P42658 (DPP6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

DPP6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	865 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Neurodegeneration
Domain	Signal-anchor Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro regulation of action potential in neuron Inferred from electronic annotation. Source: Compara regulation of potassium ion transport Inferred from electronic annotation. Source: Compara
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	dipeptidyl-peptidase activity Traceable author statement Ref.1. Source: ProtInc serine-type peptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 865

865

Dipeptidyl aminopeptidase-like protein 6

PRO_0000122409

Regions

Topological domain

1 – 95

95

Cytoplasmic Potential

Transmembrane

96 – 116

21

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

117 – 865

749

Extracellular Potential

Amino acid modifications

Glycosylation

173

1

N-linked (GlcNAc...) Ref.6

Glycosylation

319

1

N-linked (GlcNAc...) Ref.6

Glycosylation

404

1

N-linked (GlcNAc...) Ref.6

Glycosylation

471

1

N-linked (GlcNAc...) Potential

Glycosylation

535

1

N-linked (GlcNAc...) Ref.6

Glycosylation

566

1

N-linked (GlcNAc...) Ref.6

Glycosylation

813

1

N-linked (GlcNAc...) Ref.6

Disulfide bond

411 ↔ 418

Ref.6

Disulfide bond

527 ↔ 530

Ref.6

Disulfide bond

536 ↔ 554

Ref.6

Disulfide bond

735 ↔ 846

Ref.6

Natural variations

Alternative sequence

1 – 81

81

MASLY…GDEED → MTTAKEPSASGKSVQQQEQ in isoform DPPX-S.

VSP_005365

Natural variant

854

1

L → P. Ref.1
Corresponds to variant rs3734960 [ dbSNP | Ensembl ].

VAR_051579

Experimental info

Sequence conflict

73

1

A → G in AAA35760. Ref.1

Sequence conflict

520

1

V → E in AAA35760. Ref.1

Sequence conflict

520

1

V → E in AAA35761. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

865

Helix Strand Turn

Details...

Helix

133 – 136

4

Turn

139 – 141

3

Beta strand

150 – 154

5

Beta strand

161 – 163

3

Beta strand

165 – 168

4

Helix

170 – 172

3

Beta strand

176 – 179

4

Turn

181 – 188

8

Beta strand

190 – 194

5

Beta strand

198 – 206

9

Beta strand

211 – 213

3

Beta strand

217 – 226

10

Beta strand

254 – 258

5

Beta strand

261 – 270

10

Beta strand

273 – 276

4

Turn

281 – 283

3

Beta strand

284 – 288

5

Helix

291 – 295

5

Beta strand

298 – 306

9

Beta strand

310 – 319

10

Beta strand

325 – 328

4

Beta strand

332 – 336

5

Beta strand

340 – 343

4

Beta strand

353 – 364

12

Helix

376 – 378

3

Beta strand

379 – 400

22

Beta strand

405 – 412

8

Turn

413 – 415

3

Beta strand

418 – 425

8

Beta strand

445 – 452

8

Beta strand

455 – 458

4

Beta strand

460 – 466

7

Beta strand

472 – 474

3

Beta strand

483 – 485

3

Beta strand

487 – 494

8

Turn

495 – 498

4

Beta strand

499 – 507

9

Beta strand

513 – 517

5

Beta strand

532 – 535

4

Beta strand

540 – 543

4

Beta strand

547 – 553

7

Beta strand

556 – 559

4

Beta strand

562 – 566

5

Turn

567 – 569

3

Beta strand

572 – 577

6

Helix

580 – 587

8

Beta strand

599 – 601

3

Beta strand

604 – 606

3

Beta strand

609 – 612

4

Beta strand

618 – 620

3

Beta strand

622 – 627

6

Helix

645 – 651

7

Beta strand

656 – 658

3

Beta strand

666 – 668

3

Helix

669 – 674

6

Turn

675 – 678

4

Turn

680 – 682

3

Helix

683 – 696

14

Beta strand

697 – 711

15

Helix

713 – 720

8

Beta strand

725 – 727

3

Beta strand

734 – 740

7

Beta strand

747 – 749

3

Helix

750 – 757

8

Turn

767 – 770

4

Helix

773 – 776

4

Beta strand

783 – 789

7

Beta strand

793 – 795

3

Helix

797 – 809

13

Beta strand

815 – 819

5

Helix

829 – 843

15

Turn

844 – 847

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform DPPX-L [UniParc]. Last modified December 16, 2008. Version 2. Checksum: D3E654013F19D951	FASTA	865	97,588
	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
	Isoform DPPX-S [UniParc]. Checksum: ECBC607A432CE82C	FASTA	803	91,341
	10 20 30 40 50 60 MTTAKEPSAS GKSVQQQEQE LVGSNPPQRN WKGIAIALLV ILVICSLIVT SVILLTPAED 70 80 90 100 110 120 NSLSQKKKVT VEDLFSEDFK IHDPEAKWIS DTEFIYREQK GTVRLWNVET NTSTVLIEGK 130 140 150 160 170 180 KIESLRAIRY EISPDREYAL FSYNVEPIYQ HSYTGYYVLS KIPHGDPQSL DPPEVSNAKL 190 200 210 220 230 240 QYAGWGPKGQ QLIFIFENNI YYCAHVGKQA IRVVSTGKEG VIYNGLSDWL YEEEILKTHI 250 260 270 280 290 300 AHWWSPDGTR LAYAAINDSR VPIMELPTYT GSIYPTVKPY HYPKAGSENP SISLHVIGLN 310 320 330 340 350 360 GPTHDLEMMP PDDPRMREYY ITMVKWATST KVAVTWLNRA QNVSILTLCD ATTGVCTKKH 370 380 390 400 410 420 EDESEAWLHR QNEEPVFSKD GRKFFFIRAI PQGGRGKFYH ITVSSSQPNS SNDNIQSITS 430 440 450 460 470 480 GDWDVTKILA YDEKGNKIYF LSTEDLPRRR QLYSANTVGN FNRQCLSCDL VENCTYFSAS 490 500 510 520 530 540 FSHSMDFFLL KCEGPGVPMV TVHNTTDKKK MFDLETNEHV KKAINDRQMP KVEYRDIEID 550 560 570 580 590 600 DYNLPMQILK PATFTDTTHY PLLLVVDGTP GSQSVAEKFE VSWETVMVSS HGAVVVKCDG 610 620 630 640 650 660 RGSGFQGTKL LHEVRRRLGL LEEKDQMEAV RTMLKEQYID RTRVAVFGKD YGGYLSTYIL 670 680 690 700 710 720 PAKGENQGQT FTCGSALSPI TDFKLYASAF SERYLGLHGL DNRAYEMTKV AHRVSALEEQ 730 740 750 760 770 780 QFLIIHPTAD EKIHFQHTAE LITQLIRGKA NYSLQIYPDE SHYFTSSSLK QHLYRSIINF 790 800 FVECFRIQDK LLTVTAKEDE EED

References

	« Hide 'large scale' referencesShow '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. , 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. , 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 ABOUT 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.

IPI

IPI00252731.
IPI00301512.

PIR

I54331.
I68600.

RefSeq

NP_001034439.1. NM_001039350.1.
NP_001927.3. NM_001936.3.
NP_570629.2. NM_130797.2.

UniGene

Hs.490684.
Hs.669076.
Hs.703229.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XFD	X-ray	3.00	A/B/C/D	127-849	[»]

ProteinModelPortal

P42658.

ModBase

Search...

Protein-protein interaction databases

IntAct

P42658. 1 interaction.

STRING

9606.ENSP00000367001.

Protein family/group databases

MEROPS

S09.973.

PTM databases

PhosphoSite

P42658.

Polymorphism databases

DMDM

218512016.

Proteomic databases

PaxDb

P42658.

PRIDE

P42658.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000332007; ENSP00000328226; ENSG00000130226.
ENST00000377770; ENSP00000367001; ENSG00000130226.

GeneID

1804.

KEGG

hsa:1804.

UCSC

uc003wlk.3. human.
uc003wlm.3. human.

Organism-specific databases

CTD

1804.

GeneCards

GC07P153584.

H-InvDB

HIX0020629.

HGNC

HGNC:3010. DPP6.

HPA

HPA050509.

MIM

126141. gene.
612956. phenotype.

neXtProt

NX_P42658.

Orphanet

228140. Idiopathic ventricular fibrillation, not Brugada type.

PharmGKB

PA27468.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1506.

HOGENOM

HOG000231875.

HOVERGEN

HBG105877.

InParanoid

P42658.

OMA

KGENQGQ.

PhylomeDB

P42658.

Gene expression databases

ArrayExpress

P42658.

Bgee

P42658.

CleanEx

HS_DPP6.

Genevestigator

P42658.

GermOnline

ENSG00000130226. Homo sapiens.

Family and domain databases

InterPro

IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B.
[Graphical view]

Pfam

PF00930. DPPIV_N. 1 hit.
PF00326. Peptidase_S9. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

DPP6. human.

EvolutionaryTrace

P42658.

GenomeRNAi

1804.

NextBio

7349.

SOURCE

Search...

Entry information

Entry name

DPP6_HUMAN

Accession

Primary (citable) accession number: P42658

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	December 16, 2008
Last modified:	May 1, 2013
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.