Reviewed, UniProtKB/Swiss-Prot Q08495 (DEMA_HUMAN)

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.
Sequence processing	The displayed sequence is not processed.
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.
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 Direct protein sequencing
Gene Ontology (GO)
Biological process	actin filament bundle formation Ref.2 Traceable author statement. Source: UniProtKB barbed-end actin filament capping Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	actin cytoskeleton Ref.1 Traceable author statement. Source: UniProtKB
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

Modified residue

105

1

Phosphoserine Ref.7

Modified residue

156

1

Phosphoserine Ref.7

Modified residue

226

1

Phosphoserine Ref.7 Ref.8

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

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. 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]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.
IPI00796556.

PIR

A48222.
I39062.

RefSeq

NP_001107607.1.
NP_001107608.1.
NP_001107609.1.
NP_001107610.1.
NP_001969.2.

UniGene

Hs.106124
Hs.186350

3D structure databases

PDBPDBe

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

ModBase

Search...

Protein-protein interaction databases

IntAct

Q08495. 4 interactions.

PTM databases

PhosphoSite

Q08495.

Proteomic databases

PRIDE

Q08495.

Genome annotation databases

Ensembl

ENSG00000158856. Homo sapiens. [Contig view]

GeneID

2039.

KEGG

hsa:2039.

Organism-specific databases

GeneCards

GC08P021967.

H-InvDB

HIX0007358.

HGNC

HGNC:3382. EPB49.

MIM

125305. gene.

PharmGKB

PA27815.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q08495.

OMA

Q08495. PSYGRTT.

Gene expression databases

ArrayExpress

Q08495.

Bgee

Q08495.

CleanEx

HS_EPB49.

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]

PROSITE

PS51089. HP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

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:	June 16, 2009
This is version 100 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)