ID DEMA_PONAB Reviewed; 405 AA.
AC Q5R4B6;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 24-JAN-2024, entry version 100.
DE RecName: Full=Dematin;
DE AltName: Full=Dematin actin-binding protein;
DE AltName: Full=Erythrocyte membrane protein band 4.9;
GN Name=DMTN; Synonyms=EPB49;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Monomeric; under reducing conditions. Self-associates. Exists
CC under oxidizing condition as a trimer linked by disulfide bonds. Found
CC in a complex with DMTN, F-actin and spectrin. Found in a complex with
CC ADD2, DMTN and SLC2A1. Interacts with F-actin, ITPKB and spectrin.
CC Interacts with SLC2A1 (via C-terminus cytoplasmic region). Interacts
CC with RASGRF2 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, cytosol
CC {ECO:0000250}. Cytoplasm, perinuclear region {ECO:0000250}. Cytoplasm,
CC cytoskeleton {ECO:0000250}. Cell membrane {ECO:0000250}. Membrane
CC {ECO:0000250}. Endomembrane system {ECO:0000250}. 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 (By similarity). {ECO:0000250}.
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. {ECO:0000250}.
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 (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the villin/gelsolin family. {ECO:0000305}.
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DR EMBL; CR861337; CAH93400.1; -; mRNA.
DR RefSeq; NP_001126921.1; NM_001133449.1.
DR AlphaFoldDB; Q5R4B6; -.
DR BMRB; Q5R4B6; -.
DR SMR; Q5R4B6; -.
DR STRING; 9601.ENSPPYP00000020629; -.
DR Ensembl; ENSPPYT00000021458.3; ENSPPYP00000020629.2; ENSPPYG00000018410.3.
DR GeneID; 100173938; -.
DR KEGG; pon:100173938; -.
DR CTD; 2039; -.
DR eggNOG; KOG1044; Eukaryota.
DR GeneTree; ENSGT00950000182850; -.
DR HOGENOM; CLU_001357_12_1_1; -.
DR InParanoid; Q5R4B6; -.
DR OMA; MLEHKIY; -.
DR OrthoDB; 370973at2759; -.
DR TreeFam; TF318042; -.
DR Proteomes; UP000001595; Chromosome 8.
DR GO; GO:0005884; C:actin filament; ISS: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; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS: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; ISS:UniProtKB.
DR GO; GO:0031095; C:platelet dense tubular network membrane; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0014731; C:spectrin-associated cytoskeleton; ISS:UniProtKB.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0043621; F:protein self-association; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; ISS:UniProtKB.
DR GO; GO:0030507; F:spectrin binding; ISS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0051017; P:actin filament bundle assembly; ISS:UniProtKB.
DR GO; GO:0051693; P:actin filament capping; IEA:UniProtKB-KW.
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; ISS:UniProtKB.
DR GO; GO:0048821; P:erythrocyte development; ISS:UniProtKB.
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:0090303; P:positive regulation of wound healing; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
DR GO; GO:0051489; P:regulation of filopodium assembly; ISS:UniProtKB.
DR GO; GO:0010591; P:regulation of lamellipodium assembly; ISS:UniProtKB.
DR Gene3D; 1.10.950.10; Villin headpiece domain; 1.
DR InterPro; IPR032402; AbLIM_anchor.
DR InterPro; IPR003128; Villin_headpiece.
DR InterPro; IPR036886; Villin_headpiece_dom_sf.
DR PANTHER; PTHR24213; ACTIN-BINDING LIM PROTEIN; 1.
DR PANTHER; PTHR24213:SF17; DEMATIN; 1.
DR Pfam; PF16182; AbLIM_anchor; 2.
DR Pfam; PF02209; VHP; 1.
DR SMART; SM00153; VHP; 1.
DR SUPFAM; SSF47050; VHP, Villin headpiece domain; 1.
DR PROSITE; PS51089; HP; 1.
PE 2: Evidence at transcript level;
KW Actin capping; Actin-binding; Cell membrane; Cell projection; Cytoplasm;
KW Cytoskeleton; Disulfide bond; Membrane; Phosphoprotein; Reference proteome;
KW Repeat; Tumor suppressor.
FT CHAIN 1..405
FT /note="Dematin"
FT /id="PRO_0000218757"
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:0000250"
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:0000250|UniProtKB:Q08495"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
FT MOD_RES 105
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
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:0000250|UniProtKB:Q08495"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
FT MOD_RES 279
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
FT MOD_RES 289
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
FT MOD_RES 315
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WV69"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
FT MOD_RES 403
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q08495"
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
//
