Reviewed, UniProtKB/Swiss-Prot Q02487 (DSC2_HUMAN)

Names and origin

Protein names

Recommended name:
    Desmocollin-2
Alternative name(s):
    Desmosomal glycoprotein II and III
    Desmocollin-3

Gene names

Name:	DSC2
Synonyms:	CDHF2, DSC3

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	901 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. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms.
Subcellular location	Cell membrane; Single-pass type I membrane protein. Cell junction › desmosome.
Tissue specificity	Expressed in epithelia, myocardium and lymph nodes.
Domain	Calcium may be bound by the cadherin-like repeats Potential.
Involvement in disease	Defects in DSC2 are the cause of familial arrhythmogenic right ventricular dysplasia 11 (ARVD11) [MIM:610476]. Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited myocardial disorder associated with ventricular arrhythmias, heart failure, and sudden death. The main pathologic characteristic of ARVD is loss of myocardium, predominately in the right ventricle, and its replacement with adipose and fibrous tissue. Familial ARVD is believed to account for at least 30%-50% of all cases, although penetrance in some families is estimated to be <30%. Ref.5
Sequence similarities	Contains 5 cadherin domains.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Cardiomyopathy
Domain	Repeat Signal Transmembrane
Ligand	Calcium
PTM	Cleavage on pair of basic residues Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	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
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein 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 2A (identifier: Q02487-1)

Also known as: DGII;

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 2B (identifier: Q02487-2)

Also known as: DGIII;

The sequence of this isoform differs from the canonical sequence as follows:
     837-847: KVYLCNQDENH → ESIRGHTLIKN
     848-901: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Propeptide	28 – 135	108	Potential		PRO_0000003869
	Chain	136 – 901	766	Desmocollin-2		PRO_0000003870
Regions
	Topological domain	136 – 694	559	Extracellular Potential
	Transmembrane	695 – 715	21	Potential
	Topological domain	716 – 901	186	Cytoplasmic Potential
	Domain	136 – 243	108	Cadherin 1
	Domain	244 – 355	112	Cadherin 2
	Domain	356 – 471	116	Cadherin 3
	Domain	472 – 579	108	Cadherin 4
	Domain	580 – 694	115	Cadherin 5
Amino acid modifications
	Modified residue	864	1	Phosphoserine Potential
	Glycosylation	34	1	N-linked (GlcNAc...) Potential
	Glycosylation	166	1	N-linked (GlcNAc...) Potential
	Glycosylation	392	1	N-linked (GlcNAc...) Ref.4
	Glycosylation	546	1	N-linked (GlcNAc...) Ref.3
	Glycosylation	629	1	N-linked (GlcNAc...) Ref.4
Natural variations
	Alternative sequence	837 – 847	11	KVYLCNQDENH → ESIRGHTLIKN in isoform 2B.		VSP_000657
	Alternative sequence	848 – 901	54	Missing in isoform 2B.		VSP_000658
	Natural variant	11	1	N → S: dbSNP rs868333.		VAR_029480
	Natural variant	776	1	I → V: dbSNP rs1893963.		VAR_024388

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2A (DGII) [UniParc]. Last modified February 1, 1994. Version 1. Checksum: 30F7E3D33ECA67CC	FASTA	901	99,962
	10 20 30 40 50 60 MEAARPSGSW NGALCRLLLL TLAILIFASD ACKNVTLHVP SKLDAEKLVG RVNLKECFTA 70 80 90 100 110 120 ANLIHSSDPD FQILEDGSVY TTNTILLSSE KRSFTILLSN TENQEKKKIF VFLEHQTKVL 130 140 150 160 170 180 KKRHTKEKVL RRAKRRWAPI PCSMLENSLG PFPLFLQQVQ SDTAQNYTIY YSIRGPGVDQ 190 200 210 220 230 240 EPRNLFYVER DTGNLYCTRP VDREQYESFE IIAFATTPDG YTPELPLPLI IKIEDENDNY 250 260 270 280 290 300 PIFTEETYTF TIFENCRVGT TVGQVCATDK DEPDTMHTRL KYSIIGQVPP SPTLFSMHPT 310 320 330 340 350 360 TGVITTTSSQ LDRELIDKYQ LKIKVQDMDG QYFGLQTTST CIINIDDVND HLPTFTRTSY 370 380 390 400 410 420 VTSVEENTVD VEILRVTVED KDLVNTANWR ANYTILKGNE NGNFKIVTDA KTNEGVLCVV 430 440 450 460 470 480 KPLNYEEKQQ MILQIGVVNE APFSREASPR SAMSTATVTV NVEDQDEGPE CNPPIQTVRM 490 500 510 520 530 540 KENAEVGTTS NGYKAYDPET RSSSGIRYKK LTDPTGWVTI DENTGSIKVF RSLDREAETI 550 560 570 580 590 600 KNGIYNITVL ASDQGGRTCT GTLGIILQDV NDNSPFIPKK TVIICKPTMS SAEIVAVDPD 610 620 630 640 650 660 EPIHGPPFDF SLESSTSEVQ RMWRLKAIND TAARLSYQND PPFGSYVVPI TVRDRLGMSS 670 680 690 700 710 720 VTSLDVTLCD CITENDCTHR VDPRIGGGGV QLGKWAILAI LLGIALLFCI LFTLVCGASG 730 740 750 760 770 780 TSKQPKVIPD DLAQQNLIVS NTEAPGDDKV YSANGFTTQT VGASAQGVCG TVGSGIKNGG 790 800 810 820 830 840 QETIEMVKGG HQTSESCRGA GHHHTLDSCR GGHTEVDNCR YTYSEWHSFT QPRLGEKVYL 850 860 870 880 890 900 CNQDENHKHA QDYVLTYNYE GRGSVAGSVG CCSERQEEDG LEFLDNLEPK FRTLAEACMK R
	Isoform 2B (DGIII). Checksum: A53588B1D490CD8F	FASTA	847	93,769
	10 20 30 40 50 60 MEAARPSGSW NGALCRLLLL TLAILIFASD ACKNVTLHVP SKLDAEKLVG RVNLKECFTA 70 80 90 100 110 120 ANLIHSSDPD FQILEDGSVY TTNTILLSSE KRSFTILLSN TENQEKKKIF VFLEHQTKVL 130 140 150 160 170 180 KKRHTKEKVL RRAKRRWAPI PCSMLENSLG PFPLFLQQVQ SDTAQNYTIY YSIRGPGVDQ 190 200 210 220 230 240 EPRNLFYVER DTGNLYCTRP VDREQYESFE IIAFATTPDG YTPELPLPLI IKIEDENDNY 250 260 270 280 290 300 PIFTEETYTF TIFENCRVGT TVGQVCATDK DEPDTMHTRL KYSIIGQVPP SPTLFSMHPT 310 320 330 340 350 360 TGVITTTSSQ LDRELIDKYQ LKIKVQDMDG QYFGLQTTST CIINIDDVND HLPTFTRTSY 370 380 390 400 410 420 VTSVEENTVD VEILRVTVED KDLVNTANWR ANYTILKGNE NGNFKIVTDA KTNEGVLCVV 430 440 450 460 470 480 KPLNYEEKQQ MILQIGVVNE APFSREASPR SAMSTATVTV NVEDQDEGPE CNPPIQTVRM 490 500 510 520 530 540 KENAEVGTTS NGYKAYDPET RSSSGIRYKK LTDPTGWVTI DENTGSIKVF RSLDREAETI 550 560 570 580 590 600 KNGIYNITVL ASDQGGRTCT GTLGIILQDV NDNSPFIPKK TVIICKPTMS SAEIVAVDPD 610 620 630 640 650 660 EPIHGPPFDF SLESSTSEVQ RMWRLKAIND TAARLSYQND PPFGSYVVPI TVRDRLGMSS 670 680 690 700 710 720 VTSLDVTLCD CITENDCTHR VDPRIGGGGV QLGKWAILAI LLGIALLFCI LFTLVCGASG 730 740 750 760 770 780 TSKQPKVIPD DLAQQNLIVS NTEAPGDDKV YSANGFTTQT VGASAQGVCG TVGSGIKNGG 790 800 810 820 830 840 QETIEMVKGG HQTSESCRGA GHHHTLDSCR GGHTEVDNCR YTYSEWHSFT QPRLGEESIR GHTLIKN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Desmosomal glycoproteins II and III. Cadherin-like junctional molecules generated by alternative splicing." Parker A.E., Wheeler G.N., Arnemann J., Pidsley S.C., Ataliotis P., Thomas C.L., Rees D.A., Magee A.I., Buxton R.S. J. Biol. Chem. 266:10438-10445(1991) [PubMed: 2037591] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2A AND 2B). Tissue: Keratinocyte.
[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] (ISOFORM 2A). Tissue: Placenta.
[3]	"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-546, MASS SPECTROMETRY. Tissue: Plasma.
[4]	"Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry." Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A. J. Proteome Res. 5:1493-1503(2006) [PubMed: 16740002] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-392 AND ASN-629, MASS SPECTROMETRY. Tissue: Saliva.
[5]	"Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2." Syrris P., Ward D., Evans A., Asimaki A., Gandjbakhch E., Sen-Chowdhry S., McKenna W.J. Am. J. Hum. Genet. 79:978-984(2006) [PubMed: 17033975] [Abstract] Cited for: INVOLVEMENT IN ARVD11.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	X56807 mRNA. Translation: CAA40141.1. Different initiation. X56807 mRNA. Translation: CAA40142.1. Different initiation. BC063291 mRNA. Translation: AAH63291.1.
IPI	IPI00025846. IPI00220146.
PIR	IJHUDB. A40390. IJHUDA. B40390.
RefSeq	NP_004940.1. NP_077740.1.
UniGene	Hs.95612
3D structure databases
HSSP	HSSP built from PDB template 1NCJ based on UniProtKB P15116.
ModBase	Search...
PTM databases
PhosphoSite	Q02487.
Proteomic databases
PRIDE	Q02487.
Genome annotation databases
Ensembl	ENSG00000134755. Homo sapiens. [Contig view]
GeneID	1824.
KEGG	hsa:1824.
Organism-specific databases
GeneCards	GC18M026900.
H-InvDB	HIX0027434.
HGNC	HGNC:3036. DSC2.
HPA	HPA011911. HPA012615.
MIM	125645. gene. 610476. phenotype.
Orphanet	247. Arrhythmogenic right ventricular dysplasia.
PharmGKB	PA27489.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q02487.
HOVERGEN	Q02487.
OMA	Q02487. GNFKIVT.
Gene expression databases
ArrayExpress	Q02487.
Bgee	Q02487.
CleanEx	HS_DSC2. HS_DSC3.
GermOnline	ENSG00000134755. Homo sapiens.
Family and domain databases
InterPro	IPR002126. Cadherin. IPR014868. Cadherin_pro. IPR009122. Desmo_cadherin. IPR009124. Desmocollin. [Graphical view]
Gene3D	G3DSA:2.60.40.60. Cadherin. 4 hits.
Pfam	PF00028. Cadherin. 4 hits. PF08758. Cadherin_pro. 1 hit. [Graphical view]
PRINTS	PR00205. CADHERIN. PR01818. DESMOCADHERN. PR01820. DESMOCOLLIN.
SMART	SM00112. CA. 5 hits. [Graphical view]
PROSITE	PS00232. CADHERIN_1. 3 hits. PS50268. CADHERIN_2. 5 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	7437.
SOURCE	Search...

Entry information

Entry name

DSC2_HUMAN

Accession

Primary (citable) accession number: Q02487

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	June 16, 2009
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)