UniProtKB - P42658 (DPP6_HUMAN)
Protein
Dipeptidyl aminopeptidase-like protein 6
Gene
DPP6
Organism
Homo sapiens (Human)
Status
Functioni
Promotes cell surface expression of the potassium channel KCND2 (PubMed:15454437, PubMed:19441798). Modulates the activity and gating characteristics of the potassium channel KCND2 (PubMed:18364354). Has no dipeptidyl aminopeptidase activity (PubMed:8103397, PubMed:15476821).1 Publication3 Publications
Miscellaneous
Genetic variation in DPP6 may influence susceptibility to amyotrophic lateral sclerosis (ALS). ALS is a severely disabling and lethal disorder caused by progressive degeneration of motor neurons in the brain, spinal cord and brainstem.
GO - Molecular functioni
- potassium channel regulator activity Source: UniProtKB
- serine-type peptidase activity Source: InterPro
GO - Biological processi
- protein localization to plasma membrane Source: UniProtKB
- regulation of potassium ion transmembrane transport Source: UniProtKB
Enzyme and pathway databases
PathwayCommonsi | P42658 |
Protein family/group databases
ESTHERi | human-DPP6, DPP4N_Peptidase_S9 |
MEROPSi | S09.973 |
TCDBi | 8.A.51.1.1, the dipeptidyl-aminopeptidase-like protein 6 beta subunit of kv4 channels (dpp6) family |
Names & Taxonomyi
Protein namesi | Recommended name: Dipeptidyl aminopeptidase-like protein 6Alternative name(s): DPPX Dipeptidyl aminopeptidase-related protein Dipeptidyl peptidase 6 Dipeptidyl peptidase IV-like protein Dipeptidyl peptidase VI Short name: DPP VI |
Gene namesi | Name:DPP6 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000130226.16 |
HGNCi | HGNC:3010, DPP6 |
MIMi | 126141, gene |
neXtProti | NX_P42658 |
Subcellular locationi
Plasma membrane
- Cell membrane 2 Publications; Single-pass type II membrane protein Curated
Plasma Membrane
- plasma membrane Source: UniProtKB
- voltage-gated potassium channel complex Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 95 | CytoplasmicSequence analysisAdd BLAST | 95 | |
Transmembranei | 96 – 116 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 117 – 865 | ExtracellularSequence analysisAdd BLAST | 749 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Involvement in diseasei
Familial paroxysmal ventricular fibrillation 2 (VF2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry. A genetic variation 340 bases upstream from the ATG start site of the DPP6 gene is the cause of familial paroxysmal ventricular fibrillation type 2.
Disease descriptionA cardiac arrhythmia marked by fibrillary contractions of the ventricular muscle due to rapid repetitive excitation of myocardial fibers without coordinated contraction of the ventricle and by absence of atrial activity.
Related information in OMIMMental retardation, autosomal dominant 33 (MRD33)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD33 patients manifest microcephaly and intellectual disability.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_073680 | 385 | M → L in MRD33. 1 PublicationCorresponds to variant dbSNP:rs786205143EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease mutation, Mental retardation, NeurodegenerationOrganism-specific databases
DisGeNETi | 1804 |
MalaCardsi | DPP6 |
MIMi | 612956, phenotype 616311, phenotype |
OpenTargetsi | ENSG00000130226 |
Orphaneti | 2514, Autosomal dominant primary microcephaly 228140, Idiopathic ventricular fibrillation, non Brugada type |
PharmGKBi | PA27468 |
Miscellaneous databases
Pharosi | P42658, Tbio |
Polymorphism and mutation databases
BioMutai | DPP6 |
DMDMi | 218512016 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000122409 | 1 – 865 | Dipeptidyl aminopeptidase-like protein 6Add BLAST | 865 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 173 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 319 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 404 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 411 ↔ 418 | 1 Publication | ||
Glycosylationi | 471 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 527 ↔ 530 | 1 Publication | ||
Glycosylationi | 535 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 536 ↔ 554 | 1 Publication | ||
Glycosylationi | 566 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 735 ↔ 846 | 1 Publication | ||
Glycosylationi | 813 | N-linked (GlcNAc...) asparagine1 Publication | 1 |
Post-translational modificationi
N-glycosylated.1 Publication
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
MassIVEi | P42658 |
PaxDbi | P42658 |
PeptideAtlasi | P42658 |
PRIDEi | P42658 |
ProteomicsDBi | 55521 [P42658-1] 55522 [P42658-2] |
PTM databases
GlyGeni | P42658, 7 sites |
iPTMneti | P42658 |
PhosphoSitePlusi | P42658 |
SwissPalmi | P42658 |
Expressioni
Tissue specificityi
Expressed predominantly in brain.
Gene expression databases
Bgeei | ENSG00000130226, Expressed in middle temporal gyrus and 175 other tissues |
ExpressionAtlasi | P42658, baseline and differential |
Genevisiblei | P42658, HS |
Organism-specific databases
HPAi | ENSG00000130226, Tissue enhanced (brain, endometrium, thyroid gland) |
Interactioni
Subunit structurei
Protein-protein interaction databases
BioGRIDi | 108138, 13 interactors |
IntActi | P42658, 3 interactors |
STRINGi | 9606.ENSP00000367001 |
Miscellaneous databases
RNActi | P42658, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P42658 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P42658 |
Family & Domainsi
Sequence similaritiesi
Belongs to the peptidase S9B family.Curated
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2100, Eukaryota |
GeneTreei | ENSGT00940000156280 |
InParanoidi | P42658 |
OMAi | MYGERYM |
OrthoDBi | 269253at2759 |
PhylomeDBi | P42658 |
TreeFami | TF313309 |
Family and domain databases
Gene3Di | 2.140.10.30, 1 hit 3.40.50.1820, 1 hit |
InterProi | View protein in InterPro IPR029058, AB_hydrolase IPR001375, Peptidase_S9 IPR002469, Peptidase_S9B_N IPR038554, Peptidase_S9B_N_sf |
Pfami | View protein in Pfam PF00930, DPPIV_N, 1 hit PF00326, Peptidase_S9, 1 hit |
SUPFAMi | SSF53474, SSF53474, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform DPPX-L (identifier: P42658-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MASLYQRFTG KINTSRSFPA PPEASHLLGG QGPEEDGGAG AKPLGPRAQA
60 70 80 90 100
AAPRERGGGG GGAGGRPRFQ YQARSDGDEE DELVGSNPPQ RNWKGIAIAL
110 120 130 140 150
LVILVICSLI VTSVILLTPA EDNSLSQKKK VTVEDLFSED FKIHDPEAKW
160 170 180 190 200
ISDTEFIYRE QKGTVRLWNV ETNTSTVLIE GKKIESLRAI RYEISPDREY
210 220 230 240 250
ALFSYNVEPI YQHSYTGYYV LSKIPHGDPQ SLDPPEVSNA KLQYAGWGPK
260 270 280 290 300
GQQLIFIFEN NIYYCAHVGK QAIRVVSTGK EGVIYNGLSD WLYEEEILKT
310 320 330 340 350
HIAHWWSPDG TRLAYAAIND SRVPIMELPT YTGSIYPTVK PYHYPKAGSE
360 370 380 390 400
NPSISLHVIG LNGPTHDLEM MPPDDPRMRE YYITMVKWAT STKVAVTWLN
410 420 430 440 450
RAQNVSILTL CDATTGVCTK KHEDESEAWL HRQNEEPVFS KDGRKFFFIR
460 470 480 490 500
AIPQGGRGKF YHITVSSSQP NSSNDNIQSI TSGDWDVTKI LAYDEKGNKI
510 520 530 540 550
YFLSTEDLPR RRQLYSANTV GNFNRQCLSC DLVENCTYFS ASFSHSMDFF
560 570 580 590 600
LLKCEGPGVP MVTVHNTTDK KKMFDLETNE HVKKAINDRQ MPKVEYRDIE
610 620 630 640 650
IDDYNLPMQI LKPATFTDTT HYPLLLVVDG TPGSQSVAEK FEVSWETVMV
660 670 680 690 700
SSHGAVVVKC DGRGSGFQGT KLLHEVRRRL GLLEEKDQME AVRTMLKEQY
710 720 730 740 750
IDRTRVAVFG KDYGGYLSTY ILPAKGENQG QTFTCGSALS PITDFKLYAS
760 770 780 790 800
AFSERYLGLH GLDNRAYEMT KVAHRVSALE EQQFLIIHPT ADEKIHFQHT
810 820 830 840 850
AELITQLIRG KANYSLQIYP DESHYFTSSS LKQHLYRSII NFFVECFRIQ
860
DKLLTVTAKE DEEED
Isoform DPPX-S (identifier: P42658-2) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
1-81: MASLYQRFTG...QARSDGDEED → MTTAKEPSASGKSVQQQEQ
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ8IYG9 | Q8IYG9_HUMAN | DPP6 protein | DPP6 | 353 | Annotation score: | ||
E9PF59 | E9PF59_HUMAN | Dipeptidyl aminopeptidase-like prot... | DPP6 | 801 | Annotation score: | ||
E9PDL2 | E9PDL2_HUMAN | Dipeptidyl aminopeptidase-like prot... | DPP6 | 758 | Annotation score: | ||
A0A087WTG7 | A0A087WTG7_HUMAN | Dipeptidyl aminopeptidase-like prot... | DPP6 | 291 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 73 | A → G in AAA35760 (PubMed:8103397).Curated | 1 | |
Sequence conflicti | 520 | V → E in AAA35760 (PubMed:8103397).Curated | 1 | |
Sequence conflicti | 520 | V → E in AAA35761 (PubMed:8103397).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_073680 | 385 | M → L in MRD33. 1 PublicationCorresponds to variant dbSNP:rs786205143EnsemblClinVar. | 1 | |
Natural variantiVAR_051579 | 854 | L → P1 PublicationCorresponds to variant dbSNP:rs3734960Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_005365 | 1 – 81 | MASLY…GDEED → MTTAKEPSASGKSVQQQEQ in isoform DPPX-S. 1 PublicationAdd BLAST | 81 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M96859 mRNA Translation: AAA35760.1 M96860 mRNA Translation: AAA35761.1 AC006019 Genomic DNA No translation available. AC024239 Genomic DNA No translation available. AC024730 Genomic DNA No translation available. AC073336 Genomic DNA No translation available. |
CCDSi | CCDS75683.1 [P42658-1] CCDS75684.1 [P42658-2] |
PIRi | I54331 I68600 |
RefSeqi | NP_570629.2, NM_130797.3 [P42658-1] |
Genome annotation databases
Ensembli | ENST00000332007; ENSP00000328226; ENSG00000130226 [P42658-2] ENST00000377770; ENSP00000367001; ENSG00000130226 [P42658-1] |
GeneIDi | 1804 |
KEGGi | hsa:1804 |
UCSCi | uc003wlk.4, human [P42658-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M96859 mRNA Translation: AAA35760.1 M96860 mRNA Translation: AAA35761.1 AC006019 Genomic DNA No translation available. AC024239 Genomic DNA No translation available. AC024730 Genomic DNA No translation available. AC073336 Genomic DNA No translation available. |
CCDSi | CCDS75683.1 [P42658-1] CCDS75684.1 [P42658-2] |
PIRi | I54331 I68600 |
RefSeqi | NP_570629.2, NM_130797.3 [P42658-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1XFD | X-ray | 3.00 | A/B/C/D | 127-849 | [»] | |
SMRi | P42658 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108138, 13 interactors |
IntActi | P42658, 3 interactors |
STRINGi | 9606.ENSP00000367001 |
Protein family/group databases
ESTHERi | human-DPP6, DPP4N_Peptidase_S9 |
MEROPSi | S09.973 |
TCDBi | 8.A.51.1.1, the dipeptidyl-aminopeptidase-like protein 6 beta subunit of kv4 channels (dpp6) family |
PTM databases
GlyGeni | P42658, 7 sites |
iPTMneti | P42658 |
PhosphoSitePlusi | P42658 |
SwissPalmi | P42658 |
Polymorphism and mutation databases
BioMutai | DPP6 |
DMDMi | 218512016 |
Proteomic databases
MassIVEi | P42658 |
PaxDbi | P42658 |
PeptideAtlasi | P42658 |
PRIDEi | P42658 |
ProteomicsDBi | 55521 [P42658-1] 55522 [P42658-2] |
Protocols and materials databases
ABCDi | P42658, 5 sequenced antibodies |
Antibodypediai | 33071, 226 antibodies |
Genome annotation databases
Ensembli | ENST00000332007; ENSP00000328226; ENSG00000130226 [P42658-2] ENST00000377770; ENSP00000367001; ENSG00000130226 [P42658-1] |
GeneIDi | 1804 |
KEGGi | hsa:1804 |
UCSCi | uc003wlk.4, human [P42658-1] |
Organism-specific databases
CTDi | 1804 |
DisGeNETi | 1804 |
EuPathDBi | HostDB:ENSG00000130226.16 |
GeneCardsi | DPP6 |
HGNCi | HGNC:3010, DPP6 |
HPAi | ENSG00000130226, Tissue enhanced (brain, endometrium, thyroid gland) |
MalaCardsi | DPP6 |
MIMi | 126141, gene 612956, phenotype 616311, phenotype |
neXtProti | NX_P42658 |
OpenTargetsi | ENSG00000130226 |
Orphaneti | 2514, Autosomal dominant primary microcephaly 228140, Idiopathic ventricular fibrillation, non Brugada type |
PharmGKBi | PA27468 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2100, Eukaryota |
GeneTreei | ENSGT00940000156280 |
InParanoidi | P42658 |
OMAi | MYGERYM |
OrthoDBi | 269253at2759 |
PhylomeDBi | P42658 |
TreeFami | TF313309 |
Enzyme and pathway databases
PathwayCommonsi | P42658 |
Miscellaneous databases
BioGRID-ORCSi | 1804, 3 hits in 113 CRISPR screens |
ChiTaRSi | DPP6, human |
EvolutionaryTracei | P42658 |
GeneWikii | DPP6 |
GenomeRNAii | 1804 |
Pharosi | P42658, Tbio |
PROi | PR:P42658 |
RNActi | P42658, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000130226, Expressed in middle temporal gyrus and 175 other tissues |
ExpressionAtlasi | P42658, baseline and differential |
Genevisiblei | P42658, HS |
Family and domain databases
Gene3Di | 2.140.10.30, 1 hit 3.40.50.1820, 1 hit |
InterProi | View protein in InterPro IPR029058, AB_hydrolase IPR001375, Peptidase_S9 IPR002469, Peptidase_S9B_N IPR038554, Peptidase_S9B_N_sf |
Pfami | View protein in Pfam PF00930, DPPIV_N, 1 hit PF00326, Peptidase_S9, 1 hit |
SUPFAMi | SSF53474, SSF53474, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | DPP6_HUMAN | |
Accessioni | P42658Primary (citable) accession number: P42658 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1995 |
Last sequence update: | December 16, 2008 | |
Last modified: | December 2, 2020 | |
This is version 180 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Peptidase families
Classification of peptidase families and list of entries