Q14126 (DSG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Desmoglein-2

Alternative name(s):
Cadherin family member 5
HDGC

Gene names

Name:	DSG2
Synonyms:	CDHF5

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	1118 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.
Subcellular location	Cell membrane; Single-pass type I membrane protein. Cell junction › desmosome.
Tissue specificity	All of the tissues tested and carcinomas.
Domain	Calcium may be bound by the cadherin-like repeats Potential.
Involvement in disease	Defects in DSG2 are the cause of familial arrhythmogenic right ventricular dysplasia type 10 (ARVD10) [MIM:610193]; also known as arrhythmogenic right ventricular cardiomyopathy 10 (ARVC10). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall. Ref.16 Ref.18 Ref.19 Ref.20 Genetic variations in DSG2 are the cause of susceptibility to cardiomyopathy dilated type 1BB (CMD1BB) [MIM:612877]. A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. Ref.17
Sequence similarities	Contains 4 cadherin domains.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Cardiomyopathy Disease mutation
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium
PTM	Cleavage on pair of basic residues Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cellular component disassembly involved in apoptosis Traceable author statement. Source: Reactome homophilic cell adhesion Inferred from electronic annotation. Source: InterPro
Cellular component	desmosome Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay. Source: HPA
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Potential

Propeptide

24 – 49

26

Potential

PRO_0000003845

Chain

50 – 1118

1069

Desmoglein-2

PRO_0000003846

Regions

Topological domain

50 – 609

560

Extracellular Potential

Transmembrane

610 – 634

25

Helical; Potential

Topological domain

635 – 1118

484

Cytoplasmic Potential

Domain

50 – 160

111

Cadherin 1

Domain

161 – 273

113

Cadherin 2

Domain

274 – 388

115

Cadherin 3

Domain

389 – 503

115

Cadherin 4

Repeat

881 – 912

32

Desmoglein repeat 1

Repeat

913 – 942

30

Desmoglein repeat 2

Repeat

943 – 968

26

Desmoglein repeat 3

Repeat

969 – 992

24

Desmoglein repeat 4

Repeat

993 – 1021

29

Desmoglein repeat 5

Repeat

1022 – 1051

30

Desmoglein repeat 6

Amino acid modifications

Modified residue

680

1

Phosphoserine Ref.7 Ref.8 Ref.9 Ref.13

Modified residue

968

1

Phosphotyrosine Ref.5

Modified residue

979

1

Phosphotyrosine Ref.11

Modified residue

1013

1

Phosphotyrosine Ref.7 Ref.11

Glycosylation

112

1

N-linked (GlcNAc...) Ref.4 Ref.10

Glycosylation

182

1

N-linked (GlcNAc...) Ref.6 Ref.10 Ref.12

Glycosylation

309

1

N-linked (GlcNAc...) Potential

Glycosylation

462

1

N-linked (GlcNAc...) Ref.12

Glycosylation

514

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

46

1

R → Q in ARVD10. Ref.16 Ref.18

VAR_029365

Natural variant

49

1

R → H in ARVD10. Ref.16 Ref.18 Ref.19 Ref.20

VAR_029366

Natural variant

56

1

V → M Associated with CMD1BB and ARVD10 although it may not be sufficient by itself to result in cardiomyopathy. Ref.17 Ref.18

VAR_062387

Natural variant

89

1

Y → C.
Corresponds to variant rs2230232 [ dbSNP | Ensembl ].

VAR_048508

Natural variant

158

1

V → G. Ref.17

VAR_062388

Natural variant

293

1

I → V. Ref.17 Ref.19
Corresponds to variant rs2230234 [ dbSNP | Ensembl ].

VAR_048509

Natural variant

335

1

T → A in ARVD10. Ref.18

VAR_065686

Natural variant

507

1

C → Y in ARVD10. Ref.16 Ref.18

VAR_029367

Natural variant

515

1

V → I.
Corresponds to variant rs2230235 [ dbSNP | Ensembl ].

VAR_048510

Natural variant

713

1

E → K. Ref.17 Ref.19

VAR_062389

Natural variant

773

1

R → K. Ref.17 Ref.19
Corresponds to variant rs2278792 [ dbSNP | Ensembl ].

VAR_048511

Natural variant

812

1

G → C in ARVD10. Ref.16 Ref.18

VAR_029368

Natural variant

863

1

M → L.
Corresponds to variant rs16962093 [ dbSNP | Ensembl ].

VAR_048512

Natural variant

903

1

T → I.
Corresponds to variant rs34065672 [ dbSNP | Ensembl ].

VAR_048513

Natural variant

920

1

V → G. Ref.17 Ref.19

VAR_062390

Experimental info

Sequence conflict

4 – 10

7

SPGRAYA → TRDRVR in CAA81226. Ref.1

Sequence conflict

593

1

C → V in CAA81226. Ref.1

Sequence conflict

643

1

G → A in CAA81226. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1118

Helix Strand Turn

Details...

Beta strand

56 – 59

4

Helix

77 – 80

4

Beta strand

86 – 90

5

Beta strand

102 – 104

3

Beta strand

111 – 113

3

Turn

119 – 121

3

Beta strand

122 – 126

5

Beta strand

130 – 132

3

Beta strand

138 – 140

3

Beta strand

146 – 150

5

Sequences

	Sequence		Length	Mass (Da)
	Q14126 [UniParc]. Last modified May 29, 2007. Version 2. Checksum: E1481AA1686DB80A	FASTA	1,118	122,294
	10 20 30 40 50 60 MARSPGRAYA LLLLLICFNV GSGLHLQVLS TRNENKLLPK HPHLVRQKRA WITAPVALRE 70 80 90 100 110 120 GEDLSKKNPI AKIHSDLAEE RGLKITYKYT GKGITEPPFG IFVFNKDTGE LNVTSILDRE 130 140 150 160 170 180 ETPFFLLTGY ALDARGNNVE KPLELRIKVL DINDNEPVFT QDVFVGSVEE LSAAHTLVMK 190 200 210 220 230 240 INATDADEPN TLNSKISYRI VSLEPAYPPV FYLNKDTGEI YTTSVTLDRE EHSSYTLTVE 250 260 270 280 290 300 ARDGNGEVTD KPVKQAQVQI RILDVNDNIP VVENKVLEGM VEENQVNVEV TRIKVFDADE 310 320 330 340 350 360 IGSDNWLANF TFASGNEGGY FHIETDAQTN EGIVTLIKEV DYEEMKNLDF SVIVANKAAF 370 380 390 400 410 420 HKSIRSKYKP TPIPIKVKVK NVKEGIHFKS SVISIYVSES MDRSSKGQII GNFQAFDEDT 430 440 450 460 470 480 GLPAHARYVK LEDRDNWISV DSVTSEIKLA KLPDFESRYV QNGTYTVKIV AISEDYPRKT 490 500 510 520 530 540 ITGTVLINVE DINDNCPTLI EPVQTICHDA EYVNVTAEDL DGHPNSGPFS FSVIDKPPGM 550 560 570 580 590 600 AEKWKIARQE STSVLLQQSE KKLGRSEIQF LISDNQGFSC PEKQVLTLTV CECLHGSGCR 610 620 630 640 650 660 EAQHDSYVGL GPAAIALMIL AFLLLLLVPL LLLMCHCGKG AKGFTPIPGT IEMLHPWNNE 670 680 690 700 710 720 GAPPEDKVVP SFLPVDQGGS LVGRNGVGGM AKEATMKGSS SASIVKGQHE MSEMDGRWEE 730 740 750 760 770 780 HRSLLSGRAT QFTGATGAIM TTETTKTARA TGASRDMAGA QAAAVALNEE FLRNYFTDKA 790 800 810 820 830 840 ASYTEEDENH TAKDCLLVYS QEETESLNAS IGCCSFIEGE LDDRFLDDLG LKFKTLAEVC 850 860 870 880 890 900 LGQKIDINKE IEQRQKPATE TSMNTASHSL CEQTMVNSEN TYSSGSSFPV PKSLQEANAE 910 920 930 940 950 960 KVTQEIVTER SVSSRQAQKV ATPLPDPMAS RNVIATETSY VTGSTMPPTT VILGPSQPQS 970 980 990 1000 1010 1020 LIVTERVYAP ASTLVDQPYA NEGTVVVTER VIQPHGGGSN PLEGTQHLQD VPYVMVRERE 1030 1040 1050 1060 1070 1080 SFLAPSSGVQ PTLAMPNIAV GQNVTVTERV LAPASTLQSS YQIPTENSMT ARNTTVSGAG 1090 1100 1110 VPGPLPDFGL EESGHSNSTI TTSSTRVTKH STVQHSYS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of the ubiquitous human desmoglein, Dsg2, and the expression catalogue of the desmoglein subfamily of desmosomal cadherins." Schaefer S., Koch P.J., Franke W.W. Exp. Cell Res. 211:391-399(1994) [PubMed: 8143788] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Colon carcinoma.
[2]	"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].
[3]	"Complete amino acid sequence of the epidermal desmoglein precursor polypeptide and identification of a second type of desmoglein gene." Koch P.J., Goldschmidt M.D., Walsh M.J., Zimbelmann R., Franke W.W. Eur. J. Cell Biol. 55:200-208(1991) [PubMed: 1935985] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 778-1118.
[4]	"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry." Zhang H., Li X.-J., Martin D.B., Aebersold R. Nat. Biotechnol. 21:660-666(2003) [PubMed: 12754519] [Abstract] Cited for: GLYCOSYLATION AT ASN-112.
[5]	"Phosphoproteome analysis of HeLa cells using stable isotope labeling with amino acids in cell culture (SILAC)." Amanchy R., Kalume D.E., Iwahori A., Zhong J., Pandey A. J. Proteome Res. 4:1661-1671(2005) [PubMed: 16212419] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-968, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-182, MASS SPECTROMETRY. Tissue: Plasma.
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-680 AND TYR-1013, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-680, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-680, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-112 AND ASN-182, MASS SPECTROMETRY. Tissue: Liver.
[11]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-979 AND TYR-1013, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[12]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-182 AND ASN-462, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"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-680, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Solution structure of the first cadherin domain from human desmoglein-2." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 47-162.
[16]	"DSG2 mutations contribute to arrhythmogenic right ventricular dysplasia/cardiomyopathy." Awad M.M., Dalal D., Cho E., Amat-Alarcon N., James C., Tichnell C., Tucker A., Russell S.D., Bluemke D.A., Dietz H.C., Calkins H., Judge D.P. Am. J. Hum. Genet. 79:136-142(2006) [PubMed: 16773573] [Abstract] Cited for: VARIANTS ARVD10 GLN-46; HIS-49; TYR-507 AND CYS-812.
[17]	"A missense variant in desmoglein-2 predisposes to dilated cardiomyopathy." Posch M.G., Posch M.J., Geier C., Erdmann B., Mueller W., Richter A., Ruppert V., Pankuweit S., Maisch B., Perrot A., Buttgereit J., Dietz R., Haverkamp W., Ozcelik C. Mol. Genet. Metab. 95:74-80(2008) [PubMed: 18678517] [Abstract] Cited for: VARIANTS MET-56; GLY-158; VAL-293; LYS-713; LYS-773 AND GLY-920, INVOLVEMENT IN SUSCEPTIBILITY TO CMD1BB.
[18]	"Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy." den Haan A.D., Tan B.Y., Zikusoka M.N., Llado L.I., Jain R., Daly A., Tichnell C., James C., Amat-Alarcon N., Abraham T., Russell S.D., Bluemke D.A., Calkins H., Dalal D., Judge D.P. Circ. Cardiovasc. Genet. 2:428-435(2009) [PubMed: 20031617] [Abstract] Cited for: VARIANTS ARVD10 GLN-46; HIS-49; ALA-335; TYR-507 AND CYS-812, VARIANT MET-56.
[19]	"Role of genetic testing in arrhythmogenic right ventricular cardiomyopathy/dysplasia." Barahona-Dussault C., Benito B., Campuzano O., Iglesias A., Leung T.L., Robb L., Talajic M., Brugada R. Clin. Genet. 77:37-48(2010) [PubMed: 19863551] [Abstract] Cited for: VARIANT ARVD10 HIS-49, VARIANTS VAL-293; LYS-713; LYS-773 AND GLY-920.
[20]	"Mechanistic insights into arrhythmogenic right ventricular cardiomyopathy caused by desmocollin-2 mutations." Gehmlich K., Syrris P., Peskett E., Evans A., Ehler E., Asimaki A., Anastasakis A., Tsatsopoulou A., Vouliotis A.I., Stefanadis C., Saffitz J.E., Protonotarios N., McKenna W.J. Cardiovasc. Res. 90:77-87(2011) [PubMed: 21062920] [Abstract] Cited for: VARIANT ARVD10 HIS-49.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z26317 mRNA. Translation: CAA81226.1.
BC099655 mRNA. Translation: AAH99655.1.
BC099656 mRNA. Translation: AAH99656.1.
BC099657 mRNA. Translation: AAH99657.1.

IPI

IPI00028931.

PIR

S38673.

RefSeq

NP_001934.2. NM_001943.3.

UniGene

Hs.412597.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YQG	NMR	-	A	47-162	[»]

ProteinModelPortal

Q14126.

SMR

Q14126. Positions 47-599, 765-842.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46250N.

IntAct

Q14126. 3 interactions.

STRING

Q14126.

PTM databases

PhosphoSite

Q14126.

Polymorphism databases

DMDM

148876773.

Proteomic databases

PRIDE

Q14126.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261590; ENSP00000261590; ENSG00000046604.

GeneID

1829.

KEGG

hsa:1829.

NMPDR

fig|9606.3.peg.14914.

UCSC

uc002kwu.2. human.

Organism-specific databases

CTD

1829.

GeneCards

GC18P029101.

H-InvDB

HIX0039840.

HGNC

HGNC:3049. DSG2.

HPA

CAB025122.
HPA004896.

MIM

125671. gene.
610193. phenotype.
612877. phenotype.

neXtProt

NX_Q14126.

Orphanet

217656. Familial isolated arrhythmogenic right ventricular dysplasia.
154. Familial isolated dilated cardiomyopathy.

PharmGKB

PA27502.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08383.

GeneTree

ENSGT00550000074342.

HOGENOM

HBG282617.

HOVERGEN

HBG005532.

InParanoid

Q14126.

OMA

RAWITAP.

OrthoDB

EOG4RR6H9.

PhylomeDB

Q14126.

Enzyme and pathway databases

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

Q14126.

Bgee

Q14126.

CleanEx

HS_DSG2.

Genevestigator

Q14126.

GermOnline

ENSG00000046604. Homo sapiens.

Family and domain databases

InterPro

IPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR020894. Cadherin_CS.
IPR000233. Cadherin_cytoplasmic-dom.
IPR009122. Desmo_cadherin.
IPR009123. Desmoglein.
IPR015488. Desmoglein2.
[Graphical view]

Gene3D

G3DSA:2.60.40.60. Cadherin. 4 hits.

KO

K07597.

PANTHER

PTHR24025:SF33. PTHR24025:SF33. 1 hit.

Pfam

PF00028. Cadherin. 3 hits.
PF01049. Cadherin_C. 1 hit.
[Graphical view]

PRINTS

PR00205. CADHERIN.
PR01818. DESMOCADHERN.
PR01819. DESMOGLEIN.

SMART

SM00112. CA. 4 hits.
[Graphical view]

SUPFAM

SSF49313. Cadherin. 4 hits.

PROSITE

PS00232. CADHERIN_1. 3 hits.
PS50268. CADHERIN_2. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

NextBio

7465.

PMAP-CutDB

Q14126.

SOURCE

Search...

Entry information

Entry name

DSG2_HUMAN

Accession

Primary (citable) accession number: Q14126
Secondary accession number(s): Q4KKU6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 29, 2007
Last modified:	January 25, 2012
This is version 111 of the entry and version 2 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.