DSG3_HUMAN
ID DSG3_HUMAN Reviewed; 999 AA.
AC P32926; A8K2V2;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Desmoglein-3 {ECO:0000305};
DE AltName: Full=130 kDa pemphigus vulgaris antigen;
DE Short=PVA;
DE AltName: Full=Cadherin family member 6;
DE Flags: Precursor;
GN Name=DSG3 {ECO:0000312|HGNC:HGNC:3050}; Synonyms=CDHF6;
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], INVOLVEMENT IN PEMPHIGUS VULGARIS, AND VARIANT
RP ALA-912.
RX PubMed=1720352; DOI=10.1016/0092-8674(91)90360-b;
RA Amagai M., Klaus-Kovtun V., Stanley J.R.;
RT "Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris,
RT a disease of cell adhesion.";
RL Cell 67:869-877(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-912.
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
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 [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-459 AND ASN-545.
RC TISSUE=Saliva;
RX PubMed=16740002; DOI=10.1021/pr050492k;
RA Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A.;
RT "Identification of N-linked glycoproteins in human saliva by glycoprotein
RT capture and mass spectrometry.";
RL J. Proteome Res. 5:1493-1503(2006).
RN [5]
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).
RN [6]
RP VARIANT ABOLM 287-ARG--ILE-999 DEL, CHARACTERIZATION OF VARIANT ABOLM
RP 287-ARG--ILE-999 DEL, AND TISSUE SPECIFICITY.
RX PubMed=30528827; DOI=10.1016/j.jid.2018.09.038;
RA Kim J.H., Kim S.E., Park H.S., Lee S.H., Lee S.E., Kim S.C.;
RT "A Homozygous Nonsense Mutation in the DSG3 Gene Causes Acantholytic
RT Blisters in the Oral and Laryngeal Mucosa.";
RL J. Invest. Dermatol. 139:1187-1190(2019).
CC -!- FUNCTION: Component of intercellular desmosome junctions. Involved in
CC the interaction of plaque proteins and intermediate filaments mediating
CC cell-cell adhesion.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000255}. Cell junction, desmosome {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Epidermis, tongue, tonsil, esophagus and
CC carcinomas. Expressed in skin and mucosa (at protein level)
CC (PubMed:30528827). {ECO:0000269|PubMed:30528827}.
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: Blistering, acantholytic, of oral and laryngeal mucosa (ABOLM)
CC [MIM:619226]: An autosomal recessive disorder characterized by
CC recurrent, suprabasal acantholytic blisters in the oral and laryngeal
CC mucosa. Skin, conjunctival and genital mucosa, nail folds, and nails
CC are unaffected. Normal structure is observed in the scalp epidermis and
CC hair follicle. {ECO:0000269|PubMed:30528827}. Note=The disease may be
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Pemphigus vulgaris (PV) is a potentially lethal skin
CC disease in which epidermal blisters occur as the result of the loss of
CC cell-cell adhesion caused by the action of autoantibodies against
CC desmoglein 3. {ECO:0000269|PubMed:1720352}.
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DR EMBL; M76482; AAA60230.1; -; mRNA.
DR EMBL; AK290367; BAF83056.1; -; mRNA.
DR EMBL; AC021549; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS11898.1; -.
DR PIR; A41088; IJHUG3.
DR RefSeq; NP_001935.2; NM_001944.2.
DR PDB; 5EQX; X-ray; 3.05 A; A=50-598.
DR PDBsum; 5EQX; -.
DR AlphaFoldDB; P32926; -.
DR SMR; P32926; -.
DR BioGRID; 108164; 42.
DR ELM; P32926; -.
DR IntAct; P32926; 2.
DR STRING; 9606.ENSP00000257189; -.
DR Allergome; 8248; Hom s DSG3.
DR GlyGen; P32926; 7 sites.
DR iPTMnet; P32926; -.
DR PhosphoSitePlus; P32926; -.
DR SwissPalm; P32926; -.
DR BioMuta; DSG3; -.
DR DMDM; 239938621; -.
DR CPTAC; CPTAC-62; -.
DR CPTAC; CPTAC-63; -.
DR EPD; P32926; -.
DR jPOST; P32926; -.
DR MassIVE; P32926; -.
DR MaxQB; P32926; -.
DR PaxDb; P32926; -.
DR PeptideAtlas; P32926; -.
DR PRIDE; P32926; -.
DR ProteomicsDB; 54887; -.
DR ABCD; P32926; 48 sequenced antibodies.
DR Antibodypedia; 3464; 725 antibodies from 36 providers.
DR DNASU; 1830; -.
DR Ensembl; ENST00000257189.5; ENSP00000257189.4; ENSG00000134757.5.
DR GeneID; 1830; -.
DR KEGG; hsa:1830; -.
DR MANE-Select; ENST00000257189.5; ENSP00000257189.4; NM_001944.3; NP_001935.2.
DR UCSC; uc002kws.4; human.
DR CTD; 1830; -.
DR DisGeNET; 1830; -.
DR GeneCards; DSG3; -.
DR HGNC; HGNC:3050; DSG3.
DR HPA; ENSG00000134757; Tissue enhanced (esophagus, lymphoid tissue, vagina).
DR MalaCards; DSG3; -.
DR MIM; 169615; gene.
DR MIM; 619226; phenotype.
DR neXtProt; NX_P32926; -.
DR OpenTargets; ENSG00000134757; -.
DR PharmGKB; PA27503; -.
DR VEuPathDB; HostDB:ENSG00000134757; -.
DR eggNOG; KOG3594; Eukaryota.
DR GeneTree; ENSGT01030000234624; -.
DR HOGENOM; CLU_005284_0_0_1; -.
DR InParanoid; P32926; -.
DR OMA; KYVMGRN; -.
DR OrthoDB; 250139at2759; -.
DR PhylomeDB; P32926; -.
DR TreeFam; TF331809; -.
DR PathwayCommons; P32926; -.
DR Reactome; R-HSA-351906; Apoptotic cleavage of cell adhesion proteins.
DR Reactome; R-HSA-6805567; Keratinization.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; P32926; -.
DR BioGRID-ORCS; 1830; 9 hits in 1063 CRISPR screens.
DR ChiTaRS; DSG3; human.
DR GeneWiki; Desmoglein_3; -.
DR GenomeRNAi; 1830; -.
DR Pharos; P32926; Tbio.
DR PRO; PR:P32926; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; P32926; protein.
DR Bgee; ENSG00000134757; Expressed in gingiva and 102 other tissues.
DR Genevisible; P32926; HS.
DR GO; GO:0005911; C:cell-cell junction; IBA:GO_Central.
DR GO; GO:0001533; C:cornified envelope; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030057; C:desmosome; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; IPR027397; Catenin-bd_sf.
DR InterPro; IPR009123; Desmoglein.
DR InterPro; IPR009122; Desmosomal_cadherin.
DR Pfam; PF00028; Cadherin; 3.
DR PRINTS; PR00205; CADHERIN.
DR PRINTS; PR01818; DESMOCADHERN.
DR PRINTS; PR01819; DESMOGLEIN.
DR SMART; SM00112; CA; 4.
DR SUPFAM; SSF49313; SSF49313; 4.
DR PROSITE; PS00232; CADHERIN_1; 3.
DR PROSITE; PS50268; CADHERIN_2; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell adhesion; Cell junction; Cell membrane;
KW Cleavage on pair of basic residues; Glycoprotein; Membrane; Metal-binding;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..49
FT /evidence="ECO:0000255"
FT /id="PRO_0000003851"
FT CHAIN 50..999
FT /note="Desmoglein-3"
FT /id="PRO_0000003852"
FT TOPO_DOM 50..615
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 616..640
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 641..999
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 50..158
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 159..268
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 269..383
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 386..499
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT REPEAT 910..935
FT /note="Desmoglein repeat 1"
FT REPEAT 936..966
FT /note="Desmoglein repeat 2"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16740002"
FT CARBOHYD 545
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16740002"
FT VARIANT 287..999
FT /note="Missing (in ABOLM; unknown pathological
FT significance; loss of expression in skin and mucosa)"
FT /evidence="ECO:0000269|PubMed:30528827"
FT /id="VAR_085271"
FT VARIANT 509
FT /note="V -> M (in dbSNP:rs16961975)"
FT /id="VAR_055578"
FT VARIANT 912
FT /note="T -> A (in dbSNP:rs1380866)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:1720352"
FT /id="VAR_059178"
FT CONFLICT 110
FT /note="N -> D (in Ref. 2; BAF83056)"
FT /evidence="ECO:0000305"
FT CONFLICT 298
FT /note="T -> A (in Ref. 2; BAF83056)"
FT /evidence="ECO:0000305"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:5EQX"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:5EQX"
FT TURN 90..92
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 98..102
FT /evidence="ECO:0007829|PDB:5EQX"
FT TURN 104..106
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:5EQX"
FT TURN 117..119
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 121..130
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 141..148
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 160..166
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 175..178
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:5EQX"
FT TURN 190..192
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 198..201
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:5EQX"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 217..220
FT /evidence="ECO:0007829|PDB:5EQX"
FT TURN 227..229
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 231..241
FT /evidence="ECO:0007829|PDB:5EQX"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 248..257
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 272..277
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 282..288
FT /evidence="ECO:0007829|PDB:5EQX"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 303..310
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 316..320
FT /evidence="ECO:0007829|PDB:5EQX"
FT TURN 322..324
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 327..331
FT /evidence="ECO:0007829|PDB:5EQX"
FT TURN 337..339
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 341..353
FT /evidence="ECO:0007829|PDB:5EQX"
FT TURN 357..359
FT /evidence="ECO:0007829|PDB:5EQX"
FT HELIX 360..362
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 368..375
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 384..391
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 412..419
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 422..429
FT /evidence="ECO:0007829|PDB:5EQX"
FT HELIX 431..433
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 435..437
FT /evidence="ECO:0007829|PDB:5EQX"
FT TURN 439..441
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 443..446
FT /evidence="ECO:0007829|PDB:5EQX"
FT TURN 453..456
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 459..470
FT /evidence="ECO:0007829|PDB:5EQX"
FT TURN 471..473
FT /evidence="ECO:0007829|PDB:5EQX"
FT STRAND 477..484
FT /evidence="ECO:0007829|PDB:5EQX"
SQ SEQUENCE 999 AA; 107533 MW; 7553CC917E8719BA CRC64;
MMGLFPRTTG ALAIFVVVIL VHGELRIETK GQYDEEEMTM QQAKRRQKRE WVKFAKPCRE
GEDNSKRNPI AKITSDYQAT QKITYRISGV GIDQPPFGIF VVDKNTGDIN ITAIVDREET
PSFLITCRAL NAQGLDVEKP LILTVKILDI NDNPPVFSQQ IFMGEIEENS ASNSLVMILN
ATDADEPNHL NSKIAFKIVS QEPAGTPMFL LSRNTGEVRT LTNSLDREQA SSYRLVVSGA
DKDGEGLSTQ CECNIKVKDV NDNFPMFRDS QYSARIEENI LSSELLRFQV TDLDEEYTDN
WLAVYFFTSG NEGNWFEIQT DPRTNEGILK VVKALDYEQL QSVKLSIAVK NKAEFHQSVI
SRYRVQSTPV TIQVINVREG IAFRPASKTF TVQKGISSKK LVDYILGTYQ AIDEDTNKAA
SNVKYVMGRN DGGYLMIDSK TAEIKFVKNM NRDSTFIVNK TITAEVLAID EYTGKTSTGT
VYVRVPDFND NCPTAVLEKD AVCSSSPSVV VSARTLNNRY TGPYTFALED QPVKLPAVWS
ITTLNATSAL LRAQEQIPPG VYHISLVLTD SQNNRCEMPR SLTLEVCQCD NRGICGTSYP
TTSPGTRYGR PHSGRLGPAA IGLLLLGLLL LLLAPLLLLT CDCGAGSTGG VTGGFIPVPD
GSEGTIHQWG IEGAHPEDKE ITNICVPPVT ANGADFMESS EVCTNTYARG TAVEGTSGME
MTTKLGAATE SGGAAGFATG TVSGAASGFG AATGVGICSS GQSGTMRTRH STGGTNKDYA
DGAISMNFLD SYFSQKAFAC AEEDDGQEAN DCLLIYDNEG ADATGSPVGS VGCCSFIADD
LDDSFLDSLG PKFKKLAEIS LGVDGEGKEV QPPSKDSGYG IESCGHPIEV QQTGFVKCQT
LSGSQGASAL STSGSVQPAV SIPDPLQHGN YLVTETYSAS GSLVQPSTAG FDPLLTQNVI
VTERVICPIS SVPGNLAGPT QLRGSHTMLC TEDPCSRLI
