Homo sapiens · seed P27487 · 766 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt P27487 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 2.140.10.30 CATH 3.40.50.1820 CATH 2.130.10.150 SCOP 8039749 SCOP 8039750 SCOP 8042437 RCSB 9JMM PDBe
CATH and SCOP identifiers come from the RCSB's own structure annotations, which the Domains panel already reads, so these are looked up rather than guessed at.
Every figure here is counted over the whole family rather than quoted from one entry.
9JMM, the structure every other member of this family is superposed onto. Rendered by the RCSB and embedded here: the live app shows an interactive viewport, which a document that fetches nothing cannot.
How many of this family's constructs contain each residue of the seed. A trough is a stretch nobody has put in a construct, which is a construct-design answer rather than a disorder one.
55 distinct constructs across 160 entries. 157 polymer entities differ from the UniProt canonical sequence in some way, 45 carry a recognised expression tag and 0 carry a fusion partner.
"Differs from canonical" is not the same as "engineered". The canonical sequence is the full gene product, so a secreted protein whose structures all start after its signal peptide counts every one of them as different: lysozyme's most-used construct, residues 19–147 on 1,239 entities, is simply the mature protein. Read the construct column below for what was actually done, rather than this count.
| Entities | Length | Best (Å) | Best entry | What was made |
|---|---|---|---|---|
| 29 | 728 | 2.00 | 1TK3 | residues 39-766 |
| 23 | 728 | 1.76 | 5T4B | residues 39-766; S39T |
| 11 | 740 | 2.24 | 5KBY | His6; residues 37-766 |
| 9 | 728 | 1.80 | 1ORV | residues 39-766 |
| 8 | 730 | 2.40 | 4FFV | residues 38-767 |
| 7 | 726 | 2.00 | 2G63 | residues 39-764 |
| 6 | 740 | 2.10 | 3VJM | His6; residues 33-766 |
| 4 | 753 | 2.00 | 3SWW | His6+Myc; residues 37-766; A37E, D38F |
| 4 | 791 | 2.88 | 22EB | His8; 1 internal deletion; M1S, T3M, P4V +18 more |
| 3 | 582 | 1.82 | 3O4H | D524A |
| 3 | 734 | 2.59 | 4QZV | His6; residues 39-766 |
| 3 | 740 | 1.62 | 4A5S | Strep-II; residues 39-766; S437I |
| 2 | 727 | 2.40 | 9V2P | residues 40-766 |
| 2 | 729 | 2.60 | 8ZDX | residues 38-766 |
| 2 | 729 | 4.00 | 7E89 | residues 121-849 |
| 2 | 734 | 2.75 | 5J3J | His6; residues 40-766 |
| 2 | 747 | 2.70 | 9DVQ | His8; residues 27-760 |
| 2 | 748 | 2.20 | 2QJR | His6; Thrombin site; residues 31-766 |
| 2 | 766 | 2.10 | 2QT9 | S39T |
| 2 | 766 | 3.02 | 9CAR | matches the canonical sequence |
| 1 | 714 | 2.74 | 8HAY | residues 23-736; T46M, N56S, K107R +9 more |
| 1 | 715 | 1.97 | 7Y4G | residues 22-736; T46M, N56S, K107R +9 more |
| 1 | 719 | 2.60 | 1Z68 | residues 39-757 |
| 1 | 719 | 3.40 | 4WJL | residues 65-783; V288M, V401I |
| 1 | 722 | 2.92 | 6Y0F | residues 36-757 |
Showing the 25 most-used of 55.
Columns where the wild-type residue still dominates but a real minority carries something else, which is a different question from "what varies across species".
| Oligomeric state | Chains | Entries | Share |
|---|---|---|---|
| dimeric | 2 | 112 | 70.0% |
| tetrameric | 4 | 19 | 11.9% |
| trimeric | 3 | 9 | 5.6% |
| monomeric | 1 | 6 | 3.8% |
| hexameric | 6 | 3 | 1.9% |
| octameric | 8 | 3 | 1.9% |
| pentameric | 5 | 2 | 1.2% |
| decameric | 10 | 2 | 1.2% |
134 entries have the depositor's assembly corroborated by PISA, 22 carry the depositor's word alone and 4 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 22 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1R9M, 2AJ8, 2AJB, 2AJC, 2AJD, 2GBC, 2GBF, 2GBG, 2GBI, 2I3Z, 2OAE, 2QJR, 3F8S, 3G0C, 3G0D, 3G0G, 3O95, 3O9V, 3OPM, 4G1F.
Every source's own domains on the seed axis, one row each. They are not merged: Pfam, CATH, SCOP and InterPro disagree about boundaries, and a merged track would state a consensus none of them gave.
| Domain | Source | Span (seed) | Chains |
|---|---|---|---|
| Dipeptidylpeptidase IV, N-terminal domain | CATH 2.140.10.30 | 55–499 | 125 |
| Alpha/Beta hydrolase fold, catalytic domain | CATH 3.40.50.1820 | 506–766 | 202 |
| Peptidase/esterase 'gauge' domain | CATH 2.130.10.150 | 562–766 | 2 |
| DPP6 N-terminal domain-like | SCOP2B 8039749 | 39–508 | 117 |
| alpha/beta-Hydrolases | SCOP2B 8039750 | 509–766 | 117 |
| Peptidase/esterase 'gauge' domain | SCOP2B 8042437 | 549–766 | 3 |
NAG111 entries
7153 entries
XIH2 entries
3562 entries
LF72 entries
A3M1 entries
PHI1 entries
P2Y1 entries
FUC1 entries
5AP1 entries
DFP1 entries
SC31 entries
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| NAG | cofactor | 2-Acetamido-2-Deoxy-Beta-D-Glucopyranose | 111 | 1.62 |
| NA | ion | Sodium Ion | 21 | 1.76 |
| SO4 | ion | Sulfate Ion | 15 | 1.62 |
| GOL | cryoprotectant | Glycerol | 6 | 1.82 |
| 715 | ligand | (2r)-4-Oxo-4-[3-(Trifluoromethyl)-5,6-Dihydro[1,2,4]triazolo[4,3 | 3 | 1.97 |
| HG | ion | Mercury (Ii) Ion | 2 | 2.10 |
| ZN | ion | Zinc Ion | 2 | 3.03 |
| XIH | ligand | 2-({8-[(3r)-3-Aminopiperidin-1-Yl]-1,3-Dimethyl-2,6-Dioxo-1,2,3, | 2 | 2.39 |
| 356 | ligand | 8-[(3r)-3-Aminopiperidin-1-Yl]-7-But-2-Yn-1-Yl-3-Methyl-1-[(4-Me | 2 | 2.60 |
| LF7 | ligand | 2-{[(1r,3s,5r,7s)-3-Hydroxytricyclo[3.3.1.1~3,7~]decan-1-Yl]amin | 2 | 1.77 |
| EDO | cryoprotectant | 1,2-Ethanediol | 2 | 2.38 |
| A3M | ligand | 2-Amino-3-Methyl-1-Pyrrolidin-1-Yl-Butan-1-One | 1 | 2.50 |
| PHI | ligand | Iodo-Phenylalanine | 1 | 2.84 |
| P2Y | ligand | (2s)-Pyrrolidin-2-Ylmethylamine | 1 | 2.84 |
| FUC | cofactor | Alpha-L-Fucopyranose | 1 | 2.10 |
| 5AP | ligand | 5-(Aminomethyl)-6-(2,4-Dichlorophenyl)-2-(3,5-Dimethoxyphenyl)py | 1 | 2.20 |
| DFP | ligand | Diisopropyl Phosphonate | 1 | 2.70 |
| SC3 | ligand | 7-Benzyl-1,3-Dimethyl-8-Piperazin-1-Yl-3,7-Dihydro-Purine-2,6-Di | 1 | 2.11 |
| 0QG | ligand | 3-Methyl-L-Valyl-L-Prolyl-L-Isoleucine | 1 | 2.75 |
| AES | ligand | 4-(2-Aminoethyl)benzenesulfonyl Fluoride | 1 | 1.95 |
Parsed from the free text 122 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 123
entries that recorded anything at all.
Median pH 8.0
(range 4.2 to 9.5).
160 entries carry a wwPDB validation report: 70 clean, 33 worth a check and 57 with something to explain. Median clashscore 8.09, median RSRZ outliers 1.65%, median R-free minus R-work 0.042. 148 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 131 | 1.62 | 119 | 100% |
| Sus scrofa | 10 | 1.80 | 10 | 100% |
| Rattus norvegicus | 9 | 2.40 | 8 | 95% |
| Bacteroides thetaiotaomicron | 3 | 1.92 | 2 | 86% |
| Aeropyrum pernix | 2 | 1.82 | 0 | 16% |
| Porphyromonas gingivalis | 1 | 2.20 | 0 | 86% |
| Aeropyrum pernix K1 | 1 | 2.30 | 1 | 16% |
| Manis javanica | 1 | 2.70 | 1 | 95% |
| Myotis davidii | 1 | 3.10 | 1 | 95% |
| Mus musculus | 1 | 3.85 | 0 | 99% |
766 residues, numbered every ten. Every identity figure in this document is measured against this sequence.
active or binding site modified residue or glycosylation disulphide cysteine transmembrane or signal the 15 most-substituted positions
Sites are UniProt's curated features where the seed is a UniProt accession; the substituted positions are measured from this family's own alignment rather than annotated, and only the fifteen most substituted are marked: every position carrying a minority substitution would be most of the protein, because the family holds orthologues. A residue can carry more than one and is drawn with the first that applies, in the order of the key above.
One record per paper, not per entry.
| Year | Citation |
|---|---|
| 2025 | Ligand binding Pro-miscuity of acylpeptide hydrolase, structural analysis of a detoxifying serine hydrolase. Protein Sci. doi:10.1002/pro.70320 |
| 2025 | Sulphostin-inspired N-phosphonopiperidones as selective covalent DPP8 and DPP9 inhibitors. Nat Commun doi:10.1038/s41467-025-58493-z |
| 2025 | Rational design of human CD26 receptor for a strong neutralizing ability against MjHKU4r-CoV-1 and MERS-CoV Hlife doi:10.1016/j.hlife.2025.05.005 |
| 2025 | Cryo-electron microscopy reveals a single domain antibody with a unique binding epitope on fibroblast activation protein alpha. Rsc Chem Biol doi:10.1039/d4cb00267a |
| 2025 | Structures and receptor binding activities of merbecovirus spike proteins reveal key signatures for human DPP4 adaptation. Sci Adv doi:10.1126/sciadv.adv7296 |
| 2024 | Structural basis for human DPP4 receptor recognition by a pangolin MERS-like coronavirus. Plos Pathog. doi:10.1371/journal.ppat.1012695 |
| 2024 | Molecular basis for receptor recognition and broad host tropism for merbecovirus MjHKU4r-CoV-1. Embo Rep. doi:10.1038/s44319-024-00169-8 |
| 2023 | Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target. Science doi:10.1126/science.add5787 |
| 2022 | Activation and closed-state inactivation mechanisms of the human voltage-gated K V 4 channel complexes. Mol.Cell doi:10.1016/j.molcel.2022.04.032 |
| 2022 | Structural basis for the gating modulation of Kv4.3 by auxiliary subunits. Cell Res. doi:10.1038/s41422-021-00608-4 |
| 2021 | A Single Second Shell Amino Acid Determines Affinity and Kinetics of Linagliptin Binding to Type 4 Dipeptidyl Peptidase and Fibroblast Activation Protein. Chemmedchem doi:10.1002/cmdc.202000591 |
| 2021 | Structural basis of gating modulation of Kv4 channel complexes. Nature doi:10.1038/s41586-021-03935-z |
| 2020 | Molecular Basis of Binding between Middle East Respiratory Syndrome Coronavirus and CD26 from Seven Bat Species. J.Virol. doi:10.1128/JVI.01387-19 |
| 2018 | A comparative study of the binding properties, dipeptidyl peptidase-4 (DPP-4) inhibitory activity and glucose-lowering efficacy of the DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin in mice. Endocrinol Diabetes Metab doi:10.1002/edm2.2 |
| 2018 | Structure-guided Discovery of Dual-recognition Chemibodies. Sci Rep doi:10.1038/s41598-018-25848-0 |
| 2017 | Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4 and structure-activity relationships based on inhibitor profiling. Eur J Med Chem doi:10.1016/j.ejmech.2017.08.024 |
| 2017 | Unique binding mode of Evogliptin with human dipeptidyl peptidase IV. Biochem.Biophys.Res.Commun. doi:10.1016/j.bbrc.2017.10.101 |
| 2016 | Scaffold-hopping from xanthines to tricyclic guanines: A case study of dipeptidyl peptidase 4 (DPP4) inhibitors. Bioorg.Med.Chem. doi:10.1016/j.bmc.2016.09.007 |
| 2016 | Discovery of Novel Tricyclic Heterocycles as Potent and Selective DPP-4 Inhibitors for the Treatment of Type 2 Diabetes. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.6b00027 |
| 2016 | The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors. Bioorg.Med.Chem.Lett. doi:10.1016/j.bmcl.2016.04.020 |
| 2016 | Trelagliptin (SYR-472, Zafatek), Novel Once-Weekly Treatment for Type 2 Diabetes, Inhibits Dipeptidyl Peptidase-4 (DPP-4) via a Non-Covalent Mechanism. Plos One doi:10.1371/journal.pone.0157509 |
| 2016 | Comparative Analysis of Binding Kinetics and Thermodynamics of Dipeptidyl Peptidase-4 Inhibitors and Their Relationship to Structure. J.Med.Chem. doi:10.1021/acs.jmedchem.6b00475 |
| 2015 | Anagliptin, a potent dipeptidyl peptidase IV inhibitor: its single-crystal structure and enzyme interactions. J Enzyme Inhib Med Chem doi:10.3109/14756366.2014.1002402 |
| 2015 | Structure of human dipeptidyl peptidase 10 (DPPY): a modulator of neuronal Kv4 channels. Sci Rep doi:10.1038/srep08769 |
| 2014 | Discovery of C-(1-aryl-cyclohexyl)-methylamines as selective, orally available inhibitors of dipeptidyl peptidase IV. Bioorg.Med.Chem.Lett. doi:10.1016/j.bmcl.2013.12.118 |
| 2014 | Omarigliptin (MK-3102): A Novel Long-Acting DPP-4 Inhibitor for Once-Weekly Treatment of Type 2 Diabetes. J.Med.Chem. doi:10.1021/jm401992e |
| 2014 | Bat Origins of MERS-CoV Supported by Bat Coronavirus HKU4 Usage of Human Receptor CD26. Cell Host Microbe doi:10.1016/j.chom.2014.08.009 |
| 2014 | Discovery of dipeptidyl peptidase IV (DPP4) inhibitors based on a novel indole scaffold Chin.Chem.Lett. doi:10.1016/j.cclet.2014.03.047 |
| 2013 | Optimization of Activity, Selectivity, and Liability Profiles in 5-Oxopyrrolopyridine DPP4 Inhibitors Leading to Clinical Candidate (Sa)-2-(3-(Aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778). J.Med.Chem. doi:10.1021/jm4008906 |
| 2013 | A comparative study of the binding modes of recently launched dipeptidyl peptidase IV inhibitors in the active site Biochem.Biophys.Res.Commun. doi:10.1016/j.bbrc.2013.03.010 |
| 2013 | Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature doi:10.1038/nature12328 |
| 2013 | Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4 Cell Res. doi:10.1038/cr.2013.92 |
| 2013 | Design and synthesis of 4-(2,4,5-trifluorophenyl)butane-1,3-diamines as dipeptidyl peptidase IV inhibitors Chemmedchem doi:10.1002/cmdc.201300104 |
| 2012 | Novel Heterocyclic Dpp-4 Inhibitors for the Treatment of Type 2 Diabetes. Bioorg.Med.Chem.Lett. doi:10.1016/J.BMCL.2011.11.054 |
| 2012 | Fused bicyclic heteroarylpiperazine-substituted l-prolylthiazolidines as highly potent DPP-4 inhibitors lacking the electrophilic nitrile group Bioorg.Med.Chem. doi:10.1016/j.bmc.2012.06.033 |
| 2012 | Discovery and preclinical profile of teneligliptin (3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine): A highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes Bioorg.Med.Chem. doi:10.1016/j.bmc.2012.08.012 |
| 2012 | Structure-based design of pyridopyrimidinediones as dipeptidyl peptidase IV inhibitors. Bioorg.Med.Chem.Lett. doi:10.1016/j.bmcl.2012.08.110 |
| 2011 | Structure and Catalysis of Acylaminoacyl Peptidase: CLOSED AND OPEN SUBUNITS OF A DIMER OLIGOPEPTIDASE. J.Biol.Chem. doi:10.1074/jbc.M110.169862 |
| 2011 | 7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site. Bioorg.Med.Chem.Lett. doi:10.1016/j.bmcl.2011.09.074 |
| 2011 | Design and Synthesis of Pyrimidinone and Pyrimidinedione Inhibitors of Dipeptidyl Peptidase IV. J.Med.Chem. doi:10.1021/jm101016w |