Dipeptidyl peptidase 4 - Sus scrofa (Pig)

Preferred order of sections

Names and origin

Protein names

Recommended name:
Dipeptidyl peptidase 4
EC=3.4.14.5

Alternative name(s):
Dipeptidyl peptidase IV
Short name=DPP IV
T-cell activation antigen CD26
CD_antigen=CD26

Cleaved into the following 2 chains:

Dipeptidyl peptidase 4 membrane form
Alternative name(s):
Dipeptidyl peptidase IV membrane form
Dipeptidyl peptidase 4 soluble form
Alternative name(s):
Dipeptidyl peptidase IV soluble form

Gene names

Name:	DPP4
Synonyms:	CD26

Organism

Sus scrofa (Pig) [Reference proteome]

Taxonomic identifier

9823 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus

Protein attributes

Sequence length	766 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones By similarity. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline. Ref.1
Catalytic activity	Release of an N-terminal dipeptide, Xaa-Yaa-\|-Zaa-, from a polypeptide, preferentially when Yaa is Pro, provided Zaa is neither Pro nor hydroxyproline.
Enzyme regulation	Inhibited by GPC3 and diprotin A By similarity.
Subunit structure	Monomer. Heterodimer with Seprase (FAP). Requires homodimerization for optimal dipeptidyl peptidase activity and T-cell costimulation. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. Associates with collagen. Interacts with PTPRC; the interaction is enhanced in a interleukin-12-dependent manner in activated lymphocytes. Interacts (extracellular domain) with ADA; does not inhibit its dipeptidyl peptidase activity. Interacts with CAV1 (via the N-terminus); the interaction is direct. Interacts (via cytoplasmic tail) with CARD11 (via PDZ domain); its homodimerization is necessary for interaction with CARD11. Interacts with IGF2R; the interaction is direct. Interacts with GPC3 By similarity. Homodimer. Ref.4
Subcellular location	Dipeptidyl peptidase 4 soluble form: Secreted. Note: Detected in the serum and the seminal fluid By similarity. Cell membrane; Single-pass type II membrane protein. Apical cell membrane; Single-pass type II membrane protein By similarity. Cell projection › invadopodium membrane; Single-pass type II membrane protein By similarity. Cell projection › lamellipodium membrane; Single-pass type II membrane protein By similarity. Cell junction By similarity. Membrane raft By similarity. Note: Translocated to the apical membrane through the concerted action of N- and O-Glycans and its association with lipid microdomains containing cholesterol and sphingolipids. Redistributed to membrane rafts in T-cell in a interleukin-12-dependent activation. Its interaction with CAV1 is necessary for its translocation to membrane rafts. Colocalized with PTPRC in membrane rafts. Colocalized with FAP in invadopodia and lamellipodia of migratory activated endothelial cells in collagenous matrix. Colocalized with FAP on endothelial cells of capillary-like microvessels but not large vessels within invasive breast ductal carcinoma. Colocalized with ADA at the cell junction in lymphocyte-epithelial cell adhesion. Colocalized with IGF2R in internalized cytoplasmic vesicles adjacent to the cell surface By similarity.
Post-translational modification	The soluble form (Dipeptidyl peptidase 4 soluble form also named SDPP) derives from the membrane form (Dipeptidyl peptidase 4 membrane form also named MDPP) by proteolytic processing. N- and O-Glycosylated By similarity. Ref.4 Phosphorylated. Mannose 6-phosphate residues in the carbohydrate moiety are necessary for interaction with IGF2R in activated T-cells. Mannose 6-phosphorylation is induced during T-cell activation By similarity.
Sequence similarities	Belongs to the peptidase S9B family. DPPIV subfamily.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction Cell membrane Cell projection Membrane Secreted
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Aminopeptidase Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	T cell costimulation Inferred from sequence or structural similarity. Source: UniProtKB cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW endothelial cell migration Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of extracellular matrix disassembly Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cell junction Inferred from electronic annotation. Source: UniProtKB-SubCell cell surface Inferred from sequence or structural similarity. Source: UniProtKB endocytic vesicle Inferred from sequence or structural similarity. Source: UniProtKB extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW invadopodium membrane Inferred from sequence or structural similarity. Source: UniProtKB lamellipodium Inferred from sequence or structural similarity. Source: UniProtKB lamellipodium membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane raft Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	aminopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW dipeptidyl-peptidase activity Inferred from sequence or structural similarity. Source: UniProtKB protease binding Inferred from sequence or structural similarity. Source: UniProtKB protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB receptor binding Inferred from sequence or structural similarity. Source: UniProtKB serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 766

766

Dipeptidyl peptidase 4 membrane form

PRO_0000027217

Chain

38 – 766

729

Dipeptidyl peptidase 4 soluble form

PRO_0000027218

Regions

Topological domain

1 – 6

6

Cytoplasmic Potential

Transmembrane

7 – 27

21

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

Topological domain

28 – 766

739

Extracellular Potential

Sites

Active site

630

1

Charge relay system By similarity

Active site

708

1

Charge relay system By similarity

Active site

740

1

Charge relay system By similarity

Amino acid modifications

Glycosylation

85

1

N-linked (GlcNAc...) Ref.4

Glycosylation

92

1

N-linked (GlcNAc...) Ref.4

Glycosylation

229

1

N-linked (GlcNAc...) Ref.4

Glycosylation

279

1

N-linked (GlcNAc...) Ref.4

Glycosylation

321

1

N-linked (GlcNAc...) Ref.4

Glycosylation

685

1

N-linked (GlcNAc...) Ref.4

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Experimental info

Sequence conflict

32

1

Missing Ref.2

Secondary structure

1

.

766

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P22411 [UniParc].

Last modified September 13, 2004. Version 3.
Checksum: 8800D520BAEA856D
Show »

FASTA

766

88,242

        10         20         30         40         50         60 
MKTPWKVLLG LLGIAALVTV ITVPVVLLNK GTDDAAADSR RTYTLTDYLK STFRVKFYTL 

        70         80         90        100        110        120 
QWISDHEYLY KQENNILLFN AEYGNSSIFL ENSTFDELGY STNDYSVSPD RQFILFEYNY 

       130        140        150        160        170        180 
VKQWRHSYTA SYDIYDLNKR QLITEERIPN NTQWITWSPV GHKLAYVWNN DIYVKNEPNL 

       190        200        210        220        230        240 
SSQRITWTGK ENVIYNGVTD WVYEEEVFSA YSALWWSPNG TFLAYAQFND TEVPLIEYSF 

       250        260        270        280        290        300 
YSDESLQYPK TVRIPYPKAG AENPTVKFFV VDTRTLSPNA SVTSYQIVPP ASVLIGDHYL 

       310        320        330        340        350        360 
CGVTWVTEER ISLQWIRRAQ NYSIIDICDY DESTGRWISS VARQHIEIST TGWVGRFRPA 

       370        380        390        400        410        420 
EPHFTSDGNS FYKIISNEEG YKHICHFQTD KSNCTFITKG AWEVIGIEAL TSDYLYYISN 

       430        440        450        460        470        480 
EHKGMPGGRN LYRIQLNDYT KVTCLSCELN PERCQYYSAS FSNKAKYYQL RCFGPGLPLY 

       490        500        510        520        530        540 
TLHSSSSDKE LRVLEDNSAL DKMLQDVQMP SKKLDVINLH GTKFWYQMIL PPHFDKSKKY 

       550        560        570        580        590        600 
PLLIEVYAGP CSQKVDTVFR LSWATYLAST ENIIVASFDG RGSGYQGDKI MHAINRRLGT 

       610        620        630        640        650        660 
FEVEDQIEAT RQFSKMGFVD DKRIAIWGWS YGGYVTSMVL GAGSGVFKCG IAVAPVSKWE 

       670        680        690        700        710        720 
YYDSVYTERY MGLPTPEDNL DYYRNSTVMS RAENFKQVEY LLIHGTADDN VHFQQSAQLS 

       730        740        750        760 
KALVDAGVDF QTMWYTDEDH GIASNMAHQH IYTHMSHFLK QCFSLP

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References

[1]	"Characterisation of human dipeptidyl peptidase IV expressed in Pichia pastoris. A structural and mechanistic comparison between the recombinant human and the purified porcine enzyme." Baer J., Weber A., Hoffmann T., Stork J., Wermann M., Wagner L., Aust S., Gerhartz B., Demuth H.-U. Biol. Chem. 384:1553-1563(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Kidney.
[2]	"Assignment of the dipeptidylpeptidase IV (DPP4) gene to pig chromosome 15q21." Thomsen P.D., Qvist H., Marklund L., Andersson L., Sjostrom H., Noren O. Mamm. Genome 4:604-607(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-67. Tissue: Kidney.
[3]	"N-terminal amino-acid sequence of pig kidney dipeptidyl peptidase IV solubilized by autolysis." Seidl R., Mann K., Schaeffer W. Biol. Chem. Hoppe-Seyler 372:213-214(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 38-71. Tissue: Kidney.
[4]	"The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism." Engel M., Hoffmann T., Wagner L., Wermann M., Heiser U., Kiefersauer R., Huber R., Bode W., Demuth H.-U., Brandstetter H. Proc. Natl. Acad. Sci. U.S.A. 100:5063-5068(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 39-766, GLYCOSYLATION AT ASN-85; ASN-92; ASN-229; ASN-279; ASN-321 AND ASN-685, HOMODIMERIZATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY198323 mRNA. Translation: AAO43404.1.
X73276 mRNA. Translation: CAA51717.1.

PIR

I47134.
S14746.

RefSeq

NP_999422.1. NM_214257.1.

UniGene

Ssc.16236.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ORV	X-ray	1.80	A/B/C/D	39-766	[»]
1ORW	X-ray	2.84	A/B/C/D	39-766	[»]
2AJ8	X-ray	2.11	A/B/C/D	39-766	[»]
2AJB	X-ray	2.75	A/B/C/D	39-766	[»]
2AJC	X-ray	1.95	A/B/C/D	39-766	[»]
2AJD	X-ray	2.56	A/B/C/D	39-766	[»]
2BUA	X-ray	2.56	A/B/C/D	39-766	[»]
2BUC	X-ray	2.50	A/B/C/D	39-766	[»]

ProteinModelPortal

P22411.

SMR

P22411. Positions 39-766.

ModBase

Search...

Protein-protein interaction databases

STRING

9823.ENSSSCP00000016843.

Protein family/group databases

MEROPS

S09.003.

Proteomic databases

PaxDb

P22411.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSSSCT00000017306; ENSSSCP00000016843; ENSSSCG00000015894.
ENSSSCT00000035225; ENSSSCP00000028692; ENSSSCG00000015894.

GeneID

397492.

KEGG

ssc:397492.

Organism-specific databases

CTD

1803.

Phylogenomic databases

eggNOG

COG1506.

GeneTree

ENSGT00530000062751.

HOGENOM

HOG000231875.

HOVERGEN

HBG005527.

KO

K01278.

OMA

HFIKQCF.

OrthoDB

EOG4XSKPF.

Enzyme and pathway databases

BRENDA

3.4.14.5. 6170.

Family and domain databases

InterPro

IPR002471. Pept_S9_AS.
IPR001375. Peptidase_S9.
IPR002469. Peptidase_S9B.
[Graphical view]

Pfam

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

PROSITE

PS00708. PRO_ENDOPEP_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P22411.

ChEMBL

CHEMBL3813.

EvolutionaryTrace

P22411.

Entry information

Entry name

DPP4_PIG

Accession

Primary (citable) accession number: P22411
Secondary accession number(s): Q866G2

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	September 13, 2004
Last modified:	April 3, 2013
This is version 111 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families