Homo sapiens · seed Q06124 · 593 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt Q06124 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 3.30.505.10 CATH 2.30.30.40 CATH 3.90.190.10 SCOP 8035711 SCOP 8040052 SCOP 8035564 SCOP 8035713 SCOP 8036103 SCOP 8044348 SCOP 8033173 SCOP 8078049 SCOP 8078061 SCOP 8040614 SCOP 8041144 SCOP 8086334 SCOP 8078069 SCOP 8078037 RCSB 8B5Y 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.
8B5Y, 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.
390 distinct constructs across 927 entries. 847 polymer entities differ from the UniProt canonical sequence in some way, 50 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 |
|---|---|---|---|---|
| 223 | 321 | 1.51 | 7GTW | residues 1-321; C32S, C92V |
| 42 | 321 | 1.80 | 1OEM | residues 1-321 |
| 21 | 298 | 1.45 | 8G65 | residues 1-298 |
| 19 | 526 | 1.70 | 5EHR | residues 1-525 |
| 14 | 117 | 1.60 | 3OV1 | residues 53-169; L164H, F165H, D166H +3 more |
| 14 | 537 | 1.83 | 8S07 | residues 1-536; I529L, E531H, E532H +4 more |
| 12 | 299 | 1.91 | 4QBW | residues 1-299 |
| 11 | 120 | 1.60 | 5EEQ | residues 413-532; P413G, M414S |
| 10 | 310 | 1.80 | 3QCD | residues 819-1128; I819G, P820S, I821H +3 more |
| 8 | 305 | 1.27 | 9EEX | residues 266-563; 7-residue insertion after 274; L266M, M267H, S268H +10 more |
| 8 | 313 | 1.65 | 2I4G | residues 1661-1973; R1661S |
| 7 | 310 | 2.10 | 1Q6N | FLAG; residues 1-298 |
| 6 | 298 | 1.80 | 1C83 | residues 1-298; S151T, E252D |
| 5 | 304 | 1.50 | 2CM2 | His5; residues 1-298; M1H |
| 5 | 314 | 1.40 | 4GE6 | residues 276-589; D276M, S583A, G584H +5 more |
| 5 | 525 | 1.80 | 7RCT | residues 1-525 |
| 5 | 536 | 2.40 | 6WU8 | residues 1-530 |
| 4 | 101 | 1.40 | 5TNW | residues 659-759; Q659G, T660S, N661H +1 more |
| 4 | 101 | 2.05 | 1AYA | residues 3-103; S3M |
| 4 | 109 | 1.59 | 9EHD | residues 1-106 |
| 4 | 110 | residues 237-346; S345G | ||
| 4 | 116 | 1.70 | 3C7I | residues 53-168; A163H, L164H, F165H +3 more |
| 4 | 123 | 1.48 | 5DC4 | residues 110-232; W110G, V111S |
| 4 | 298 | 2.00 | 1G1F | residues 1-298; C215A |
| 4 | 307 | 2.40 | 3S3E | residues 1227-1533; R1227M, K1228G, T1229S +19 more |
Showing the 25 most-used of 390.
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 | 729 | 78.6% |
| dimeric | 2 | 168 | 18.1% |
| trimeric | 3 | 15 | 1.6% |
| tetrameric | 4 | 14 | 1.5% |
| dodecameric | 12 | 1 | 0.1% |
572 entries have the depositor's assembly corroborated by PISA, 337 carry the depositor's word alone and 18 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: 1BM2, 1BMB, 1FPR, 1FYR, 1JYQ, 1JYR, 1JYU, 1K9A, 1R1Q, 1R1S, 1TZE, 1ZFP, 2AOA, 2AOB, 2DX0, 2GJT, 2H03, 2H46, 2NZ6, 3I7Z.
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 |
|---|---|---|---|
| SH2 domain | CATH 3.30.505.10 | 19–124 | 282 |
| SH3 Domains | CATH 2.30.30.40 | 225–292 | 17 |
| Protein tyrosine phosphatase superfamily | CATH 3.90.190.10 | 273–556 | 484 |
| SH2 domain | SCOP2B 8035711 | 4–111 | 98 |
| SH2 domain | SCOP2B 8040052 | 8–99 | 41 |
| SH2 domain | SCOP2B 8035564 | 110–213 | 14 |
| SH2 domain | SCOP2B 8035713 | 112–219 | 85 |
| SH2 domain | SCOP2B 8036103 | 114–218 | 12 |
| (Phosphotyrosine protein) phosphatases II | SCOP2B 8044348 | 220–526 | 93 |
| (Phosphotyrosine protein) phosphatases II | SCOP2B 8033173 | 248–530 | 9 |
| (Phosphotyrosine protein) phosphatases II | SCOP2B 8078049 | 258–549 | 17 |
| (Phosphotyrosine protein) phosphatases II | SCOP2B 8078061 | 262–552 | 12 |
OTA15 entries
5OD8 entries
BEN6 entries
PTR4 entries
FRJ3 entries
1BO3 entries
JG43 entries
JGD3 entries
GV13 entries
JHD3 entries
JJY3 entries
JKA3 entries
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| TRS | buffer | 2-Amino-2-Hydroxymethyl-Propane-1,3-Diol | 269 | 1.24 |
| GOL | cryoprotectant | Glycerol | 104 | 1.15 |
| CL | ion | Chloride Ion | 94 | 1.20 |
| MG | ion | Magnesium Ion | 77 | 1.40 |
| PO4 | ion | Phosphate Ion | 54 | 1.37 |
| SO4 | ion | Sulfate Ion | 53 | 1.15 |
| EDO | cryoprotectant | 1,2-Ethanediol | 35 | 1.25 |
| NA | ion | Sodium Ion | 18 | 1.25 |
| VO4 | ion | Vanadate Ion | 17 | 1.55 |
| OTA | ligand | 2-(Oxalyl-Amino)-4,5,6,7-Tetrahydro-Thieno[2,3-C]pyridine-3-Carb | 15 | 1.47 |
| ACT | cryoprotectant | Acetate Ion | 12 | 1.30 |
| FMT | buffer | Formic Acid | 9 | 1.60 |
| 5OD | ligand | 6-(4-Azanyl-4-Methyl-Piperidin-1-Yl)-3-[2,3-Bis(Chloranyl)phenyl | 8 | 1.70 |
| DMS | cryoprotectant | Dimethyl Sulfoxide | 8 | 1.45 |
| ACY | cryoprotectant | Acetic Acid | 6 | 1.35 |
| ZN | ion | Zinc Ion | 6 | 1.80 |
| BEN | ligand | Benzamidine | 6 | 1.55 |
| PEG | cryoprotectant | Di(Hydroxyethyl)ether | 5 | 1.30 |
| FLC | buffer | Citrate Anion | 5 | 1.40 |
| PTR | ligand | O-Phosphotyrosine | 4 | 1.70 |
Parsed from the free text 814 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 837
entries that recorded anything at all.
Median pH 7.5
(range 4.0 to 10.2).
926 entries carry a wwPDB validation report: 207 clean, 317 worth a check and 402 with something to explain. Median clashscore 5.77, median RSRZ outliers 6.29%, median R-free minus R-work 0.036. 828 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 864 | 1.00 | 448 | 93% |
| Mus musculus | 33 | 1.77 | 1 | 83% |
| Rattus norvegicus | 9 | 1.50 | 1 | 78% |
| Bos taurus | 7 | 1.40 | 0 | 17% |
| Drosophila melanogaster | 5 | 2.40 | 4 | 55% |
| synthetic construct | 3 | 1.40 | 0 | 26% |
| Arabidopsis thaliana | 2 | 1.40 | 0 | 43% |
| Trypanosoma cruzi | 1 | 2.18 | 0 | 42% |
| Trypanosoma brucei | 1 | 2.39 | 0 | 42% |
| Gallus gallus | 1 | 2.59 | 0 | 42% |
| Monosiga brevicollis | 1 | 0 | 16% |
593 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 | Phosphatase SHP2 pathogenic mutations enhance activity by altering conformational sampling. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2513851123 |
| 2026 | Constraining regulatory domain dynamics of the Src kinase Fgr increases ATP-site inhibitor sensitivity and impairs bone marrow engraftment. Cell Rep doi:10.1016/j.celrep.2026.117551 |
| 2026 | Discovery of Potent and Selective Benzothiophene Difluoromethyl Phosphonate (DFMP) PTPN2/N1-Dual Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.5c03738 |
| 2026 | Targeting PTPN22 at Nonorthosteric Binding SitesA Fragment Approach. Acs Omega doi:10.1021/acsomega.5c11028 |
| 2026 | Probing 3-Amino-2H-Azaindazoles as Allosteric Inhibitors of the Protein Tyrosine Phosphatase SHP2. Chemmedchem doi:10.1002/cmdc.70341 |
| 2026 | Mechanism of SHP2 activation by bis-Tyr-phosphorylated Gab1. Structure doi:10.1016/j.str.2025.11.018 |
| 2026 | Discovery and Preclinical Characterization of I-0436650, a Selective SHP2 Allosteric Inhibitor for RAS-Driven Cancers. J.Med.Chem. doi:10.1021/acs.jmedchem.6c01182 |
| 2026 | Mapping the SHP2 Allosteric Pocket With Target-Biased Covalent Fragments. Chembiochem doi:10.1002/cbic.70310 |
| 2026 | Structural basis of Fumosorinone-mediated allosteric inhibition of PTP1B for cancer immunotherapy. Commun Biol doi:10.1038/s42003-026-10329-2 |
| 2026 | Structural and mechanistic insights into the constitutive Themis-Grb2 complex in T cell signalling. Nat Commun doi:10.1038/s41467-026-73359-8 |
| 2026 | Repression of RIPK1 kinase by INPP5D inhibits expression of diverse proinflammatory mediators and late-onset Alzheimer's disease risk factors. Immunity doi:10.1016/j.immuni.2026.01.014 |
| 2025 | Three STEPs Forward: A Trio of Unexpected Structures of PTPN5. Proteins doi:10.1002/prot.70013 |
| 2025 | Structures of human protein tyrosine phosphatase variants reveal targetable allosteric sites. J.Biol.Chem. doi:10.1016/j.jbc.2025.110852 |
| 2025 | SHP2 genetic variants in NSML-associated RASopathies disrupt the PZR-IRX transcription factor signaling axis. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2503631122 |
| 2025 | Development of Novel PTPN2/1 Inhibitors for the Treatment of Melanoma. J.Med.Chem. doi:10.1021/acs.jmedchem.5c02300 |
| 2025 | PTPN9 dephosphorylates IGF1R Y1165/1166 and alleviates IGF1R-mediated resistance to tyrosine kinase inhibitor in cholangiocarcinoma. J Exp Clin Cancer Res doi:10.1186/s13046-025-03594-2 |
| 2025 | Targeting Protein Tyrosine Phosphatase Nonreceptor Type 2 with a Novel Inhibitor for the Treatment of Melanoma. J.Med.Chem. doi:10.1021/acs.jmedchem.5c02622 |
| 2025 | A Hotspot Phosphorylation Site on SHP2 Drives Oncoprotein Activation and Drug Resistance. Res Sq doi:10.21203/rs.3.rs-7032881/v1 |
| 2024 | High-resolution double vision of the allosteric phosphatase PTP1B. Acta Crystallogr.,Sect.F doi:10.1107/S2053230X23010749 |
| 2024 | An expanded trove of fragment-bound structures for the allosteric enzyme PTP1B from computational reanalysis of large-scale crystallographic data. Structure doi:10.1016/j.str.2024.05.010 |
| 2024 | Pushed to extremes: distinct effects of high temperature versus pressure on the structure of STEP. Commun Biol doi:10.1038/s42003-023-05609-0 |
| 2024 | Structural analysis of PTPN21 reveals a dominant-negative effect of the FERM domain on its phosphatase activity. Sci Adv doi:10.1126/sciadv.adi7404 |
| 2024 | Fragment-Based Discovery of Allosteric Inhibitors of SH2 Domain-Containing Protein Tyrosine Phosphatase-2 (SHP2). J.Med.Chem. doi:10.1021/acs.jmedchem.3c02118 |
| 2024 | Mechanistic insights into a heterobifunctional degrader-induced PTPN2/N1 complex. Commun Chem doi:10.1038/s42004-024-01263-7 |
| 2024 | Discovery of JAB-3312, a Potent SHP2 Allosteric Inhibitor for Cancer Treatment. J.Med.Chem. doi:10.1021/acs.jmedchem.4c00360 |
| 2024 | Enhancing the apo protein tyrosine phosphatase non-receptor type 2 crystal soaking strategy through inhibitor-accessible binding sites. Acta Crystallogr.,Sect.F doi:10.1107/S2053230X24007866 |
| 2024 | Development of mirror-image monobodies targeting the oncogenic BCR::ABL1 kinase. Nat Commun doi:10.1038/s41467-024-54901-y |
| 2024 | Structure and Dynamics of Drk-SH2 Domain and Its Site-Specific Interaction with Sev Receptor Tyrosine Kinase. Int J Mol Sci doi:10.3390/ijms25126386 |
| 2023 | Discovery and Validation of the Binding Poses of Allosteric Fragment Hits to Protein Tyrosine Phosphatase 1b: From Molecular Dynamics Simulations to X-ray Crystallography. J.Chem.Inf.Model. doi:10.1021/acs.jcim.3c00236 |
| 2023 | A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity. Nat Commun doi:10.1038/s41467-023-40170-8 |
| 2023 | Structure guided studies of the interaction between PTP1B and JAK. Commun Biol doi:10.1038/s42003-023-05020-9 |
| 2023 | Room-temperature crystallography reveals altered binding of small-molecule fragments to PTP1B. Elife doi:10.7554/eLife.84632 |
| 2023 | Discovery of a Novel Series of Imidazopyrazine Derivatives as Potent SHP2 Allosteric Inhibitors. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.2c00454 |
| 2023 | Identification of GDC-1971 (RLY-1971), a SHP2 Inhibitor Designed for the Treatment of Solid Tumors. J.Med.Chem. doi:10.1021/acs.jmedchem.3c00483 |
| 2023 | Fragment-Based Discovery of Novel VE-PTP Inhibitors Using Orthogonal Biophysical Techniques. Biochemistry doi:10.1021/acs.biochem.3c00079 |
| 2023 | The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity. Nature doi:10.1038/s41586-023-06575-7 |
| 2023 | Discovery of 5-Azaquinoxaline Derivatives as Potent and Orally Bioavailable Allosteric SHP2 Inhibitors. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.3c00310 |
| 2023 | SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy. Cancer Discov doi:10.1158/2159-8290.CD-23-0361 |
| 2023 | Discovery of the SHP2 allosteric inhibitor 2-((3R,4R)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-5-(2,3-dichlorophenyl)-3-methylpyrrolo[2,1-f][1,2,4] triazin-4(3H)-one. J Enzyme Inhib Med Chem doi:10.1080/14756366.2022.2151594 |
| 2023 | Structural mapping of PEAK pseudokinase interactions identifies 14-3-3 as a molecular switch for PEAK3 signaling. Nat Commun doi:10.1038/s41467-023-38869-9 |