DPP6

Protein identityUniProt · HPA

UniProt accession

P42658

Gene

DPP6

Ensembl

ENSG00000130226

Chromosome

7

Canonical length

865 aa

Protein class

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

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a single-pass type II membrane protein that is a member of the peptidase S9B family of serine proteases. This protein has no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it does bind specific voltage-gated potassium channels and alters their expression and biophysical properties. Variations in this gene may be associated with susceptibility to amyotrophic lateral sclerosis and with idiopathic ventricular fibrillation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

Canonical amino-acid sequenceUniProt

865 residues, UniProt reviewed canonical sequence.

>P42658|DPP6
     1  MASLYQRFTG KINTSRSFPA PPEASHLLGG QGPEEDGGAG AKPLGPRAQA AAPRERGGGG
    61  GGAGGRPRFQ YQARSDGDEE DELVGSNPPQ RNWKGIAIAL LVILVICSLI VTSVILLTPA
   121  EDNSLSQKKK VTVEDLFSED FKIHDPEAKW ISDTEFIYRE QKGTVRLWNV ETNTSTVLIE
   181  GKKIESLRAI RYEISPDREY ALFSYNVEPI YQHSYTGYYV LSKIPHGDPQ SLDPPEVSNA
   241  KLQYAGWGPK GQQLIFIFEN NIYYCAHVGK QAIRVVSTGK EGVIYNGLSD WLYEEEILKT
   301  HIAHWWSPDG TRLAYAAIND SRVPIMELPT YTGSIYPTVK PYHYPKAGSE NPSISLHVIG
   361  LNGPTHDLEM MPPDDPRMRE YYITMVKWAT STKVAVTWLN RAQNVSILTL CDATTGVCTK
   421  KHEDESEAWL HRQNEEPVFS KDGRKFFFIR AIPQGGRGKF YHITVSSSQP NSSNDNIQSI
   481  TSGDWDVTKI LAYDEKGNKI YFLSTEDLPR RRQLYSANTV GNFNRQCLSC DLVENCTYFS
   541  ASFSHSMDFF LLKCEGPGVP MVTVHNTTDK KKMFDLETNE HVKKAINDRQ MPKVEYRDIE
   601  IDDYNLPMQI LKPATFTDTT HYPLLLVVDG TPGSQSVAEK FEVSWETVMV SSHGAVVVKC
   661  DGRGSGFQGT KLLHEVRRRL GLLEEKDQME AVRTMLKEQY IDRTRVAVFG KDYGGYLSTY
   721  ILPAKGENQG QTFTCGSALS PITDFKLYAS AFSERYLGLH GLDNRAYEMT KVAHRVSALE
   781  EQQFLIIHPT ADEKIHFQHT AELITQLIRG KANYSLQIYP DESHYFTSSS LKQHLYRSII
   841  NFFVECFRIQ DKLLTVTAKE DEEED

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DPP6 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)

0.3

Highest tissue expression

56 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DPP6.

Disease | AllUniProt

Conditions DPP6 is implicated in, by any mechanism.

• Familial paroxysmal ventricular fibrillation 2 (VF2) MIM:612956
• Intellectual developmental disorder, autosomal dominant 33 (MRD33) MIM:616311

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 304 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Intellectual disability, autosomal dominant 33
• Ventricular fibrillation, paroxysmal familial, 2

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)

0.38

gnomAD pLI

0.34

gnomAD missense Z

2.24

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

• protein localization to plasma membrane
• proteolysis
• regulation of potassium ion transmembrane transport

Molecular functions

• potassium channel regulator activity
• serine-type peptidase activity

Cellular components

• membrane
• plasma membrane
• voltage-gated potassium channel complex

Protein domainsUniProt · Pfam · InterPro

• Peptidase S9, prolyl oligopeptidase, catalytic domain
• Dipeptidylpeptidase IV, N-terminal domain
• Alpha/Beta hydrolase fold
• Serine protease S9B/DPPIV
• Prolyl oligopeptidase family
• Dipeptidyl peptidase IV (DPP IV) N-terminal region

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Glycoprotein
• Intellectual disability
• Membrane
• Neurodegeneration
• Signal-anchor
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of DPP6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• KCND2
• KCND3