PEA15

Summary: PEA15 directly modulates ERK MAP kinase signaling.

Reason: The ERK2–PEA15 structures and biochemical experiments establish direct binding and altered kinase conformation/activity. Participation in the MAPK cascade is a supported regulatory role; PEA15 need not itself be a kinase.

Summary: Retain the curated interaction without treating generic protein binding as core function.

Reason: The IPI observation from PMID:10442631 is retained as an interaction observation. PEA15's established mechanistic functions are ERK regulation and death-receptor signaling; generic binding alone does not establish a distinct core activity or physiological role for every partner.

Summary: Retain the curated interaction without treating generic protein binding as core function.

Reason: The IPI observation from PMID:10442631 is retained as an interaction observation. PEA15's established mechanistic functions are ERK regulation and death-receptor signaling; generic binding alone does not establish a distinct core activity or physiological role for every partner.

Summary: Retain the curated interaction without treating generic protein binding as core function.

Reason: The IPI observation from PMID:17255949 is retained as an interaction observation. PEA15's established mechanistic functions are ERK regulation and death-receptor signaling; generic binding alone does not establish a distinct core activity or physiological role for every partner.

Summary: Retain the curated interaction without treating generic protein binding as core function.

Reason: The IPI observation from PMID:21044950 is retained as an interaction observation. PEA15's established mechanistic functions are ERK regulation and death-receptor signaling; generic binding alone does not establish a distinct core activity or physiological role for every partner.

Summary: Retain the curated interaction without treating generic protein binding as core function.

Reason: The IPI observation from PMID:21900206 is retained as an interaction observation. PEA15's established mechanistic functions are ERK regulation and death-receptor signaling; generic binding alone does not establish a distinct core activity or physiological role for every partner.

Summary: Retain the curated interaction without treating generic protein binding as core function.

Reason: The IPI observation from PMID:23575685 is retained as an interaction observation. PEA15's established mechanistic functions are ERK regulation and death-receptor signaling; generic binding alone does not establish a distinct core activity or physiological role for every partner.

Summary: Retain the curated interaction without treating generic protein binding as core function.

Reason: The IPI observation from PMID:32296183 is retained as an interaction observation. PEA15's established mechanistic functions are ERK regulation and death-receptor signaling; generic binding alone does not establish a distinct core activity or physiological role for every partner.

Summary: Retain the curated interaction without treating generic protein binding as core function.

Reason: The IPI observation from PMID:32296183 is retained as an interaction observation. PEA15's established mechanistic functions are ERK regulation and death-receptor signaling; generic binding alone does not establish a distinct core activity or physiological role for every partner.

Summary: Retain the curated interaction without treating generic protein binding as core function.

Reason: The IPI observation from PMID:33961781 is retained as an interaction observation. PEA15's established mechanistic functions are ERK regulation and death-receptor signaling; generic binding alone does not establish a distinct core activity or physiological role for every partner.

Summary: Retain the curated interaction without treating generic protein binding as core function.

Reason: The IPI observation from PMID:33961781 is retained as an interaction observation. PEA15's established mechanistic functions are ERK regulation and death-receptor signaling; generic binding alone does not establish a distinct core activity or physiological role for every partner.

Summary: Retain the curated interaction without treating generic protein binding as core function.

Reason: The IPI observation from PMID:40205054 is retained as an interaction observation. PEA15's established mechanistic functions are ERK regulation and death-receptor signaling; generic binding alone does not establish a distinct core activity or physiological role for every partner.

Summary: Cytoplasmic/cytosolic localization is consistent with PEA15 signaling regulation.

Reason: PEA15 binds cytoplasmic ERK and regulates its distribution; the soluble death-effector-domain architecture and curated localization support this compartment. The selected horse sequence retains the entire human core, but its extra N-terminal segment is not assumed to be functionally neutral.

Summary: Cytoplasmic/cytosolic localization is consistent with PEA15 signaling regulation.

Reason: PEA15 binds cytoplasmic ERK and regulates its distribution; the soluble death-effector-domain architecture and curated localization support this compartment. The selected horse sequence retains the entire human core, but its extra N-terminal segment is not assumed to be functionally neutral.

Summary: Cytoplasmic/cytosolic localization is consistent with PEA15 signaling regulation.

Reason: PEA15 binds cytoplasmic ERK and regulates its distribution; the soluble death-effector-domain architecture and curated localization support this compartment. The selected horse sequence retains the entire human core, but its extra N-terminal segment is not assumed to be functionally neutral.

Summary: The microtubule-associated-complex assignment requires source verification.

Reason: The cached abstract of PMID:8662970 describes a microtubule-associated protein in mouse astrocytes and conservation of mouse and human transcripts. The full text is unavailable, so the experimental basis for assigning human PEA15 to a microtubule-associated complex remains unresolved. ERK binding and cytoplasmic localization alone do not establish this complex membership.

Summary: PEA15 regulates apoptotic signaling through death-effector-domain interactions.

Reason: Human-cell overexpression and co-precipitation experiments demonstrate inhibition of Fas/TNFR1-dependent caspase-8 activation involving FADD. This supports apoptotic regulation; the conserved horse core supports transfer of the mechanism.

Summary: PEA15 inhibits insulin-stimulated glucose import by regulating GLUT4 recruitment.

Reason: The primary study expresses cloned human PEA15 in L6 skeletal muscle cells and observes reduced insulin-stimulated transport and surface GLUT4. This is regulatory involvement in glucose import, not intrinsic carbohydrate-transporter activity.

Summary: PEA15 can inhibit death-receptor-mediated extrinsic apoptosis.

Reason: The human primary experiment shows protection from FasL and TNFalpha effects and impaired FADD–caspase-8 association. This is the specific pathway represented by the annotation. The horse protein preserves the human death-effector-domain sequence, although the effect of its N-terminal extension has not been measured.

Summary: PEA15 can inhibit death-receptor-mediated extrinsic apoptosis.

Reason: The human primary experiment shows protection from FasL and TNFalpha effects and impaired FADD–caspase-8 association. This is the specific pathway represented by the annotation. The horse protein preserves the human death-effector-domain sequence, although the effect of its N-terminal extension has not been measured.

Summary: PEA15 can inhibit death-receptor-mediated extrinsic apoptosis.

Reason: The human primary experiment shows protection from FasL and TNFalpha effects and impaired FADD–caspase-8 association. This is the specific pathway represented by the annotation. The horse protein preserves the human death-effector-domain sequence, although the effect of its N-terminal extension has not been measured.