PEAK FAMILY MEMBER 3; PEAK3

Alternative titles; symbols

• CHROMOSOME 19 OPEN READING FRAME 35; C19ORF35

HGNC Approved Gene Symbol: PEAK3

Cytogenetic location: 19p13.3 Genomic coordinates (GRCh38): 19:2,274,630-2,282,174 (from NCBI)

▼ Description
The PEAK3 gene encodes a kinase-like protein (pseudokinase) of the NKF3 family (New Kinase Family 3), which includes PEAK1 (614248) and PRAG1 (617344). PEAK3 plays a role in cell motility (Lopez et al., 2019).

▼ Cloning and Expression
The PEAK3 gene encodes a 473-amino acid protein. Like other members of the NKF3 family, PEAK3 has a split helical dimerization (SHED) domain that supports its homodimerization; however, PEAK3 contains a significantly shorter N-terminal domain and a less conserved kinase-like domain than PEAK1 and PRAG1. Using transient transfection experiments in COS-7 and U2OS cells, Lopez et al. (2019) showed that PEAK3 is distributed diffusely throughout the cytoplasm. PEAK3 is evolutionarily conserved in birds and mammals and in some reptilian lineages (Lopez et al., 2019).

▼ Gene Function
Lopez et al. (2019) showed that cells overexpressing PEAK3 exhibited notably fewer stress fibers and shorter, less organized actin filaments, similar to a phenotype seen in CRKII knockdown cells. Lopez et al. (2019) also showed that PEAK3 homodimers bound to the adaptor protein CRKII (CRK; 164762), which prevented CRKII-dependent membrane ruffling. Binding to CRKII required the PEAK3 N-terminal domain, containing the CrkII-binding site, and the C-terminal domain, containing the pseudokinase domain. Lopez et al. (2019) noted that expression of PEAK was reported to be elevated in acute myeloid leukemia relative to other cancers.

▼ Mapping
Gross (2019) mapped the PEAK3 gene to chromosome 19p13.3 based on an alignment of the PEAK3 sequence (GenBank NM_198532) with the genomic sequence (GRCh38).