ID   DSG4_HUMAN              Reviewed;        1040 AA.
AC   Q86SJ6; A2RUI1; Q6Y9L9; Q8IXV4;
DT   01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   01-OCT-2014, entry version 104.
DE   RecName: Full=Desmoglein-4;
DE   AltName: Full=Cadherin family member 13;
DE   Flags: Precursor;
GN   Name=DSG4; Synonyms=CDHF13;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, VARIANT LAH1 125-ILE--LYS-335 DEL, AND IDENTIFICATION AS
RP   AN AUTOANTIGEN IN PV.
RC   TISSUE=Epithelium;
RX   PubMed=12705872; DOI=10.1016/S0092-8674(03)00273-3;
RA   Kljuic A., Bazzi H., Sundberg J.P., Martinez-Mir A., O'Shaughnessy R.,
RA   Mahoney M.G., Levy M., Montagutelli X., Ahmad W., Aita V.M.,
RA   Gordon D., Uitto J., Whiting D., Ott J., Fischer S., Gilliam T.C.,
RA   Jahoda C.A.B., Morris R.J., Panteleyev A.A., Nguyen V.T.,
RA   Christiano A.M.;
RT   "Desmoglein 4 in hair follicle differentiation and epidermal adhesion.
RT   Evidence from inherited hypotrichosis and acquired pemphigus
RT   vulgaris.";
RL   Cell 113:249-260(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Skin, and Testis;
RX   PubMed=12648213; DOI=10.1046/j.1523-1747.2003.12113.x;
RA   Whittock N.V., Bower C.;
RT   "Genetic evidence for a novel human desmosomal cadherin, desmoglein
RT   4.";
RL   J. Invest. Dermatol. 120:523-530(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   TISSUE=Epidermis;
RA   Nguyen V.T.;
RT   "Experimental mouse model-passive transfer of nondesmoglein 1 and 3
RT   antibodies for Pemphigus Vulgaris.";
RL   (In) Chan L.S. (eds.);
RL   Animal models of human inflammatory skin diseases, pp.285-306, CRC
RL   Press, Boca Raton (2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA   Nguyen V.T.;
RT   "Novel Pemphigus vulgaris antigen desmoglein 4 has an important role
RT   in mediating keratinocyte adhesion.";
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP   LEU-644.
RC   TISSUE=Testis;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   VARIANT HYPT6 125-ILE--LYS-335 DEL.
RX   PubMed=15191570; DOI=10.1111/j.0022-202X.2004.22715.x;
RA   Rafiq M.A., Ansar M., Mahmood S., Haque S., Faiyaz-ul-Haque M.,
RA   Leal S.M., Ahmad W.;
RT   "A recurrent intragenic deletion mutation in DSG4 gene in three
RT   Pakistani families with autosomal recessive hypotrichosis.";
RL   J. Invest. Dermatol. 123:247-248(2004).
CC   -!- FUNCTION: Component of intercellular desmosome junctions. Involved
CC       in the interaction of plaque proteins and intermediate filaments
CC       mediating cell-cell adhesion. Coordinates the transition from
CC       proliferation to differentiation in hair follicle keratinocytes
CC       (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass
CC       type I membrane protein {ECO:0000250}. Cell junction, desmosome
CC       {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q86SJ6-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q86SJ6-2; Sequence=VSP_012907;
CC   -!- TISSUE SPECIFICITY: Highly expressed in skin, testis and prostate;
CC       less in salivary gland. In scalp follicles, present in the inner
CC       root sheath (IRS) and all layers of the matrix and precortex.
CC       {ECO:0000269|PubMed:12648213, ECO:0000269|PubMed:12705872}.
CC   -!- DOMAIN: Three calcium ions are usually bound at the interface of
CC       each cadherin domain and rigidify the connections, imparting a
CC       strong curvature to the full-length ectodomain. {ECO:0000250}.
CC   -!- DISEASE: Hypotrichosis 6 (HYPT6) [MIM:607903]: A condition
CC       characterized by the presence of less than the normal amount of
CC       hair and abnormal hair follicles and shafts, which are thin and
CC       atrophic. The disorder affects the trunk and extremities as well
CC       as the scalp, and the eyebrows and eyelashes may also be involved,
CC       whereas beard, pubic, and axillary hairs are largely spared. In
CC       addition, patients can develop hyperkeratotic follicular papules,
CC       erythema, and pruritus in affected areas. In some patients with
CC       congenital hypotrichosis, monilethrix-like hairs showing
CC       elliptical nodes have been observed.
CC       {ECO:0000269|PubMed:15191570}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Note=Autoantibodies against DSG4 are found in patients
CC       with pemphigus vulgaris. Pemphigus vulgaris is a potentially
CC       lethal skin disease in which epidermal blisters occur as the
CC       result of the loss of cell-cell adhesion.
CC   -!- SIMILARITY: Contains 4 cadherin domains. {ECO:0000255|PROSITE-
CC       ProRule:PRU00043}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AY227350; AAP45000.1; -; mRNA.
DR   EMBL; AY177663; AAO47077.1; -; Genomic_DNA.
DR   EMBL; AY177664; AAO47078.1; -; mRNA.
DR   EMBL; AY168788; AAO43657.1; -; mRNA.
DR   EMBL; AY228236; AAP49811.1; -; mRNA.
DR   EMBL; BC039098; AAH39098.1; -; mRNA.
DR   EMBL; BC132907; AAI32908.1; -; mRNA.
DR   EMBL; BC132909; AAI32910.1; -; mRNA.
DR   CCDS; CCDS11897.1; -. [Q86SJ6-1]
DR   CCDS; CCDS45845.1; -. [Q86SJ6-2]
DR   RefSeq; NP_001127925.1; NM_001134453.1. [Q86SJ6-2]
DR   RefSeq; NP_817123.1; NM_177986.3. [Q86SJ6-1]
DR   UniGene; Hs.407618; -.
DR   ProteinModelPortal; Q86SJ6; -.
DR   SMR; Q86SJ6; 47-573.
DR   IntAct; Q86SJ6; 1.
DR   STRING; 9606.ENSP00000352785; -.
DR   PhosphoSite; Q86SJ6; -.
DR   DMDM; 60389774; -.
DR   MaxQB; Q86SJ6; -.
DR   PaxDb; Q86SJ6; -.
DR   PeptideAtlas; Q86SJ6; -.
DR   PRIDE; Q86SJ6; -.
DR   Ensembl; ENST00000308128; ENSP00000311859; ENSG00000175065. [Q86SJ6-1]
DR   Ensembl; ENST00000359747; ENSP00000352785; ENSG00000175065. [Q86SJ6-2]
DR   GeneID; 147409; -.
DR   KEGG; hsa:147409; -.
DR   UCSC; uc002kwq.2; human. [Q86SJ6-1]
DR   UCSC; uc002kwr.2; human. [Q86SJ6-2]
DR   CTD; 147409; -.
DR   GeneCards; GC18P028956; -.
DR   HGNC; HGNC:21307; DSG4.
DR   HPA; HPA059456; -.
DR   MIM; 607892; gene.
DR   MIM; 607903; phenotype.
DR   neXtProt; NX_Q86SJ6; -.
DR   Orphanet; 55654; Hypotrichosis simplex.
DR   Orphanet; 573; Monilethrix.
DR   PharmGKB; PA134925919; -.
DR   eggNOG; NOG250212; -.
DR   HOGENOM; HOG000236266; -.
DR   HOVERGEN; HBG005532; -.
DR   KO; K07599; -.
DR   OMA; WRIEGAH; -.
DR   OrthoDB; EOG7FBRGV; -.
DR   PhylomeDB; Q86SJ6; -.
DR   TreeFam; TF331809; -.
DR   GeneWiki; DSG4; -.
DR   GenomeRNAi; 147409; -.
DR   NextBio; 85608; -.
DR   PRO; PR:Q86SJ6; -.
DR   Bgee; Q86SJ6; -.
DR   CleanEx; HS_DSG4; -.
DR   Genevestigator; Q86SJ6; -.
DR   GO; GO:0030057; C:desmosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005509; F:calcium ion binding; IEA:Ensembl.
DR   GO; GO:0042640; P:anagen; IEA:Ensembl.
DR   GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR   GO; GO:0007156; P:homophilic cell adhesion; IEA:InterPro.
DR   GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl.
DR   GO; GO:0016337; P:single organismal cell-cell adhesion; IEA:Ensembl.
DR   Gene3D; 2.60.40.60; -; 4.
DR   Gene3D; 4.10.900.10; -; 1.
DR   InterPro; IPR002126; Cadherin.
DR   InterPro; IPR015919; Cadherin-like.
DR   InterPro; IPR020894; Cadherin_CS.
DR   InterPro; IPR000233; Cadherin_cytoplasmic-dom.
DR   InterPro; IPR027397; Catenin_binding_dom.
DR   InterPro; IPR009123; Desmoglein.
DR   InterPro; IPR009122; Desmosomal_cadherin.
DR   PANTHER; PTHR24025; PTHR24025; 1.
DR   Pfam; PF00028; Cadherin; 4.
DR   Pfam; PF01049; Cadherin_C; 1.
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; 2.
DR   PROSITE; PS50268; CADHERIN_2; 4.
PE   1: Evidence at protein level;
KW   Alternative splicing; Calcium; Cell adhesion; Cell junction;
KW   Cell membrane; Cleavage on pair of basic residues; Complete proteome;
KW   Disease mutation; Glycoprotein; Hypotrichosis; Membrane;
KW   Metal-binding; Polymorphism; Reference proteome; Repeat; Signal;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL        1     23       {ECO:0000255}.
FT   PROPEP       24     49       {ECO:0000255}.
FT                                /FTId=PRO_0000003855.
FT   CHAIN        50   1040       Desmoglein-4.
FT                                /FTId=PRO_0000003856.
FT   TOPO_DOM     50    631       Extracellular. {ECO:0000255}.
FT   TRANSMEM    632    652       Helical. {ECO:0000255}.
FT   TOPO_DOM    653   1040       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN       50    157       Cadherin 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00043}.
FT   DOMAIN      158    269       Cadherin 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00043}.
FT   DOMAIN      270    385       Cadherin 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00043}.
FT   DOMAIN      386    497       Cadherin 4. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00043}.
FT   REPEAT      884    909       Desmoglein repeat 1.
FT   REPEAT      910    940       Desmoglein repeat 2.
FT   CARBOHYD    110    110       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    545    545       N-linked (GlcNAc...). {ECO:0000255}.
FT   VAR_SEQ     692    711       DVSNICAPMTASNTQDRMDS -> LFSAYALPGGGGTADGG
FT                                GSVLGRCALQATPALLNQHPPF (in isoform 2).
FT                                {ECO:0000303|PubMed:15489334,
FT                                ECO:0000303|Ref.3, ECO:0000303|Ref.4}.
FT                                /FTId=VSP_012907.
FT   VARIANT     125    335       Missing (in HYPT6).
FT                                {ECO:0000269|PubMed:12705872,
FT                                ECO:0000269|PubMed:15191570}.
FT                                /FTId=VAR_021291.
FT   VARIANT     154    154       A -> T (in dbSNP:rs13381457).
FT                                /FTId=VAR_048514.
FT   VARIANT     535    535       I -> T (in dbSNP:rs7229252).
FT                                /FTId=VAR_033700.
FT   VARIANT     644    644       I -> L (in dbSNP:rs4799570).
FT                                {ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_024387.
SQ   SEQUENCE   1040 AA;  113824 MW;  0385401584C55CF6 CRC64;
     MDWLFFRNIC LLIILMVVME VNSEFIVEVK EFDIENGTTK WQTVRRQKRE WIKFAAACRE
     GEDNSKRNPI AKIRSDCESN QKITYRISGV GIDRPPYGVF TINPRTGEIN ITSVVDREIT
     PLFLIYCRAL NSRGEDLERP LELRVKVMDI NDNAPVFSQS VYTASIEENS DANTLVVKLC
     ATDADEENHL NSKIAYKIVS QEPSGAPMFI LNRYTGEVCT MSSFLDREQH SMYNLVVRGS
     DRDGAADGLS SECDCRIKVL DVNDNFPTLE KTSYSASIEE NCLSSELIRL QAIDLDEEGT
     DNWLAQYLIL SGNDGNWFDI QTDPQTNEGI LKVVKMLDYE QAPNIQLSIG VKNQADFHYS
     VASQFQMHPT PVRIQVVDVR EGPAFHPSTM AFSVREGIKG SSLLNYVLGT YTAIDLDTGN
     PATDVRYIIG HDAGSWLKID SRTGEIQFSR EFDKKSKYII NGIYTAEILA IDDGSGKTAT
     GTICIEVPDI NDYCPNIFPE RRTICIDSPS VLISVNEHSY GSPFTFCVVD EPPGIADMWD
     VRSTNATSAI LTAKQVLSPG FYEIPILVKD SYNRACELAQ MVQLYACDCD DNHMCLDSGA
     AGIYTEDITG DTYGPVTEDQ AGVSNVGLGP AGIGMMVLGI LLLILAPLLL LLCCCKQRQP
     EGLGTRFAPV PEGGEGVMQS WRIEGAHPED RDVSNICAPM TASNTQDRMD SSEIYTNTYA
     AGGTVEGGVS GVELNTGMGT AVGLMAAGAA GASGAARKRS STMGTLRDYA DADINMAFLD
     SYFSEKAYAY ADEDEGRPAN DCLLIYDHEG VGSPVGSIGC CSWIVDDLDE SCMETLDPKF
     RTLAEICLNT EIEPFPSHQA CIPISTDLPL LGPNYFVNES SGLTPSEVEF QEEMAASEPV
     VHGDIIVTET YGNADPCVQP TTIIFDPQLA PNVVVTEAVM APVYDIQGNI CVPAELADYN
     NVIYAERVLA SPGVPDMSNS STTEGCMGPV MSGNILVGPE IQVMQMMSPD LPIGQTVGST
     SPMTSRHRVT RYSNIHYTQQ
//