DSP

Protein identityUniProt · HPA

UniProt accession

P15924

Gene

DSP

Ensembl

ENSG00000096696

Chromosome

6

Canonical length

2871 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Transporters

Subcellular location

Cell Junctions

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a protein that anchors intermediate filaments to desmosomal plaques and forms an obligate component of functional desmosomes. Mutations in this gene are the cause of several cardiomyopathies and keratodermas, including skin fragility-woolly hair syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Canonical amino-acid sequenceUniProt

2871 residues, UniProt reviewed canonical sequence.

>P15924|DSP
     1  MSCNGGSHPR INTLGRMIRA ESGPDLRYEV TSGGGGTSRM YYSRRGVITD QNSDGYCQTG
    61  TMSRHQNQNT IQELLQNCSD CLMRAELIVQ PELKYGDGIQ LTRSRELDEC FAQANDQMEI
   121  LDSLIREMRQ MGQPCDAYQK RLLQLQEQMR ALYKAISVPR VRRASSKGGG GYTCQSGSGW
   181  DEFTKHVTSE CLGWMRQQRA EMDMVAWGVD LASVEQHINS HRGIHNSIGD YRWQLDKIKA
   241  DLREKSAIYQ LEEEYENLLK ASFERMDHLR QLQNIIQATS REIMWINDCE EEELLYDWSD
   301  KNTNIAQKQE AFSIRMSQLE VKEKELNKLK QESDQLVLNQ HPASDKIEAY MDTLQTQWSW
   361  ILQITKCIDV HLKENAAYFQ FFEEAQSTEA YLKGLQDSIR KKYPCDKNMP LQHLLEQIKE
   421  LEKEREKILE YKRQVQNLVN KSKKIVQLKP RNPDYRSNKP IILRALCDYK QDQKIVHKGD
   481  ECILKDNNER SKWYVTGPGG VDMLVPSVGL IIPPPNPLAV DLSCKIEQYY EAILALWNQL
   541  YINMKSLVSW HYCMIDIEKI RAMTIAKLKT MRQEDYMKTI ADLELHYQEF IRNSQGSEMF
   601  GDDDKRKIQS QFTDAQKHYQ TLVIQLPGYP QHQTVTTTEI THHGTCQDVN HNKVIETNRE
   661  NDKQETWMLM ELQKIRRQIE HCEGRMTLKN LPLADQGSSH HITVKINELK SVQNDSQAIA
   721  EVLNQLKDML ANFRGSEKYC YLQNEVFGLF QKLENINGVT DGYLNSLCTV RALLQAILQT
   781  EDMLKVYEAR LTEEETVCLD LDKVEAYRCG LKKIKNDLNL KKSLLATMKT ELQKAQQIHS
   841  QTSQQYPLYD LDLGKFGEKV TQLTDRWQRI DKQIDFRLWD LEKQIKQLRN YRDNYQAFCK
   901  WLYDAKRRQD SLESMKFGDS NTVMRFLNEQ KNLHSEISGK RDKSEEVQKI AELCANSIKD
   961  YELQLASYTS GLETLLNIPI KRTMIQSPSG VILQEAADVH ARYIELLTRS GDYYRFLSEM
  1021  LKSLEDLKLK NTKIEVLEEE LRLARDANSE NCNKNKFLDQ NLQKYQAECS QFKAKLASLE
  1081  ELKRQAELDG KSAKQNLDKC YGQIKELNEK ITRLTYEIED EKRRRKSVED RFDQQKNDYD
  1141  QLQKARQCEK ENLGWQKLES EKAIKEKEYE IERLRVLLQE EGTRKREYEN ELAKVRNHYN
  1201  EEMSNLRNKY ETEINITKTT IKEISMQKED DSKNLRNQLD RLSRENRDLK DEIVRLNDSI
  1261  LQATEQRRRA EENALQQKAC GSEIMQKKQH LEIELKQVMQ QRSEDNARHK QSLEEAAKTI
  1321  QDKNKEIERL KAEFQEEAKR RWEYENELSK VRNNYDEEII SLKNQFETEI NITKTTIHQL
  1381  TMQKEEDTSG YRAQIDNLTR ENRSLSEEIK RLKNTLTQTT ENLRRVEEDI QQQKATGSEV
  1441  SQRKQQLEVE LRQVTQMRTE ESVRYKQSLD DAAKTIQDKN KEIERLKQLI DKETNDRKCL
  1501  EDENARLQRV QYDLQKANSS ATETINKLKV QEQELTRLRI DYERVSQERT VKDQDITRFQ
  1561  NSLKELQLQK QKVEEELNRL KRTASEDSCK RKKLEEELEG MRRSLKEQAI KITNLTQQLE
  1621  QASIVKKRSE DDLRQQRDVL DGHLREKQRT QEELRRLSSE VEALRRQLLQ EQESVKQAHL
  1681  RNEHFQKAIE DKSRSLNESK IEIERLQSLT ENLTKEHLML EEELRNLRLE YDDLRRGRSE
  1741  ADSDKNATIL ELRSQLQISN NRTLELQGLI NDLQRERENL RQEIEKFQKQ ALEASNRIQE
  1801  SKNQCTQVVQ ERESLLVKIK VLEQDKARLQ RLEDELNRAK STLEAETRVK QRLECEKQQI
  1861  QNDLNQWKTQ YSRKEEAIRK IESEREKSER EKNSLRSEIE RLQAEIKRIE ERCRRKLEDS
  1921  TRETQSQLET ERSRYQREID KLRQRPYGSH RETQTECEWT VDTSKLVFDG LRKKVTAMQL
  1981  YECQLIDKTT LDKLLKGKKS VEEVASEIQP FLRGAGSIAG ASASPKEKYS LVEAKRKKLI
  2041  SPESTVMLLE AQAATGGIID PHRNEKLTVD SAIARDLIDF DDRQQIYAAE KAITGFDDPF
  2101  SGKTVSVSEA IKKNLIDRET GMRLLEAQIA SGGVVDPVNS VFLPKDVALA RGLIDRDLYR
  2161  SLNDPRDSQK NFVDPVTKKK VSYVQLKERC RIEPHTGLLL LSVQKRSMSF QGIRQPVTVT
  2221  ELVDSGILRP STVNELESGQ ISYDEVGERI KDFLQGSSCI AGIYNETTKQ KLGIYEAMKI
  2281  GLVRPGTALE LLEAQAATGF IVDPVSNLRL PVEEAYKRGL VGIEFKEKLL SAERAVTGYN
  2341  DPETGNIISL FQAMNKELIE KGHGIRLLEA QIATGGIIDP KESHRLPVDI AYKRGYFNEE
  2401  LSEILSDPSD DTKGFFDPNT EENLTYLQLK ERCIKDEETG LCLLPLKEKK KQVQTSQKNT
  2461  LRKRRVVIVD PETNKEMSVQ EAYKKGLIDY ETFKELCEQE CEWEEITITG SDGSTRVVLV
  2521  DRKTGSQYDI QDAIDKGLVD RKFFDQYRSG SLSLTQFADM ISLKNGVGTS SSMGSGVSDD
  2581  VFSSSRHESV SKISTISSVR NLTIRSSSFS DTLEESSPIA AIFDTENLEK ISITEGIERG
  2641  IVDSITGQRL LEAQACTGGI IHPTTGQKLS LQDAVSQGVI DQDMATRLKP AQKAFIGFEG
  2701  VKGKKKMSAA EAVKEKWLPY EAGQRFLEFQ YLTGGLVDPE VHGRISTEEA IRKGFIDGRA
  2761  AQRLQDTSSY AKILTCPKTK LKISYKDAIN RSMVEDITGL RLLEAASVSS KGLPSPYNMS
  2821  SAPGSRSGSR SGSRSGSRSG SRSGSRRGSF DATGNSSYSY SYSFSSSSIG H

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DSP 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

0

Mean surface accessibility (rSASA)

0

Highest tissue expression

808 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DSP.

Disease | AllUniProt

Conditions DSP is implicated in, by any mechanism.

• Keratoderma, palmoplantar, striate 2 (SPPK2) MIM:612908
• Cardiomyopathy, dilated, with woolly hair and keratoderma (DCWHK) MIM:605676
• Arrhythmogenic right ventricular dysplasia, familial, 8 (ARVD8) MIM:607450
• Epidermolysis bullosa, lethal acantholytic (EBLA) MIM:609638
• Cardiomyopathy, dilated, with woolly hair, keratoderma, and tooth agenesis (DCWHKTA) MIM:615821

Disease | GeneticClinVar

830 pathogenic / likely-pathogenic of 6,123 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Arrhythmogenic cardiomyopathy with wooly hair and keratoderma
• Arrhythmogenic right ventricular dysplasia 8
• Cardiovascular phenotype
• Cardiomyopathy
• Arrhythmogenic right ventricular cardiomyopathy

Disease | AutoantibodyPubMed

Conditions in which antibodies against DSP are reported. Each links to that disease's full target list.

• Pemphigus 9
• Pemphigoid, Bullous 4

ReferencesPubMed · IEDB

Publications for DSP 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. 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)

0.26

gnomAD pLI

1

gnomAD missense Z

0.6

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adherens junction organization
• bundle of His cell-Purkinje myocyte adhesion involved in cell communication
• cell-cell adhesion
• desmosome organization
• epidermis development
• epithelial cell-cell adhesion
• intermediate filament cytoskeleton organization
• intermediate filament organization
• keratinocyte differentiation
• peptide cross-linking
• protein localization to cell-cell junction
• regulation of heart rate by cardiac conduction
• regulation of ventricular cardiac muscle cell action potential
• skin development
• ventricular compact myocardium morphogenesis
• wound healing

Molecular functions

• cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication
• protein kinase C binding
• RNA binding
• scaffold protein binding
• structural constituent of cytoskeleton
• structural molecule activity

Cellular components

• adherens junction
• basolateral plasma membrane
• cornified envelope
• cytoplasm
• desmosome
• extracellular exosome
• fascia adherens
• ficolin-1-rich granule membrane
• intercalated disc
• intermediate filament
• nucleus
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Plectin repeat
• SH3 domain
• Spectrin/alpha-actinin
• Plakin repeat superfamily
• Desmoplakin, spectrin-like domain
• Desmoplakin, SH3 domain
• Plakin
• Plectin repeat
• SH3 domain
• Spectrin like domain
• Spectrin-like repeat

KeywordsUniProt

• Cardiomyopathy
• Cell junction
• Cell membrane
• Cell projection
• Coiled coil
• Cytoplasm
• DNA-binding
• Epidermolysis bullosa
• Membrane
• Methylation
• Nucleus
• Palmoplantar keratoderma
• Phosphoprotein
• Repeat
• SH3 domain

InteractionsUniProt · HPA

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

• COL17A1
• DSC2
• PKP1
• PKP2
• TRF2
• NIN
• TERF2
• MYZAP
• FES
• JUP
• KRT18