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Protein

Dipeptidyl aminopeptidase-like protein 6

Gene

DPP6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

GO - Molecular functioni

  • potassium channel regulator activity Source: UniProtKB
  • serine-type peptidase activity Source: InterPro

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000130226-MONOMER.

Protein family/group databases

ESTHERihuman-DPP6. DPP4N_Peptidase_S9.
MEROPSiS09.973.
TCDBi8.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 6
Alternative 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:3010. DPP6.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 95CytoplasmicSequence analysisAdd BLAST95
Transmembranei96 – 116Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini117 – 865ExtracellularSequence analysisAdd BLAST749

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • voltage-gated potassium channel complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & 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.
See also OMIM:612956
Mental 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.
See also OMIM:616311
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073680385M → L in MRD33. 1 PublicationCorresponds to variant rs786205143dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Mental retardation, Neurodegeneration

Organism-specific databases

DisGeNETi1804.
MalaCardsiDPP6.
MIMi612956. phenotype.
616311. phenotype.
OpenTargetsiENSG00000130226.
ENSG00000282974.
Orphaneti2514. Autosomal dominant microcephaly.
228140. Idiopathic ventricular fibrillation, not Brugada type.
PharmGKBiPA27468.

Polymorphism and mutation databases

BioMutaiDPP6.
DMDMi218512016.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001224091 – 865Dipeptidyl aminopeptidase-like protein 6Add BLAST865

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi173N-linked (GlcNAc...)1 Publication1
Glycosylationi319N-linked (GlcNAc...)1 Publication1
Glycosylationi404N-linked (GlcNAc...)1 Publication1
Disulfide bondi411 ↔ 4181 Publication
Glycosylationi471N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi527 ↔ 5301 Publication
Glycosylationi535N-linked (GlcNAc...)1 Publication1
Disulfide bondi536 ↔ 5541 Publication
Glycosylationi566N-linked (GlcNAc...)1 Publication1
Disulfide bondi735 ↔ 8461 Publication
Glycosylationi813N-linked (GlcNAc...)1 Publication1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP42658.
PaxDbiP42658.
PeptideAtlasiP42658.
PRIDEiP42658.

PTM databases

iPTMnetiP42658.
PhosphoSitePlusiP42658.
SwissPalmiP42658.

Expressioni

Tissue specificityi

Expressed predominantly in brain.

Gene expression databases

BgeeiENSG00000130226.
CleanExiHS_DPP6.
ExpressionAtlasiP42658. baseline and differential.
GenevisibleiP42658. HS.

Organism-specific databases

HPAiHPA050509.

Interactioni

Subunit structurei

Homodimer (in vitro) (PubMed:15476821). Interacts with KCND2 (PubMed:15454437, PubMed:18364354). Identified in a complex with KCND2 and KCNIP2 (PubMed:18364354). Forms an octameric complex composed of four DPP6 subunits bound to the KCND2 tetramer (PubMed:18364354).4 Publications

Protein-protein interaction databases

BioGridi108138. 4 interactors.
IntActiP42658. 1 interactor.
STRINGi9606.ENSP00000367001.

Structurei

Secondary structure

1865
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi133 – 136Combined sources4
Turni139 – 141Combined sources3
Beta strandi150 – 154Combined sources5
Beta strandi161 – 163Combined sources3
Beta strandi165 – 168Combined sources4
Helixi170 – 172Combined sources3
Beta strandi176 – 179Combined sources4
Turni181 – 188Combined sources8
Beta strandi190 – 194Combined sources5
Beta strandi198 – 206Combined sources9
Beta strandi211 – 213Combined sources3
Beta strandi217 – 226Combined sources10
Beta strandi254 – 258Combined sources5
Beta strandi261 – 270Combined sources10
Beta strandi273 – 276Combined sources4
Turni281 – 283Combined sources3
Beta strandi284 – 288Combined sources5
Helixi291 – 295Combined sources5
Beta strandi298 – 306Combined sources9
Beta strandi310 – 319Combined sources10
Beta strandi325 – 328Combined sources4
Beta strandi332 – 336Combined sources5
Beta strandi340 – 343Combined sources4
Beta strandi353 – 364Combined sources12
Helixi376 – 378Combined sources3
Beta strandi379 – 400Combined sources22
Beta strandi405 – 412Combined sources8
Turni413 – 415Combined sources3
Beta strandi418 – 425Combined sources8
Beta strandi445 – 452Combined sources8
Beta strandi455 – 458Combined sources4
Beta strandi460 – 466Combined sources7
Beta strandi472 – 474Combined sources3
Beta strandi483 – 485Combined sources3
Beta strandi487 – 494Combined sources8
Turni495 – 498Combined sources4
Beta strandi499 – 507Combined sources9
Beta strandi513 – 517Combined sources5
Beta strandi532 – 535Combined sources4
Beta strandi540 – 543Combined sources4
Beta strandi547 – 553Combined sources7
Beta strandi556 – 559Combined sources4
Beta strandi562 – 566Combined sources5
Turni567 – 569Combined sources3
Beta strandi572 – 577Combined sources6
Helixi580 – 587Combined sources8
Beta strandi599 – 601Combined sources3
Beta strandi604 – 606Combined sources3
Beta strandi609 – 612Combined sources4
Beta strandi618 – 620Combined sources3
Beta strandi622 – 627Combined sources6
Helixi645 – 651Combined sources7
Beta strandi656 – 658Combined sources3
Beta strandi666 – 668Combined sources3
Helixi669 – 674Combined sources6
Turni675 – 678Combined sources4
Turni680 – 682Combined sources3
Helixi683 – 696Combined sources14
Beta strandi697 – 711Combined sources15
Helixi713 – 720Combined sources8
Beta strandi725 – 727Combined sources3
Beta strandi734 – 740Combined sources7
Beta strandi747 – 749Combined sources3
Helixi750 – 757Combined sources8
Turni767 – 770Combined sources4
Helixi773 – 776Combined sources4
Beta strandi783 – 789Combined sources7
Beta strandi793 – 795Combined sources3
Helixi797 – 809Combined sources13
Beta strandi815 – 819Combined sources5
Helixi829 – 843Combined sources15
Turni844 – 847Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XFDX-ray3.00A/B/C/D127-849[»]
ProteinModelPortaliP42658.
SMRiP42658.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42658.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase S9B family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2100. Eukaryota.
COG1506. LUCA.
GeneTreeiENSGT00760000119233.
HOGENOMiHOG000231875.
HOVERGENiHBG105877.
InParanoidiP42658.
OMAiHLYSANT.
OrthoDBiEOG091G0GBJ.
PhylomeDBiP42658.
TreeFamiTF313309.

Family and domain databases

Gene3Di2.140.10.30. 1 hit.
3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B_N.
[Graphical view]
PfamiPF00930. DPPIV_N. 1 hit.
PF00326. Peptidase_S9. 1 hit.
[Graphical view]
SUPFAMiSSF53474. SSF53474. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform DPPX-L (identifier: P42658-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:865
Mass (Da):97,588
Last modified:December 16, 2008 - v2
Checksum:iD3E654013F19D951
GO
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

Show »
Length:803
Mass (Da):91,341
Checksum:iECBC607A432CE82C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti73A → G in AAA35760 (PubMed:8103397).Curated1
Sequence conflicti520V → E in AAA35760 (PubMed:8103397).Curated1
Sequence conflicti520V → E in AAA35761 (PubMed:8103397).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073680385M → L in MRD33. 1 PublicationCorresponds to variant rs786205143dbSNPEnsembl.1
Natural variantiVAR_051579854L → P.1 PublicationCorresponds to variant rs3734960dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0053651 – 81MASLY…GDEED → MTTAKEPSASGKSVQQQEQ in isoform DPPX-S. 1 PublicationAdd BLAST81

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.
CCDSiCCDS75683.1. [P42658-1]
CCDS75684.1. [P42658-2]
PIRiI54331.
I68600.
RefSeqiNP_570629.2. NM_130797.3. [P42658-1]
UniGeneiHs.490684.
Hs.551097.
Hs.669076.
Hs.703229.

Genome annotation databases

EnsembliENST00000332007; ENSP00000328226; ENSG00000130226. [P42658-2]
ENST00000377770; ENSP00000367001; ENSG00000130226. [P42658-1]
ENST00000634466; ENSP00000488956; ENSG00000282974. [P42658-2]
ENST00000634541; ENSP00000489137; ENSG00000282974. [P42658-1]
GeneIDi1804.
KEGGihsa:1804.
UCSCiuc003wlk.4. human. [P42658-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
CCDSiCCDS75683.1. [P42658-1]
CCDS75684.1. [P42658-2]
PIRiI54331.
I68600.
RefSeqiNP_570629.2. NM_130797.3. [P42658-1]
UniGeneiHs.490684.
Hs.551097.
Hs.669076.
Hs.703229.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XFDX-ray3.00A/B/C/D127-849[»]
ProteinModelPortaliP42658.
SMRiP42658.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108138. 4 interactors.
IntActiP42658. 1 interactor.
STRINGi9606.ENSP00000367001.

Protein family/group databases

ESTHERihuman-DPP6. DPP4N_Peptidase_S9.
MEROPSiS09.973.
TCDBi8.A.51.1.1. the dipeptidyl-aminopeptidase-like protein 6 beta subunit of kv4 channels (dpp6) family.

PTM databases

iPTMnetiP42658.
PhosphoSitePlusiP42658.
SwissPalmiP42658.

Polymorphism and mutation databases

BioMutaiDPP6.
DMDMi218512016.

Proteomic databases

EPDiP42658.
PaxDbiP42658.
PeptideAtlasiP42658.
PRIDEiP42658.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000332007; ENSP00000328226; ENSG00000130226. [P42658-2]
ENST00000377770; ENSP00000367001; ENSG00000130226. [P42658-1]
ENST00000634466; ENSP00000488956; ENSG00000282974. [P42658-2]
ENST00000634541; ENSP00000489137; ENSG00000282974. [P42658-1]
GeneIDi1804.
KEGGihsa:1804.
UCSCiuc003wlk.4. human. [P42658-1]

Organism-specific databases

CTDi1804.
DisGeNETi1804.
GeneCardsiDPP6.
H-InvDBHIX0020629.
HGNCiHGNC:3010. DPP6.
HPAiHPA050509.
MalaCardsiDPP6.
MIMi126141. gene.
612956. phenotype.
616311. phenotype.
neXtProtiNX_P42658.
OpenTargetsiENSG00000130226.
ENSG00000282974.
Orphaneti2514. Autosomal dominant microcephaly.
228140. Idiopathic ventricular fibrillation, not Brugada type.
PharmGKBiPA27468.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2100. Eukaryota.
COG1506. LUCA.
GeneTreeiENSGT00760000119233.
HOGENOMiHOG000231875.
HOVERGENiHBG105877.
InParanoidiP42658.
OMAiHLYSANT.
OrthoDBiEOG091G0GBJ.
PhylomeDBiP42658.
TreeFamiTF313309.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000130226-MONOMER.

Miscellaneous databases

ChiTaRSiDPP6. human.
EvolutionaryTraceiP42658.
GeneWikiiDPP6.
GenomeRNAii1804.
PROiP42658.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130226.
CleanExiHS_DPP6.
ExpressionAtlasiP42658. baseline and differential.
GenevisibleiP42658. HS.

Family and domain databases

Gene3Di2.140.10.30. 1 hit.
3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B_N.
[Graphical view]
PfamiPF00930. DPPIV_N. 1 hit.
PF00326. Peptidase_S9. 1 hit.
[Graphical view]
SUPFAMiSSF53474. SSF53474. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiDPP6_HUMAN
AccessioniPrimary (citable) accession number: P42658
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: December 16, 2008
Last modified: November 2, 2016
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.