Full text data of DMTN
DMTN
(DMT, EPB49)
[Confidence: high (present in two of the MS resources)]
Dematin (Dematin actin-binding protein; Erythrocyte membrane protein band 4.9)
Dematin (Dematin actin-binding protein; Erythrocyte membrane protein band 4.9)
hRBCD
IPI00216633
IPI00216633 Splice isoform Short of Q08495 Dematin Splice isoform Short of Q08495 Dematin membrane 5 1 3 2 4 n/a 3 2 23 n/a 3 2 1 3 n/a 1 n/a 11 n/a 1 integral membrane protein splice isoform Short and Long found at its expected molecular weight found at molecular weight
IPI00216633 Splice isoform Short of Q08495 Dematin Splice isoform Short of Q08495 Dematin membrane 5 1 3 2 4 n/a 3 2 23 n/a 3 2 1 3 n/a 1 n/a 11 n/a 1 integral membrane protein splice isoform Short and Long found at its expected molecular weight found at molecular weight
Comments
Isoform Q08495-2 was detected.
Isoform Q08495-2 was detected.
UniProt
Q08495
ID DEMA_HUMAN Reviewed; 405 AA.
AC Q08495; A8K0T5; B3KP70; B3KRH3; E9PEJ0; Q13215; Q9BRE3;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-AUG-2002, sequence version 3.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Dematin;
DE AltName: Full=Dematin actin-binding protein;
DE AltName: Full=Erythrocyte membrane protein band 4.9;
GN Name=DMTN; Synonyms=DMT, EPB49;
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 2), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Reticulocyte;
RX PubMed=8341682; DOI=10.1073/pnas.90.14.6651;
RA Rana A.P., Ruff P., Maalouf G.J., Speicher D.W., Chishti A.H.;
RT "Cloning of human erythroid dematin reveals another member of the
RT villin family.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:6651-6655(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION BY CAPK,
RP SUBUNIT, AND ALTERNATIVE SPLICING.
RC TISSUE=Reticulocyte;
RX PubMed=7615546; DOI=10.1074/jbc.270.29.17407;
RA Azim A.C., Knoll J.H.M., Beggs A.H., Chishti A.H.;
RT "Isoform cloning, actin binding, and chromosomal localization of human
RT erythroid dematin, a member of the villin superfamily.";
RL J. Biol. Chem. 270:17407-17413(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Amygdala, Brain, and Kidney;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Liver;
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 FUNCTION.
RX PubMed=10565303; DOI=10.1016/S0165-4608(99)00081-3;
RA Lutchman M., Pack S., Kim A.C., Azim A., Emmert-Buck M.,
RA van Huffel C., Zhuang Z., Chishti A.H.;
RT "Loss of heterozygosity on 8p in prostate cancer implicates a role for
RT dematin in tumor progression.";
RL Cancer Genet. Cytogenet. 115:65-69(1999).
RN [8]
RP FUNCTION, INTERACTION WITH RASGRF2, AND SUBCELLULAR LOCATION.
RX PubMed=11856323; DOI=10.1046/j.0014-2956.2001.02694.x;
RA Lutchman M., Kim A.C., Cheng L., Whitehead I.P., Oh S.S., Hanspal M.,
RA Boukharov A.A., Hanada T., Chishti A.H.;
RT "Dematin interacts with the Ras-guanine nucleotide exchange factor
RT Ras-GRF2 and modulates mitogen-activated protein kinase pathways.";
RL Eur. J. Biochem. 269:638-649(2002).
RN [9]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH ADD2 AND SLC2A1, AND
RP INTERACTION WITH SLC2A1.
RX PubMed=18347014; DOI=10.1074/jbc.M707818200;
RA Khan A.A., Hanada T., Mohseni M., Jeong J.J., Zeng L., Gaetani M.,
RA Li D., Reed B.C., Speicher D.W., Chishti A.H.;
RT "Dematin and adducin provide a novel link between the spectrin
RT cytoskeleton and human erythrocyte membrane by directly interacting
RT with glucose transporter-1.";
RL J. Biol. Chem. 283:14600-14609(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, AND MASS
RP SPECTROMETRY.
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96; SER-105; SER-156;
RP SER-226; SER-333 AND SER-372, AND MASS SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [13]
RP FUNCTION, AND INTERACTION WITH F-ACTIN.
RX PubMed=19241372; DOI=10.1002/pro.59;
RA Chen L., Jiang Z.G., Khan A.A., Chishti A.H., McKnight C.J.;
RT "Dematin exhibits a natively unfolded core domain and an independently
RT folded headpiece domain.";
RL Protein Sci. 18:629-636(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96 AND SER-105, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-105, 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 [16]
RP INTERACTION WITH PLASMODIUM BERGHEI 14-3-3 PROTEIN, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF SER-124; SER-333 AND SER-403.
RX PubMed=21084299; DOI=10.1074/jbc.M110.194613;
RA Lalle M., Curra C., Ciccarone F., Pace T., Cecchetti S., Fantozzi L.,
RA Ay B., Breton C.B., Ponzi M.;
RT "Dematin, a component of the erythrocyte membrane skeleton, is
RT internalized by the malaria parasite and associates with Plasmodium
RT 14-3-3.";
RL J. Biol. Chem. 286:1227-1236(2011).
RN [17]
RP FUNCTION, PHOSPHORYLATION AT SER-403, AND IDENTIFICATION IN A COMPLEX
RP WITH SPECTRIN AND F-ACTIN.
RX PubMed=22927433; DOI=10.1074/jbc.M111.305441;
RA Koshino I., Mohandas N., Takakuwa Y.;
RT "Identification of a novel role for dematin in regulating red cell
RT membrane function by modulating spectrin-actin interaction.";
RL J. Biol. Chem. 287:35244-35250(2012).
RN [18]
RP INTERACTION WITH DMTN, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23060452; DOI=10.1074/jbc.M112.364679;
RA Wieschhaus A.J., Le Breton G.C., Chishti A.H.;
RT "Headpiece domain of dematin regulates calcium mobilization and
RT signaling in platelets.";
RL J. Biol. Chem. 287:41218-41231(2012).
RN [19]
RP FUNCTION, SUBUNIT, PHOSPHORYLATION AT SER-403, AND MUTAGENESIS OF
RP SER-403.
RX PubMed=23355471; DOI=10.1074/jbc.M112.438861;
RA Chen L., Brown J.W., Mok Y.F., Hatters D.M., McKnight C.J.;
RT "The allosteric mechanism induced by protein kinase A (PKA)
RT phosphorylation of dematin (band 4.9).";
RL J. Biol. Chem. 288:8313-8320(2013).
RN [20]
RP STRUCTURE BY NMR OF 342-405.
RX PubMed=14660664; DOI=10.1074/jbc.M310524200;
RA Frank B.S., Vardar D., Chishti A.H., McKnight C.J.;
RT "The NMR structure of dematin headpiece reveals a dynamic loop that is
RT conformationally altered upon phosphorylation at a distal site.";
RL J. Biol. Chem. 279:7909-7916(2004).
RN [21]
RP STRUCTURE BY NMR OF 342-405, AND PHOSPHORYLATION AT SER-403.
RX PubMed=16472756; DOI=10.1016/j.str.2005.11.007;
RA Jiang Z.G., McKnight C.J.;
RT "A phosphorylation-induced conformation change in dematin headpiece.";
RL Structure 14:379-387(2006).
CC -!- FUNCTION: Membrane-cytoskeleton-associated protein with F-actin-
CC binding activity that induces F-actin bundles formation and
CC stabilization. Its F-actin-bundling activity is reversibly
CC regulated upon its phosphorylation by the cAMP-dependent protein
CC kinase A (PKA). Binds to the erythrocyte membrane glucose
CC transporter-1 SLC2A1/GLUT1, and hence stabilizes and attaches the
CC spectrin-actin network to the erythrocytic plasma membrane. Plays
CC a role in maintaining the functional integrity of PKA-activated
CC erythrocyte shape and the membrane mechanical properties. Plays
CC also a role as a modulator of actin dynamics in fibroblasts; acts
CC as a negative regulator of the RhoA activation pathway. In
CC platelets, functions as a regulator of internal calcium
CC mobilization across the dense tubular system that affects platelet
CC granule secretion pathways and aggregation. Also required for the
CC formation of a diverse set of cell protrusions, such as filopodia
CC and lamellipodia, necessary for platelet cell spreading, motility
CC and migration. Acts as a tumor suppressor and inhibits malignant
CC cell transformation.
CC -!- SUBUNIT: Monomeric (isoform 2); under reducing conditions. Self-
CC associates. Exists under oxidizing condition as a trimer of two
CC isoforms 2 and isoform 1 linked by disulfide bonds (Probable).
CC Found in a complex with DMTN, F-actin and spectrin. Found in a
CC complex with ADD2, DMTN and SLC2A1. Interacts with F-actin, ITPKB,
CC RASGRF2 and spectrin. Isoform 2 interacts with SLC2A1 (via C-
CC terminus cytoplasmic region). Isoform 1 and isoform 2 interact
CC (phosphorylated form) with plasmodium berghei 14-3-3 protein; the
CC interaction occurs in a PKA-dependent manner.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytosol. Cytoplasm,
CC perinuclear region (By similarity). Cytoplasm, cytoskeleton. Cell
CC membrane. Membrane (By similarity). Endomembrane system. Cell
CC projection (By similarity). Note=Localized at the spectrin-actin
CC junction of erythrocyte plasma membrane. Localized to
CC intracellular membranes and the cytoskeletal network. Localized at
CC intracellular membrane-bounded organelle compartment in platelets
CC that likely represent the dense tubular network membrane. Detected
CC at the cell membrane and at the parasitophorous vacuol in malaria-
CC infected erythrocytes at late stages of plasmodium berghei or
CC falciparum development.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Long;
CC IsoId=Q08495-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=Q08495-2; Sequence=VSP_004189;
CC Name=3;
CC IsoId=Q08495-3; Sequence=VSP_044803, VSP_004189;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in platelets (at protein level).
CC Expressed in heart, brain, lung, skeletal muscle, and kidney.
CC -!- DOMAIN: Both the N-terminal core domain and the C-terminal
CC headpiece domain are sufficient for binding to F-actin and
CC necessary for actin bundling activity.
CC -!- PTM: Phosphorylated. Phosphorylation at Ser-403 by PKA causes the
CC C-terminal headpiece domain to associate with the N-terminal core
CC domain, and leads to the inhibition of its actin bundling
CC activity.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the villin/gelsolin family.
CC -!- SIMILARITY: Contains 1 HP (headpiece) domain.
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DR EMBL; L19713; AAA58438.1; -; mRNA.
DR EMBL; U28389; AAC50223.1; -; mRNA.
DR EMBL; AK055842; BAG51582.1; -; mRNA.
DR EMBL; AK091581; BAG52385.1; -; mRNA.
DR EMBL; AK289650; BAF82339.1; -; mRNA.
DR EMBL; BT007396; AAP36060.1; -; mRNA.
DR EMBL; AC091171; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006318; AAH06318.1; -; mRNA.
DR EMBL; BC017445; AAH17445.1; -; mRNA.
DR EMBL; BC052805; AAH52805.1; -; mRNA.
DR PIR; A48222; A48222.
DR PIR; I39062; I39062.
DR RefSeq; NP_001107607.1; NM_001114135.2.
DR RefSeq; NP_001107608.1; NM_001114136.1.
DR RefSeq; NP_001107609.1; NM_001114137.1.
DR RefSeq; NP_001107610.1; NM_001114138.1.
DR RefSeq; NP_001107611.1; NM_001114139.1.
DR RefSeq; NP_001969.2; NM_001978.2.
DR RefSeq; XP_005273488.1; XM_005273431.1.
DR RefSeq; XP_005273489.1; XM_005273432.1.
DR RefSeq; XP_005273490.1; XM_005273433.1.
DR RefSeq; XP_005273491.1; XM_005273434.1.
DR RefSeq; XP_005273494.1; XM_005273437.1.
DR RefSeq; XP_005273495.1; XM_005273438.1.
DR UniGene; Hs.106124; -.
DR PDB; 1QZP; NMR; -; A=342-405.
DR PDB; 1ZV6; NMR; -; A=342-405.
DR PDBsum; 1QZP; -.
DR PDBsum; 1ZV6; -.
DR ProteinModelPortal; Q08495; -.
DR SMR; Q08495; 341-405.
DR IntAct; Q08495; 5.
DR MINT; MINT-1390442; -.
DR STRING; 9606.ENSP00000265800; -.
DR PhosphoSite; Q08495; -.
DR DMDM; 22654240; -.
DR PaxDb; Q08495; -.
DR PRIDE; Q08495; -.
DR DNASU; 2039; -.
DR Ensembl; ENST00000265800; ENSP00000265800; ENSG00000158856.
DR Ensembl; ENST00000358242; ENSP00000350977; ENSG00000158856.
DR Ensembl; ENST00000381470; ENSP00000370879; ENSG00000158856.
DR Ensembl; ENST00000415253; ENSP00000401291; ENSG00000158856.
DR Ensembl; ENST00000432128; ENSP00000416111; ENSG00000158856.
DR Ensembl; ENST00000443491; ENSP00000397904; ENSG00000158856.
DR Ensembl; ENST00000519907; ENSP00000429377; ENSG00000158856.
DR Ensembl; ENST00000523266; ENSP00000427866; ENSG00000158856.
DR Ensembl; ENST00000523782; ENSP00000429234; ENSG00000158856.
DR GeneID; 2039; -.
DR KEGG; hsa:2039; -.
DR UCSC; uc022ass.1; human.
DR CTD; 2039; -.
DR GeneCards; GC08P021907; -.
DR HGNC; HGNC:3382; DMTN.
DR HPA; HPA024290; -.
DR MIM; 125305; gene.
DR neXtProt; NX_Q08495; -.
DR PharmGKB; PA27815; -.
DR eggNOG; NOG253396; -.
DR HOGENOM; HOG000285997; -.
DR HOVERGEN; HBG031499; -.
DR OMA; WAESRTP; -.
DR PhylomeDB; Q08495; -.
DR ChiTaRS; EPB49; human.
DR EvolutionaryTrace; Q08495; -.
DR GeneWiki; EPB49; -.
DR GenomeRNAi; 2039; -.
DR NextBio; 8281; -.
DR PRO; PR:Q08495; -.
DR ArrayExpress; Q08495; -.
DR Bgee; Q08495; -.
DR CleanEx; HS_EPB49; -.
DR Genevestigator; Q08495; -.
DR GO; GO:0005884; C:actin filament; IDA:UniProtKB.
DR GO; GO:0031253; C:cell projection membrane; ISS:UniProtKB.
DR GO; GO:0030863; C:cortical cytoskeleton; IEA:Ensembl.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0031095; C:platelet dense tubular network membrane; IDA:UniProtKB.
DR GO; GO:0014731; C:spectrin-associated cytoskeleton; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB.
DR GO; GO:0005102; F:receptor binding; IDA:UniProtKB.
DR GO; GO:0030507; F:spectrin binding; IDA:UniProtKB.
DR GO; GO:0051017; P:actin filament bundle assembly; IDA:UniProtKB.
DR GO; GO:0051693; P:actin filament capping; IEA:UniProtKB-KW.
DR GO; GO:0090527; P:actin filament reorganization; ISS:UniProtKB.
DR GO; GO:0035585; P:calcium-mediated signaling using extracellular calcium source; ISS:UniProtKB.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; ISS:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:UniProtKB.
DR GO; GO:0048821; P:erythrocyte development; ISS:UniProtKB.
DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; ISS:UniProtKB.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; ISS:UniProtKB.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0090315; P:negative regulation of protein targeting to membrane; ISS:UniProtKB.
DR GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR GO; GO:0030194; P:positive regulation of blood coagulation; ISS:UniProtKB.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; ISS:UniProtKB.
DR GO; GO:2001046; P:positive regulation of integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:1901731; P:positive regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR GO; GO:0090303; P:positive regulation of wound healing; ISS:UniProtKB.
DR GO; GO:0006461; P:protein complex assembly; IDA:UniProtKB.
DR GO; GO:0070560; P:protein secretion by platelet; ISS:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0051489; P:regulation of filopodium assembly; IMP:UniProtKB.
DR GO; GO:0010591; P:regulation of lamellipodium assembly; IMP:UniProtKB.
DR Gene3D; 1.10.950.10; -; 1.
DR InterPro; IPR028451; Dematin.
DR InterPro; IPR003128; Villin_headpiece.
DR PANTHER; PTHR24213:SF7; PTHR24213:SF7; 1.
DR Pfam; PF02209; VHP; 1.
DR SMART; SM00153; VHP; 1.
DR SUPFAM; SSF47050; SSF47050; 1.
DR PROSITE; PS51089; HP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin capping; Actin-binding; Alternative splicing;
KW Cell membrane; Cell projection; Complete proteome; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Disulfide bond; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Tumor suppressor.
FT CHAIN 1 405 Dematin.
FT /FTId=PRO_0000218755.
FT DOMAIN 337 405 HP.
FT REGION 224 308 Interaction with RASGRF2.
FT COMPBIAS 216 222 Poly-Glu.
FT MOD_RES 96 96 Phosphoserine.
FT MOD_RES 105 105 Phosphoserine.
FT MOD_RES 156 156 Phosphoserine.
FT MOD_RES 226 226 Phosphoserine.
FT MOD_RES 333 333 Phosphoserine.
FT MOD_RES 372 372 Phosphoserine.
FT MOD_RES 403 403 Phosphoserine; by PKA.
FT VAR_SEQ 7 31 Missing (in isoform 3).
FT /FTId=VSP_044803.
FT VAR_SEQ 320 341 Missing (in isoform 2 and isoform 3).
FT /FTId=VSP_004189.
FT MUTAGEN 124 124 S->A: Reduces interaction with plasmodium
FT berghei 14-3-3 protein. Inhibits
FT phosphorylation and interaction with
FT plasmodium berghei 14-3-3 protein; when
FT associated with A-333 and A-403.
FT MUTAGEN 333 333 S->A: Reduces interaction with plasmodium
FT berghei 14-3-3 protein. Inhibits
FT phosphorylation and interaction with
FT plasmodium berghei 14-3-3 protein; when
FT associated with A-124 and A-403.
FT MUTAGEN 403 403 S->A: Inhibits phosphorylation and
FT interaction with plasmodium berghei 14-3-
FT 3 protein; when associated with A-124 and
FT A-333.
FT MUTAGEN 403 403 S->E: Reduces F-actin bundling but not F-
FT actin binding activity.
FT CONFLICT 81 81 S -> Q (in Ref. 1; AAA58438 and 2;
FT AAC50223).
FT CONFLICT 155 155 G -> A (in Ref. 3; BAG52385).
FT CONFLICT 292 292 A -> R (in Ref. 1; AAA58438 and 2;
FT AAC50223).
FT CONFLICT 347 347 M -> V (in Ref. 1; AAA58438).
FT CONFLICT 380 380 F -> S (in Ref. 1; AAA58438).
FT CONFLICT 403 403 S -> P (in Ref. 3; BAG52385).
FT TURN 346 348
FT HELIX 364 366
FT HELIX 368 370
FT HELIX 373 379
FT STRAND 380 382
FT HELIX 384 389
FT HELIX 392 402
SQ SEQUENCE 405 AA; 45514 MW; 77D6372E5B16EFF4 CRC64;
MERLQKQPLT SPGSVSPSRD SSVPGSPSSI VAKMDNQVLG YKDLAAIPKD KAILDIERPD
LMIYEPHFTY SLLEHVELPR SRERSLSPKS TSPPPSPEVW ADSRSPGIIS QASAPRTTGT
PRTSLPHFHH PETSRPDSNI YKKPPIYKQR ESVGGSPQTK HLIEDLIIES SKFPAAQPPD
PNQPAKIETD YWPCPPSLAV VETEWRKRKA SRRGAEEEEE EEDDDSGEEM KALRERQREE
LSKVTSNLGK MILKEEMEKS LPIRRKTRSL PDRTPFHTSL HQGTSKSSSL PAYGRTTLSR
LQSTEFSPSG SETGSPGLQN GEGQRGRMDR GNSLPCVLEQ KIYPYEMLVV TNKGRTKLPP
GVDRMRLERH LSAEDFSRVF AMSPEEFGKL ALWKRNELKK KASLF
//
ID DEMA_HUMAN Reviewed; 405 AA.
AC Q08495; A8K0T5; B3KP70; B3KRH3; E9PEJ0; Q13215; Q9BRE3;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-AUG-2002, sequence version 3.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Dematin;
DE AltName: Full=Dematin actin-binding protein;
DE AltName: Full=Erythrocyte membrane protein band 4.9;
GN Name=DMTN; Synonyms=DMT, EPB49;
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 2), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Reticulocyte;
RX PubMed=8341682; DOI=10.1073/pnas.90.14.6651;
RA Rana A.P., Ruff P., Maalouf G.J., Speicher D.W., Chishti A.H.;
RT "Cloning of human erythroid dematin reveals another member of the
RT villin family.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:6651-6655(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION BY CAPK,
RP SUBUNIT, AND ALTERNATIVE SPLICING.
RC TISSUE=Reticulocyte;
RX PubMed=7615546; DOI=10.1074/jbc.270.29.17407;
RA Azim A.C., Knoll J.H.M., Beggs A.H., Chishti A.H.;
RT "Isoform cloning, actin binding, and chromosomal localization of human
RT erythroid dematin, a member of the villin superfamily.";
RL J. Biol. Chem. 270:17407-17413(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Amygdala, Brain, and Kidney;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Liver;
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 FUNCTION.
RX PubMed=10565303; DOI=10.1016/S0165-4608(99)00081-3;
RA Lutchman M., Pack S., Kim A.C., Azim A., Emmert-Buck M.,
RA van Huffel C., Zhuang Z., Chishti A.H.;
RT "Loss of heterozygosity on 8p in prostate cancer implicates a role for
RT dematin in tumor progression.";
RL Cancer Genet. Cytogenet. 115:65-69(1999).
RN [8]
RP FUNCTION, INTERACTION WITH RASGRF2, AND SUBCELLULAR LOCATION.
RX PubMed=11856323; DOI=10.1046/j.0014-2956.2001.02694.x;
RA Lutchman M., Kim A.C., Cheng L., Whitehead I.P., Oh S.S., Hanspal M.,
RA Boukharov A.A., Hanada T., Chishti A.H.;
RT "Dematin interacts with the Ras-guanine nucleotide exchange factor
RT Ras-GRF2 and modulates mitogen-activated protein kinase pathways.";
RL Eur. J. Biochem. 269:638-649(2002).
RN [9]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH ADD2 AND SLC2A1, AND
RP INTERACTION WITH SLC2A1.
RX PubMed=18347014; DOI=10.1074/jbc.M707818200;
RA Khan A.A., Hanada T., Mohseni M., Jeong J.J., Zeng L., Gaetani M.,
RA Li D., Reed B.C., Speicher D.W., Chishti A.H.;
RT "Dematin and adducin provide a novel link between the spectrin
RT cytoskeleton and human erythrocyte membrane by directly interacting
RT with glucose transporter-1.";
RL J. Biol. Chem. 283:14600-14609(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, AND MASS
RP SPECTROMETRY.
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96; SER-105; SER-156;
RP SER-226; SER-333 AND SER-372, AND MASS SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [13]
RP FUNCTION, AND INTERACTION WITH F-ACTIN.
RX PubMed=19241372; DOI=10.1002/pro.59;
RA Chen L., Jiang Z.G., Khan A.A., Chishti A.H., McKnight C.J.;
RT "Dematin exhibits a natively unfolded core domain and an independently
RT folded headpiece domain.";
RL Protein Sci. 18:629-636(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96 AND SER-105, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-105, 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 [16]
RP INTERACTION WITH PLASMODIUM BERGHEI 14-3-3 PROTEIN, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF SER-124; SER-333 AND SER-403.
RX PubMed=21084299; DOI=10.1074/jbc.M110.194613;
RA Lalle M., Curra C., Ciccarone F., Pace T., Cecchetti S., Fantozzi L.,
RA Ay B., Breton C.B., Ponzi M.;
RT "Dematin, a component of the erythrocyte membrane skeleton, is
RT internalized by the malaria parasite and associates with Plasmodium
RT 14-3-3.";
RL J. Biol. Chem. 286:1227-1236(2011).
RN [17]
RP FUNCTION, PHOSPHORYLATION AT SER-403, AND IDENTIFICATION IN A COMPLEX
RP WITH SPECTRIN AND F-ACTIN.
RX PubMed=22927433; DOI=10.1074/jbc.M111.305441;
RA Koshino I., Mohandas N., Takakuwa Y.;
RT "Identification of a novel role for dematin in regulating red cell
RT membrane function by modulating spectrin-actin interaction.";
RL J. Biol. Chem. 287:35244-35250(2012).
RN [18]
RP INTERACTION WITH DMTN, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23060452; DOI=10.1074/jbc.M112.364679;
RA Wieschhaus A.J., Le Breton G.C., Chishti A.H.;
RT "Headpiece domain of dematin regulates calcium mobilization and
RT signaling in platelets.";
RL J. Biol. Chem. 287:41218-41231(2012).
RN [19]
RP FUNCTION, SUBUNIT, PHOSPHORYLATION AT SER-403, AND MUTAGENESIS OF
RP SER-403.
RX PubMed=23355471; DOI=10.1074/jbc.M112.438861;
RA Chen L., Brown J.W., Mok Y.F., Hatters D.M., McKnight C.J.;
RT "The allosteric mechanism induced by protein kinase A (PKA)
RT phosphorylation of dematin (band 4.9).";
RL J. Biol. Chem. 288:8313-8320(2013).
RN [20]
RP STRUCTURE BY NMR OF 342-405.
RX PubMed=14660664; DOI=10.1074/jbc.M310524200;
RA Frank B.S., Vardar D., Chishti A.H., McKnight C.J.;
RT "The NMR structure of dematin headpiece reveals a dynamic loop that is
RT conformationally altered upon phosphorylation at a distal site.";
RL J. Biol. Chem. 279:7909-7916(2004).
RN [21]
RP STRUCTURE BY NMR OF 342-405, AND PHOSPHORYLATION AT SER-403.
RX PubMed=16472756; DOI=10.1016/j.str.2005.11.007;
RA Jiang Z.G., McKnight C.J.;
RT "A phosphorylation-induced conformation change in dematin headpiece.";
RL Structure 14:379-387(2006).
CC -!- FUNCTION: Membrane-cytoskeleton-associated protein with F-actin-
CC binding activity that induces F-actin bundles formation and
CC stabilization. Its F-actin-bundling activity is reversibly
CC regulated upon its phosphorylation by the cAMP-dependent protein
CC kinase A (PKA). Binds to the erythrocyte membrane glucose
CC transporter-1 SLC2A1/GLUT1, and hence stabilizes and attaches the
CC spectrin-actin network to the erythrocytic plasma membrane. Plays
CC a role in maintaining the functional integrity of PKA-activated
CC erythrocyte shape and the membrane mechanical properties. Plays
CC also a role as a modulator of actin dynamics in fibroblasts; acts
CC as a negative regulator of the RhoA activation pathway. In
CC platelets, functions as a regulator of internal calcium
CC mobilization across the dense tubular system that affects platelet
CC granule secretion pathways and aggregation. Also required for the
CC formation of a diverse set of cell protrusions, such as filopodia
CC and lamellipodia, necessary for platelet cell spreading, motility
CC and migration. Acts as a tumor suppressor and inhibits malignant
CC cell transformation.
CC -!- SUBUNIT: Monomeric (isoform 2); under reducing conditions. Self-
CC associates. Exists under oxidizing condition as a trimer of two
CC isoforms 2 and isoform 1 linked by disulfide bonds (Probable).
CC Found in a complex with DMTN, F-actin and spectrin. Found in a
CC complex with ADD2, DMTN and SLC2A1. Interacts with F-actin, ITPKB,
CC RASGRF2 and spectrin. Isoform 2 interacts with SLC2A1 (via C-
CC terminus cytoplasmic region). Isoform 1 and isoform 2 interact
CC (phosphorylated form) with plasmodium berghei 14-3-3 protein; the
CC interaction occurs in a PKA-dependent manner.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytosol. Cytoplasm,
CC perinuclear region (By similarity). Cytoplasm, cytoskeleton. Cell
CC membrane. Membrane (By similarity). Endomembrane system. Cell
CC projection (By similarity). Note=Localized at the spectrin-actin
CC junction of erythrocyte plasma membrane. Localized to
CC intracellular membranes and the cytoskeletal network. Localized at
CC intracellular membrane-bounded organelle compartment in platelets
CC that likely represent the dense tubular network membrane. Detected
CC at the cell membrane and at the parasitophorous vacuol in malaria-
CC infected erythrocytes at late stages of plasmodium berghei or
CC falciparum development.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Long;
CC IsoId=Q08495-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=Q08495-2; Sequence=VSP_004189;
CC Name=3;
CC IsoId=Q08495-3; Sequence=VSP_044803, VSP_004189;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in platelets (at protein level).
CC Expressed in heart, brain, lung, skeletal muscle, and kidney.
CC -!- DOMAIN: Both the N-terminal core domain and the C-terminal
CC headpiece domain are sufficient for binding to F-actin and
CC necessary for actin bundling activity.
CC -!- PTM: Phosphorylated. Phosphorylation at Ser-403 by PKA causes the
CC C-terminal headpiece domain to associate with the N-terminal core
CC domain, and leads to the inhibition of its actin bundling
CC activity.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the villin/gelsolin family.
CC -!- SIMILARITY: Contains 1 HP (headpiece) domain.
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DR EMBL; L19713; AAA58438.1; -; mRNA.
DR EMBL; U28389; AAC50223.1; -; mRNA.
DR EMBL; AK055842; BAG51582.1; -; mRNA.
DR EMBL; AK091581; BAG52385.1; -; mRNA.
DR EMBL; AK289650; BAF82339.1; -; mRNA.
DR EMBL; BT007396; AAP36060.1; -; mRNA.
DR EMBL; AC091171; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006318; AAH06318.1; -; mRNA.
DR EMBL; BC017445; AAH17445.1; -; mRNA.
DR EMBL; BC052805; AAH52805.1; -; mRNA.
DR PIR; A48222; A48222.
DR PIR; I39062; I39062.
DR RefSeq; NP_001107607.1; NM_001114135.2.
DR RefSeq; NP_001107608.1; NM_001114136.1.
DR RefSeq; NP_001107609.1; NM_001114137.1.
DR RefSeq; NP_001107610.1; NM_001114138.1.
DR RefSeq; NP_001107611.1; NM_001114139.1.
DR RefSeq; NP_001969.2; NM_001978.2.
DR RefSeq; XP_005273488.1; XM_005273431.1.
DR RefSeq; XP_005273489.1; XM_005273432.1.
DR RefSeq; XP_005273490.1; XM_005273433.1.
DR RefSeq; XP_005273491.1; XM_005273434.1.
DR RefSeq; XP_005273494.1; XM_005273437.1.
DR RefSeq; XP_005273495.1; XM_005273438.1.
DR UniGene; Hs.106124; -.
DR PDB; 1QZP; NMR; -; A=342-405.
DR PDB; 1ZV6; NMR; -; A=342-405.
DR PDBsum; 1QZP; -.
DR PDBsum; 1ZV6; -.
DR ProteinModelPortal; Q08495; -.
DR SMR; Q08495; 341-405.
DR IntAct; Q08495; 5.
DR MINT; MINT-1390442; -.
DR STRING; 9606.ENSP00000265800; -.
DR PhosphoSite; Q08495; -.
DR DMDM; 22654240; -.
DR PaxDb; Q08495; -.
DR PRIDE; Q08495; -.
DR DNASU; 2039; -.
DR Ensembl; ENST00000265800; ENSP00000265800; ENSG00000158856.
DR Ensembl; ENST00000358242; ENSP00000350977; ENSG00000158856.
DR Ensembl; ENST00000381470; ENSP00000370879; ENSG00000158856.
DR Ensembl; ENST00000415253; ENSP00000401291; ENSG00000158856.
DR Ensembl; ENST00000432128; ENSP00000416111; ENSG00000158856.
DR Ensembl; ENST00000443491; ENSP00000397904; ENSG00000158856.
DR Ensembl; ENST00000519907; ENSP00000429377; ENSG00000158856.
DR Ensembl; ENST00000523266; ENSP00000427866; ENSG00000158856.
DR Ensembl; ENST00000523782; ENSP00000429234; ENSG00000158856.
DR GeneID; 2039; -.
DR KEGG; hsa:2039; -.
DR UCSC; uc022ass.1; human.
DR CTD; 2039; -.
DR GeneCards; GC08P021907; -.
DR HGNC; HGNC:3382; DMTN.
DR HPA; HPA024290; -.
DR MIM; 125305; gene.
DR neXtProt; NX_Q08495; -.
DR PharmGKB; PA27815; -.
DR eggNOG; NOG253396; -.
DR HOGENOM; HOG000285997; -.
DR HOVERGEN; HBG031499; -.
DR OMA; WAESRTP; -.
DR PhylomeDB; Q08495; -.
DR ChiTaRS; EPB49; human.
DR EvolutionaryTrace; Q08495; -.
DR GeneWiki; EPB49; -.
DR GenomeRNAi; 2039; -.
DR NextBio; 8281; -.
DR PRO; PR:Q08495; -.
DR ArrayExpress; Q08495; -.
DR Bgee; Q08495; -.
DR CleanEx; HS_EPB49; -.
DR Genevestigator; Q08495; -.
DR GO; GO:0005884; C:actin filament; IDA:UniProtKB.
DR GO; GO:0031253; C:cell projection membrane; ISS:UniProtKB.
DR GO; GO:0030863; C:cortical cytoskeleton; IEA:Ensembl.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0031095; C:platelet dense tubular network membrane; IDA:UniProtKB.
DR GO; GO:0014731; C:spectrin-associated cytoskeleton; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB.
DR GO; GO:0005102; F:receptor binding; IDA:UniProtKB.
DR GO; GO:0030507; F:spectrin binding; IDA:UniProtKB.
DR GO; GO:0051017; P:actin filament bundle assembly; IDA:UniProtKB.
DR GO; GO:0051693; P:actin filament capping; IEA:UniProtKB-KW.
DR GO; GO:0090527; P:actin filament reorganization; ISS:UniProtKB.
DR GO; GO:0035585; P:calcium-mediated signaling using extracellular calcium source; ISS:UniProtKB.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; ISS:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:UniProtKB.
DR GO; GO:0048821; P:erythrocyte development; ISS:UniProtKB.
DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; ISS:UniProtKB.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; ISS:UniProtKB.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0090315; P:negative regulation of protein targeting to membrane; ISS:UniProtKB.
DR GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR GO; GO:0030194; P:positive regulation of blood coagulation; ISS:UniProtKB.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; ISS:UniProtKB.
DR GO; GO:2001046; P:positive regulation of integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:1901731; P:positive regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR GO; GO:0090303; P:positive regulation of wound healing; ISS:UniProtKB.
DR GO; GO:0006461; P:protein complex assembly; IDA:UniProtKB.
DR GO; GO:0070560; P:protein secretion by platelet; ISS:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0051489; P:regulation of filopodium assembly; IMP:UniProtKB.
DR GO; GO:0010591; P:regulation of lamellipodium assembly; IMP:UniProtKB.
DR Gene3D; 1.10.950.10; -; 1.
DR InterPro; IPR028451; Dematin.
DR InterPro; IPR003128; Villin_headpiece.
DR PANTHER; PTHR24213:SF7; PTHR24213:SF7; 1.
DR Pfam; PF02209; VHP; 1.
DR SMART; SM00153; VHP; 1.
DR SUPFAM; SSF47050; SSF47050; 1.
DR PROSITE; PS51089; HP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin capping; Actin-binding; Alternative splicing;
KW Cell membrane; Cell projection; Complete proteome; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Disulfide bond; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Tumor suppressor.
FT CHAIN 1 405 Dematin.
FT /FTId=PRO_0000218755.
FT DOMAIN 337 405 HP.
FT REGION 224 308 Interaction with RASGRF2.
FT COMPBIAS 216 222 Poly-Glu.
FT MOD_RES 96 96 Phosphoserine.
FT MOD_RES 105 105 Phosphoserine.
FT MOD_RES 156 156 Phosphoserine.
FT MOD_RES 226 226 Phosphoserine.
FT MOD_RES 333 333 Phosphoserine.
FT MOD_RES 372 372 Phosphoserine.
FT MOD_RES 403 403 Phosphoserine; by PKA.
FT VAR_SEQ 7 31 Missing (in isoform 3).
FT /FTId=VSP_044803.
FT VAR_SEQ 320 341 Missing (in isoform 2 and isoform 3).
FT /FTId=VSP_004189.
FT MUTAGEN 124 124 S->A: Reduces interaction with plasmodium
FT berghei 14-3-3 protein. Inhibits
FT phosphorylation and interaction with
FT plasmodium berghei 14-3-3 protein; when
FT associated with A-333 and A-403.
FT MUTAGEN 333 333 S->A: Reduces interaction with plasmodium
FT berghei 14-3-3 protein. Inhibits
FT phosphorylation and interaction with
FT plasmodium berghei 14-3-3 protein; when
FT associated with A-124 and A-403.
FT MUTAGEN 403 403 S->A: Inhibits phosphorylation and
FT interaction with plasmodium berghei 14-3-
FT 3 protein; when associated with A-124 and
FT A-333.
FT MUTAGEN 403 403 S->E: Reduces F-actin bundling but not F-
FT actin binding activity.
FT CONFLICT 81 81 S -> Q (in Ref. 1; AAA58438 and 2;
FT AAC50223).
FT CONFLICT 155 155 G -> A (in Ref. 3; BAG52385).
FT CONFLICT 292 292 A -> R (in Ref. 1; AAA58438 and 2;
FT AAC50223).
FT CONFLICT 347 347 M -> V (in Ref. 1; AAA58438).
FT CONFLICT 380 380 F -> S (in Ref. 1; AAA58438).
FT CONFLICT 403 403 S -> P (in Ref. 3; BAG52385).
FT TURN 346 348
FT HELIX 364 366
FT HELIX 368 370
FT HELIX 373 379
FT STRAND 380 382
FT HELIX 384 389
FT HELIX 392 402
SQ SEQUENCE 405 AA; 45514 MW; 77D6372E5B16EFF4 CRC64;
MERLQKQPLT SPGSVSPSRD SSVPGSPSSI VAKMDNQVLG YKDLAAIPKD KAILDIERPD
LMIYEPHFTY SLLEHVELPR SRERSLSPKS TSPPPSPEVW ADSRSPGIIS QASAPRTTGT
PRTSLPHFHH PETSRPDSNI YKKPPIYKQR ESVGGSPQTK HLIEDLIIES SKFPAAQPPD
PNQPAKIETD YWPCPPSLAV VETEWRKRKA SRRGAEEEEE EEDDDSGEEM KALRERQREE
LSKVTSNLGK MILKEEMEKS LPIRRKTRSL PDRTPFHTSL HQGTSKSSSL PAYGRTTLSR
LQSTEFSPSG SETGSPGLQN GEGQRGRMDR GNSLPCVLEQ KIYPYEMLVV TNKGRTKLPP
GVDRMRLERH LSAEDFSRVF AMSPEEFGKL ALWKRNELKK KASLF
//
MIM
125305
*RECORD*
*FIELD* NO
125305
*FIELD* TI
*125305 ERYTHROCYTE MEMBRANE PROTEIN BAND 4.9; EPB49
;;DEMATIN
*FIELD* TX
DESCRIPTION
read more
Dematin, or EPB49, is an actin-bundling protein originally identified in
the erythroid membrane skeleton. Its actin-bundling activity is
abolished upon phosphorylation by cAMP-dependent protein kinase and is
restored after dephosphorylation (Rana et al., 1993).
CLONING
Chishti et al. (1989) proposed the name dematin (from the Greek 'dema,'
a bundle) for an actin-bundling protein identified in the human
erythroid membrane skeleton. Rana et al. (1993) noted that dematin
consists of 2 polypeptide chains of 48 and 52 kD that were identified as
protein 4.9 on SDS-polyacrylamide gels. In solution, dematin exists as a
trimer and bundles actin filaments in a phosphorylation-dependent
manner. Rana et al. (1993) cloned dematin from a human reticulocyte cDNA
library. The deduced 383-amino acid protein has a calculated molecular
mass of 43 kD. Dematin has a polyglutamine motif that may constitute a
nuclear localization signal, a PEST sequence, a C-terminal domain highly
similar to the C-terminal headpiece domain of villin (VIL; 193040), and
several putative phosphorylation sites. Northern blot analysis detected
variable dematin expression in all tissues examined. Immunofluorescence
microscopy revealed punctate dematin staining around the cell nucleus in
cultured human erythroblasts.
Although dematin is an actin-bundling protein of the erythroid membrane
skeleton, it is abundantly expressed in human brain, heart, skeletal
muscle, kidney, and lung. Azim et al. (1995) reported the primary
structure of the 52-kD subunit of dematin, which differs from the 48-kD
subunit by a 22-amino acid insertion within its headpiece domain. A
unique feature of the insertion sequence of the 52-kD subunit is its
homology to erythrocyte protein 4.2 (177070).
GENE FUNCTION
Rana et al. (1993) confirmed that purified human dematin possessed
actin-bundling activity in vitro. Protease treatment and microsequencing
revealed that the C-terminal headpiece domain bound actin filaments, but
it did not have actin-bundling activity.
Azim et al. (1996) demonstrated that dematin and protein 4.2 bound ATP.
Gilligan and Bennett (1993) provided a review.
MAPPING
Using somatic cell hybrid panels and fluorescence in situ hybridization,
Azim et al. (1995) localized the dematin gene to chromosome 8p21.1, a
site distal to the locus of ankyrin (612641) at chromosome 8p11.2.
Peters et al. (1995) demonstrated that the murine dematin gene,
symbolized Epb4.9, maps to chromosome 14. They raised the possibility
that dematin mutations may be involved in neurologic abnormalities in
the mouse.
ANIMAL MODEL
By using homologous recombination in mouse embryonic stem cells, Khanna
et al. (2002) deleted the headpiece domain of dematin to evaluate its
function in vivo. Dematin headpiece-null mice were viable and born at
the expected mendelian ratio. Hematologic evaluation showed evidence of
compensated anemia and spherocytosis in these mice, however. The
headpiece-null erythrocytes were osmotically fragile, and displayed
reduced deformability and filterability. In vitro, significantly greater
membrane fragmentation of these erythrocytes was demonstrated.
Biochemical characterization showed a weakened membrane skeleton
evidenced by reduced association of spectrin and actin to the plasma
membrane. Together, these results provided evidence for the physiologic
significance of dematin and demonstrated a role for the headpiece domain
in the maintenance of structural integrity and mechanical properties of
red cells in vivo.
Chen et al. (2007) created double-knockout mice lacking beta-adducin
(ADD2; 102681) and the headpiece domain of dematin. Double-knockout pups
were pale compared with wildtype pups, but otherwise they appeared
grossly normal. Peripheral blood analysis showed severe hemolytic anemia
with reduced number of erythrocytes/hematocrit/hemoglobin and an
approximately 12-fold increase in the number of circulating
reticulocytes. The presence of a variety of misshapen and fragmented
erythrocytes correlated with increased osmotic fragility and reduced in
vivo life span. Mutant erythrocyte membranes showed weak retention of
spectrin-actin complexes, increased grain size, decreased filament
number, and features consistent with the presence of large protein
aggregates. Chen et al. (2007) concluded that dematin and adducin are
essential for the maintenance of erythrocyte shape and membrane
stability.
*FIELD* RF
1. Azim, A. C.; Knoll, J. H. M.; Beggs, A. H.; Chisti, A. H.: Isoform
cloning, actin binding, and chromosomal localization of human erythroid
dematin, a member of the villin superfamily. J. Biol. Chem. 270:
17407-17413, 1995.
2. Azim, A. C.; Marfatia, S. M.; Korsgren, C.; Dotimas, E.; Cohen,
C. M.; Chishti, A. H.: Human erythrocyte dematin and protein 4.2
(pallidin) are ATP binding proteins. Biochemistry 35: 3001-3006,
1996.
3. Chen, H.; Khan, A. A.; Liu, F.; Gilligan, D. M.; Peters, L. L.;
Messick, J.; Haschek-Hock, W. M.; Li, X.; Ostafin, A. E.; Chishti,
A. H.: Combined deletion of mouse dematin-headpiece and beta-adducin
exerts a novel effect on the spectrin-actin junctions leading to erythrocyte
fragility and hemolytic anemia. J. Biol. Chem. 282: 4124-4135, 2007.
4. Chishti, A. H.; Faquin, W.; Wu, C.-C.; Branton, D.: Purification
of erythrocyte dematin (protein 4.9) reveals an endogenous protein
kinase that modulates actin-bundling activity. J. Biol. Chem. 264:
8985-8991, 1989.
5. Gilligan, D. M.; Bennett, V.: The junctional complex of the membrane
skeleton. Seminars Hemat. 30: 74-83, 1993.
6. Khanna, R.; Chang, S. H.; Andrabi, S.; Azam, M.; Kim, A.; Rivera,
A.; Brugnara, C.; Low, P. S.; Liu, S.-C.; Chishti, A. H.: Headpiece
domain of dematin is required for the stability of the erythrocyte
membrane. Proc. Nat. Acad. Sci. 99: 6637-6642, 2002.
7. Peters, L. L.; Eicher, E. M.; Azim, A. C.; Chishti, A. H.: The
gene encoding the erythrocyte membrane skeleton protein dematin (Epb4.9)
maps to mouse chromosome 14. Genomics 26: 634-635, 1995.
8. Rana, A. P.; Ruff, P.; Maalouf, G. J.; Speicher, D. W.; Chishti,
A. H.: Cloning of human erythroid dematin reveals another member
of the villin family. Proc. Nat. Acad. Sci. 90: 6651-6655, 1993.
*FIELD* CN
Patricia A. Hartz - updated: 4/10/2009
Victor A. McKusick - updated: 6/14/2002
*FIELD* CD
Victor A. McKusick: 2/18/1993
*FIELD* ED
mgross: 04/13/2009
terry: 4/10/2009
carol: 2/26/2009
cwells: 6/27/2002
terry: 6/14/2002
mgross: 4/28/1999
dkim: 9/11/1998
mark: 4/26/1996
terry: 4/24/1996
mark: 12/6/1995
mark: 10/19/1995
terry: 4/27/1994
carol: 8/25/1993
carol: 2/19/1993
carol: 2/18/1993
*RECORD*
*FIELD* NO
125305
*FIELD* TI
*125305 ERYTHROCYTE MEMBRANE PROTEIN BAND 4.9; EPB49
;;DEMATIN
*FIELD* TX
DESCRIPTION
read more
Dematin, or EPB49, is an actin-bundling protein originally identified in
the erythroid membrane skeleton. Its actin-bundling activity is
abolished upon phosphorylation by cAMP-dependent protein kinase and is
restored after dephosphorylation (Rana et al., 1993).
CLONING
Chishti et al. (1989) proposed the name dematin (from the Greek 'dema,'
a bundle) for an actin-bundling protein identified in the human
erythroid membrane skeleton. Rana et al. (1993) noted that dematin
consists of 2 polypeptide chains of 48 and 52 kD that were identified as
protein 4.9 on SDS-polyacrylamide gels. In solution, dematin exists as a
trimer and bundles actin filaments in a phosphorylation-dependent
manner. Rana et al. (1993) cloned dematin from a human reticulocyte cDNA
library. The deduced 383-amino acid protein has a calculated molecular
mass of 43 kD. Dematin has a polyglutamine motif that may constitute a
nuclear localization signal, a PEST sequence, a C-terminal domain highly
similar to the C-terminal headpiece domain of villin (VIL; 193040), and
several putative phosphorylation sites. Northern blot analysis detected
variable dematin expression in all tissues examined. Immunofluorescence
microscopy revealed punctate dematin staining around the cell nucleus in
cultured human erythroblasts.
Although dematin is an actin-bundling protein of the erythroid membrane
skeleton, it is abundantly expressed in human brain, heart, skeletal
muscle, kidney, and lung. Azim et al. (1995) reported the primary
structure of the 52-kD subunit of dematin, which differs from the 48-kD
subunit by a 22-amino acid insertion within its headpiece domain. A
unique feature of the insertion sequence of the 52-kD subunit is its
homology to erythrocyte protein 4.2 (177070).
GENE FUNCTION
Rana et al. (1993) confirmed that purified human dematin possessed
actin-bundling activity in vitro. Protease treatment and microsequencing
revealed that the C-terminal headpiece domain bound actin filaments, but
it did not have actin-bundling activity.
Azim et al. (1996) demonstrated that dematin and protein 4.2 bound ATP.
Gilligan and Bennett (1993) provided a review.
MAPPING
Using somatic cell hybrid panels and fluorescence in situ hybridization,
Azim et al. (1995) localized the dematin gene to chromosome 8p21.1, a
site distal to the locus of ankyrin (612641) at chromosome 8p11.2.
Peters et al. (1995) demonstrated that the murine dematin gene,
symbolized Epb4.9, maps to chromosome 14. They raised the possibility
that dematin mutations may be involved in neurologic abnormalities in
the mouse.
ANIMAL MODEL
By using homologous recombination in mouse embryonic stem cells, Khanna
et al. (2002) deleted the headpiece domain of dematin to evaluate its
function in vivo. Dematin headpiece-null mice were viable and born at
the expected mendelian ratio. Hematologic evaluation showed evidence of
compensated anemia and spherocytosis in these mice, however. The
headpiece-null erythrocytes were osmotically fragile, and displayed
reduced deformability and filterability. In vitro, significantly greater
membrane fragmentation of these erythrocytes was demonstrated.
Biochemical characterization showed a weakened membrane skeleton
evidenced by reduced association of spectrin and actin to the plasma
membrane. Together, these results provided evidence for the physiologic
significance of dematin and demonstrated a role for the headpiece domain
in the maintenance of structural integrity and mechanical properties of
red cells in vivo.
Chen et al. (2007) created double-knockout mice lacking beta-adducin
(ADD2; 102681) and the headpiece domain of dematin. Double-knockout pups
were pale compared with wildtype pups, but otherwise they appeared
grossly normal. Peripheral blood analysis showed severe hemolytic anemia
with reduced number of erythrocytes/hematocrit/hemoglobin and an
approximately 12-fold increase in the number of circulating
reticulocytes. The presence of a variety of misshapen and fragmented
erythrocytes correlated with increased osmotic fragility and reduced in
vivo life span. Mutant erythrocyte membranes showed weak retention of
spectrin-actin complexes, increased grain size, decreased filament
number, and features consistent with the presence of large protein
aggregates. Chen et al. (2007) concluded that dematin and adducin are
essential for the maintenance of erythrocyte shape and membrane
stability.
*FIELD* RF
1. Azim, A. C.; Knoll, J. H. M.; Beggs, A. H.; Chisti, A. H.: Isoform
cloning, actin binding, and chromosomal localization of human erythroid
dematin, a member of the villin superfamily. J. Biol. Chem. 270:
17407-17413, 1995.
2. Azim, A. C.; Marfatia, S. M.; Korsgren, C.; Dotimas, E.; Cohen,
C. M.; Chishti, A. H.: Human erythrocyte dematin and protein 4.2
(pallidin) are ATP binding proteins. Biochemistry 35: 3001-3006,
1996.
3. Chen, H.; Khan, A. A.; Liu, F.; Gilligan, D. M.; Peters, L. L.;
Messick, J.; Haschek-Hock, W. M.; Li, X.; Ostafin, A. E.; Chishti,
A. H.: Combined deletion of mouse dematin-headpiece and beta-adducin
exerts a novel effect on the spectrin-actin junctions leading to erythrocyte
fragility and hemolytic anemia. J. Biol. Chem. 282: 4124-4135, 2007.
4. Chishti, A. H.; Faquin, W.; Wu, C.-C.; Branton, D.: Purification
of erythrocyte dematin (protein 4.9) reveals an endogenous protein
kinase that modulates actin-bundling activity. J. Biol. Chem. 264:
8985-8991, 1989.
5. Gilligan, D. M.; Bennett, V.: The junctional complex of the membrane
skeleton. Seminars Hemat. 30: 74-83, 1993.
6. Khanna, R.; Chang, S. H.; Andrabi, S.; Azam, M.; Kim, A.; Rivera,
A.; Brugnara, C.; Low, P. S.; Liu, S.-C.; Chishti, A. H.: Headpiece
domain of dematin is required for the stability of the erythrocyte
membrane. Proc. Nat. Acad. Sci. 99: 6637-6642, 2002.
7. Peters, L. L.; Eicher, E. M.; Azim, A. C.; Chishti, A. H.: The
gene encoding the erythrocyte membrane skeleton protein dematin (Epb4.9)
maps to mouse chromosome 14. Genomics 26: 634-635, 1995.
8. Rana, A. P.; Ruff, P.; Maalouf, G. J.; Speicher, D. W.; Chishti,
A. H.: Cloning of human erythroid dematin reveals another member
of the villin family. Proc. Nat. Acad. Sci. 90: 6651-6655, 1993.
*FIELD* CN
Patricia A. Hartz - updated: 4/10/2009
Victor A. McKusick - updated: 6/14/2002
*FIELD* CD
Victor A. McKusick: 2/18/1993
*FIELD* ED
mgross: 04/13/2009
terry: 4/10/2009
carol: 2/26/2009
cwells: 6/27/2002
terry: 6/14/2002
mgross: 4/28/1999
dkim: 9/11/1998
mark: 4/26/1996
terry: 4/24/1996
mark: 12/6/1995
mark: 10/19/1995
terry: 4/27/1994
carol: 8/25/1993
carol: 2/19/1993
carol: 2/18/1993