CODSWALLOP

Vascular endothelial growth factor receptor 1

Homo sapiens · seed P17948 · 1338 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026

Open in CODSWALLOP UniProt P17948 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 2.30.30.40 CATH 3.30.200.20 CATH 3.30.505.10 CATH 1.10.510.10 CATH 3.80.20.20 SCOP 8034993 SCOP 8034606 SCOP 8036668 SCOP 8091373 SCOP 8034200 SCOP 8069205 SCOP 8041589 SCOP 8069209 SCOP 8069207 SCOP 8039520 SCOP 8069229 SCOP 8069235 SCOP 8069187 SCOP 8036040 SCOP 8040157 SCOP 8032830 SCOP 8035661 SCOP 8036656 SCOP 8043964 SCOP 8032837 SCOP 8069259 SCOP 8040719 SCOP 8032832 RCSB 3HNG 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.

1,336Entries 1,338Entities 555Constructs 9Organisms 1,163Ligand-bound
1.07 ÅBest res.
2.30 ÅMedian res.

Every figure here is counted over the whole family rather than quoted from one entry.

The reference structure

3HNG, 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.

Rendered structure of 3HNG
3HNG at the RCSB · open it in the 3D viewer

Which residues anyone has ever seen

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.

166913381321 constructs

Constructs, most-used first

555 distinct constructs across 1,336 entries. 1,272 polymer entities differ from the UniProt canonical sequence in some way, 65 carry a recognised expression tag and 6 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.

EntitiesLengthBest (Å)Best entryWhat was made
29 331 2.10 5CAS residues 694-1024; P694G, T790M, L858R +5 more
26 327 1.50 3POZ residues 696-1022
25 327 1.50 8PQD residues 548-934; 2 internal deletions; L548G, Q549S, K550M +25 more
21 331 1.83 7JXQ residues 692-1022; L692G, T693S, P694T +2 more
21 454 1.65 5H0B residues 72-526; 1 internal deletion; I73A, R74M, E75G +6 more
17 309 1.63 5EW8 residues 457-765; L457G, C488A, C584S
15 314 1.64 7DUA residues 700-1013; M700G, E701P, N702L +2 more
15 327 1.73 4CMT residues 1085-1411; T1085M, S1086A, T1087H +5 more
14 333 1.50 6TFV residues 690-1022; E690G, P691S, L692H +4 more
14 1370 3.24 8X06 1 internal deletion
13 298 1.74 7AB0 residues 567-864; L567G, G568S, V569H +5 more
12 313 1.90 3BRB residues 556-864; 4-residue insertion after 569; C556M, R557G, R558S +8 more
12 314 1.60 3EWH residues 815-1178; 1 internal deletion; C817A, V916T, T940V +7 more
12 329 1.33 5UG9 residues 694-1022; P694G, T790M, L858R +1 more
11 309 1.75 4XMO residues 1048-1356; V1352H, N1353H, A1354H +2 more
11 328 1.76 6WXN residues 695-1022; T790M, V948R
11 330 1.70 3W33 residues 693-1022; T693G, P694A, S695M
11 1372 3.10 7SL7 matches the canonical sequence
10 293 1.74 3K5V residues 223-515; P223G, T224A, I225M +3 more
10 299 1.75 7B3Q residues 1048-1346; Q1048G
10 309 1.54 9T0B residues 1038-1346; D1228V
10 311 1.97 6NSS residues 485-795
9 277 1.75 3FZS residues 416-692
9 306 1.40 3ZCL residues 1050-1355; T1050M, Y1349H, V1350H +4 more
9 310 1.66 9U7G residues 456-765; M456G, L457P, C584S

Showing the 25 most-used of 555.

Positions people deliberately mutate

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".

S1098K 69% G886D 68% K1056E 68% S1111K 68% T995G 67% V1035H 67% D998Y 66% K828V 65% I994L 65% L813A 65% Y1085F 64% D816Q 64% K1017R 64% L1158F 64% D1073H 63% D1140E 63% Y1048A 62% V1006I 62% T899L 62% V1151I 62% P805G 62% A846G 61% G903S 61% E1128D 61% Y911L 61% E1032T 61% L827F 60% G830I 60% Q901E 60% I1019V 60%

What it assembles into

Oligomeric stateChainsEntriesShare
monomeric1 1,076 80.5%
dimeric2 168 12.6%
tetrameric4 43 3.2%
hexameric6 21 1.6%
trimeric3 12 0.9%
octameric8 5 0.4%
dodecameric12 4 0.3%
pentameric5 4 0.3%

720 entries have the depositor's assembly corroborated by PISA, 568 carry the depositor's word alone and 48 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 53 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1FLT, 1GAG, 1K9A, 1OPL, 1P4O, 1PKG, 1QTY, 2G2F, 2G2I, 2RFE, 2ZM3, 3B2T, 3C4F, 3CLY, 3EFJ, 3EFK, 3EQP, 3EQR, 3ETA, 3F5P.

Domain architecture

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.

CATHPhosphorylase Kinase; domaSH2 domainTransferase(PhosphotransfeReceptor L-domainSCOP2BProtein kinase-like (PK-liProtein kinase-like (PK-liProtein kinase-like (PK-liProtein kinase-like (PK-liProtein kinase-like (PK-liProtein kinase-like (PK-liProtein kinase-like (PK-liProtein kinase-like (PK-liProtein kinase-like (PK-liProtein kinase-like (PK-liProtein kinase-like (PK-liProtein kinase-like (PK-liProtein kinase-like (PK-liProtein kinase-like (PK-liL domain-likeSH2 domainProtein kinase-like (PK-liProtein kinase-like (PK-liGrowth factor receptor domProtein kinase-like (PK-liProtein kinase-like (PK-liL domain-like16691338
DomainSourceSpan (seed)Chains
SH3 DomainsCATH 2.30.30.40 821–882 21
Phosphorylase Kinase; domain 1CATH 3.30.200.20 837–939 890
SH2 domainCATH 3.30.505.10 883–984 26
Transferase(Phosphotransferase) domain 1CATH 1.10.510.10 940–1130 926
Receptor L-domainCATH 3.80.20.20 1141–1274 13
Protein kinase-like (PK-like)SCOP2B 8034993 813–1111 28
Protein kinase-like (PK-like)SCOP2B 8034606 819–1120 20
Protein kinase-like (PK-like)SCOP2B 8036668 821–1119 69
Protein kinase-like (PK-like)SCOP2B 8091373 821–1091 46
Protein kinase-like (PK-like)SCOP2B 8034200 821–1097 20
Protein kinase-like (PK-like)SCOP2B 8069205 822–1120 47
SH3-domainSCOP2B 8041589 822–882 21

What binds it

ANP ANP41 entries ACP ACP27 entries NAG NAG21 entries STI STI19 entries PHU PHU11 entries STU STU10 entries 0LI 0LI10 entries YY3 YY310 entries VGH VGH9 entries ADP ADP7 entries Q6K Q6K7 entries 1N1 1N16 entries
ComponentClassNameEntriesBest (Å)
SO4ion Sulfate Ion 224 1.31
CLion Chloride Ion 148 1.30
EDOcryoprotectant 1,2-Ethanediol 97 1.07
GOLcryoprotectant Glycerol 84 1.33
MGion Magnesium Ion 71 1.52
ANPcofactor Phosphoaminophosphonic Acid-Adenylate Ester 41 1.55
ACPcofactor Phosphomethylphosphonic Acid Adenylate Ester 27 1.80
CAion Calcium Ion 22 2.15
NAGcofactor 2-Acetamido-2-Deoxy-Beta-D-Glucopyranose 21 2.70
MESbuffer 2-(N-Morpholino)-Ethanesulfonic Acid 21 1.11
FMTbuffer Formic Acid 20 1.65
DMScryoprotectant Dimethyl Sulfoxide 20 1.76
STIligand 4-(4-Methyl-Piperazin-1-Ylmethyl)-N-[4-Methyl-3-(4-Pyridin-3-Yl- 19 1.60
PO4ion Phosphate Ion 17 1.60
NAion Sodium Ion 17 1.40
ACTcryoprotectant Acetate Ion 12 1.80
PHUligand 1-Phenylurea 11 1.55
STUligand Staurosporine 10 1.75
PEGcryoprotectant Di(Hydroxyethyl)ether 10 1.13
0LIligand 3-(Imidazo[1,2-B]pyridazin-3-Ylethynyl)-4-Methyl-N-{4-[(4-Methyl 10 1.85

How it crystallises

Parsed from the free text 1,204 depositors typed into _exptl_crystal_grow.pdbx_details, out of 1,216 entries that recorded anything at all. Median pH 7.2 (range 0.0 to 10.5).

Precipitants

PEG × Ammonium sulfate × Sodium chloride × Sodium citrate × Magnesium chloride × Lithium sulfate × Isopropanol × Calcium chloride × Sodium formate × Tacsimate × Ethanol × MPD × PEG (unspecified) × Sodium malonate ×

Buffers

Tris × HEPES × MES × Citrate × Bis-Tris × Sodium acetate × Sodium cacodylate × Bis-Tris propane × Phosphate × Imidazole × CAPS × Glycine × Succinate × CHES ×

Which entries to trust

1,335 entries carry a wwPDB validation report: 350 clean, 625 worth a check and 360 with something to explain. Median clashscore 4.88, median RSRZ outliers 6.12%, median R-free minus R-work 0.04. 1,302 have released structure factors.

Across species

OrganismEntriesBest (Å)Ligand-boundSeed covered
Homo sapiens1,272 1.07 1121 87%
Mus musculus46 1.22 28 84%
Gallus gallus6 2.70 6 26%
Drosophila melanogaster4 3.60 4 26%
Rattus norvegicus2 2.05 0 25%
synthetic construct2 2.05 2 26%
Solanum pimpinellifolium2 3.20 0 7%
Monosiga brevicollis1 1.95 1 25%
Spodoptera frugiperda1 2.59 1 12%

Seed sequence

1338 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

1MVSYWDTGVL LCALLSCLLL TGSSSGSKLK DPELSLKGTQ HIMQAGQTLH LQCRGEAAHK
61WSLPEMVSKE SERLSITKSA CGRNGKQFCS TLTLNTAQAN HTGFYSCKYL AVPTSKKKET
121ESAIYIFISD TGRPFVEMYS EIPEIIHMTE GRELVIPCRV TSPNITVTLK KFPLDTLIPD
181GKRIIWDSRK GFIISNATYK EIGLLTCEAT VNGHLYKTNY LTHRQTNTII DVQISTPRPV
241KLLRGHTLVL NCTATTPLNT RVQMTWSYPD EKNKRASVRR RIDQSNSHAN IFYSVLTIDK
301MQNKDKGLYT CRVRSGPSFK SVNTSVHIYD KAFITVKHRK QQVLETVAGK RSYRLSMKVK
361AFPSPEVVWL KDGLPATEKS ARYLTRGYSL IIKDVTEEDA GNYTILLSIK QSNVFKNLTA
421TLIVNVKPQI YEKAVSSFPD PALYPLGSRQ ILTCTAYGIP QPTIKWFWHP CNHNHSEARC
481DFCSNNEESF ILDADSNMGN RIESITQRMA IIEGKNKMAS TLVVADSRIS GIYICIASNK
541VGTVGRNISF YITDVPNGFH VNLEKMPTEG EDLKLSCTVN KFLYRDVTWI LLRTVNNRTM
601HYSISKQKMA ITKEHSITLN LTIMNVSLQD SGTYACRARN VYTGEEILQK KEITIRDQEA
661PYLLRNLSDH TVAISSSTTL DCHANGVPEP QITWFKNNHK IQQEPGIILG PGSSTLFIER
721VTEEDEGVYH CKATNQKGSV ESSAYLTVQG TSDKSNLELI TLTCTCVAAT LFWLLLTLFI
781RKMKRSSSEI KTDYLSIIMD PDEVPLDEQC ERLPYDASKW EFARERLKLG KSLGRGAFGK
841VVQASAFGIK KSPTCRTVAV KMLKEGATAS EYKALMTELK ILTHIGHHLN VVNLLGACTK
901QGGPLMVIVE YCKYGNLSNY LKSKRDLFFL NKDAALHMEP KKEKMEPGLE QGKKPRLDSV
961TSSESFASSG FQEDKSLSDV EEEEDSDGFY KEPITMEDLI SYSFQVARGM EFLSSRKCIH
1021RDLAARNILL SENNVVKICD FGLARDIYKN PDYVRKGDTR LPLKWMAPES IFDKIYSTKS
1081DVWSYGVLLW EIFSLGGSPY PGVQMDEDFC SRLREGMRMR APEYSTPEIY QIMLDCWHRD
1141PKERPRFAEL VEKLGDLLQA NVQQDGKDYI PINAILTGNS GFTYSTPAFS EDFFKESISA
1201PKFNSGSSDD VRYVNAFKFM SLERIKTFEE LLPNATSMFD DYQGDSSTLL ASPMLKRFTW
1261TDSKPKASLK IDLRVTSKSK ESGLSDVSRP SFCHSSCGHV SEGKRRFTYD HAELERKIAC
1321CSPPPDYNSV VLYSTPPI

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.

Primary citations

One record per paper, not per entry.

YearCitation
2026 Molecular Basis of c‐MET Inhibition by Approved Small Molecule Drugs: A Structural Perspective. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.5c00713
2026 Design and Synthesis of BLU-654, a Potent and Selective Mutant KIT V654A Inhibitor for the Treatment of Imatinib-Resistant GIST. J.Med.Chem. doi:10.1021/acs.jmedchem.5c03554
2026 Late-stage functionalization with strain-release warheads enables tunable covalent inhibition. Science doi:10.1126/science.adx7219
2026 Structure-based scaffold hopping reveals strategies to overcome oncogenic KIT and PDGFRA mutation-driven drug-resistance in GIST. Nat Commun doi:10.1038/s41467-026-76340-7
2026 Structure-Based Design of a Novel Covalent 4-(1-Methylindol-3-yl)pyrimidin-2-amine Series Targeting FGFR2 Resistance Mutations. J.Med.Chem. doi:10.1021/acs.jmedchem.6c00514
2026 Structure-Based Design of 4-(1-Methyl-1 H -indol-3-yl)pyrimidin-2-amine Derivatives as the First Covalent FGFR3 Selective Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.5c02552
2026 Design, Synthesis, and Biological Evaluation of the First Novel Macrocycle-Based FGFR Inhibitors That Overcome Clinically Acquired Resistance. J.Med.Chem. doi:10.1021/acs.jmedchem.5c02462
2026 Structural Studies of Fourth-Generation EGFR Inhibitors Reveal Insights into Selective T790M and C797S Targeting. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.5c00725
2026 Sevabertinib, a Reversible HER2 Inhibitor with Activity in Lung Cancer. Cancer Discov doi:10.1158/2159-8290.CD-25-0605
2026 Leveraging Structure-Based Design to Overcome Class III RTK Off-Target Activity in the Development of Selective Wild-Type KIT Inhibitors J.Med.Chem. doi:10.1021/acs.jmedchem.6c01334
2026 An S752D activation loop mutation dynamically primes Muscle-Specific Kinase for activation. Biochem.J. doi:10.1042/BCJ20260159
2026 Identification of an Inhaled Pulmonary Selective PDGFR Inhibitor with Sustained Target Engagement. J Aerosol Med Pulm Drug Deliv doi:10.1177/19412711261449635
2026 TAS3351 is a brain penetrable EGFR-TKI that overcomes T790M and C797S resistant mutations. Commun Med (Lond) doi:10.1038/s43856-026-01546-1
2026 Covalent Alkynylpyridopyrimidinones Targeting Cysteine 775 of the Epidermal Growth Factor Receptor Overcome Resistance to Current Therapies. J.Med.Chem. doi:10.1021/acs.jmedchem.5c02924
2026 Discovery of a Potent, Orally Bioavailable Small-Molecule Inhibitor of Wildtype KIT with Exceptionally High Kinome Selectivity. J.Med.Chem. doi:10.1021/acs.jmedchem.6c00898
2026 Discovery of 2H-Pyrrolo[3,4‐ c ]pyridin-3-one Derivatives as Type-III c‐MET Inhibitors Enabled by Free-Energy Perturbation Calculations. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.6c00158
2026 Structural insights into the activation of the chicken ROS1 receptor by the NEL/NICOL ligand complex. Nat Commun doi:10.1038/s41467-026-69942-8
2026 TRI-611, a selective, brain-penetrant molecular glue degrader of ALK. Nature doi:10.1038/s41586-026-10998-3
2026 Discovery of LAS194046: A Potent and Selective pan-Janus Kinase (JAK) Inhibitor with a Suitable Profile for Inhaled Administration. J.Med.Chem. doi:10.1021/acs.jmedchem.6c00169
2026 Design, synthesis and biological evaluation of 2,4,5-trisubstituted 7H-Pyrrolo[2,3-d]pyrimidine derivatives as potent EGFR tyrosine kinase inhibitors against the C797S acquired resistance mutation. Bioorg.Med.Chem. doi:10.1016/j.bmc.2026.118679
2026 A Dichloropropionamide-Substituted Diaminopyrimidine EGFR-TKI Overcomes Osimertinib Resistance in NSCLC via Dual Anchoring at Ser797 and Met793. J.Med.Chem. doi:10.1021/acs.jmedchem.5c02807
2026 The role of kinase domain dimerization in EGFR activation. Structure doi:10.1016/j.str.2025.11.017
2026 Structural Basis of Lymphangiogenic Receptor VEGFR-3 Activation Mediated by Distinctive Clustering of the Ligand-Receptor Complex. Adv Sci doi:10.1002/advs.77728
2026 Mechanisms of VEGFR2 activation by VEGF, neuropilin, and heparin. Sci Adv doi:10.1126/sciadv.aeg6323
2026 Enozertinib Is a Selective, Brain-Penetrant EGFR Inhibitor for Treating Non-Small Cell Lung Cancers with EGFR Exon 20 and Atypical Mutations. Cancer Res. doi:10.1158/0008-5472.CAN-25-3502
2026 Structural basis of insulin receptor antagonism by bivalent site 1-site 2 ligands S961 and Ins-AC-S2. Nat Commun doi:10.1038/s41467-026-73851-1
2025 Electron-density-informed effective and reliable de novo molecular design and optimization with ED2Mol Nat Mach Intell doi:10.1038/s42256-025-01095-7
2025 STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20-Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models. Clin.Cancer Res. doi:10.1158/1078-0432.CCR-24-3833
2025 Design, Synthesis and Biological Evaluation of 7-(1-Methyl-1 H -indole-3-yl)-5 H -pyrrolo[2,3- b ]pyrazine Derivatives as Novel Covalent pan-FGFR Inhibitors to Overcome Clinical Resistance. J.Med.Chem. doi:10.1021/acs.jmedchem.5c01594
2025 Discovery of STX-721, a Covalent, Potent, and Highly Mutant-Selective EGFR/HER2 Exon20 Insertion Inhibitor for the Treatment of Non-Small Cell Lung Cancer. J.Med.Chem. doi:10.1021/acs.jmedchem.4c02377
2025 A twist in the tale: shifting from covalent targeting of a tyrosine in JAK3 to a lysine in MK2. Rsc Med Chem doi:10.1039/d5md00440c
2025 Highly Optimized CNS Penetrant Inhibitors of EGFR Exon20 Insertion Mutations. J.Med.Chem. doi:10.1021/acs.jmedchem.4c02811
2025 Profiling and Optimizing Targeted Covalent Inhibitors through EGFR-Guided Studies. J.Med.Chem. doi:10.1021/acs.jmedchem.5c01661
2025 Factors affecting irreversible inhibition of EGFR and influence of chirality on covalent binding. Commun Chem doi:10.1038/s42004-025-01501-6
2025 A model for decoding resistance in precision oncology: acquired resistance to FGFR inhibitors in cholangiocarcinoma. Ann Oncol doi:10.1016/j.annonc.2024.12.011
2025 Optimization of Aminoindazole derivatives as highly selective covalent inhibitors for wild-type and mutant FGFR4. Bioorg.Chem. doi:10.1016/j.bioorg.2025.108469
2025 Design, Synthesis, and SAR of Covalent KIT and PDGFRA Inhibitors─Exploring Their Potential in Targeting GIST. J.Med.Chem. doi:10.1021/acs.jmedchem.4c02472
2025 O -Cyanobenzaldehydes Irreversibly Modify Both Buried and Exposed Lysine Residues in Live Cells. J.Am.Chem.Soc. doi:10.1021/jacs.4c18006
2025 Zidesamtinib Selective Targeting of Diverse ROS1 Drug-Resistant Mutations. Mol.Cancer Ther. doi:10.1158/1535-7163.MCT-25-0025
2025 Structure-Based Design of Potent and Selective MerTK Inhibitors by Modulating the Conformation of alpha C Helix. J.Med.Chem. doi:10.1021/acs.jmedchem.4c03092