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P42658 (DPP6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:DPP6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length865 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6

Subunit structure

Homodimer. Binds KCND2. Ref.6

Subcellular location

Membrane; Single-pass type II membrane protein Probable.

Tissue specificity

Expressed predominantly in brain.

Involvement in disease

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. Ref.5

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.

Sequence similarities

Belongs to the peptidase S9B family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform DPPX-L (identifier: P42658-1)

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.
Isoform DPPX-S (identifier: P42658-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-81: MASLYQRFTG...QARSDGDEED → MTTAKEPSASGKSVQQQEQ

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 865865Dipeptidyl aminopeptidase-like protein 6
PRO_0000122409

Regions

Topological domain1 – 9595Cytoplasmic Potential
Transmembrane96 – 11621Helical; Signal-anchor for type II membrane protein; Potential
Topological domain117 – 865749Extracellular Potential

Amino acid modifications

Glycosylation1731N-linked (GlcNAc...) Ref.6
Glycosylation3191N-linked (GlcNAc...) Ref.6
Glycosylation4041N-linked (GlcNAc...) Ref.6
Glycosylation4711N-linked (GlcNAc...) Potential
Glycosylation5351N-linked (GlcNAc...) Ref.6
Glycosylation5661N-linked (GlcNAc...) Ref.6
Glycosylation8131N-linked (GlcNAc...) Ref.6
Disulfide bond411 ↔ 418 Ref.6
Disulfide bond527 ↔ 530 Ref.6
Disulfide bond536 ↔ 554 Ref.6
Disulfide bond735 ↔ 846 Ref.6

Natural variations

Alternative sequence1 – 8181MASLY…GDEED → MTTAKEPSASGKSVQQQEQ in isoform DPPX-S.
VSP_005365
Natural variant8541L → P. Ref.1
Corresponds to variant rs3734960 [ dbSNP | Ensembl ].
VAR_051579

Experimental info

Sequence conflict731A → G in AAA35760. Ref.1
Sequence conflict5201V → E in AAA35760. Ref.1
Sequence conflict5201V → E in AAA35761. Ref.1

Secondary structure

..................................................................................................................................... 865
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform DPPX-L [UniParc].

Last modified December 16, 2008. Version 2.
Checksum: D3E654013F19D951

FASTA86597,588
        10         20         30         40         50         60 
MASLYQRFTG KINTSRSFPA PPEASHLLGG QGPEEDGGAG AKPLGPRAQA AAPRERGGGG 

        70         80         90        100        110        120 
GGAGGRPRFQ YQARSDGDEE DELVGSNPPQ RNWKGIAIAL LVILVICSLI VTSVILLTPA 

       130        140        150        160        170        180 
EDNSLSQKKK VTVEDLFSED FKIHDPEAKW ISDTEFIYRE QKGTVRLWNV ETNTSTVLIE 

       190        200        210        220        230        240 
GKKIESLRAI RYEISPDREY ALFSYNVEPI YQHSYTGYYV LSKIPHGDPQ SLDPPEVSNA 

       250        260        270        280        290        300 
KLQYAGWGPK GQQLIFIFEN NIYYCAHVGK QAIRVVSTGK EGVIYNGLSD WLYEEEILKT 

       310        320        330        340        350        360 
HIAHWWSPDG TRLAYAAIND SRVPIMELPT YTGSIYPTVK PYHYPKAGSE NPSISLHVIG 

       370        380        390        400        410        420 
LNGPTHDLEM MPPDDPRMRE YYITMVKWAT STKVAVTWLN RAQNVSILTL CDATTGVCTK 

       430        440        450        460        470        480 
KHEDESEAWL HRQNEEPVFS KDGRKFFFIR AIPQGGRGKF YHITVSSSQP NSSNDNIQSI 

       490        500        510        520        530        540 
TSGDWDVTKI LAYDEKGNKI YFLSTEDLPR RRQLYSANTV GNFNRQCLSC DLVENCTYFS 

       550        560        570        580        590        600 
ASFSHSMDFF LLKCEGPGVP MVTVHNTTDK KKMFDLETNE HVKKAINDRQ MPKVEYRDIE 

       610        620        630        640        650        660 
IDDYNLPMQI LKPATFTDTT HYPLLLVVDG TPGSQSVAEK FEVSWETVMV SSHGAVVVKC 

       670        680        690        700        710        720 
DGRGSGFQGT KLLHEVRRRL GLLEEKDQME AVRTMLKEQY IDRTRVAVFG KDYGGYLSTY 

       730        740        750        760        770        780 
ILPAKGENQG QTFTCGSALS PITDFKLYAS AFSERYLGLH GLDNRAYEMT KVAHRVSALE 

       790        800        810        820        830        840 
EQQFLIIHPT ADEKIHFQHT AELITQLIRG KANYSLQIYP DESHYFTSSS LKQHLYRSII 

       850        860 
NFFVECFRIQ DKLLTVTAKE DEEED 

« Hide

Isoform DPPX-S [UniParc].

Checksum: ECBC607A432CE82C
Show »

FASTA80391,341

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis."
van Es M.A., van Vught P.W.J., Blauw H.M., Franke L., Saris C.G.J., Van den Bosch L., de Jong S.W., de Jong V., Baas F., van't Slot R., Lemmens R., Schelhaas H.J., Birve A., Sleegers K., Van Broeckhoven C., Schymick J.C., Traynor B.J., Wokke J.H.J. expand/collapse author list , Wijmenga C., Robberecht W., Andersen P.M., Veldink J.H., Ophoff R.A., van den Berg L.H.
Nat. Genet. 40:29-31(2008) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRI54331.
I68600.
RefSeqNP_570629.2. NM_130797.3. [P42658-1]
UniGeneHs.490684.
Hs.551097.
Hs.669076.
Hs.703229.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1XFDX-ray3.00A/B/C/D127-849[»]
ProteinModelPortalP42658.
SMRP42658. Positions 127-849.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108138. 1 interaction.
IntActP42658. 1 interaction.
STRING9606.ENSP00000367001.

Protein family/group databases

MEROPSS09.973.

PTM databases

PhosphoSiteP42658.

Polymorphism databases

DMDM218512016.

Proteomic databases

PaxDbP42658.
PRIDEP42658.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000332007; ENSP00000328226; ENSG00000130226. [P42658-2]
ENST00000377770; ENSP00000367001; ENSG00000130226. [P42658-1]
GeneID1804.
KEGGhsa:1804.
UCSCuc003wlk.3. human. [P42658-1]
uc003wlm.3. human. [P42658-2]

Organism-specific databases

CTD1804.
GeneCardsGC07P153584.
H-InvDBHIX0020629.
HGNCHGNC:3010. DPP6.
HPAHPA050509.
MIM126141. gene.
612956. phenotype.
neXtProtNX_P42658.
Orphanet2514. Autosomal dominant microcephaly.
228140. Idiopathic ventricular fibrillation, not Brugada type.
PharmGKBPA27468.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1506.
HOGENOMHOG000231875.
HOVERGENHBG105877.
InParanoidP42658.
OMASCDLVEN.
PhylomeDBP42658.
TreeFamTF313309.

Gene expression databases

ArrayExpressP42658.
BgeeP42658.
CleanExHS_DPP6.
GenevestigatorP42658.

Family and domain databases

Gene3D2.140.10.30. 1 hit.
3.40.50.1820. 1 hit.
InterProIPR029058. AB_hydrolase.
IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B.
[Graphical view]
PfamPF00930. DPPIV_N. 1 hit.
PF00326. Peptidase_S9. 1 hit.
[Graphical view]
SUPFAMSSF53474. SSF53474. 1 hit.
ProtoNetSearch...

Other

ChiTaRSDPP6. human.
EvolutionaryTraceP42658.
GeneWikiDPP6.
GenomeRNAi1804.
NextBio7349.
PROP42658.
SOURCESearch...

Entry information

Entry nameDPP6_HUMAN
AccessionPrimary (citable) accession number: P42658
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: December 16, 2008
Last modified: June 11, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM