DSG4

Protein identityUniProt · HPA

UniProt accession

Q86SJ6

Gene

DSG4

Ensembl

ENSG00000175065

Chromosome

18

Canonical length

1040 aa

Protein class

Disease related genes, Human disease related genes, Predicted membrane proteins

OverviewNCBI Gene

This gene encodes a member of the desmoglein subgroup of desmosomal cadherins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a transmembrane component of desmosomes and may play a role in cell-cell adhesion in epithelial cells. Mutations in the gene are associated with localized autosomal recessive hypotrichosis and monilethrix, characterized by impaired hair growth. [provided by RefSeq, May 2016]

Canonical amino-acid sequenceUniProt

1040 residues, UniProt reviewed canonical sequence.

>Q86SJ6|DSG4
     1  MDWLFFRNIC LLIILMVVME VNSEFIVEVK EFDIENGTTK WQTVRRQKRE WIKFAAACRE
    61  GEDNSKRNPI AKIRSDCESN QKITYRISGV GIDRPPYGVF TINPRTGEIN ITSVVDREIT
   121  PLFLIYCRAL NSRGEDLERP LELRVKVMDI NDNAPVFSQS VYTASIEENS DANTLVVKLC
   181  ATDADEENHL NSKIAYKIVS QEPSGAPMFI LNRYTGEVCT MSSFLDREQH SMYNLVVRGS
   241  DRDGAADGLS SECDCRIKVL DVNDNFPTLE KTSYSASIEE NCLSSELIRL QAIDLDEEGT
   301  DNWLAQYLIL SGNDGNWFDI QTDPQTNEGI LKVVKMLDYE QAPNIQLSIG VKNQADFHYS
   361  VASQFQMHPT PVRIQVVDVR EGPAFHPSTM AFSVREGIKG SSLLNYVLGT YTAIDLDTGN
   421  PATDVRYIIG HDAGSWLKID SRTGEIQFSR EFDKKSKYII NGIYTAEILA IDDGSGKTAT
   481  GTICIEVPDI NDYCPNIFPE RRTICIDSPS VLISVNEHSY GSPFTFCVVD EPPGIADMWD
   541  VRSTNATSAI LTAKQVLSPG FYEIPILVKD SYNRACELAQ MVQLYACDCD DNHMCLDSGA
   601  AGIYTEDITG DTYGPVTEDQ AGVSNVGLGP AGIGMMVLGI LLLILAPLLL LLCCCKQRQP
   661  EGLGTRFAPV PEGGEGVMQS WRIEGAHPED RDVSNICAPM TASNTQDRMD SSEIYTNTYA
   721  AGGTVEGGVS GVELNTGMGT AVGLMAAGAA GASGAARKRS STMGTLRDYA DADINMAFLD
   781  SYFSEKAYAY ADEDEGRPAN DCLLIYDHEG VGSPVGSIGC CSWIVDDLDE SCMETLDPKF
   841  RTLAEICLNT EIEPFPSHQA CIPISTDLPL LGPNYFVNES SGLTPSEVEF QEEMAASEPV
   901  VHGDIIVTET YGNADPCVQP TTIIFDPQLA PNVVVTEAVM APVYDIQGNI CVPAELADYN
   961  NVIYAERVLA SPGVPDMSNS STTEGCMGPV MSGNILVGPE IQVMQMMSPD LPIGQTVGST
  1021  SPMTSRHRVT RYSNIHYTQQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DSG4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.48

Highest tissue expression

2.4 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DSG4.

Disease | AllUniProt

Conditions DSG4 is implicated in, by any mechanism.

• Hypotrichosis 6 (HYPT6) MIM:607903

Disease | GeneticClinVar

19 pathogenic / likely-pathogenic of 338 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hypotrichosis 6

Disease | ImmuneIEDB

Conditions an epitope on DSG4 was assayed in.

• pemphigus B cell

ReferencesPubMed · IEDB

Publications for DSG4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.82

gnomAD pLI

0

gnomAD missense Z

-1.02

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• BMP signaling pathway
• cell-cell adhesion
• hair follicle development
• homophilic cell adhesion via plasma membrane adhesion molecules
• keratinocyte differentiation

Molecular functions

• calcium ion binding

Cellular components

• cornified envelope
• desmosome
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Cadherin, Y-type LIR-motif
• Cadherin-like
• Desmosomal cadherin
• Cadherin-like superfamily
• Cadherin conserved site
• Catenin binding domain superfamily
• Cadherin domain-containing protein
• Cadherin domain
• Cadherin, Y-type LIR-motif

KeywordsUniProt

• Calcium
• Cell adhesion
• Cell junction
• Cell membrane
• Cleavage on pair of basic residues
• Glycoprotein
• Hypotrichosis
• Membrane
• Metal-binding
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of DSG4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• JUP