin cDNAs
demonstrated a protein highly homologous to ezrin (123900) and moesin
(309845). Wilgenbus et al. (1993) cloned and sequenced the human radixin
cDNA and found the predicted amino acid sequence for the human protein
to be nearly identical to those predicted for radixin in the two other
species.
By immunocytochemical analysis of isolated inner ear hair cells, Pataky
et al. (2004) demonstrated that radixin is expressed at the base of hair
bundles in chicken, frog, mouse, and zebrafish. Electron microscopic
analysis found labeling in the stereociliary taper and the lower
stereociliary shaft, with progressively less labeling toward the top of
the hair bundle. Pataky et al. (2004) concluded that radixin may
participate in anchoring the 'pointed' ends of actin filaments to the
membrane in stereocilia.
Khan et al. (2007) identified 6 alternatively spliced RDX isoforms in
human retina and inner eye. The major full-length protein contains 627
amino acids forming 3 known functional domains: an N-terminal FERM
domain that localizes the protein to the plasma membrane, a central
helical alpha-domain, and a C-terminal actin-binding domain. By
immunohistochemical analysis of mouse inner ear, Khan et al. (2007)
confirmed the localization of radixin along the length of cochlear hair
cell stereocilia and in hair cells of the crista ampullaris at postnatal
day 30.
GENE FUNCTION
Using antigen-activated T cells, Faure et al. (2004) showed that the
ezrin-radixin-moesin (ERM) proteins are rapidly inactivated through a
VAV1 (164875)-RAC1 (602048) pathway. The resulting disanchoring of the
cortical actin cytoskeleton from the plasma membrane decreased cellular
rigidity, leading to more efficient T cell-APC (antigen-presenting cell)
conjugate formation. The authors concluded that this pathway favors
immunologic synapse formation and the development of an effective immune
response.
MAPPING
Wilgenbus et al. (1993) used PCR of Chinese hamster/human somatic cell
hybrid DNAs, as well as standard Southern analysis of somatic cell
hybrids, to assign the RDX gene to 11q. By fluorescence in situ
hybridization, they further localized the gene to 11q23.
- Pseudogenes
Wilgenbus et al. (1993) assigned a truncated version of the RDX gene
representing a pseudogene (RDXP2) was assigned to Xp21.3. Another
pseudogene that seemed to lack introns (RDXP1) was mapped to 11p by
Southern and PCR analyses.
MOLECULAR GENETICS
Khan et al. (2007) identified 3 respective pathogenic mutations in the
RDX gene (179410.0001-179410.0003) in affected members of 3 Pakistani
families with autosomal recessive deafness-24 (DFNB24; 611022). The
mutations were predicted to disrupt or delete the actin-binding domain
of the protein. None of the affected individuals had vestibular
dysfunction or hyperbilirubinemia.
ANIMAL MODEL
The ERM family of proteins crosslink actin filaments and integral
membrane proteins. Radixin is the dominant ERM protein in the liver of
wildtype mice and is concentrated at bile canalicular membranes (BCM).
Kikuchi et al. (2002) showed that Rdx -/- mice are normal at birth, but
their serum concentrations of conjugated bilirubin begin to increase
gradually around 4 weeks of age, and they show mild liver injury after 8
weeks. This phenotype is similar to human conjugated hyperbilirubinemia
in Dubin-Johnson syndrome (237500), which is caused by mutations in the
ABCC2 gene (601107), although Dubin-Johnson syndrome is not associated
with overt liver injury. In wildtype mice, the protein product of the
ABCC2 gene, multidrug resistance protein-2, or MRP2, concentrates at
BCMs to secrete conjugated bilirubin into bile. In the BCMs of Rdx -/-
mice, Mrp2 is decreased compared with other BCM proteins such as
dipeptidyl peptidase IV (CD26; 102720) and P-glycoproteins. In vitro
binding studies showed that radixin associates directly with the
C-terminal cytoplasmic domain of human MRP2. These findings indicated
that radixin is required for secretion of conjugated bilirubin through
its support of Mrp2 localization at BCMs.
In the adult mouse, Kitajiri et al. (2004) demonstrated that radixin was
enriched in stereocilia of cochlear and vestibular sensory hair cells.
Rdx-null mice adult mice were deaf but had no obvious vestibular
dysfunction. As the Rdx-null mice grew, ezrin-based cochlear stereocilia
progressively degenerated, whereas ezrin-based vestibular stereocilia
were maintained normally. Kitajiri et al. (2004) concluded that radixin
is indispensable for hearing ability in mice through the maintenance of
cochlear stereocilia, but that ezrin can compensate for radixin
deficiency in vestibular stereocilia.
*FIELD* AV
.0001
DEAFNESS, AUTOSOMAL RECESSIVE, 24
RDX, ASP578ASN
In 2 affected sisters from a consanguineous Pakistani family with
autosomal recessive deafness-24 (DFNB24; 611022), Khan et al. (2007)
identified a homozygous 1732G-A transition in exon 14 of the RDX gene,
resulting in an asp578-to-asn (D578N) substitution predicted to disrupt
the actin binding domain of radixin. The mutation was not identified in
200 ethnically matched chromosomes.
.0002
DEAFNESS, AUTOSOMAL RECESSIVE, 24
RDX, 1-BP INS, 1404G
In 4 affected members of a consanguineous Pakistani family with DFNB24
(611022), Khan et al. (2007) identified a homozygous 1-bp insertion
(1404insG) in exon 13 of the RDX gene, resulting in a frameshift and a
truncated protein of 486 amino acids that would lack the actin-binding
domain. The mutation was not identified in 200 ethnically matched
chromosomes.
.0003
DEAFNESS, AUTOSOMAL RECESSIVE, 24
RDX, GLN155TER
In affected members of a family with DFNB24 (611022), Khan et al. (2007)
identified a homozygous 463C-T transition in exon 5 of the RDX gene,
resulting in a gln155-to-ter (Q155X) substitution in the FERM domain.
The mutation was not identified in 200 ethnically matched chromosomes.
.0004
DEAFNESS, AUTOSOMAL RECESSIVE, 24
RDX, IVS7DS, G-A, +1
In 4 affected members of a consanguineous Iranian family with DFNB24
(611022), Shearer et al. (2009) identified a homozygous G-to-A
transition in intron 7 of the RDX gene (689+1G-A), predicted to result
in premature termination following exon 7 or nonsense-mediated mRNA
decay. Affected individuals had congenital onset of severe to profound
hearing loss. The mutation was not identified in 53 Iranian and 133
European controls.
*FIELD* RF
1. Faure, S.; Salazar-Fontana, L. I.; Semichon, M.; Tybulewicz, V.
L. J.; Bismuth, G.; Trautmann, A.; Germain, R. N.; Delon, J.: ERM
proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation. Nature
Immun. 5: 272-279, 2004.
2. Khan, S. Y.; Ahmed, Z. M.; Shabbir, M. I.; Kitajiri, S.; Kalsoom,
S.; Tasneem, S.; Shayiq, S.; Ramesh, A.; Srisailpathy, S.; Khan, S.
N.; Smith, R. J. H.; Riazuddin, S.; Friedman, T. B.; Riazuddin, S.
: Mutations of the RDX gene cause nonsyndromic hearing loss at the
DFNB24 locus. Hum. Mutat. 28: 417-423, 2007.
3. Kikuchi, S.; Hata, M.; Fukumoto, K.; Yamane, Y.; Matsui, T.; Tamura,
A.; Yonemura, S.; Yamagishi, H.; Keppler, D.; Tsukita, S.; Tsukita,
S.: Radixin deficiency causes conjugated hyperbilirubinemia with
loss of Mrp2 from bile canalicular membranes. Nature Genet. 31:
320-325, 2002.
4. Kitajiri, S.; Fukumoto, K.; Hata, M.; Sasaki, H.; Katsuno, T.;
Nakagawa, T.; Ito, J.; Tsukita, S.; Tsukita, S.: Radixin deficiency
causes deafness associated with progressive degeneration of cochlear
stereocilia. J. Cell Biol. 166: 559-570, 2004.
5. Pataky, F.; Pironkova, R.; Hudspeth, A. J.: Radixin is a constituent
of stereocilia in hair cells. Proc. Nat. Acad. Sci. 101: 2601-2606,
2004.
6. Shearer, A. E.; Hildebrand, M. S.; Bromhead, C. J.; Kahrizi, K.;
Webster, J. A.; Azadeh, B.; Kimberling, W. J.; Anousheh, A.; Nazeri,
A.; Stephan, D.; Najmabadi, H.; Smith, R. J. H.; Bahlo, M.: A novel
splice site mutation in the RDX gene causes DFNB24 hearing loss in
an Iranian family. (Letter) Am. J. Med. Genet. 149A: 555-558, 2009.
7. Wilgenbus, K. K.; Milatovich, A.; Francke, U.; Furthmayr, H.:
Molecular cloning, cDNA sequence, and chromosomal assignment of the
human radixin gene and two dispersed pseudogenes. Genomics 16: 199-206,
1993.
*FIELD* CN
Cassandra L. Kniffin - updated: 5/14/2007
Patricia A. Hartz - updated: 3/16/2004
Paul J. Converse - updated: 2/13/2004
Victor A. McKusick - updated: 6/18/2002
*FIELD* CD
Victor A. McKusick: 5/4/1993
*FIELD* ED
carol: 09/17/2013
wwang: 2/18/2010
ckniffin: 2/8/2010
wwang: 6/7/2007
ckniffin: 5/14/2007
mgross: 3/24/2004
terry: 3/16/2004
alopez: 3/1/2004
mgross: 2/13/2004
alopez: 7/25/2002
alopez: 6/20/2002
terry: 6/18/2002
carol: 4/15/1994
carol: 5/4/1993
MIM
611022
*RECORD*
*FIELD* NO
611022
*FIELD* TI
#611022 DEAFNESS, AUTOSOMAL RECESSIVE 24; DFNB24
*FIELD* TX
A number sign (#) is used with this entry because autosomal recessive
read morenonsyndromic deafness-24 (DFNB24) is caused by mutation in the gene
encoding radixin (RDX; 179410).
CLINICAL FEATURES
Khan et al. (2007) reported 3 Pakistani families with isolated autosomal
recessive sensorineural deafness, Two of the families were known to be
consanguineous. The deafness showed prelingual onset and was bilateral
and profound. None of the affected individuals had vestibular
dysfunction or hyperbilirubinemia.
Shearer et al. (2009) reported a consanguineous Iranian family with
DFNB24. Affected individuals had congenital onset of severe to profound
hearing loss and no evidence of liver dysfunction.
MOLECULAR GENETICS
In affected members of 3 Pakistani families with isolated autosomal
recessive sensorineural deafness, Khan et al. (2007) identified 3
respective homozygous mutations in the RDX gene
(179410.0001-179410.0003).
In 4 affected members of a consanguineous Iranian family with DFNB24,
Shearer et al. (2009) identified a homozygous splice site mutation in
the RDX gene (179410.0004).
*FIELD* RF
1. Khan, S. Y.; Ahmed, Z. M.; Shabbir, M. I.; Kitajiri, S.; Kalsoom,
S.; Tasneem, S.; Shayiq, S.; Ramesh, A.; Srisailpathy, S.; Khan, S.
N.; Smith, R. J. H.; Riazuddin, S.; Friedman, T. B.; Riazuddin, S.
: Mutations of the RDX gene cause nonsyndromic hearing loss at the
DFNB24 locus. Hum. Mutat. 28: 417-423, 2007.
2. Shearer, A. E.; Hildebrand, M. S.; Bromhead, C. J.; Kahrizi, K.;
Webster, J. A.; Azadeh, B.; Kimberling, W. J.; Anousheh, A.; Nazeri,
A.; Stephan, D.; Najmabadi, H.; Smith, R. J. H.; Bahlo, M.: A novel
splice site mutation in the RDX gene causes DFNB24 hearing loss in
an Iranian family. (Letter) Am. J. Med. Genet. 149A: 555-558, 2009.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Ears];
Deafness, profound, sensorineural
MISCELLANEOUS:
Prelingual onset
MOLECULAR BASIS:
Caused by mutation in the radixin gene (RDX, 179410.0001)
*FIELD* CD
Cassandra L. Kniffin: 5/11/2007
*FIELD* ED
joanna: 03/19/2008
ckniffin: 5/14/2007
*FIELD* CN
Cassandra L. Kniffin - updated: 2/16/2010
*FIELD* CD
Cassandra L. Kniffin: 5/11/2007
*FIELD* ED
carol: 08/31/2011
wwang: 2/18/2010
ckniffin: 2/16/2010
wwang: 6/7/2007
ckniffin: 5/14/2007
*RECORD*
*FIELD* NO
611022
*FIELD* TI
#611022 DEAFNESS, AUTOSOMAL RECESSIVE 24; DFNB24
*FIELD* TX
A number sign (#) is used with this entry because autosomal recessive
read morenonsyndromic deafness-24 (DFNB24) is caused by mutation in the gene
encoding radixin (RDX; 179410).
CLINICAL FEATURES
Khan et al. (2007) reported 3 Pakistani families with isolated autosomal
recessive sensorineural deafness, Two of the families were known to be
consanguineous. The deafness showed prelingual onset and was bilateral
and profound. None of the affected individuals had vestibular
dysfunction or hyperbilirubinemia.
Shearer et al. (2009) reported a consanguineous Iranian family with
DFNB24. Affected individuals had congenital onset of severe to profound
hearing loss and no evidence of liver dysfunction.
MOLECULAR GENETICS
In affected members of 3 Pakistani families with isolated autosomal
recessive sensorineural deafness, Khan et al. (2007) identified 3
respective homozygous mutations in the RDX gene
(179410.0001-179410.0003).
In 4 affected members of a consanguineous Iranian family with DFNB24,
Shearer et al. (2009) identified a homozygous splice site mutation in
the RDX gene (179410.0004).
*FIELD* RF
1. Khan, S. Y.; Ahmed, Z. M.; Shabbir, M. I.; Kitajiri, S.; Kalsoom,
S.; Tasneem, S.; Shayiq, S.; Ramesh, A.; Srisailpathy, S.; Khan, S.
N.; Smith, R. J. H.; Riazuddin, S.; Friedman, T. B.; Riazuddin, S.
: Mutations of the RDX gene cause nonsyndromic hearing loss at the
DFNB24 locus. Hum. Mutat. 28: 417-423, 2007.
2. Shearer, A. E.; Hildebrand, M. S.; Bromhead, C. J.; Kahrizi, K.;
Webster, J. A.; Azadeh, B.; Kimberling, W. J.; Anousheh, A.; Nazeri,
A.; Stephan, D.; Najmabadi, H.; Smith, R. J. H.; Bahlo, M.: A novel
splice site mutation in the RDX gene causes DFNB24 hearing loss in
an Iranian family. (Letter) Am. J. Med. Genet. 149A: 555-558, 2009.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Ears];
Deafness, profound, sensorineural
MISCELLANEOUS:
Prelingual onset
MOLECULAR BASIS:
Caused by mutation in the radixin gene (RDX, 179410.0001)
*FIELD* CD
Cassandra L. Kniffin: 5/11/2007
*FIELD* ED
joanna: 03/19/2008
ckniffin: 5/14/2007
*FIELD* CN
Cassandra L. Kniffin - updated: 2/16/2010
*FIELD* CD
Cassandra L. Kniffin: 5/11/2007
*FIELD* ED
carol: 08/31/2011
wwang: 2/18/2010
ckniffin: 2/16/2010
wwang: 6/7/2007
ckniffin: 5/14/2007