DSC1_HUMAN
ID DSC1_HUMAN Reviewed; 894 AA.
AC Q08554; Q9HB01;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 2.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Desmocollin-1;
DE AltName: Full=Cadherin family member 1;
DE AltName: Full=Desmosomal glycoprotein 2/3;
DE Short=DG2/DG3;
DE Flags: Precursor;
GN Name=DSC1; Synonyms=CDHF1;
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] (ISOFORMS 1A AND 1B), AND VARIANT PHE-848.
RC TISSUE=Foreskin;
RX PubMed=8507556;
RA Theis D.G., Koch P.J., Franke W.W.;
RT "Differential synthesis of type 1 and type 2 desmocollin mRNAs in human
RT stratified epithelia.";
RL Int. J. Dev. Biol. 37:101-110(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A AND 1B).
RC TISSUE=Skin;
RX PubMed=8288219; DOI=10.1006/geno.1993.1453;
RA King I.A., Arnemann J., Spurr N.K., Buxton R.S.;
RT "Cloning of the cDNA (DSC1) coding for human type 1 desmocollin and its
RT assignment to chromosome 18.";
RL Genomics 18:185-194(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PROTEIN SEQUENCE OF 135-151 AND 283-292.
RX PubMed=1713860; DOI=10.1016/0014-5793(91)80929-w;
RA King I.A., Magee A.I., Rees D.A., Buxton R.S.;
RT "Keratinization is associated with the expression of a new protein related
RT to the desmosomal cadherins DGII/III.";
RL FEBS Lett. 286:9-12(1991).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-385, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Prostate cancer;
RX PubMed=17487921; DOI=10.1002/elps.200600782;
RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
RT "Toward a global characterization of the phosphoproteome in prostate cancer
RT cells: identification of phosphoproteins in the LNCaP cell line.";
RL Electrophoresis 28:2027-2034(2007).
RN [7]
RP INTERACTION WITH JUP/PLAKOGLOBIN.
RX PubMed=19759396; DOI=10.1074/jbc.m109.047928;
RA Choi H.J., Gross J.C., Pokutta S., Weis W.I.;
RT "Interactions of plakoglobin and beta-catenin with desmosomal cadherins:
RT basis of selective exclusion of alpha- and beta-catenin from desmosomes.";
RL J. Biol. Chem. 284:31776-31788(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
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. Linked to the keratinization of
CC epithelial tissues.
CC -!- SUBUNIT: Binds to JUP/plakoglobin.
CC -!- INTERACTION:
CC Q08554; Q02413: DSG1; NbExp=2; IntAct=EBI-2371346, EBI-1045757;
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=1A; Synonyms=DG2;
CC IsoId=Q08554-1; Sequence=Displayed;
CC Name=1B; Synonyms=DG3;
CC IsoId=Q08554-2; Sequence=VSP_000651, VSP_000652;
CC -!- TISSUE SPECIFICITY: Strongly expressed in epidermis, less in lymph node
CC and tongue.
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}.
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DR EMBL; Z34522; CAA84279.1; -; mRNA.
DR EMBL; Z34522; CAA84278.1; -; mRNA.
DR EMBL; X72925; CAA51428.1; -; mRNA.
DR EMBL; X72925; CAA51429.1; -; mRNA.
DR EMBL; AF293358; AAG23424.1; -; Genomic_DNA.
DR EMBL; CH471088; EAX01252.1; -; Genomic_DNA.
DR CCDS; CCDS11894.1; -. [Q08554-1]
DR CCDS; CCDS11895.1; -. [Q08554-2]
DR PIR; A48910; A48910.
DR PIR; I37281; I37281.
DR PIR; I37282; I37282.
DR RefSeq; NP_004939.1; NM_004948.3. [Q08554-2]
DR RefSeq; NP_077739.1; NM_024421.2. [Q08554-1]
DR PDB; 5IRY; X-ray; 3.10 A; A/B=135-676.
DR PDBsum; 5IRY; -.
DR AlphaFoldDB; Q08554; -.
DR SMR; Q08554; -.
DR BioGRID; 108157; 108.
DR IntAct; Q08554; 22.
DR STRING; 9606.ENSP00000257198; -.
DR GlyGen; Q08554; 9 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q08554; -.
DR PhosphoSitePlus; Q08554; -.
DR BioMuta; DSC1; -.
DR DMDM; 223590198; -.
DR EPD; Q08554; -.
DR jPOST; Q08554; -.
DR MassIVE; Q08554; -.
DR MaxQB; Q08554; -.
DR PaxDb; Q08554; -.
DR PeptideAtlas; Q08554; -.
DR PRIDE; Q08554; -.
DR ProteomicsDB; 58632; -. [Q08554-1]
DR ProteomicsDB; 58633; -. [Q08554-2]
DR Antibodypedia; 2439; 232 antibodies from 28 providers.
DR DNASU; 1823; -.
DR Ensembl; ENST00000257197.7; ENSP00000257197.3; ENSG00000134765.10. [Q08554-2]
DR Ensembl; ENST00000257198.6; ENSP00000257198.6; ENSG00000134765.10. [Q08554-1]
DR GeneID; 1823; -.
DR KEGG; hsa:1823; -.
DR MANE-Select; ENST00000257198.6; ENSP00000257198.6; NM_024421.2; NP_077739.1.
DR UCSC; uc002kwn.4; human. [Q08554-1]
DR CTD; 1823; -.
DR DisGeNET; 1823; -.
DR GeneCards; DSC1; -.
DR HGNC; HGNC:3035; DSC1.
DR HPA; ENSG00000134765; Tissue enriched (skin).
DR MIM; 125643; gene.
DR neXtProt; NX_Q08554; -.
DR OpenTargets; ENSG00000134765; -.
DR PharmGKB; PA27488; -.
DR VEuPathDB; HostDB:ENSG00000134765; -.
DR eggNOG; KOG3594; Eukaryota.
DR GeneTree; ENSGT01030000234624; -.
DR HOGENOM; CLU_005284_0_2_1; -.
DR InParanoid; Q08554; -.
DR OMA; QVTAIDH; -.
DR OrthoDB; 120970at2759; -.
DR PhylomeDB; Q08554; -.
DR TreeFam; TF316817; -.
DR PathwayCommons; Q08554; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-6805567; Keratinization.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; Q08554; -.
DR BioGRID-ORCS; 1823; 6 hits in 1057 CRISPR screens.
DR ChiTaRS; DSC1; human.
DR GeneWiki; DSC1; -.
DR GenomeRNAi; 1823; -.
DR Pharos; Q08554; Tbio.
DR PRO; PR:Q08554; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q08554; protein.
DR Bgee; ENSG00000134765; Expressed in upper leg skin and 66 other tissues.
DR ExpressionAtlas; Q08554; baseline and differential.
DR Genevisible; Q08554; HS.
DR GO; GO:0005911; C:cell-cell junction; IBA:GO_Central.
DR GO; GO:0001533; C:cornified envelope; TAS:Reactome.
DR GO; GO:0030057; C:desmosome; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
DR GO; GO:0005921; C:gap junction; TAS:ProtInc.
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; TAS:Reactome.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
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 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 3D-structure; Alternative splicing; Calcium; Cell adhesion; Cell junction;
KW Cell membrane; Cleavage on pair of basic residues;
KW Direct protein sequencing; Glycoprotein; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT PROPEP 30..134
FT /evidence="ECO:0000255"
FT /id="PRO_0000003863"
FT CHAIN 135..894
FT /note="Desmocollin-1"
FT /id="PRO_0000003864"
FT TOPO_DOM 135..691
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 692..714
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 715..894
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 135..242
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 243..354
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 355..471
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 472..575
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 576..682
FT /note="Cadherin 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT MOD_RES 385
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17487921"
FT CARBOHYD 165
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 546
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 830..840
FT /note="KVYLCGQDEEH -> ESIRGHTLIKN (in isoform 1B)"
FT /evidence="ECO:0000303|PubMed:8288219,
FT ECO:0000303|PubMed:8507556"
FT /id="VSP_000651"
FT VAR_SEQ 841..894
FT /note="Missing (in isoform 1B)"
FT /evidence="ECO:0000303|PubMed:8288219,
FT ECO:0000303|PubMed:8507556"
FT /id="VSP_000652"
FT VARIANT 93
FT /note="S -> F (in dbSNP:rs35338395)"
FT /id="VAR_061059"
FT VARIANT 460
FT /note="V -> I (in dbSNP:rs17800159)"
FT /id="VAR_055579"
FT VARIANT 848
FT /note="C -> F (in dbSNP:rs985861)"
FT /evidence="ECO:0000269|PubMed:8507556"
FT /id="VAR_055580"
FT CONFLICT 132
FT /note="S -> T (in Ref. 1; CAA84278/CAA84279)"
FT /evidence="ECO:0000305"
FT STRAND 141..146
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 150..157
FT /evidence="ECO:0007829|PDB:5IRY"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 169..174
FT /evidence="ECO:0007829|PDB:5IRY"
FT TURN 175..178
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:5IRY"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 193..196
FT /evidence="ECO:0007829|PDB:5IRY"
FT TURN 202..204
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 206..215
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 226..233
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 241..252
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 260..263
FT /evidence="ECO:0007829|PDB:5IRY"
FT TURN 275..277
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 280..288
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:5IRY"
FT TURN 298..300
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 302..306
FT /evidence="ECO:0007829|PDB:5IRY"
FT TURN 312..314
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 316..325
FT /evidence="ECO:0007829|PDB:5IRY"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 335..345
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 353..366
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 369..375
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 383..385
FT /evidence="ECO:0007829|PDB:5IRY"
FT TURN 386..388
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 390..397
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 399..401
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 403..407
FT /evidence="ECO:0007829|PDB:5IRY"
FT TURN 409..411
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 414..418
FT /evidence="ECO:0007829|PDB:5IRY"
FT TURN 424..426
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 428..440
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 444..450
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 455..463
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 472..481
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 498..500
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:5IRY"
FT TURN 522..524
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 527..529
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 544..549
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 554..556
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 561..568
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 585..587
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 589..593
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 608..611
FT /evidence="ECO:0007829|PDB:5IRY"
FT TURN 614..618
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 619..622
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 624..627
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 629..633
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 639..649
FT /evidence="ECO:0007829|PDB:5IRY"
FT STRAND 655..664
FT /evidence="ECO:0007829|PDB:5IRY"
SQ SEQUENCE 894 AA; 99987 MW; 2E0C835F6FE2E77F CRC64;
MALASAAPGS IFCKQLLFSL LVLTLLCDAC QKVYLRVPSH LQAETLVGKV NLEECLKSAS
LIRSSDPAFR ILEDGSIYTT HDLILSSERK SFSIFLSDGQ RREQQEIKVV LSARENKSPK
KRHTKDTALK RSKRRWAPIP ASLMENSLGP FPQHVQQIQS DAAQNYTIFY SISGPGVDKE
PFNLFYIEKD TGDIFCTRSI DREKYEQFAL YGYATTADGY APEYPLPLII KIEDDNDNAP
YFEHRVTIFT VPENCRSGTS VGKVTATDLD EPDTLHTRLK YKILQQIPDH PKHFSIHPDT
GVITTTTPFL DREKCDTYQL IMEVRDMGGQ PFGLFNTGTI TISLEDENDN PPSFTETSYV
TEVEENRIDV EILRMKVQDQ DLPNTPHSKA VYKILQGNEN GNFIISTDPN TNEGVLCVVK
PLNYEVNRQV ILQVGVINEA QFSKAASSQT PTMCTTTVTV KIIDSDEGPE CHPPVKVIQS
QDGFPAGQEL LGYKALDPEI SSGEGLRYQK LGDEDNWFEI NQHTGDLRTL KVLDRESKFV
KNNQYNISVV AVDAVGRSCT GTLVVHLDDY NDHAPQIDKE VTICQNNEDF AVLKPVDPDG
PENGPPFQFF LDNSASKNWN IEEKDGKTAI LRQRQNLDYN YYSVPIQIKD RHGLVATHML
TVRVCDCSTP SECRMKDKST RDVRPNVILG RWAILAMVLG SVLLLCILFT CFCVTAKRTV
KKCFPEDIAQ QNLIVSNTEG PGEEVTEANI RLPMQTSNIC DTSMSVGTVG GQGIKTQQSF
EMVKGGYTLD SNKGGGHQTL ESVKGVGQGD TGRYAYTDWQ SFTQPRLGEK VYLCGQDEEH
KHCEDYVCSY NYEGKGSLAG SVGCCSDRQE EEGLEFLDHL EPKFRTLAKT CIKK
