DSC3_HUMAN
ID DSC3_HUMAN Reviewed; 896 AA.
AC Q14574; A6NN35; Q14200; Q9HAZ9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Desmocollin-3;
DE AltName: Full=Cadherin family member 3;
DE AltName: Full=Desmocollin-4;
DE AltName: Full=HT-CP;
DE Flags: Precursor;
GN Name=DSC3; Synonyms=CDHF3, DSC4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3A), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Urinary bladder carcinoma;
RX PubMed=7929347; DOI=10.1016/s0021-9258(18)47193-1;
RA Kawamura K., Watanabe K., Suzuki T., Yamakawa T., Kamiyama T., Nakagawa H.,
RA Tsurufuji S.;
RT "cDNA cloning and expression of a novel human desmocollin.";
RL J. Biol. Chem. 269:26295-26302(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3A), AND VARIANT ASP-28.
RC TISSUE=Foreskin, and Keratinocyte;
RX PubMed=7665906; DOI=10.1111/1523-1747.ep12319935;
RA King I.A., Sullivan K.H., Bennett R. Jr., Buxton R.S.;
RT "The desmocollins of human foreskin epidermis: identification and
RT chromosomal assignment of a third gene and expression patterns of the three
RT isoforms.";
RL J. Invest. Dermatol. 105:314-321(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 3A AND 3B), AND VARIANT ASP-28.
RX PubMed=11027496; DOI=10.1006/bbrc.2000.3500;
RA Whittock N.V., Hunt D.M., Rickman L., Malhi S., Vogazianou A.P.,
RA Dawson L.F., Eady R.A.J., Buxton R.S., McGrath J.A.;
RT "Genomic organization and amplification of the human desmosomal cadherin
RT genes DSC1 and DSC3, encoding desmocollin types 1 and 3.";
RL Biochem. Biophys. Res. Commun. 276:454-460(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [5]
RP INVOLVEMENT IN HRSV.
RX PubMed=19765682; DOI=10.1016/j.ajhg.2009.08.015;
RA Ayub M., Basit S., Jelani M., Ur Rehman F., Iqbal M., Yasinzai M.,
RA Ahmad W.;
RT "A homozygous nonsense mutation in the human desmocollin-3 (DSC3) gene
RT underlies hereditary hypotrichosis and recurrent skin vesicles.";
RL Am. J. Hum. Genet. 85:515-520(2009).
CC -!- FUNCTION: Component of intercellular desmosome junctions. Involved in
CC the interaction of plaque proteins and intermediate filaments mediating
CC cell-cell adhesion. May contribute to epidermal cell positioning
CC (stratification) by mediating differential adhesiveness between cells
CC that express different isoforms.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Cell junction, desmosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=3A;
CC IsoId=Q14574-1; Sequence=Displayed;
CC Name=3B;
CC IsoId=Q14574-2; Sequence=VSP_000663, VSP_000664;
CC -!- TISSUE SPECIFICITY: Epidermis, buccal mucosa, esophagus and cervix.
CC -!- DOMAIN: Calcium may be bound by the cadherin-like repeats.
CC {ECO:0000305}.
CC -!- DOMAIN: Three calcium ions are usually bound at the interface of each
CC cadherin domain and rigidify the connections, imparting a strong
CC curvature to the full-length ectodomain. {ECO:0000250}.
CC -!- DISEASE: Hypotrichosis and recurrent skin vesicles (HRSV) [MIM:613102]:
CC A disorder characterized by hypotrichosis and the appearance of
CC recurrent skin vesicle formation. Affected individuals show sparse and
CC fragile hair on scalp, as well as absent eyebrows and eyelashes.
CC Vesicles filled with thin, watery fluid are observed on the scalp and
CC skin of most of the body. Mucosal vesicles are absent.
CC {ECO:0000269|PubMed:19765682}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; D17427; BAA04249.1; -; mRNA.
DR EMBL; X83929; CAA58781.1; -; mRNA.
DR EMBL; AF293359; AAG23426.1; -; Genomic_DNA.
DR EMBL; AF293359; AAG23427.1; -; Genomic_DNA.
DR EMBL; AC025212; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS32810.1; -. [Q14574-1]
DR PIR; A55363; A55363.
DR RefSeq; NP_001932.2; NM_001941.4. [Q14574-1]
DR RefSeq; NP_077741.2; NM_024423.3. [Q14574-2]
DR AlphaFoldDB; Q14574; -.
DR SMR; Q14574; -.
DR BioGRID; 108159; 110.
DR IntAct; Q14574; 24.
DR MINT; Q14574; -.
DR STRING; 9606.ENSP00000353608; -.
DR GlyGen; Q14574; 5 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q14574; -.
DR PhosphoSitePlus; Q14574; -.
DR SwissPalm; Q14574; -.
DR BioMuta; DSC3; -.
DR DMDM; 116241342; -.
DR EPD; Q14574; -.
DR jPOST; Q14574; -.
DR MassIVE; Q14574; -.
DR MaxQB; Q14574; -.
DR PaxDb; Q14574; -.
DR PeptideAtlas; Q14574; -.
DR PRIDE; Q14574; -.
DR ProteomicsDB; 60052; -. [Q14574-1]
DR ProteomicsDB; 60053; -. [Q14574-2]
DR TopDownProteomics; Q14574-1; -. [Q14574-1]
DR Antibodypedia; 7988; 240 antibodies from 33 providers.
DR DNASU; 1825; -.
DR Ensembl; ENST00000360428.9; ENSP00000353608.4; ENSG00000134762.17. [Q14574-1]
DR Ensembl; ENST00000434452.5; ENSP00000392068.1; ENSG00000134762.17. [Q14574-2]
DR GeneID; 1825; -.
DR KEGG; hsa:1825; -.
DR MANE-Select; ENST00000360428.9; ENSP00000353608.4; NM_001941.5; NP_001932.2.
DR UCSC; uc002kwi.4; human. [Q14574-1]
DR CTD; 1825; -.
DR DisGeNET; 1825; -.
DR GeneCards; DSC3; -.
DR HGNC; HGNC:3037; DSC3.
DR HPA; ENSG00000134762; Group enriched (esophagus, skin).
DR MalaCards; DSC3; -.
DR MIM; 600271; gene.
DR MIM; 613102; phenotype.
DR neXtProt; NX_Q14574; -.
DR OpenTargets; ENSG00000134762; -.
DR Orphanet; 217407; Hereditary hypotrichosis with recurrent skin vesicles.
DR PharmGKB; PA164741482; -.
DR VEuPathDB; HostDB:ENSG00000134762; -.
DR eggNOG; KOG3594; Eukaryota.
DR GeneTree; ENSGT01030000234624; -.
DR HOGENOM; CLU_005284_2_0_1; -.
DR InParanoid; Q14574; -.
DR OMA; TLIMKVQ; -.
DR OrthoDB; 120970at2759; -.
DR PhylomeDB; Q14574; -.
DR TreeFam; TF316817; -.
DR PathwayCommons; Q14574; -.
DR Reactome; R-HSA-6805567; Keratinization.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; Q14574; -.
DR BioGRID-ORCS; 1825; 12 hits in 1081 CRISPR screens.
DR ChiTaRS; DSC3; human.
DR GeneWiki; DSC3; -.
DR GenomeRNAi; 1825; -.
DR Pharos; Q14574; Tbio.
DR PRO; PR:Q14574; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q14574; protein.
DR Bgee; ENSG00000134762; Expressed in upper leg skin and 115 other tissues.
DR ExpressionAtlas; Q14574; baseline and differential.
DR Genevisible; Q14574; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005911; C:cell-cell junction; IBA:GO_Central.
DR GO; GO:0001533; C:cornified envelope; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0030057; C:desmosome; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0045295; F:gamma-catenin binding; IPI:BHF-UCL.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0050821; P:protein stabilization; IDA:BHF-UCL.
DR Gene3D; 4.10.900.10; -; 1.
DR InterPro; IPR002126; Cadherin-like_dom.
DR InterPro; IPR015919; Cadherin-like_sf.
DR InterPro; IPR020894; Cadherin_CS.
DR InterPro; IPR000233; Cadherin_cytoplasmic-dom.
DR InterPro; IPR014868; Cadherin_pro_dom.
DR InterPro; IPR027397; Catenin-bd_sf.
DR InterPro; IPR009122; Desmosomal_cadherin.
DR Pfam; PF00028; Cadherin; 4.
DR Pfam; PF01049; Cadherin_C; 1.
DR Pfam; PF08758; Cadherin_pro; 1.
DR PRINTS; PR00205; CADHERIN.
DR PRINTS; PR01818; DESMOCADHERN.
DR SMART; SM00112; CA; 5.
DR SMART; SM01055; Cadherin_pro; 1.
DR SUPFAM; SSF49313; SSF49313; 6.
DR PROSITE; PS00232; CADHERIN_1; 3.
DR PROSITE; PS50268; CADHERIN_2; 5.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell adhesion; Cell junction; Cell membrane;
KW Cleavage on pair of basic residues; Direct protein sequencing;
KW Glycoprotein; Hypotrichosis; Membrane; Metal-binding; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT PROPEP 28..135
FT /evidence="ECO:0000255"
FT /id="PRO_0000003875"
FT CHAIN 136..896
FT /note="Desmocollin-3"
FT /id="PRO_0000003876"
FT TOPO_DOM 136..690
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 691..711
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 712..896
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 136..243
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 244..355
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 356..471
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 472..579
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 580..690
FT /note="Cadherin 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 392
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 546
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 629
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 832..839
FT /note="KLHRCNQN -> ESIRGHTG (in isoform 3B)"
FT /evidence="ECO:0000305"
FT /id="VSP_000663"
FT VAR_SEQ 840..896
FT /note="Missing (in isoform 3B)"
FT /evidence="ECO:0000305"
FT /id="VSP_000664"
FT VARIANT 28
FT /note="A -> D (in dbSNP:rs2852003)"
FT /evidence="ECO:0000269|PubMed:11027496,
FT ECO:0000269|PubMed:7665906"
FT /id="VAR_048515"
FT VARIANT 78
FT /note="S -> T (in dbSNP:rs276937)"
FT /id="VAR_048516"
FT VARIANT 102
FT /note="R -> K (in dbSNP:rs276938)"
FT /id="VAR_048517"
FT VARIANT 180
FT /note="K -> Q (in dbSNP:rs35296997)"
FT /id="VAR_048518"
FT VARIANT 199
FT /note="R -> W (in dbSNP:rs276921)"
FT /id="VAR_048519"
FT VARIANT 239
FT /note="N -> S (in dbSNP:rs35630063)"
FT /id="VAR_048520"
SQ SEQUENCE 896 AA; 99969 MW; 6685B0A8B4C1ED85 CRC64;
MAAAGPRRSV RGAVCLHLLL TLVIFSRAGE ACKKVILNVP SKLEADKIIG RVNLEECFRS
ADLIRSSDPD FRVLNDGSVY TARAVALSDK KRSFTIWLSD KRKQTQKEVT VLLEHQKKVS
KTRHTRETVL RRAKRRWAPI PCSMQENSLG PFPLFLQQVE SDAAQNYTVF YSISGRGVDK
EPLNLFYIER DTGNLFCTRP VDREEYDVFD LIAYASTADG YSADLPLPLP IRVEDENDNH
PVFTEAIYNF EVLESSRPGT TVGVVCATDR DEPDTMHTRL KYSILQQTPR SPGLFSVHPS
TGVITTVSHY LDREVVDKYS LIMKVQDMDG QFFGLIGTST CIITVTDSND NAPTFRQNAY
EAFVEENAFN VEILRIPIED KDLINTANWR VNFTILKGNE NGHFKISTDK ETNEGVLSVV
KPLNYEENRQ VNLEIGVNNE APFARDIPRV TALNRALVTV HVRDLDEGPE CTPAAQYVRI
KENLAVGSKI NGYKAYDPEN RNGNGLRYKK LHDPKGWITI DEISGSIITS KILDREVETP
KNELYNITVL AIDKDDRSCT GTLAVNIEDV NDNPPEILQE YVVICKPKMG YTDILAVDPD
EPVHGAPFYF SLPNTSPEIS RLWSLTKVND TAARLSYQKN AGFQEYTIPI TVKDRAGQAA
TKLLRVNLCE CTHPTQCRAT SRSTGVILGK WAILAILLGI ALLFSVLLTL VCGVFGATKG
KRFPEDLAQQ NLIISNTEAP GDDRVCSANG FMTQTTNNSS QGFCGTMGSG MKNGGQETIE
MMKGGNQTLE SCRGAGHHHT LDSCRGGHTE VDNCRYTYSE WHSFTQPRLG EKLHRCNQNE
DRMPSQDYVL TYNYEGRGSP AGSVGCCSEK QEEDGLDFLN NLEPKFITLA EACTKR
