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P42658

- DPP6_HUMAN

UniProt

P42658 - DPP6_HUMAN

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Protein

Dipeptidyl aminopeptidase-like protein 6

Gene
DPP6
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

May be involved in the physiological processes of brain function. Has no dipeptidyl aminopeptidase activity. May modulate the cell surface expression and the activity of the potassium channel KCND2.1 Publication

GO - Molecular functioni

  1. dipeptidyl-peptidase activity Source: ProtInc
  2. serine-type peptidase activity Source: InterPro

GO - Biological processi

  1. cell death Source: UniProtKB-KW
  2. neuronal action potential Source: Ensembl
  3. regulation of potassium ion transport Source: Ensembl
Complete GO annotation...

Protein family/group databases

MEROPSiS09.973.

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
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:3010. DPP6.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 9595Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei96 – 11621Helical; Signal-anchor for type II membrane protein; Reviewed predictionAdd
BLAST
Topological domaini117 – 865749Extracellular Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. extracellular vesicular exosome Source: UniProt
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Familial paroxysmal ventricular fibrillation 2 (VF2) [MIM:612956]: A 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.
Note: 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 2.1 Publication

Keywords - Diseasei

Neurodegeneration

Organism-specific databases

MIMi612956. phenotype.
Orphaneti2514. Autosomal dominant microcephaly.
228140. Idiopathic ventricular fibrillation, not Brugada type.
PharmGKBiPA27468.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 865865Dipeptidyl aminopeptidase-like protein 6PRO_0000122409Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi173 – 1731N-linked (GlcNAc...)1 Publication
Glycosylationi319 – 3191N-linked (GlcNAc...)1 Publication
Glycosylationi404 – 4041N-linked (GlcNAc...)1 Publication
Disulfide bondi411 ↔ 4181 Publication
Glycosylationi471 – 4711N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi527 ↔ 5301 Publication
Glycosylationi535 – 5351N-linked (GlcNAc...)1 Publication
Disulfide bondi536 ↔ 5541 Publication
Glycosylationi566 – 5661N-linked (GlcNAc...)1 Publication
Disulfide bondi735 ↔ 8461 Publication
Glycosylationi813 – 8131N-linked (GlcNAc...)1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP42658.
PRIDEiP42658.

PTM databases

PhosphoSiteiP42658.

Expressioni

Tissue specificityi

Expressed predominantly in brain.

Gene expression databases

ArrayExpressiP42658.
BgeeiP42658.
CleanExiHS_DPP6.
GenevestigatoriP42658.

Organism-specific databases

HPAiHPA050509.

Interactioni

Subunit structurei

Homodimer. Binds KCND2.1 Publication

Protein-protein interaction databases

BioGridi108138. 1 interaction.
IntActiP42658. 1 interaction.
STRINGi9606.ENSP00000367001.

Structurei

Secondary structure

1
865
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi133 – 1364
Turni139 – 1413
Beta strandi150 – 1545
Beta strandi161 – 1633
Beta strandi165 – 1684
Helixi170 – 1723
Beta strandi176 – 1794
Turni181 – 1888
Beta strandi190 – 1945
Beta strandi198 – 2069
Beta strandi211 – 2133
Beta strandi217 – 22610
Beta strandi254 – 2585
Beta strandi261 – 27010
Beta strandi273 – 2764
Turni281 – 2833
Beta strandi284 – 2885
Helixi291 – 2955
Beta strandi298 – 3069
Beta strandi310 – 31910
Beta strandi325 – 3284
Beta strandi332 – 3365
Beta strandi340 – 3434
Beta strandi353 – 36412
Helixi376 – 3783
Beta strandi379 – 40022
Beta strandi405 – 4128
Turni413 – 4153
Beta strandi418 – 4258
Beta strandi445 – 4528
Beta strandi455 – 4584
Beta strandi460 – 4667
Beta strandi472 – 4743
Beta strandi483 – 4853
Beta strandi487 – 4948
Turni495 – 4984
Beta strandi499 – 5079
Beta strandi513 – 5175
Beta strandi532 – 5354
Beta strandi540 – 5434
Beta strandi547 – 5537
Beta strandi556 – 5594
Beta strandi562 – 5665
Turni567 – 5693
Beta strandi572 – 5776
Helixi580 – 5878
Beta strandi599 – 6013
Beta strandi604 – 6063
Beta strandi609 – 6124
Beta strandi618 – 6203
Beta strandi622 – 6276
Helixi645 – 6517
Beta strandi656 – 6583
Beta strandi666 – 6683
Helixi669 – 6746
Turni675 – 6784
Turni680 – 6823
Helixi683 – 69614
Beta strandi697 – 71115
Helixi713 – 7208
Beta strandi725 – 7273
Beta strandi734 – 7407
Beta strandi747 – 7493
Helixi750 – 7578
Turni767 – 7704
Helixi773 – 7764
Beta strandi783 – 7897
Beta strandi793 – 7953
Helixi797 – 80913
Beta strandi815 – 8195
Helixi829 – 84315
Turni844 – 8474

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1XFDX-ray3.00A/B/C/D127-849[»]
ProteinModelPortaliP42658.
SMRiP42658. Positions 127-849.

Miscellaneous databases

EvolutionaryTraceiP42658.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase S9B family.

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1506.
HOGENOMiHOG000231875.
HOVERGENiHBG105877.
InParanoidiP42658.
OMAiSCDLVEN.
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.
[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. Align

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

MASLYQRFTG KINTSRSFPA PPEASHLLGG QGPEEDGGAG AKPLGPRAQA    50
AAPRERGGGG GGAGGRPRFQ YQARSDGDEE DELVGSNPPQ RNWKGIAIAL 100
LVILVICSLI VTSVILLTPA EDNSLSQKKK VTVEDLFSED FKIHDPEAKW 150
ISDTEFIYRE QKGTVRLWNV ETNTSTVLIE GKKIESLRAI RYEISPDREY 200
ALFSYNVEPI YQHSYTGYYV LSKIPHGDPQ SLDPPEVSNA KLQYAGWGPK 250
GQQLIFIFEN NIYYCAHVGK QAIRVVSTGK EGVIYNGLSD WLYEEEILKT 300
HIAHWWSPDG TRLAYAAIND SRVPIMELPT YTGSIYPTVK PYHYPKAGSE 350
NPSISLHVIG LNGPTHDLEM MPPDDPRMRE YYITMVKWAT STKVAVTWLN 400
RAQNVSILTL CDATTGVCTK KHEDESEAWL HRQNEEPVFS KDGRKFFFIR 450
AIPQGGRGKF YHITVSSSQP NSSNDNIQSI TSGDWDVTKI LAYDEKGNKI 500
YFLSTEDLPR RRQLYSANTV GNFNRQCLSC DLVENCTYFS ASFSHSMDFF 550
LLKCEGPGVP MVTVHNTTDK KKMFDLETNE HVKKAINDRQ MPKVEYRDIE 600
IDDYNLPMQI LKPATFTDTT HYPLLLVVDG TPGSQSVAEK FEVSWETVMV 650
SSHGAVVVKC DGRGSGFQGT KLLHEVRRRL GLLEEKDQME AVRTMLKEQY 700
IDRTRVAVFG KDYGGYLSTY ILPAKGENQG QTFTCGSALS PITDFKLYAS 750
AFSERYLGLH GLDNRAYEMT KVAHRVSALE EQQFLIIHPT ADEKIHFQHT 800
AELITQLIRG KANYSLQIYP DESHYFTSSS LKQHLYRSII NFFVECFRIQ 850
DKLLTVTAKE DEEED 865
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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti854 – 8541L → P.1 Publication
Corresponds to variant rs3734960 [ dbSNP | Ensembl ].
VAR_051579

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 8181MASLY…GDEED → MTTAKEPSASGKSVQQQEQ in isoform DPPX-S. VSP_005365Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti73 – 731A → G in AAA35760. 1 Publication
Sequence conflicti520 – 5201V → E in AAA35760. 1 Publication
Sequence conflicti520 – 5201V → E in AAA35761. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
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]
GeneIDi1804.
KEGGihsa:1804.
UCSCiuc003wlk.3. human. [P42658-1]
uc003wlm.3. human. [P42658-2]

Polymorphism databases

DMDMi218512016.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
PIRi I54331.
I68600.
RefSeqi NP_570629.2. NM_130797.3. [P42658-1 ]
UniGenei Hs.490684.
Hs.551097.
Hs.669076.
Hs.703229.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1XFD X-ray 3.00 A/B/C/D 127-849 [» ]
ProteinModelPortali P42658.
SMRi P42658. Positions 127-849.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108138. 1 interaction.
IntActi P42658. 1 interaction.
STRINGi 9606.ENSP00000367001.

Protein family/group databases

MEROPSi S09.973.

PTM databases

PhosphoSitei P42658.

Polymorphism databases

DMDMi 218512016.

Proteomic databases

PaxDbi P42658.
PRIDEi P42658.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000332007 ; ENSP00000328226 ; ENSG00000130226 . [P42658-2 ]
ENST00000377770 ; ENSP00000367001 ; ENSG00000130226 . [P42658-1 ]
GeneIDi 1804.
KEGGi hsa:1804.
UCSCi uc003wlk.3. human. [P42658-1 ]
uc003wlm.3. human. [P42658-2 ]

Organism-specific databases

CTDi 1804.
GeneCardsi GC07P153584.
H-InvDB HIX0020629.
HGNCi HGNC:3010. DPP6.
HPAi HPA050509.
MIMi 126141. gene.
612956. phenotype.
neXtProti NX_P42658.
Orphaneti 2514. Autosomal dominant microcephaly.
228140. Idiopathic ventricular fibrillation, not Brugada type.
PharmGKBi PA27468.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1506.
HOGENOMi HOG000231875.
HOVERGENi HBG105877.
InParanoidi P42658.
OMAi SCDLVEN.
PhylomeDBi P42658.
TreeFami TF313309.

Miscellaneous databases

ChiTaRSi DPP6. human.
EvolutionaryTracei P42658.
GeneWikii DPP6.
GenomeRNAii 1804.
NextBioi 7349.
PROi P42658.
SOURCEi Search...

Gene expression databases

ArrayExpressi P42658.
Bgeei P42658.
CleanExi HS_DPP6.
Genevestigatori P42658.

Family and domain databases

Gene3Di 2.140.10.30. 1 hit.
3.40.50.1820. 1 hit.
InterProi IPR029058. AB_hydrolase.
IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B.
[Graphical view ]
Pfami PF00930. DPPIV_N. 1 hit.
PF00326. Peptidase_S9. 1 hit.
[Graphical view ]
SUPFAMi SSF53474. SSF53474. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Non-conservation of a catalytic residue in a dipeptidyl aminopeptidase IV-related protein encoded by a gene on human chromosome 7."
    Yokotani N., Doi K., Wenthold R.J., Wada K.
    Hum. Mol. Genet. 2:1037-1039(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS DPPX-L AND DPPX-S), VARIANT PRO-854.
    Tissue: Hippocampus.
  2. "The DNA sequence of human chromosome 7."
    Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
    , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
    Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ALS.
  4. "Genetics. The elusive ALS genes."
    Garber K.
    Science 319:20-20(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISCUSSION OF THE INVOLVEMENT IN SUSCEPTIBILITY TO ALS.
  5. "Haplotype-sharing analysis implicates chromosome 7q36 harboring DPP6 in familial idiopathic ventricular fibrillation."
    Alders M., Koopmann T.T., Christiaans I., Postema P.G., Beekman L., Tanck M.W., Zeppenfeld K., Loh P., Koch K.T., Demolombe S., Mannens M.M., Bezzina C.R., Wilde A.A.
    Am. J. Hum. Genet. 84:468-476(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN VF2.
  6. "Structure of a human A-type potassium channel interacting protein DPPX, a member of the dipeptidyl aminopeptidase family."
    Strop P., Bankovich A.J., Hansen K.C., Garcia K.C., Brunger A.T.
    J. Mol. Biol. 343:1055-1065(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 127-849, FUNCTION, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-173; ASN-319; ASN-404; ASN-535; ASN-566 AND ASN-813.

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: September 3, 2014
This is version 129 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

External Data

Dasty 3

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