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ALPK1

Function

Serine/threonine-protein kinase that detects bacterial pathogen-associated molecular pattern metabolites (PAMPs) and initiates an innate immune response, a critical step for pathogen elimination and engagement of adaptive immunity (PubMed:28222186, PubMed:28877472, PubMed:30111836). Specifically recognizes and binds ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria (PubMed:30111836). ADP-Heptose-binding stimulates its kinase activity to phosphorylate and activate TIFA, triggering pro-inflammatory NF-kappa-B signaling (PubMed:30111836). May be involved in monosodium urate monohydrate (MSU)-induced inflammation by mediating phosphorylation of unconventional myosin MYO9A (PubMed:27169898). May also play a role in apical protein transport by mediating phosphorylation of unconventional myosin MYO1A (PubMed:15883161). May play a role in ciliogenesis (PubMed:30967659).

Involvement in disease

Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome

ROSAH

An autosomal dominant disorder characterized by decreased vision associated with optic nerve edema, evident in childhood. Low-grade ocular inflammation is common in affected individuals. Later in childhood or the second decade of life, patients have increasing visual impairment, abnormal cone function and loss of rod function. By the third decade of life, visual acuity ranges from counting fingers to no light perception. Patients also show anhidrosis, splenomegaly, mild pancytopenia, and most experience headaches that may be migraine-like in nature.

None

The disease is caused by variants affecting the gene represented in this entry.

Sequence Similarities

Belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.

Tissue Specificity

Highly expressed in liver. Expressed in the optic nerve and retinal pigmented epithelium. Lower expression is observed in the macula and extramacular retina (PubMed:30967659).

Cellular localization

Alternative names

KIAA1527, LAK, ALPK1, Alpha-protein kinase 1, Chromosome 4 kinase, Lymphocyte alpha-protein kinase

swissprot:Q96QP1 omim:607347 entrezGene:80216