Q08495 (DEMA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dematin

Alternative name(s):
Erythrocyte membrane protein band 4.9

Gene names

Name:	EPB49
Synonyms:	DMT

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	405 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Actin-bundling protein. May function in mitogen-activated protein kinase pathway. Ref.6
Subunit structure	Exists in solution as a trimer of two short isoforms and one long isoform linked by disulfide bonds Probable. Interacts with RASGRF2. Ref.2 Ref.6
Subcellular location	Cytoplasm Ref.6.
Tissue specificity	Heart, brain, lung, skeletal muscle, and kidney.
Domain	Contains at least two actin-binding sites, one in the headpiece domain and one in the amino-terminal portion. Consists of a large core fragment, the amino-terminal portion, and a small headpiece, the C-terminal portion. The headpiece can bind but cannot bundle actin filaments.
Post-translational modification	Actin-bundling activity is abolished upon phosphorylation by cAMP-dependent protein kinase. The N-terminus is blocked.
Sequence similarities	Belongs to the villin/gelsolin family. Contains 1 HP (headpiece) domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	Actin-binding
Molecular function	Actin capping
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	actin filament bundle assembly Traceable author statement Ref.2. Source: UniProtKB actin filament capping Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	actin cytoskeleton Traceable author statement Ref.1. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Molecular function	actin binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: Q08495-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: Q08495-2)

The sequence of this isoform differs from the canonical sequence as follows:
     320-341: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 405

405

Dematin

PRO_0000218755

Regions

Domain

337 – 405

69

HP

Region

224 – 308

85

Interaction with RASGRF2

Compositional bias

216 – 222

7

Poly-Glu

Amino acid modifications

Modified residue

10

1

Phosphothreonine Ref.7

Modified residue

14

1

Phosphoserine Ref.7

Modified residue

16

1

Phosphoserine Ref.7

Modified residue

22

1

Phosphoserine Ref.7

Modified residue

26

1

Phosphoserine Ref.7

Modified residue

28

1

Phosphoserine Ref.7

Modified residue

87

1

Phosphoserine By similarity

Modified residue

91

1

Phosphothreonine By similarity

Modified residue

92

1

Phosphoserine Ref.7

Modified residue

96

1

Phosphoserine Ref.7 Ref.10

Modified residue

105

1

Phosphoserine Ref.7 Ref.10

Modified residue

156

1

Phosphoserine Ref.7

Modified residue

226

1

Phosphoserine Ref.7 Ref.8 Ref.9

Modified residue

289

1

Phosphoserine Ref.7

Modified residue

333

1

Phosphoserine Ref.7

Modified residue

372

1

Phosphoserine Ref.7

Modified residue

403

1

Phosphoserine; by PKA Ref.12

Natural variations

Alternative sequence

320 – 341

22

Missing in isoform Short.

VSP_004189

Experimental info

Sequence conflict

81

1

S → Q in AAA58438. Ref.1

Sequence conflict

81

1

S → Q in AAC50223. Ref.2

Sequence conflict

292

1

A → R in AAA58438. Ref.1

Sequence conflict

292

1

A → R in AAC50223. Ref.2

Sequence conflict

347

1

M → V in AAA58438. Ref.1

Sequence conflict

380

1

F → S in AAA58438. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

405

Helix Strand Turn

Details...

Turn

346 – 348

3

Helix

364 – 366

3

Helix

368 – 370

3

Helix

373 – 379

7

Beta strand

380 – 382

3

Helix

384 – 389

6

Helix

392 – 402

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified August 30, 2002. Version 3. Checksum: 77D6372E5B16EFF4	FASTA	405	45,514
	10 20 30 40 50 60 MERLQKQPLT SPGSVSPSRD SSVPGSPSSI VAKMDNQVLG YKDLAAIPKD KAILDIERPD 70 80 90 100 110 120 LMIYEPHFTY SLLEHVELPR SRERSLSPKS TSPPPSPEVW ADSRSPGIIS QASAPRTTGT 130 140 150 160 170 180 PRTSLPHFHH PETSRPDSNI YKKPPIYKQR ESVGGSPQTK HLIEDLIIES SKFPAAQPPD 190 200 210 220 230 240 PNQPAKIETD YWPCPPSLAV VETEWRKRKA SRRGAEEEEE EEDDDSGEEM KALRERQREE 250 260 270 280 290 300 LSKVTSNLGK MILKEEMEKS LPIRRKTRSL PDRTPFHTSL HQGTSKSSSL PAYGRTTLSR 310 320 330 340 350 360 LQSTEFSPSG SETGSPGLQN GEGQRGRMDR GNSLPCVLEQ KIYPYEMLVV TNKGRTKLPP 370 380 390 400 GVDRMRLERH LSAEDFSRVF AMSPEEFGKL ALWKRNELKK KASLF
	Isoform Short [UniParc]. Checksum: 3C46AB7704507B6E	FASTA	383	43,088
	10 20 30 40 50 60 MERLQKQPLT SPGSVSPSRD SSVPGSPSSI VAKMDNQVLG YKDLAAIPKD KAILDIERPD 70 80 90 100 110 120 LMIYEPHFTY SLLEHVELPR SRERSLSPKS TSPPPSPEVW ADSRSPGIIS QASAPRTTGT 130 140 150 160 170 180 PRTSLPHFHH PETSRPDSNI YKKPPIYKQR ESVGGSPQTK HLIEDLIIES SKFPAAQPPD 190 200 210 220 230 240 PNQPAKIETD YWPCPPSLAV VETEWRKRKA SRRGAEEEEE EEDDDSGEEM KALRERQREE 250 260 270 280 290 300 LSKVTSNLGK MILKEEMEKS LPIRRKTRSL PDRTPFHTSL HQGTSKSSSL PAYGRTTLSR 310 320 330 340 350 360 LQSTEFSPSG SETGSPGLQI YPYEMLVVTN KGRTKLPPGV DRMRLERHLS AEDFSRVFAM 370 380 SPEEFGKLAL WKRNELKKKA SLF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of human erythroid dematin reveals another member of the villin family." Rana A.P., Ruff P., Maalouf G.J., Speicher D.W., Chishti A.H. Proc. Natl. Acad. Sci. U.S.A. 90:6651-6655(1993) [PubMed: 8341682] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), PARTIAL PROTEIN SEQUENCE. Tissue: Reticulocyte.
[2]	"Isoform cloning, actin binding, and chromosomal localization of human erythroid dematin, a member of the villin superfamily." Azim A.C., Knoll J.H.M., Beggs A.H., Chishti A.H. J. Biol. Chem. 270:17407-17413(1995) [PubMed: 7615546] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), PHOSPHORYLATION BY CAPK, SUBUNIT, ALTERNATIVE SPLICING. Tissue: Reticulocyte.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND SHORT). Tissue: Amygdala and Kidney.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND SHORT). Tissue: Brain and Liver.
[6]	"Dematin interacts with the Ras-guanine nucleotide exchange factor Ras-GRF2 and modulates mitogen-activated protein kinase pathways." Lutchman M., Kim A.C., Cheng L., Whitehead I.P., Oh S.S., Hanspal M., Boukharov A.A., Hanada T., Chishti A.H. Eur. J. Biochem. 269:638-649(2002) [PubMed: 11856323] [Abstract] Cited for: FUNCTION, INTERACTION WITH RASGRF2, SUBCELLULAR LOCATION.
[7]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-10; SER-14; SER-16; SER-22; SER-26; SER-28; SER-92; SER-96; SER-105; SER-156; SER-226; SER-289; SER-333 AND SER-372, MASS SPECTROMETRY. Tissue: Platelet.
[8]	"Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment." Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J. J. Proteome Res. 7:5167-5176(2008) [PubMed: 19367720] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, MASS SPECTROMETRY. Tissue: T-cell.
[9]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96 AND SER-105, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[11]	"The NMR structure of dematin headpiece reveals a dynamic loop that is conformationally altered upon phosphorylation at a distal site." Frank B.S., Vardar D., Chishti A.H., McKnight C.J. J. Biol. Chem. 279:7909-7916(2004) [PubMed: 14660664] [Abstract] Cited for: STRUCTURE BY NMR OF 342-405.
[12]	"A phosphorylation-induced conformation change in dematin headpiece." Jiang Z.G., McKnight C.J. Structure 14:379-387(2006) [PubMed: 16472756] [Abstract] Cited for: STRUCTURE BY NMR OF 342-405, PHOSPHORYLATION AT SER-403.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L19713 mRNA. Translation: AAA58438.1.
U28389 mRNA. Translation: AAC50223.1.
AK055842 mRNA. Translation: BAG51582.1.
AK289650 mRNA. Translation: BAF82339.1.
BT007396 mRNA. Translation: AAP36060.1.
BC006318 mRNA. Translation: AAH06318.1.
BC017445 mRNA. Translation: AAH17445.1.
BC052805 mRNA. Translation: AAH52805.1.

IPI

IPI00292290.
IPI01015007.

PIR

A48222.
I39062.

RefSeq

NP_001107607.1. NM_001114135.2.
NP_001107608.1. NM_001114136.1.
NP_001107609.1. NM_001114137.1.
NP_001107610.1. NM_001114138.1.
NP_001107611.1. NM_001114139.1.
NP_001969.2. NM_001978.2.

UniGene

Hs.106124.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QZP	NMR	-	A	342-405	[»]
1ZV6	NMR	-	A	342-405	[»]

ProteinModelPortal

Q08495.

SMR

Q08495. Positions 341-405.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q08495. 4 interactions.

MINT

MINT-1390442.

STRING

Q08495.

PTM databases

PhosphoSite

Q08495.

Polymorphism databases

DMDM

22654240.

Proteomic databases

PRIDE

Q08495.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265800; ENSP00000265800; ENSG00000158856.
ENST00000358242; ENSP00000350977; ENSG00000158856.
ENST00000432128; ENSP00000416111; ENSG00000158856.

GeneID

2039.

KEGG

hsa:2039.

UCSC

uc010ltr.1. human.

Organism-specific databases

CTD

2039.

GeneCards

GC08P021906.

H-InvDB

HIX0007358.

HGNC

HGNC:3382. EPB49.

HPA

HPA024290.

MIM

125305. gene.

neXtProt

NX_Q08495.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15761.

GeneTree

ENSGT00570000079028.

HOVERGEN

HBG031499.

OMA

PSYGRTT.

OrthoDB

EOG4XD3RG.

PhylomeDB

Q08495.

Gene expression databases

ArrayExpress

Q08495.

Bgee

Q08495.

CleanEx

HS_EPB49.

Genevestigator

Q08495.

GermOnline

ENSG00000158856. Homo sapiens.

Family and domain databases

InterPro

IPR003128. Villin_headpiece.
[Graphical view]

Gene3D

G3DSA:1.10.950.10. VHP. 1 hit.

Pfam

PF02209. VHP. 1 hit.
[Graphical view]

SMART

SM00153. VHP. 1 hit.
[Graphical view]

SUPFAM

SSF47050. VHP. 1 hit.

PROSITE

PS51089. HP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

8281.

SOURCE

Search...

Entry information

Entry name

DEMA_HUMAN

Accession

Primary (citable) accession number: Q08495
Secondary accession number(s): A8K0T5 , B3KP70, Q13215, Q9BRE3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	August 30, 2002
Last modified:	January 25, 2012
This is version 124 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.