DEMA_HUMAN
ID DEMA_HUMAN Reviewed; 405 AA.
AC Q08495; A8K0T5; B3KP70; B3KRH3; B4DI75; E9PEJ0; Q13215; Q9BRE3;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2002, sequence version 3.
DT 03-AUG-2022, entry version 210.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 villin
RT family.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:6651-6655(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION BY CAPK, SUBUNIT,
RP 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; 3 AND 4).
RC TISSUE=Amygdala, Brain, Hippocampus, 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 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., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., 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., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., 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 project:
RT 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., van Huffel C.,
RA 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 Ras-GRF2
RT 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 INTERACTION
RP 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., Li D.,
RA Reed B.C., Speicher D.W., Chishti A.H.;
RT "Dematin and adducin provide a novel link between the spectrin cytoskeleton
RT and human erythrocyte membrane by directly interacting with glucose
RT transporter-1.";
RL J. Biol. Chem. 283:14600-14609(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 sequential
RT 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 IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
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 IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT 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
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP INTERACTION WITH PLASMODIUM BERGHEI 14-3-3 PROTEIN, SUBCELLULAR LOCATION,
RP 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 internalized
RT by the malaria parasite and associates with Plasmodium 14-3-3.";
RL J. Biol. Chem. 286:1227-1236(2011).
RN [17]
RP FUNCTION, PHOSPHORYLATION AT SER-403, AND IDENTIFICATION IN A COMPLEX WITH
RP 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 membrane
RT 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 signaling
RT in platelets.";
RL J. Biol. Chem. 287:41218-41231(2012).
RN [19]
RP FUNCTION, SUBUNIT, PHOSPHORYLATION AT SER-403, AND MUTAGENESIS OF 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) phosphorylation
RT of dematin (band 4.9).";
RL J. Biol. Chem. 288:8313-8320(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; SER-18; SER-26; SER-92;
RP SER-96; SER-105; SER-226; SER-269; SER-279; SER-289; SER-303; SER-333;
RP SER-372 AND SER-383, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; SER-18; SER-105; SER-289
RP AND SER-372, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
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 [23]
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-binding
CC activity that induces F-actin bundles formation and stabilization. Its
CC F-actin-bundling activity is reversibly regulated upon its
CC phosphorylation by the cAMP-dependent protein kinase A (PKA). Binds to
CC the erythrocyte membrane glucose transporter-1 SLC2A1/GLUT1, and hence
CC stabilizes and attaches the spectrin-actin network to the erythrocytic
CC plasma membrane. Plays a role in maintaining the functional integrity
CC of PKA-activated erythrocyte shape and the membrane mechanical
CC properties. Also plays a role as a modulator of actin dynamics in
CC fibroblasts; acts as a negative regulator of the RhoA activation
CC pathway. In 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 and
CC lamellipodia, necessary for platelet cell spreading, motility and
CC migration. Acts as a tumor suppressor and inhibits malignant cell
CC transformation. {ECO:0000269|PubMed:10565303,
CC ECO:0000269|PubMed:11856323, ECO:0000269|PubMed:18347014,
CC ECO:0000269|PubMed:19241372, ECO:0000269|PubMed:22927433,
CC ECO:0000269|PubMed:23355471}.
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). Found in
CC a complex with DMTN, F-actin and spectrin. Found in a complex with
CC ADD2, DMTN and SLC2A1. Interacts with F-actin, ITPKB, RASGRF2 and
CC spectrin. Isoform 2 interacts with SLC2A1 (via C-terminus cytoplasmic
CC region). Isoform 1 and isoform 2 interact (phosphorylated form) with
CC plasmodium berghei 14-3-3 protein; the interaction occurs in a PKA-
CC dependent manner. {ECO:0000269|PubMed:11856323,
CC ECO:0000269|PubMed:18347014, ECO:0000269|PubMed:19241372,
CC ECO:0000269|PubMed:21084299, ECO:0000269|PubMed:22927433,
CC ECO:0000269|PubMed:23060452, ECO:0000269|PubMed:23355471,
CC ECO:0000269|PubMed:7615546, ECO:0000305}.
CC -!- INTERACTION:
CC Q08495; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-715275, EBI-742887;
CC Q08495; Q08379: GOLGA2; NbExp=3; IntAct=EBI-715275, EBI-618309;
CC Q08495; Q8IYF3-3: TEX11; NbExp=3; IntAct=EBI-715275, EBI-11523345;
CC Q08495; Q12933: TRAF2; NbExp=3; IntAct=EBI-715275, EBI-355744;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytosol. Cytoplasm,
CC perinuclear region {ECO:0000250}. Cytoplasm, cytoskeleton. Cell
CC membrane. Membrane {ECO:0000250}. Endomembrane system. Cell projection
CC {ECO:0000250}. Note=Localized at the spectrin-actin junction of
CC erythrocyte plasma membrane. Localized to intracellular membranes and
CC the cytoskeletal network. Localized at intracellular membrane-bounded
CC organelle compartment in platelets that likely represent the dense
CC tubular network membrane. Detected at the cell membrane and at the
CC parasitophorous vacuole in malaria-infected erythrocytes at late stages
CC of plasmodium berghei or falciparum development.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
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 Name=4;
CC IsoId=Q08495-4; Sequence=VSP_044803, VSP_057428;
CC -!- TISSUE SPECIFICITY: Expressed in platelets (at protein level).
CC Expressed in heart, brain, lung, skeletal muscle, and kidney.
CC {ECO:0000269|PubMed:23060452}.
CC -!- DOMAIN: Both the N-terminal core domain and the C-terminal headpiece
CC domain are sufficient for binding to F-actin and necessary for actin
CC bundling activity.
CC -!- PTM: Phosphorylated. Phosphorylation at Ser-403 by PKA causes the C-
CC terminal headpiece domain to associate with the N-terminal core domain,
CC and leads to the inhibition of its actin bundling activity.
CC {ECO:0000269|PubMed:16472756, ECO:0000269|PubMed:22927433,
CC ECO:0000269|PubMed:23355471, ECO:0000269|PubMed:7615546}.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the villin/gelsolin family. {ECO:0000305}.
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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; AK295452; BAG58387.1; -; 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 CCDS; CCDS47820.1; -. [Q08495-2]
DR CCDS; CCDS47821.1; -. [Q08495-3]
DR CCDS; CCDS6020.1; -. [Q08495-1]
DR CCDS; CCDS78311.1; -. [Q08495-4]
DR PIR; A48222; A48222.
DR PIR; I39062; I39062.
DR RefSeq; NP_001107607.1; NM_001114135.4. [Q08495-1]
DR RefSeq; NP_001107608.1; NM_001114136.2. [Q08495-1]
DR RefSeq; NP_001107609.1; NM_001114137.3. [Q08495-2]
DR RefSeq; NP_001107610.1; NM_001114138.2. [Q08495-2]
DR RefSeq; NP_001107611.1; NM_001114139.3. [Q08495-3]
DR RefSeq; NP_001289745.1; NM_001302816.2. [Q08495-2]
DR RefSeq; NP_001289746.1; NM_001302817.2. [Q08495-4]
DR RefSeq; NP_001310307.1; NM_001323378.1. [Q08495-1]
DR RefSeq; NP_001310308.1; NM_001323379.1. [Q08495-1]
DR RefSeq; NP_001310309.1; NM_001323380.1. [Q08495-1]
DR RefSeq; NP_001310310.1; NM_001323381.1. [Q08495-1]
DR RefSeq; NP_001310311.1; NM_001323382.1. [Q08495-1]
DR RefSeq; NP_001310312.1; NM_001323383.1. [Q08495-2]
DR RefSeq; NP_001310313.1; NM_001323384.1. [Q08495-2]
DR RefSeq; NP_001310314.1; NM_001323385.1. [Q08495-2]
DR RefSeq; NP_001310316.1; NM_001323387.1. [Q08495-3]
DR RefSeq; NP_001310317.1; NM_001323388.1. [Q08495-4]
DR RefSeq; NP_001310318.1; NM_001323389.1.
DR RefSeq; NP_001310319.1; NM_001323390.1.
DR RefSeq; NP_001310320.1; NM_001323391.1.
DR RefSeq; NP_001310321.1; NM_001323392.1.
DR RefSeq; NP_001310322.1; NM_001323393.1.
DR RefSeq; NP_001310323.1; NM_001323394.1.
DR RefSeq; NP_001310324.1; NM_001323395.1.
DR RefSeq; NP_001310325.1; NM_001323396.1.
DR RefSeq; NP_001310326.1; NM_001323397.1.
DR RefSeq; NP_001310327.1; NM_001323398.1.
DR RefSeq; NP_001310328.1; NM_001323399.1.
DR RefSeq; NP_001310329.1; NM_001323400.1.
DR RefSeq; NP_001310330.1; NM_001323401.1.
DR RefSeq; NP_001969.2; NM_001978.4. [Q08495-1]
DR RefSeq; XP_005273489.1; XM_005273432.1.
DR RefSeq; XP_016868678.1; XM_017013189.1. [Q08495-2]
DR RefSeq; XP_016868682.1; XM_017013193.1. [Q08495-4]
DR RefSeq; XP_016868683.1; XM_017013194.1. [Q08495-4]
DR RefSeq; XP_016868684.1; XM_017013195.1. [Q08495-3]
DR RefSeq; XP_016868685.1; XM_017013196.1. [Q08495-3]
DR RefSeq; XP_016868686.1; XM_017013197.1. [Q08495-3]
DR RefSeq; XP_016868687.1; XM_017013198.1. [Q08495-3]
DR PDB; 1QZP; NMR; -; A=342-405.
DR PDB; 1ZV6; NMR; -; A=342-405.
DR PDBsum; 1QZP; -.
DR PDBsum; 1ZV6; -.
DR AlphaFoldDB; Q08495; -.
DR BMRB; Q08495; -.
DR SMR; Q08495; -.
DR BioGRID; 108353; 31.
DR CORUM; Q08495; -.
DR IntAct; Q08495; 17.
DR STRING; 9606.ENSP00000427866; -.
DR GlyGen; Q08495; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q08495; -.
DR PhosphoSitePlus; Q08495; -.
DR BioMuta; DMTN; -.
DR DMDM; 22654240; -.
DR EPD; Q08495; -.
DR jPOST; Q08495; -.
DR MassIVE; Q08495; -.
DR MaxQB; Q08495; -.
DR PaxDb; Q08495; -.
DR PeptideAtlas; Q08495; -.
DR PRIDE; Q08495; -.
DR ProteomicsDB; 19903; -.
DR ProteomicsDB; 4281; -.
DR ProteomicsDB; 58618; -. [Q08495-1]
DR ProteomicsDB; 58619; -. [Q08495-2]
DR Antibodypedia; 9250; 247 antibodies from 31 providers.
DR DNASU; 2039; -.
DR Ensembl; ENST00000265800.9; ENSP00000265800.5; ENSG00000158856.19. [Q08495-1]
DR Ensembl; ENST00000358242.6; ENSP00000350977.3; ENSG00000158856.19. [Q08495-1]
DR Ensembl; ENST00000381470.7; ENSP00000370879.3; ENSG00000158856.19. [Q08495-2]
DR Ensembl; ENST00000415253.5; ENSP00000401291.1; ENSG00000158856.19. [Q08495-2]
DR Ensembl; ENST00000432128.6; ENSP00000416111.1; ENSG00000158856.19. [Q08495-1]
DR Ensembl; ENST00000443491.6; ENSP00000397904.2; ENSG00000158856.19. [Q08495-3]
DR Ensembl; ENST00000517305.5; ENSP00000430609.2; ENSG00000158856.19. [Q08495-1]
DR Ensembl; ENST00000517600.5; ENSP00000430618.1; ENSG00000158856.19. [Q08495-4]
DR Ensembl; ENST00000519907.5; ENSP00000429377.1; ENSG00000158856.19. [Q08495-2]
DR Ensembl; ENST00000523266.5; ENSP00000427866.1; ENSG00000158856.19. [Q08495-1]
DR Ensembl; ENST00000523782.6; ENSP00000429234.2; ENSG00000158856.19. [Q08495-3]
DR GeneID; 2039; -.
DR KEGG; hsa:2039; -.
DR MANE-Select; ENST00000358242.6; ENSP00000350977.3; NM_001387751.1; NP_001374680.1.
DR UCSC; uc064kwf.1; human. [Q08495-1]
DR UCSC; uc064kwj.1; human.
DR CTD; 2039; -.
DR DisGeNET; 2039; -.
DR GeneCards; DMTN; -.
DR HGNC; HGNC:3382; DMTN.
DR HPA; ENSG00000158856; Tissue enhanced (brain).
DR MIM; 125305; gene.
DR neXtProt; NX_Q08495; -.
DR OpenTargets; ENSG00000158856; -.
DR PharmGKB; PA27815; -.
DR VEuPathDB; HostDB:ENSG00000158856; -.
DR eggNOG; KOG1044; Eukaryota.
DR GeneTree; ENSGT00950000182850; -.
DR HOGENOM; CLU_001357_12_1_1; -.
DR InParanoid; Q08495; -.
DR OMA; DWLENRS; -.
DR OrthoDB; 1083894at2759; -.
DR PhylomeDB; Q08495; -.
DR TreeFam; TF318042; -.
DR PathwayCommons; Q08495; -.
DR Reactome; R-HSA-5223345; Miscellaneous transport and binding events.
DR SignaLink; Q08495; -.
DR BioGRID-ORCS; 2039; 19 hits in 1039 CRISPR screens.
DR ChiTaRS; DMTN; human.
DR EvolutionaryTrace; Q08495; -.
DR GeneWiki; EPB49; -.
DR GenomeRNAi; 2039; -.
DR Pharos; Q08495; Tbio.
DR PRO; PR:Q08495; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q08495; protein.
DR Bgee; ENSG00000158856; Expressed in right frontal lobe and 186 other tissues.
DR ExpressionAtlas; Q08495; baseline and differential.
DR Genevisible; Q08495; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IBA:GO_Central.
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:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0031095; C:platelet dense tubular network membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0014731; C:spectrin-associated cytoskeleton; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IDA:UniProtKB.
DR GO; GO:0030507; F:spectrin binding; IDA:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISS: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:0007010; P:cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0048821; P:erythrocyte development; ISS:UniProtKB.
DR GO; GO:0030032; P:lamellipodium assembly; IBA:GO_Central.
DR GO; GO:0010812; P:negative regulation of cell-substrate adhesion; 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:0070560; P:protein secretion by platelet; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA: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; IPR032402; AbLIM_anchor.
DR InterPro; IPR003128; Villin_headpiece.
DR InterPro; IPR036886; Villin_headpiece_dom_sf.
DR Pfam; PF16182; AbLIM_anchor; 2.
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; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Disulfide bond; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Tumor suppressor.
FT CHAIN 1..405
FT /note="Dematin"
FT /id="PRO_0000218755"
FT DOMAIN 337..405
FT /note="HP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00595"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 79..158
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 203..332
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 224..308
FT /note="Interaction with RASGRF2"
FT /evidence="ECO:0000269|PubMed:11856323"
FT COMPBIAS 7..30
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 106..124
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 229..243
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 252..272
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..320
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 105
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WV69"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WV69"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:19367720,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 279
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 289
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 315
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WV69"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 403
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:16472756,
FT ECO:0000269|PubMed:22927433, ECO:0000269|PubMed:23355471"
FT VAR_SEQ 7..31
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044803"
FT VAR_SEQ 83..97
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057428"
FT VAR_SEQ 320..341
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8341682"
FT /id="VSP_004189"
FT MUTAGEN 124
FT /note="S->A: Reduces interaction with plasmodium berghei
FT 14-3-3 protein. Inhibits phosphorylation and interaction
FT with plasmodium berghei 14-3-3 protein; when associated
FT with A-333 and A-403."
FT /evidence="ECO:0000269|PubMed:21084299"
FT MUTAGEN 333
FT /note="S->A: Reduces interaction with plasmodium berghei
FT 14-3-3 protein. Inhibits phosphorylation and interaction
FT with plasmodium berghei 14-3-3 protein; when associated
FT with A-124 and A-403."
FT /evidence="ECO:0000269|PubMed:21084299"
FT MUTAGEN 403
FT /note="S->A: Inhibits phosphorylation and interaction with
FT plasmodium berghei 14-3-3 protein; when associated with A-
FT 124 and A-333."
FT /evidence="ECO:0000269|PubMed:21084299,
FT ECO:0000269|PubMed:23355471"
FT MUTAGEN 403
FT /note="S->E: Reduces F-actin bundling but not F-actin
FT binding activity."
FT /evidence="ECO:0000269|PubMed:21084299,
FT ECO:0000269|PubMed:23355471"
FT CONFLICT 81
FT /note="S -> Q (in Ref. 1; AAA58438 and 2; AAC50223)"
FT /evidence="ECO:0000305"
FT CONFLICT 155
FT /note="G -> A (in Ref. 3; BAG52385)"
FT /evidence="ECO:0000305"
FT CONFLICT 292
FT /note="A -> R (in Ref. 1; AAA58438 and 2; AAC50223)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="M -> V (in Ref. 1; AAA58438)"
FT /evidence="ECO:0000305"
FT CONFLICT 380
FT /note="F -> S (in Ref. 1; AAA58438)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="S -> P (in Ref. 3; BAG52385)"
FT /evidence="ECO:0000305"
FT TURN 346..348
FT /evidence="ECO:0007829|PDB:1QZP"
FT HELIX 364..366
FT /evidence="ECO:0007829|PDB:1QZP"
FT HELIX 368..370
FT /evidence="ECO:0007829|PDB:1QZP"
FT HELIX 373..379
FT /evidence="ECO:0007829|PDB:1QZP"
FT STRAND 380..382
FT /evidence="ECO:0007829|PDB:1QZP"
FT HELIX 384..389
FT /evidence="ECO:0007829|PDB:1QZP"
FT HELIX 392..402
FT /evidence="ECO:0007829|PDB:1QZP"
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
