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Q02487 (DSC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length901 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.7

Subcellular location

Cell membrane; Single-pass type I membrane protein. Cell junctiondesmosome Ref.7.

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

Arrhythmogenic right ventricular dysplasia, familial, 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.7 Ref.10

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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GJA1P173022EBI-6900677,EBI-1103439
GJA1Q6TYA93EBI-6900677,EBI-6901331From a different organism.
Pkp2F1M7L92EBI-6900677,EBI-6900770From a different organism.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Propeptide28 – 135108 Potential
PRO_0000003869
Chain136 – 901766Desmocollin-2
PRO_0000003870

Regions

Topological domain136 – 694559Extracellular Potential
Transmembrane695 – 71521Helical; Potential
Topological domain716 – 901186Cytoplasmic Potential
Domain136 – 243108Cadherin 1
Domain244 – 355112Cadherin 2
Domain356 – 471116Cadherin 3
Domain472 – 579108Cadherin 4
Domain580 – 694115Cadherin 5

Amino acid modifications

Modified residue8641Phosphoserine Potential
Glycosylation341N-linked (GlcNAc...) Potential
Glycosylation1661N-linked (GlcNAc...) Potential
Glycosylation3921N-linked (GlcNAc...) (complex) Ref.4 Ref.6
Glycosylation5461N-linked (GlcNAc...) Ref.3
Glycosylation6291N-linked (GlcNAc...) Ref.4

Natural variations

Alternative sequence837 – 84711KVYLCNQDENH → ESIRGHTLIKN in isoform 2B.
VSP_000657
Alternative sequence848 – 90154Missing in isoform 2B.
VSP_000658
Natural variant111N → S. Ref.9
Corresponds to variant rs868333 [ dbSNP | Ensembl ].
VAR_029480
Natural variant2031R → C in ARVD11; fails to undergo complete processing into a mature form; fails to localize at the desmosomes. Ref.7
VAR_065687
Natural variant2311I → T in ARVD11. Ref.10
VAR_065688
Natural variant2751T → 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.7
VAR_065689
Natural variant3401T → A in ARVD11. Ref.10
VAR_065690
Natural variant3581T → I. Ref.8
Corresponds to variant rs139399951 [ dbSNP | Ensembl ].
VAR_062391
Natural variant5961A → V. Ref.9
Corresponds to variant rs148185335 [ dbSNP | Ensembl ].
VAR_065691
Natural variant6381Q → H. Ref.9
VAR_065692
Natural variant7761I → V. Ref.8 Ref.9
Corresponds to variant rs1893963 [ dbSNP | Ensembl ].
VAR_024388
Natural variant7981R → Q. Ref.8 Ref.9 Ref.10
Corresponds to variant rs61731921 [ dbSNP | Ensembl ].
VAR_062392

Sequences

Sequence LengthMass (Da)Tools
Isoform 2A (DGII) [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: 30F7E3D33ECA67CC

FASTA90199,962
        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 

« Hide

Isoform 2B (DGIII) [UniParc].

Checksum: A53588B1D490CD8F
Show »

FASTA84793,769

References

« Hide '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.
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.
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]"A strategy for precise and large scale identification of core fucosylated glycoproteins."
Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.
Mol. Cell. Proteomics 8:913-923(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-392.
[7]"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.
[8]"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.
[9]"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.
[10]"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

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.
PIRIJHUDB. A40390.
IJHUDA. B40390.
RefSeqNP_004940.1. NM_004949.3.
NP_077740.1. NM_024422.3.
UniGeneHs.95612.

3D structure databases

ProteinModelPortalQ02487.
SMRQ02487. Positions 33-135, 137-669, 842-898.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108158. 8 interactions.
IntActQ02487. 7 interactions.
STRING9606.ENSP00000280904.

PTM databases

PhosphoSiteQ02487.

Polymorphism databases

DMDM461968.

Proteomic databases

PaxDbQ02487.
PRIDEQ02487.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000251081; ENSP00000251081; ENSG00000134755. [Q02487-2]
ENST00000280904; ENSP00000280904; ENSG00000134755. [Q02487-1]
GeneID1824.
KEGGhsa:1824.
UCSCuc002kwk.4. human. [Q02487-2]
uc002kwl.4. human. [Q02487-1]

Organism-specific databases

CTD1824.
GeneCardsGC18M028670.
HGNCHGNC:3036. DSC2.
HPAHPA011911.
HPA012615.
MIM125645. gene.
610476. phenotype.
neXtProtNX_Q02487.
Orphanet293899. 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.
PharmGKBPA27489.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG304955.
HOGENOMHOG000231253.
HOVERGENHBG102801.
InParanoidQ02487.
KOK07601.
OMAPLNYEER.
OrthoDBEOG74BJR7.
PhylomeDBQ02487.
TreeFamTF316817.

Gene expression databases

ArrayExpressQ02487.
BgeeQ02487.
CleanExHS_DSC2.
HS_DSC3.
GenevestigatorQ02487.

Family and domain databases

Gene3D2.60.40.60. 6 hits.
4.10.900.10. 1 hit.
InterProIPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR009124. Cadherin/Desmocollin.
IPR020894. Cadherin_CS.
IPR000233. Cadherin_cytoplasmic-dom.
IPR014868. Cadherin_pro_dom.
IPR027397. Catenin_binding_dom.
IPR009122. Desmosomal_cadherin.
[Graphical view]
PANTHERPTHR24025. PTHR24025. 1 hit.
PfamPF00028. Cadherin. 4 hits.
PF01049. Cadherin_C. 1 hit.
PF08758. Cadherin_pro. 1 hit.
[Graphical view]
PRINTSPR00205. CADHERIN.
PR01818. DESMOCADHERN.
PR01820. DESMOCOLLIN.
SMARTSM00112. CA. 5 hits.
SM01055. Cadherin_pro. 1 hit.
[Graphical view]
SUPFAMSSF49313. SSF49313. 6 hits.
PROSITEPS00232. CADHERIN_1. 3 hits.
PS50268. CADHERIN_2. 5 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDSC2. human.
GeneWikiDSC2.
GenomeRNAi1824.
NextBio7437.
PROQ02487.
SOURCESearch...

Entry information

Entry nameDSC2_HUMAN
AccessionPrimary (citable) accession number: Q02487
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: March 19, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM