Homo sapiens · seed Q16539 · 360 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt Q16539 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 3.30.200.20 CATH 1.10.510.10 SCOP 8036628 SCOP 8033039 SCOP 8038976 SCOP 8040900 SCOP 8040310 SCOP 8036640 SCOP 8079143 SCOP 8062460 SCOP 8036635 SCOP 8036019 RCSB 9D7N 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.
9D7N, 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.
392 distinct constructs across 1,630 entries. 853 polymer entities differ from the UniProt canonical sequence in some way, 279 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 |
|---|---|---|---|---|
| 184 | 298 | 1.38 | 7RXO | matches the canonical sequence |
| 104 | 306 | 1.00 | 6Q49 | matches the canonical sequence |
| 59 | 360 | 1.66 | 8YD9 | matches the canonical sequence |
| 57 | 360 | 1.44 | 5R97 | matches the canonical sequence |
| 55 | 299 | 1.26 | 4EK4 | matches the canonical sequence |
| 55 | 368 | 1.12 | 8AOJ | His6 |
| 38 | 302 | 1.99 | 6GUE | matches the canonical sequence |
| 33 | 364 | 1.46 | 3QYZ | His6 |
| 29 | 344 | 2.98 | 8BU1 | residues 709-1052; Y709G, E711G, K965R |
| 25 | 303 | 1.47 | 9UAU | matches the canonical sequence |
| 25 | 360 | 1.60 | 4EHV | M1G |
| 22 | 361 | 1.50 | 5LAR | L48H, T263A |
| 21 | 299 | 1.60 | 9FR2 | matches the canonical sequence |
| 21 | 349 | 1.70 | 8P79 | matches the canonical sequence |
| 18 | 360 | 1.59 | 3SA0 | matches the canonical sequence |
| 17 | 360 | 1.50 | 3LFF | M1G, C119S, C162S +2 more |
| 17 | 366 | 1.70 | 2QD9 | M1H |
| 17 | 372 | 1.70 | 3FMK | His6 |
| 15 | 366 | 1.90 | 3ZYA | matches the canonical sequence |
| 13 | 346 | 2.15 | 8PYR | matches the canonical sequence |
| 13 | 364 | 1.85 | 8WGF | residues 39-402 |
| 12 | 300 | 1.82 | 6ATH | matches the canonical sequence |
| 12 | 464 | 1.73 | 7KSI | matches the canonical sequence |
| 11 | 360 | 1.24 | 6Y80 | C162S |
| 10 | 364 | 1.65 | 8PT0 | matches the canonical sequence |
Showing the 25 most-used of 392.
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 |
|---|---|---|---|
| monomeric | 1 | 1,116 | 68.5% |
| dimeric | 2 | 354 | 21.7% |
| trimeric | 3 | 114 | 7.0% |
| tetrameric | 4 | 19 | 1.2% |
| heptameric | 7 | 4 | 0.2% |
| pentameric | 5 | 4 | 0.2% |
| hexameric | 6 | 2 | 0.1% |
| 40-meric | 40 | 2 | 0.1% |
1,168 entries have the depositor's assembly corroborated by PISA, 373 carry the depositor's word alone and 89 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 38 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1H24, 1H25, 1H26, 1H27, 1JST, 2F49, 2G01, 2GMX, 2H96, 2JLD, 2NO3, 2PK9, 2WMA, 2WMB, 2X1N, 3E7O, 3F5X, 3MTL, 3NIE, 3NIZ.
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 |
|---|---|---|---|
| Phosphorylase Kinase; domain 1 | CATH 3.30.200.20 | 27–119 | 1,429 |
| Transferase(Phosphotransferase) domain 1 | CATH 1.10.510.10 | 112–321 | 1,271 |
| Protein kinase-like (PK-like) | SCOP2B 8036628 | 5–353 | 122 |
| Protein kinase-like (PK-like) | SCOP2B 8033039 | 6–353 | 254 |
| Protein kinase-like (PK-like) | SCOP2B 8038976 | 15–360 | 61 |
| Protein kinase-like (PK-like) | SCOP2B 8040900 | 16–360 | 40 |
| Protein kinase-like (PK-like) | SCOP2B 8040310 | 23–320 | 502 |
| Protein kinase-like (PK-like) | SCOP2B 8036640 | 30–360 | 77 |
| Protein kinase-like (PK-like) | SCOP2B 8079143 | 32–360 | 32 |
| Protein kinase-like (PK-like) | SCOP2B 8062460 | 36–337 | 39 |
| Protein kinase-like (PK-like) | SCOP2B 8036635 | 40–360 | 154 |
| Protein kinase-like (PK-like) | SCOP2B 8036019 | 52–360 | 103 |
ANP49 entries
ADP31 entries
ATP20 entries
SB420 entries
GG519 entries
SF413 entries
SB210 entries
I4610 entries
IRG10 entries
AGS8 entries
4SP7 entries
I747 entries
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| SO4 | ion | Sulfate Ion | 315 | 1.12 |
| EDO | cryoprotectant | 1,2-Ethanediol | 200 | 1.06 |
| MG | ion | Magnesium Ion | 165 | 1.34 |
| GOL | cryoprotectant | Glycerol | 122 | 1.33 |
| CL | ion | Chloride Ion | 121 | 1.24 |
| DMS | cryoprotectant | Dimethyl Sulfoxide | 102 | 1.00 |
| BOG | lipid/detergent | Octyl Beta-D-Glucopyranoside | 79 | 1.45 |
| ANP | cofactor | Phosphoaminophosphonic Acid-Adenylate Ester | 49 | 1.33 |
| ADP | cofactor | Adenosine-5'-Diphosphate | 31 | 1.55 |
| ZN | ion | Zinc Ion | 30 | 2.00 |
| SGM | cryoprotectant | Monothioglycerol | 28 | 1.65 |
| FMT | buffer | Formic Acid | 25 | 2.10 |
| PEG | cryoprotectant | Di(Hydroxyethyl)ether | 23 | 1.44 |
| ACT | cryoprotectant | Acetate Ion | 22 | 1.45 |
| ATP | cofactor | Adenosine-5'-Triphosphate | 20 | 1.65 |
| SB4 | ligand | 4-(4-Fluorophenyl)-1-(4-Piperidinyl)-5-(2-Amino-4-Pyrimidinyl)-I | 20 | 1.22 |
| GG5 | ligand | 4-[3-(4-Fluorophenyl)-1h-Pyrazol-4-Yl]pyridine | 19 | 1.65 |
| PO4 | ion | Phosphate Ion | 19 | 1.70 |
| NA | ion | Sodium Ion | 19 | 1.26 |
| CA | ion | Calcium Ion | 15 | 1.22 |
Parsed from the free text 1,462 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 1,494
entries that recorded anything at all.
Median pH 7.0
(range 0.0 to 9.5).
1,630 entries carry a wwPDB validation report: 373 clean, 662 worth a check and 595 with something to explain. Median clashscore 6.15, median RSRZ outliers 6.41%, median R-free minus R-work 0.042. 1,557 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 1,362 | 0.98 | 1245 | 100% |
| Mus musculus | 133 | 1.22 | 120 | 100% |
| Rattus norvegicus | 79 | 1.34 | 58 | 93% |
| Saccharomyces cerevisiae | 10 | 1.55 | 6 | 92% |
| Plasmodium falciparum | 5 | 1.90 | 3 | 81% |
| Saccharomyces cerevisiae S288C | 4 | 1.95 | 3 | 83% |
| Toxoplasma gondii RH | 3 | 2.10 | 3 | 91% |
| Cryptosporidium parvum Iowa II | 4 | 2.37 | 3 | 91% |
| Leishmania major | 3 | 1.95 | 1 | 84% |
| Arabidopsis thaliana | 3 | 2.20 | 1 | 93% |
| Leishmania infantum | 2 | 1.66 | 2 | 81% |
| Giardia lamblia ATCC 50803 | 2 | 1.85 | 1 | 80% |
360 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 |
|---|---|
| 2026 | Discovery of Supra-Bivalent GSK3 beta Inhibitory Peptides Containing an ATP-Mimetic Amino Acid. J.Am.Chem.Soc. doi:10.1021/jacs.5c13788 |
| 2026 | Discovery of INCB127443: A Potent and Orally Available Inhibitor of Cyclin-Dependent Kinase 2 J.Med.Chem. doi:10.1021/acs.jmedchem.6c01506 |
| 2026 | Identification of potent inhibitors of JUN N-terminal kinases for treatment of endometriosis and associated pain. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2607561123 |
| 2026 | Utilizing Molecular Dynamics and Mechanistic Pharmacokinetic Studies in the Design of Selective CDK2 Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.5c03803 |
| 2026 | Conformation-Specific Design: Engineering Extracellular Signal-Regulated Kinase 2 Variants with Bias toward Active or Inactive States. Acs Omega doi:10.1021/acsomega.6c01185 |
| 2026 | Nanoscale Direct-to-Biology Optimization of Cdk2 Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.5c03614 |
| 2026 | Molecular basis of mitogen-activated protein kinase ERK2 activation by its upstream kinase MEK1. Biorxiv doi:10.64898/2026.01.19.700303 |
| 2026 | A Polypharmacology-Driven Approach to Alzheimer's Disease and Tauopathies: Rational Design, Synthesis and Characterization of Amino-Pyrazole-Based Multikinase (GSK-3 beta /FYN-alpha /DYRK1A) Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.5c01810 |
| 2026 | Cryo-EM structures of the CDK11-cyclin L-SAP30BP complex reveal mechanisms of CDK11 regulation. Nat Commun doi:10.1038/s41467-026-72329-4 |
| 2026 | Selective CDK2 Degradation via Noncanonical Recruitment. J.Med.Chem. doi:10.1021/acs.jmedchem.6c01264 |
| 2026 | Mechanistic insight into the phosphorylation of ERK by MEK Biorxiv doi:10.64898/2026.03.13.710243 |
| 2026 | Structural basis of the cyclin Y/14-3-3 protein-mediated activation of CDK16. Nat Commun doi:10.1038/s41467-026-70778-5 |
| 2026 | The +1 nucleosome functions in RNA Pol II transcription initiation and the transition to elongation. Mol.Cell doi:10.1016/j.molcel.2026.06.042 |
| 2025 | Discovery of AZD8421: A Potent CDK2 Inhibitor with Selectivity Against Other CDK Family Members and the Human Kinome. J.Med.Chem. doi:10.1021/acs.jmedchem.5c01478 |
| 2025 | Targeting bacterial kinases as a strategy to counteract antibiotic resistance. Commun Chem doi:10.1038/s42004-025-01794-7 |
| 2025 | Fulcrum Occupancy-Leverage Perturbation Strategy Enables Rapid Discovery of Potent CDK2-Cyclin A2 Interaction Inhibitors. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.202513542 |
| 2025 | An allosteric cyclin E-CDK2 site mapped by paralog hopping with covalent probes. Nat.Chem.Biol. doi:10.1038/s41589-024-01738-7 |
| 2025 | Cancer hotspot mutations rewire ERK2 specificity by selective exclusion of docking interactions. J.Biol.Chem. doi:10.1016/j.jbc.2025.108348 |
| 2025 | Targeting Neuroinflammation and Cognitive Decline: First-in-Class Dual Butyrylcholinesterase and p38 alpha Mitogen-Activated Protein Kinase Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.5c00933 |
| 2025 | Structural study of selectivity mechanisms for JNK3 and p38 alpha with indazole scaffold probing compounds J.Mol.Struct. doi:10.1016/j.molstruc.2025.142179 |
| 2025 | Structural and functional characterization of TgGSK3, a druggable kinase in Toxoplasma gondii. Nat Commun doi:10.1038/s41467-025-64701-7 |
| 2025 | A first-in-class selective inhibitor of ERK1/2 and ERK5 overcomes drug resistance with a single-molecule strategy. Signal Transduct Target Ther doi:10.1038/s41392-025-02169-z |
| 2025 | Discovery of Atirmociclib (PF-07220060): A Potent and Selective CDK4 Inhibitor. J.Med.Chem. doi:10.1021/acs.jmedchem.5c02137 |
| 2025 | Phenotype-Led Identification of IL-10 Upregulators in Human CD4 + T-cells and Elucidation of Their Pharmacology as Highly Selective CDK8/CDK19 Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.4c02630 |
| 2025 | CDK2-based CDK7 mimic as a tool for structural analysis: Biochemical validation and crystal structure with SY5609. Int.J.Biol.Macromol. doi:10.1016/j.ijbiomac.2024.139117 |
| 2025 | Crystallographic fragment screening of CDK2-cyclin A: FragLites map sites of protein-protein interaction. Structure doi:10.1016/j.str.2025.07.016 |
| 2025 | TFIIH kinase CDK7 drives cell proliferation through a common core transcription factor network. Sci Adv doi:10.1126/sciadv.adr9660 |
| 2025 | Resistance to CDK7 inhibitors directed by acquired mutation of a conserved residue in cancer cells. Embo J. doi:10.1038/s44318-025-00554-6 |
| 2025 | Bipartite binding of the intrinsically disordered scaffold protein JIP1 to the kinase JNK1. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2419915122 |
| 2025 | Structural basis of T-loop-independent recognition and activation of CDKs by the CDK-activating kinase. Science doi:10.1126/science.adw0053 |
| 2025 | CDK2 heterobifunctional degraders co-degrade CDK2 and cyclin E resulting in efficacy in CCNE1-amplified and overexpressed cancers. Cell Chem Biol doi:10.1016/j.chembiol.2025.03.006 |
| 2025 | Discovery of YJZ5118 : A Potent and Highly Selective Irreversible CDK12/13 Inhibitor with Synergistic Effects in Combination with Akt Inhibition. J.Med.Chem. doi:10.1021/acs.jmedchem.5c00127 |
| 2025 | Discovery of Selective and Orally Bioavailable Heterobifunctional Degraders of Cyclin-Dependent Kinase 2. J.Med.Chem. doi:10.1021/acs.jmedchem.5c01160 |
| 2025 | High-throughput investigation of cyclin docking interactions reveals the complexity of motif binding determinants. Nat Commun doi:10.1038/s41467-025-62765-z |
| 2025 | Rational optimization of D3R/GSK-3 beta dual target-directed ligands as potential treatment for bipolar disorder: Design, synthesis, X-ray crystallography, molecular dynamics simulations, in vitro ADME, and in vivo pharmacokinetic studies. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2025.117899 |
| 2024 | Protein engineering enables a soakable crystal form of human CDK7 primed for high-throughput crystallography and structure-based drug design. Structure doi:10.1016/j.str.2024.05.011 |
| 2024 | Discovery of (4-Pyrazolyl)-2-aminopyrimidines as Potent and Selective Inhibitors of Cyclin-Dependent Kinase 2. J.Med.Chem. doi:10.1021/acs.jmedchem.3c02287 |
| 2024 | Targeting a key protein-protein interaction surface on mitogen-activated protein kinases by a precision-guided warhead scaffold. Nat Commun doi:10.1038/s41467-024-52574-1 |
| 2024 | High-resolution cryo-EM of the human CDK-activating kinase for structure-based drug design. Nat Commun doi:10.1038/s41467-024-46375-9 |
| 2024 | Discovery and Characterization of a Chemical Probe for Cyclin-Dependent Kinase-Like 2. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.4c00219 |