PDBsum entry 2h0q

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protein Protein-protein interface(s) links
Signaling protein PDB id
Protein chains
261 a.a. *
Waters ×303
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Crystal structure of the pgm domain of the suppressor of t-c receptor (sts-1)
Structure: Suppressor of t-cell receptor signaling 1. Chain: a, b, c. Fragment: phosphoglycerate mutase domain, residues 384-643. Synonym: sts-1, cbl-interacting protein p70. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: sts-1. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.82Å     R-factor:   0.198     R-free:   0.236
Authors: N.Nassar,B.Ford,N.Carpino
Key ref:
A.Mikhailik et al. (2007). A phosphatase activity of Sts-1 contributes to the suppression of TCR signaling. Mol Cell, 27, 486-497. PubMed id: 17679096 DOI: 10.1016/j.molcel.2007.06.015
15-May-06     Release date:   06-Nov-07    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q8BGG7  (UBS3B_MOUSE) -  Ubiquitin-associated and SH3 domain-containing protein B
638 a.a.
261 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site


DOI no: 10.1016/j.molcel.2007.06.015 Mol Cell 27:486-497 (2007)
PubMed id: 17679096  
A phosphatase activity of Sts-1 contributes to the suppression of TCR signaling.
A.Mikhailik, B.Ford, J.Keller, Y.Chen, N.Nassar, N.Carpino.
Precise signaling by the T cell receptor (TCR) is crucial for a proper immune response. To ensure that T cells respond appropriately to antigenic stimuli, TCR signaling pathways are subject to multiple levels of regulation. Sts-1 negatively regulates signaling pathways downstream of the TCR by an unknown mechanism(s). Here, we demonstrate that Sts-1 is a phosphatase that can target the tyrosine kinase Zap-70 among other proteins. The X-ray structure of the Sts-1 C terminus reveals that it has homology to members of the phosphoglycerate mutase/acid phosphatase (PGM/AcP) family of enzymes, with residues known to be important for PGM/AcP catalytic activity conserved in nature and position in Sts-1. Point mutations that impair Sts-1 phosphatase activity in vitro also impair the ability of Sts-1 to regulate TCR signaling in T cells. These observations reveal a PGM/AcP-like enzyme activity involved in the control of antigen receptor signaling.
  Selected figure(s)  
Figure 3.
Figure 3. Sts-1[PGM] Structure
(A) Ribbon diagram of dimeric Sts-1[PGM]. The side chains of His-380 and His-565 are shown as ball-and-stick representations to indicate the location of the active site. Prepared with Molscript (Kraulis, 1991) and PyMOL (
(B) Secondary structure elements of the Sts-1[PGM] dimer.
Figure 4.
Figure 4. The Sts-1[PGM] Active Site
(A) Comparison of Sts-1[PGM] with E. coli PGM (ecPGM). Critical catalytic residues of ecPGM, and the homologous residues of Sts-1[PGM], are shown in gold ball-and-stick representation. The two regions that deviate between the two structures, Inserts 1 and 2 (Sts-1 residues 399–436 and 505–535), are in red and blue, respectively. The C termini are shown in green.
(B) Active site residues. Superposition of the known active site residues of ecPGM (cyan) with the homologous residues of Sts-1[PGM].
(C) Interactions made by Sts-1[PGM] active site residues with a phosphate ion. The omit map difference electron density of the phosphate is shown at 4 σ cutoff in black. The Sts-1[PGM] active site residues interacting with the phosphate molecule are shown in ball-and-stick representation. Dotted lines represent hydrogen bond interactions. Secondary structure elements are displayed in green.
(D) Mutation of Sts-1[PGM] active site residues renders Sts-1 catalytically inactive toward pNPP. Tagged wild-type or mutant proteins were expressed in 293T cells, precipitated, and evaluated for pNPP phosphatase activity. Error bars are as in Figure 1.
(E) Solvent accessibility of the Sts-1[PGM] active site. Surface representations of Sts-1[PGM] (left) and ecPGM (right) illustrate the different configurations of their respective catalytic pockets, with the active site cleft of Sts-1[PGM] broader and more exposed than that of ecPGM. Conserved basic and acidic residues that are visible are labeled and shown as blue and red patches.
(F) PGM domain activity is not regulated by the Sts-1 protein-protein interaction domains. The ΔUBA Sts-1 mutant lacks the UBA domain (residues 1–67), and the W284A point mutation renders the Sts-1 SH3 domain unable to bind its target sequences (Kowanetz et al., 2004). Proteins were expressed in 293T cells, immunoprecipitated with Flag antibodies, and evaluated for pNPP phosphatase activity relative to wild-type Sts-1. Each mutant was assayed in triplicate (error bars), and representative levels of precipitated proteins are displayed.
  The above figures are reprinted from an Open Access publication published by Cell Press: Mol Cell (2007, 27, 486-497) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20585042 D.H.Thomas, T.M.Getz, T.N.Newman, C.A.Dangelmaier, N.Carpino, S.P.Kunapuli, A.Y.Tsygankov, and J.L.Daniel (2010).
A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets.
  Blood, 116, 2570-2578.  
21176133 X.Wang, H.Zhu, H.Snieder, S.Su, D.Munn, G.Harshfield, B.L.Maria, Y.Dong, F.Treiber, B.Gutin, and H.Shi (2010).
Obesity related methylation changes in DNA of peripheral blood leukocytes.
  BMC Med, 8, 87.  
19585081 A.Y.Tsygankov (2009).
TULA-family proteins: an odd couple.
  Cell Mol Life Sci, 66, 2949-2952.  
19132916 J.E.Smith-Garvin, G.A.Koretzky, and M.S.Jordan (2009).
T cell activation.
  Annu Rev Immunol, 27, 591-619.  
19590015 K.Takeda, Y.Komuro, T.Hayakawa, H.Oguchi, Y.Ishida, S.Murakami, T.Noguchi, H.Kinoshita, Y.Sekine, S.Iemura, T.Natsume, and H.Ichijo (2009).
Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a protein serine/threonine phosphatase to activate ASK1.
  Proc Natl Acad Sci U S A, 106, 12301-12305.  
19380743 M.Brehme, O.Hantschel, J.Colinge, I.Kaupe, M.Planyavsky, T.Köcher, K.Mechtler, K.L.Bennett, and G.Superti-Furga (2009).
Charting the molecular network of the drug target Bcr-Abl.
  Proc Natl Acad Sci U S A, 106, 7414-7419.  
19733910 N.Carpino, Y.Chen, N.Nassar, and H.W.Oh (2009).
The Sts proteins target tyrosine phosphorylated, ubiquitinated proteins within TCR signaling pathways.
  Mol Immunol, 46, 3224-3231.  
19827767 S.S.Yadav, B.J.Yeh, B.P.Craddock, W.A.Lim, and W.T.Miller (2009).
Reengineering the signaling properties of a Src family kinase.
  Biochemistry, 48, 10956-10962.  
19627098 Y.Chen, J.Jakoncic, K.A.Parker, N.Carpino, and N.Nassar (2009).
Structures of the phosphorylated and VO(3)-bound 2H-phosphatase domain of Sts-2.
  Biochemistry, 48, 8129-8135.  
19196006 Y.Chen, J.Jakoncic, N.Carpino, and N.Nassar (2009).
Structural and functional characterization of the 2H-phosphatase domain of Sts-2 reveals an acid-dependent phosphatase activity.
  Biochemistry, 48, 1681-1690.
PDB codes: 3d4i 3d6a 3db1
18344182 A.Y.Tsygankov (2008).
Multidomain STS/TULA proteins are novel cellular regulators.
  IUBMB Life, 60, 224-231.  
18728635 O.Acuto, V.D.Bartolo, and F.Michel (2008).
Tailoring T-cell receptor signals by proximal negative feedback mechanisms.
  Nat Rev Immunol, 8, 699-712.  
18189269 R.Agrawal, N.Carpino, and A.Tsygankov (2008).
TULA proteins regulate activity of the protein tyrosine kinase Syk.
  J Cell Biochem, 104, 953-964.  
18387606 S.C.Lo, and M.Hannink (2008).
PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria.
  Exp Cell Res, 314, 1789-1803.  
18803405 S.S.Yadav, and W.T.Miller (2008).
The evolutionarily conserved arrangement of domains in SRC family kinases is important for substrate recognition.
  Biochemistry, 47, 10871-10880.  
18937503 Y.Chen, J.Jakoncic, J.Wang, X.Zheng, N.Carpino, and N.Nassar (2008).
Structural and functional characterization of the c-terminal domain of the ecdysteroid phosphate phosphatase from bombyx mori reveals a new enzymatic activity.
  Biochemistry, 47, 12135-12145.
PDB code: 3c7t
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.