9MQ5: Crystal structure SHP2 tandem SH2 domains

Crystal structure SHP2 tandem SH2 domains in complex with PZR doubly tyrosine phosphorylated ITIM peptide. Determined by X-ray diffraction at 1.7 Å resolution. Released 30 Jul 2025.

Method: X-ray diffraction
Resolution: 1.7 Å
Organism: Homo sapiens
Chains: 2
Atoms: 2,136
Mol. weight: 29.47 kDa
Released: 30 Jul 2025

Explore 9MQ5 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9MQ5 contains 6 α-helices and 28 β-strands across 2 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 5 helices, 24 β-strands

Element	Residues	Length	Sheet
β-strand	7	1	1
α-helix	13-23	11
β-strand	28-33	6	1
β-strand	38	1	2
β-strand	40	1	2
β-strand	41-47	7	1
β-strand	50-56	7	1
β-strand	57-58	2	3
β-strand	63-64	2	3
β-strand	70-71	2	3
α-helix	74-83	10
β-strand	89	1	4
β-strand	90	1	5
β-strand	95	1	4
β-strand	100-101	2	1
α-helix	103-106	4
β-strand	113	1	6
α-helix	119-129	11
β-strand	134-139	6	6
β-strand	147-152	6	6
β-strand	167-172	6	6
β-strand	173-175	3	7
β-strand	178-180	3	7
β-strand	186-187	2	7
α-helix	190-199	10
β-strand	203	1	8
β-strand	204	1	9
β-strand	209	1	8
β-strand	214-215	2	6

Chain B: 1 helix, 4 β-strands

Element	Residues	Length	Sheet
β-strand	244	1	5
β-strand	255-256	2	3
β-strand	263	1	6
α-helix	264-265	2
β-strand	266	1	9

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Tyrosine-protein phosphatase non-receptor type 11	A	protein	225	Homo sapiens	Q06124 (AlphaFold model)
Myelin protein zero-like protein 1	B	protein	33	Homo sapiens	O95297 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>9MQ5_1 Tyrosine-protein phosphatase non-receptor type 11 (chains A)
GPLGSMTSRRWFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIK
IQNTGDYYDLYGGEKFATLAELVQYYMEHHGQLKEKNGDVIELKYPLNCADPTSERWFHG
HLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGDDKGESNDGKSKVTHVMIRCQ
ELKYDVGGGERFDSLTDLVEHYKKNPMVETLGTVLQLKQPLNTTR

Sequence of entity 2 (B), FASTA

>9MQ5_2 Myelin protein zero-like protein 1 (chains B)
GPVIYAQLDHSGGHHSDKINKSESVVYADIRKN

Primary citation

SHP2 genetic variants in NSML-associated RASopathies disrupt the PZR-IRX transcription factor signaling axis. Perla, S., Stiegler, A.L., Yi, J.S. et al. Proc Natl Acad Sci U S A (2025) 122:e2503631122-e2503631122. DOI 10.1073/pnas.2503631122 · PubMed

Other PDB entries of the same protein (UniProt Q06124 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9EIK 1.25 Å, Crystal structure of N-SH2 domain of SHP2 with T42A mutation bound to GAB1 tyrosine…
3ZM1 1.4 Å, Catalytic domain of human SHP2
4JMG 1.4 Å, Crystal structure of the synthetic protein in complex with pY peptide
7PPM 1.48 Å, SHP2 catalytic domain in complex with IRS1 (889-901) phosphopeptide (pSer-892, pTyr-896)
3ZM0 1.5 Å, Catalytic domain of human SHP2
3ZM2 1.5 Å, Catalytic domain of human SHP2
3ZM3 1.5 Å, Catalytic domain of human SHP2
7PPL 1.53 Å, SHP2 catalytic domain in complex with IRS1 (625-639) phosphopeptide (pTyr-632, pSer-636)
9EIC 1.58 Å, Crystal structure of unbound N-SH2 domain of SHP2 with T42A mutation
9EHD 1.59 Å, Crystal structure of N-SH2 domain of SHP2 bound to GAB1 tyrosine phosphorylated peptide…
3B7O 1.6 Å, Crystal structure of the human tyrosine phosphatase SHP2 (PTPN11) with an accessible…
4RDD 1.6 Å, Co-crystal structure of SHP2 in complex with a Cefsulodin derivative

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