proline-serine-threonine phosphatase-interacting protein 1 (PEST phosphatase-interacting protein 1, CD2-binding protein 1, H-PIP, PSTPIP1, CD2BP1)

Function

• regulation of the actin cytoskeleton
• regulation of WAS actin-bundling activity
• ABL1 dephosphorylation via interaction with ABL1 & PTPN18
• scaffold protein between PTPN12 & WAS
• facilitates PTPN12 dephosphorylation of WAS
• may couple CD2 & CD2AP to WAS
• acts downstream of CD2 & CD2AP to recruit WAS to T cell:APC contact site
• actin polymerization for synapse induction during T-cell activation
• down-regulates CD2-stimulated adhesion via coupling of PTPN12 to CD2
• interacts with PTPN18, ABL1, CD2AP, WAS,CD2, PTPN12, MEFV
• dephosphorylated on Tyr-345 by PTPN18, negatively regulates association of PSTPIP1 with SH2 domain-containing proteins
• phosphorylation of Tyr-345 required for phosphorylation at other Tyr
• phosphorylation induced by activation of EGFR & PDGFR is ABL1-dependent
• interacts with FASLG

Structure

• the coiled domain mediates interaction with PTPN18, PTPN12 & CD2AP
• the SH3 domain mediates interaction with WAS & ABL1 (putative)
• the SH3 & coiled-coil domains are necessary for interaction with MEFV
• contains 1 FCH domain
• contains 1 SH3 domain

Compartment

cytoplasm

Alternative splicing

named isoforms=2

Expression

• expressed in leukocytes, granulocytes, monocytes, T-cells, NK cells, spleen
• weakly expressed in thymus, small intestine, lung, placenta

Pathology

• mutations PSTPIP1 are the cause of PAPA syndrome

More general terms

• phosphoprotein

Additional terms

• PAPA syndrome; pyogenic sterile arthritis, pyoderma gangrenosum, & acne; familial recurrent arthritis

Database

• OMIM: https://mirror.omim.org/entry/606347
• OMIM: https://mirror.omim.org/entry/604416
• UniProt: http://www.uniprot.org/uniprot/O43586.html