InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DPP4

Summary

InnateDB Protein

IDBP-73660.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DPP4

Protein Name

dipeptidyl-peptidase 4

Synonyms

ADABP; ADCP2; CD26; DPPIV; TP103;

Species

Homo sapiens

Ensembl Protein

ENSP00000353731

InnateDB Gene

IDBG-73658 (DPP4)

Protein Structure

UniProt Annotation

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. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline. {ECO:0000269PubMed:10570924, ECO:0000269PubMed:10900005, ECO:0000269PubMed:10951221, ECO:0000269PubMed:11772392, ECO:0000269PubMed:14691230, ECO:0000269PubMed:16651416, ECO:0000269PubMed:17287217, ECO:0000269PubMed:17549790, ECO:0000269PubMed:18708048}.

Subcellular Localization

Dipeptidyl peptidase 4 soluble form: Secreted. Note=Detected in the serum and the seminal fluid.Cell membrane; Single-pass type II membrane protein. Apical cell membrane; Single-pass type II membrane protein. Cell projection, invadopodium membrane; Single-pass type II membrane protein. Cell projection, lamellipodium membrane; Single-pass type II membrane protein. Cell junction. Membrane raft. 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.

Disease Associations

Tissue Specificity

Expressed specifically in lymphatic vessels but not in blood vessels in the skin, small intestine, esophagus, ovary, breast and prostate glands. Not detected in lymphatic vessels in the lung, kidney, uterus, liver and stomach (at protein level). Expressed in the poorly differentiated crypt cells of the small intestine as well as in the mature villous cells. Expressed at very low levels in the colon. {ECO:0000269PubMed:1677636, ECO:0000269PubMed:18708048}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 53 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	53 [view]
Protein-Protein	53 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002020	protease binding
GO:0004252	serine-type endopeptidase activity
GO:0005102	receptor binding
GO:0005515	protein binding
GO:0008236	serine-type peptidase activity
GO:0008239	dipeptidyl-peptidase activity
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity

Biological Process

GO:0001666	response to hypoxia
GO:0006508	proteolysis
GO:0007155	cell adhesion
GO:0008284	positive regulation of cell proliferation
GO:0010716	negative regulation of extracellular matrix disassembly
GO:0031295	T cell costimulation
GO:0033632	regulation of cell-cell adhesion mediated by integrin
GO:0042110	T cell activation
GO:0043542	endothelial cell migration

Cellular Component

GO:0005765	lysosomal membrane
GO:0005886	plasma membrane
GO:0009986	cell surface
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0016324	apical plasma membrane
GO:0030027	lamellipodium
GO:0030139	endocytic vesicle
GO:0031258	lamellipodium membrane
GO:0045121	membrane raft
GO:0046581	intercellular canaliculus
GO:0070062	extracellular vesicular exosome
GO:0071438	invadopodium membrane

Protein Structure and Domains

PDB ID

InterPro

IPR001375 Peptidase S9, prolyl oligopeptidase, catalytic domain
IPR002469 Peptidase S9B, dipeptidylpeptidase IV N-terminal
IPR029058 Alpha/Beta hydrolase fold

PFAM

PF00326
PF00930

PRINTS

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P27487

PhosphoSite