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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. positive regulation of potassium ion transmembrane 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 – 9595CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei96 – 11621Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini117 – 865749ExtracellularSequence AnalysisAdd
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.1 Publication
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.

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...)Sequence Analysis
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

BgeeiP42658.
CleanExiHS_DPP6.
ExpressionAtlasiP42658. baseline and differential.
GenevestigatoriP42658.

Organism-specific databases

HPAiHPA050509.

Interactioni

Subunit structurei

Homodimer. Binds KCND2.1 Publication

Protein-protein interaction databases

BioGridi108138. 3 interactions.
IntActiP42658. 1 interaction.
STRINGi9606.ENSP00000367001.

Structurei

Secondary structure

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

3D structure databases

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

eggNOGiCOG1506.
GeneTreeiENSGT00760000119233.
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

        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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti73 – 731A → G in AAA35760. (PubMed:8103397)Curated
Sequence conflicti520 – 5201V → E in AAA35760. (PubMed:8103397)Curated
Sequence conflicti520 – 5201V → E in AAA35761. (PubMed:8103397)Curated

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. 1 PublicationVSP_005365Add
BLAST

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]
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:
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 ]
UniGenei Hs.490684.
Hs.551097.
Hs.669076.
Hs.703229.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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. 3 interactions.
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.
GeneTreei ENSGT00760000119233.
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

Bgeei P42658.
CleanExi HS_DPP6.
ExpressionAtlasi P42658. baseline and differential.
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: November 26, 2014
This is version 132 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