P28843 (DPP4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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
Thymocyte-activating molecule
Short name=THAM
CD_antigen=CD26

Cleaved into the following 2 chains:

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

Gene names

Name:	Dpp4
Synonyms:	Cd26

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	760 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. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline By similarity.
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.
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 By similarity. N- and O-Glycosylated By similarity. 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 Receptor Serine protease
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	T cell activation Inferred from electronic annotation. Source: Compara 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 regulation of cell-cell adhesion mediated by integrin Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara
Cellular_component	apical plasma membrane 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 intercellular canaliculus Inferred from direct assay PubMed 12068294. Source: MGI 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 – 760	760	Dipeptidyl peptidase 4 membrane form		PRO_0000027215
	Chain	37 – 760	724	Dipeptidyl peptidase 4 soluble form By similarity		PRO_0000027216
Regions
	Topological domain	1 – 6	6	Cytoplasmic Potential
	Transmembrane	7 – 28	22	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	29 – 760	732	Extracellular Potential
	Compositional bias	295 – 466	172	Cys-rich
Sites
	Active site	624	1	Charge relay system By similarity
	Active site	702	1	Charge relay system By similarity
	Active site	734	1	Charge relay system By similarity
Amino acid modifications
	Glycosylation	83	1	N-linked (GlcNAc...) By similarity
	Glycosylation	90	1	N-linked (GlcNAc...) By similarity
	Glycosylation	145	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	213	1	N-linked (GlcNAc...) Potential
	Glycosylation	223	1	N-linked (GlcNAc...) By similarity
	Glycosylation	315	1	N-linked (GlcNAc...) By similarity
	Glycosylation	328	1	N-linked (GlcNAc...) Potential
	Glycosylation	514	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	679	1	N-linked (GlcNAc...) By similarity
	Disulfide bond	322 ↔ 333		By similarity
	Disulfide bond	379 ↔ 388		By similarity
	Disulfide bond	438 ↔ 441		By similarity
	Disulfide bond	448 ↔ 466		By similarity
	Disulfide bond	643 ↔ 756		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P28843 [UniParc]. Last modified February 1, 1996. Version 3. Checksum: A5F644B46E4A3DF8	FASTA	760	87,437
	10 20 30 40 50 60 MKTPWKVLLG LLGVAALVTI ITVPIVLLSK DEAAADSRRT YSLADYLKST FRVKSYSLWW 70 80 90 100 110 120 VSDFEYLYKQ ENNILLLNAE HGNSSIFLEN STFESFGYHS VSPDRLFVLL EYNYVKQWRH 130 140 150 160 170 180 SYTASYNIYD VNKRQLITEE KIPNNTQWIT WSPEGHKLAY VWKNDIYVKV EPHLPSHRIT 190 200 210 220 230 240 STGEENVIYN GITDWVYEEE VFGAYSALWW SPNNTFLAYA QFNDTGVPLI EYSFYSDESL 250 260 270 280 290 300 QYPKTVWIPY PKAGAVNPTV KFFIVNIDSL SSSSSAAPIQ IPAPASVARG DHYLCDVVWA 310 320 330 340 350 360 TEERISLQWL RRIQNYSVMA ICDYDKINLT WNCPSEQQHV EMSTTGWVGR FRPAEPHFTS 370 380 390 400 410 420 DGSSFYKIIS DKDGYKHICH FPKDKKDCTF ITKGAWEVIS IEALTSDYLY YISNQYKEMP 430 440 450 460 470 480 GGRNLYKIQL TDHTNVKCLS CDLNPERCQY YAVSFSKEAK YYQLGCWGPG LPLYTLHRST 490 500 510 520 530 540 DHKELRVLED NSALDRMLQD VQMPSKKLDF IVLNETRFWY QMILPPHFDK SKKYPLLLDV 550 560 570 580 590 600 YAGPCSQKAD ASFRLNWATY LASTENIIVA SFDGRGSGYQ GDKIMHAINR RLGTLEVEDQ 610 620 630 640 650 660 IEAARQFVKM GFVDSKRVAI WGWSYGGYVT SMVLGSGSGV FKCGIAVAPV SRWEYYDSVY 670 680 690 700 710 720 TERYMGLPIP EDNLDHYRNS TVMSRAEHFK QVEYLLIHGT ADDNVHFQQS AQISKALVDA 730 740 750 760 GVDFQAMWYT DEDHGIASST AHQHIYSHMS HFLQQCFSLH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning for mouse thymocyte-activating molecule. A multifunctional ecto-dipeptidyl peptidase IV (CD26) included in a subgroup of serine proteases." Marguet D.A., Bernard A.-M., Vivier I., Darmoul D., Naquet P., Pierres M. J. Biol. Chem. 267:2200-2208(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Swiss. Tissue: Thymus.
[2]	Marguet D.A. Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Structure of the mouse dipeptidyl peptidase IV (CD26) gene." Bernard A.-M., Mattei M.-G., Pierres M., Marguet D. Biochemistry 33:15204-15214(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: B10.A. Tissue: Liver.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Kidney and Thymus.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Evidence that thymocyte-activating molecule is mouse CD26 (dipeptidyl peptidase IV)." Vivier I., Marguet D.A., Naquet P., Bonicel J., Black D., Li C.X.-Y., Bernard A.-M., Gorvel J.-P., Pierres M. J. Immunol. 147:447-454(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-20.
[7]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-145 AND ASN-514, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X58384 mRNA. Translation: CAA41274.1. U12620 , U12599, U12600, U12601, U12602, U12603, U12604, U12605, U12606, U12607, U12608, U12609, U12610, U12611, U12612, U12613, U12614, U12615, U12616, U12617, U12618, U12619 Genomic DNA. Translation: AAA82213.1. AK085370 mRNA. Translation: BAC39434.1. AK153939 mRNA. Translation: BAE32266.1. BC022183 mRNA. Translation: AAH22183.1.
IPI	IPI00125813.
PIR	S23752.
RefSeq	NP_001153015.1. NM_001159543.1. NP_034204.1. NM_010074.3.
UniGene	Mm.1151.
3D structure databases
ProteinModelPortal	P28843.
SMR	P28843. Positions 39-759.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000044050.
Protein family/group databases
MEROPS	S09.003.
PTM databases
PhosphoSite	P28843.
Proteomic databases
PaxDb	P28843.
PRIDE	P28843.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000047812; ENSMUSP00000044050; ENSMUSG00000035000.
GeneID	13482.
KEGG	mmu:13482.
Organism-specific databases
CTD	1803.
MGI	MGI:94919. Dpp4.
Phylogenomic databases
eggNOG	COG1506.
GeneTree	ENSGT00530000062751.
HOGENOM	HOG000231875.
HOVERGEN	HBG005527.
InParanoid	P28843.
KO	K01278.
OMA	HFIKQCF.
OrthoDB	EOG4XSKPF.
Gene expression databases
ArrayExpress	P28843.
Bgee	P28843.
CleanEx	MM_DPP4.
Genevestigator	P28843.
GermOnline	ENSMUSG00000035000. Mus musculus.
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	P28843.
ChEMBL	CHEMBL3883.
ChiTaRS	DPP4. mouse.
NextBio	283979.
SOURCE	Search...

Entry information

Entry name

DPP4_MOUSE

Accession

Primary (citable) accession number: P28843
Secondary accession number(s): Q3U514

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 124 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program