DSG4_HUMAN
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 03-AUG-2022, entry version 157.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 AN
RP 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., Gordon D.,
RA Uitto J., Whiting D., Ott J., Fischer S., Gilliam T.C., Jahoda C.A.B.,
RA Morris R.J., Panteleyev A.A., Nguyen V.T., Christiano A.M.;
RT "Desmoglein 4 in hair follicle differentiation and epidermal adhesion.
RT Evidence from inherited hypotrichosis and acquired pemphigus 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 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 Press,
RL 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 in
RT 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 project:
RT 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., Leal S.M.,
RA Ahmad W.;
RT "A recurrent intragenic deletion mutation in DSG4 gene in three Pakistani
RT families with autosomal recessive hypotrichosis.";
RL J. Invest. Dermatol. 123:247-248(2004).
CC -!- FUNCTION: Component of intercellular desmosome junctions. Involved in
CC the interaction of plaque proteins and intermediate filaments mediating
CC cell-cell adhesion. Coordinates the transition from proliferation to
CC differentiation in hair follicle keratinocytes (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Cell junction, desmosome {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; less
CC in salivary gland. In scalp follicles, present in the inner root sheath
CC (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 each
CC cadherin domain and rigidify the connections, imparting a strong
CC 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 hair
CC and abnormal hair follicles and shafts, which are thin and atrophic.
CC The disorder affects the trunk and extremities as well as the scalp,
CC and the eyebrows and eyelashes may also be involved, whereas beard,
CC pubic, and axillary hairs are largely spared. In addition, patients can
CC develop hyperkeratotic follicular papules, erythema, and pruritus in
CC affected areas. In some patients with congenital hypotrichosis,
CC monilethrix-like hairs showing elliptical nodes have been observed.
CC HYPT6 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:15191570}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Autoantibodies against DSG4 are found in patients with
CC pemphigus vulgaris. Pemphigus vulgaris is a potentially lethal skin
CC disease in which epidermal blisters occur as the result of the loss of
CC cell-cell adhesion.
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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_001134453.2. [Q86SJ6-2]
DR RefSeq; NP_817123.1; NM_177986.4. [Q86SJ6-1]
DR AlphaFoldDB; Q86SJ6; -.
DR SMR; Q86SJ6; -.
DR BioGRID; 127059; 178.
DR IntAct; Q86SJ6; 37.
DR MINT; Q86SJ6; -.
DR STRING; 9606.ENSP00000352785; -.
DR GlyGen; Q86SJ6; 2 sites.
DR iPTMnet; Q86SJ6; -.
DR PhosphoSitePlus; Q86SJ6; -.
DR SwissPalm; Q86SJ6; -.
DR BioMuta; DSG4; -.
DR DMDM; 60389774; -.
DR EPD; Q86SJ6; -.
DR MassIVE; Q86SJ6; -.
DR MaxQB; Q86SJ6; -.
DR PaxDb; Q86SJ6; -.
DR PeptideAtlas; Q86SJ6; -.
DR PRIDE; Q86SJ6; -.
DR ProteomicsDB; 69597; -. [Q86SJ6-1]
DR ProteomicsDB; 69598; -. [Q86SJ6-2]
DR Antibodypedia; 22155; 112 antibodies from 25 providers.
DR DNASU; 147409; -.
DR Ensembl; ENST00000308128.9; ENSP00000311859.4; ENSG00000175065.12. [Q86SJ6-1]
DR Ensembl; ENST00000359747.4; ENSP00000352785.4; ENSG00000175065.12. [Q86SJ6-2]
DR GeneID; 147409; -.
DR KEGG; hsa:147409; -.
DR MANE-Select; ENST00000308128.9; ENSP00000311859.4; NM_177986.5; NP_817123.1.
DR UCSC; uc002kwq.3; human. [Q86SJ6-1]
DR CTD; 147409; -.
DR DisGeNET; 147409; -.
DR GeneCards; DSG4; -.
DR HGNC; HGNC:21307; DSG4.
DR HPA; ENSG00000175065; Tissue enhanced (skin).
DR MalaCards; DSG4; -.
DR MIM; 607892; gene.
DR MIM; 607903; phenotype.
DR neXtProt; NX_Q86SJ6; -.
DR OpenTargets; ENSG00000175065; -.
DR Orphanet; 55654; Hypotrichosis simplex.
DR Orphanet; 573; Monilethrix.
DR PharmGKB; PA134925919; -.
DR VEuPathDB; HostDB:ENSG00000175065; -.
DR eggNOG; KOG3594; Eukaryota.
DR GeneTree; ENSGT01030000234624; -.
DR HOGENOM; CLU_005284_0_0_1; -.
DR InParanoid; Q86SJ6; -.
DR OMA; PEPMIHG; -.
DR OrthoDB; 250139at2759; -.
DR PhylomeDB; Q86SJ6; -.
DR TreeFam; TF331809; -.
DR PathwayCommons; Q86SJ6; -.
DR Reactome; R-HSA-6805567; Keratinization.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; Q86SJ6; -.
DR SIGNOR; Q86SJ6; -.
DR BioGRID-ORCS; 147409; 13 hits in 1066 CRISPR screens.
DR GeneWiki; DSG4; -.
DR GenomeRNAi; 147409; -.
DR Pharos; Q86SJ6; Tbio.
DR PRO; PR:Q86SJ6; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q86SJ6; protein.
DR Bgee; ENSG00000175065; Expressed in esophagus mucosa and 16 other tissues.
DR Genevisible; Q86SJ6; 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: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:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro.
DR GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl.
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; 4.
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; Cell membrane;
KW Cleavage on pair of basic residues; Disease variant; Glycoprotein;
KW Hypotrichosis; Membrane; Metal-binding; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..49
FT /evidence="ECO:0000255"
FT /id="PRO_0000003855"
FT CHAIN 50..1040
FT /note="Desmoglein-4"
FT /id="PRO_0000003856"
FT TOPO_DOM 50..631
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 632..652
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 653..1040
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 50..157
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 158..269
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 270..385
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 386..497
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT REPEAT 884..909
FT /note="Desmoglein repeat 1"
FT REPEAT 910..940
FT /note="Desmoglein repeat 2"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 545
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 692..711
FT /note="DVSNICAPMTASNTQDRMDS -> LFSAYALPGGGGTADGGGSVLGRCALQA
FT TPALLNQHPPF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3,
FT ECO:0000303|Ref.4"
FT /id="VSP_012907"
FT VARIANT 125..335
FT /note="Missing (in HYPT6)"
FT /evidence="ECO:0000269|PubMed:12705872,
FT ECO:0000269|PubMed:15191570"
FT /id="VAR_021291"
FT VARIANT 154
FT /note="A -> T (in dbSNP:rs13381457)"
FT /id="VAR_048514"
FT VARIANT 535
FT /note="I -> T (in dbSNP:rs7229252)"
FT /id="VAR_033700"
FT VARIANT 644
FT /note="I -> L (in dbSNP:rs4799570)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="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
