Q02487 (DSC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Desmocollin-2

Alternative name(s):
Cadherin family member 2
Desmocollin-3
Desmosomal glycoprotein II
Desmosomal glycoprotein III

Gene names

Name:	DSC2
Synonyms:	CDHF2, DSC3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.
Subunit structure	Interacts with DSP, PKP2 and JUP. Ref.6
Subcellular location	Cell membrane; Single-pass type I membrane protein. Cell junction › desmosome Ref.6.
Tissue specificity	Expressed in epithelia, myocardium and lymph nodes.
Domain	Calcium may be bound by the cadherin-like repeats Potential. Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain By similarity.
Involvement in disease	Familial arrhythmogenic right ventricular dysplasia 11 (ARVD11) [MIM:610476]: A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6 Ref.9
Sequence similarities	Contains 5 cadherin domains.
Sequence caution	The sequence CAA40141.1 differs from that shown. Reason: Erroneous initiation. The sequence CAA40142.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Cardiomyopathy Disease mutation
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding
PTM	Cleavage on pair of basic residues Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bundle of His cell to Purkinje myocyte communication Inferred from mutant phenotype PubMed 22781308. Source: BHF-UCL cell adhesion Traceable author statement Ref.1. Source: ProtInc homophilic cell adhesion Inferred from electronic annotation. Source: InterPro regulation of heart rate by cardiac conduction Inferred from mutant phenotype PubMed 22781308. Source: BHF-UCL regulation of ventricular cardiac muscle cell action potential Inferred from mutant phenotype PubMed 22781308. Source: BHF-UCL
Cellular_component	cell-cell adherens junction Inferred from electronic annotation. Source: Compara desmosome Inferred from direct assay Ref.6. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro
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	Helical; 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. Ref.8 Corresponds to variant rs868333 [ dbSNP | Ensembl ].		VAR_029480
	Natural variant	203	1	R → C in ARVD11; fails to undergo complete processing into a mature form; fails to localize at the desmosomes. Ref.6		VAR_065687
	Natural variant	231	1	I → T in ARVD11. Ref.9		VAR_065688
	Natural variant	275	1	T → M in ARVD11; can be processed into a mature form but shows a higher pro-protein to mature protein ratio; only a proportion of the partly functional mutant is incorporated into the desmosomes. Ref.6		VAR_065689
	Natural variant	340	1	T → A in ARVD11. Ref.9		VAR_065690
	Natural variant	358	1	T → I. Ref.7		VAR_062391
	Natural variant	596	1	A → V. Ref.8		VAR_065691
	Natural variant	638	1	Q → H. Ref.8		VAR_065692
	Natural variant	776	1	I → V. Ref.7 Ref.8 Corresponds to variant rs1893963 [ dbSNP | Ensembl ].		VAR_024388
	Natural variant	798	1	R → Q. Ref.7 Ref.8 Ref.9		VAR_062392

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) [UniParc]. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN ARVD11.
[6]	"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] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH DSP; PKP2 AND JUP, VARIANTS ARVD11 CYS-203 AND MET-275, CHARACTERIZATION OF VARIANTS ARVD11 CYS-203 AND MET-275.
[7]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-358; VAL-776 AND GLN-798.
[8]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS SER-11; VAL-596; HIS-638; VAL-776 AND GLN-798.
[9]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ARVD11 THR-231 AND ALA-340, VARIANT GLN-798.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. NM_004949.3. NP_077740.1. NM_024422.3.
UniGene	Hs.95612.
3D structure databases
ProteinModelPortal	Q02487.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q02487. 1 interaction.
STRING	9606.ENSP00000280904.
PTM databases
PhosphoSite	Q02487.
Polymorphism databases
DMDM	461968.
Proteomic databases
PaxDb	Q02487.
PRIDE	Q02487.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000251081; ENSP00000251081; ENSG00000134755. ENST00000280904; ENSP00000280904; ENSG00000134755.
GeneID	1824.
KEGG	hsa:1824.
UCSC	uc002kwk.4. human. uc002kwl.4. human.
Organism-specific databases
CTD	1824.
GeneCards	GC18M028670.
HGNC	HGNC:3036. DSC2.
HPA	HPA011911. HPA012615.
MIM	125645. gene. 610476. phenotype.
neXtProt	NX_Q02487.
Orphanet	293899. Familial isolated arrhythmogenic ventricular dysplasia, biventricular form. 293888. Familial isolated arrhythmogenic ventricular dysplasia, left dominant form. 293910. Familial isolated arrhythmogenic ventricular dysplasia, right dominant form.
PharmGKB	PA27489.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG304955.
HOGENOM	HOG000231253.
HOVERGEN	HBG102801.
InParanoid	Q02487.
KO	K07601.
OrthoDB	EOG4TB49Z.
PhylomeDB	Q02487.
Gene expression databases
ArrayExpress	Q02487.
Bgee	Q02487.
CleanEx	HS_DSC2. HS_DSC3.
Genevestigator	Q02487.
GermOnline	ENSG00000134755. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.60. 6 hits.
InterPro	IPR002126. Cadherin. IPR015919. Cadherin-like. IPR009124. Cadherin/Desmocollin. IPR020894. Cadherin_CS. IPR000233. Cadherin_cytoplasmic-dom. IPR014868. Cadherin_pro_dom. IPR009122. Desmosomal_cadherin. [Graphical view]
PANTHER	PTHR24025. PTHR24025. 1 hit.
Pfam	PF00028. Cadherin. 4 hits. PF01049. Cadherin_C. 1 hit. PF08758. Cadherin_pro. 1 hit. [Graphical view]
PRINTS	PR00205. CADHERIN. PR01818. DESMOCADHERN. PR01820. DESMOCOLLIN.
SMART	SM00112. CA. 5 hits. SM01055. Cadherin_pro. 1 hit. [Graphical view]
SUPFAM	SSF49313. Cadherin. 6 hits.
PROSITE	PS00232. CADHERIN_1. 3 hits. PS50268. CADHERIN_2. 5 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	DSC2. human.
GenomeRNAi	1824.
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:	May 1, 2013
This is version 128 of the entry and version 1 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.