DnaJ homolog subfamily C member 14 (DNAJC14)

DnaJ homolog subfamily C member 14 (DNAJC14) is a type III J-domain containing co-chaperone of the heat shock protein 40 (Hsp40) family, functioning predominantly at the ER membrane with its key functional domains exposed to the cytosol[1][2]. It interacts with Hsp70 family proteins, especially Hsc70, and regulates the folding, stability, and trafficking of several membrane proteins. DNAJC14 is involved in unconventional protein secretion pathways, including enhanced cell-surface trafficking of misfolded pendrin and dopamine D1 receptor[1][2]. It also acts as a host replication modulator for multiple Flaviviridae viruses, where overexpression can inhibit viral RNA replication by being recruited into viral replication complexes on ER-derived membranes[2]. Its precise cellular and disease roles remain under investigation, but its essential function as a co-chaperone underlies protein homeostasis and response to ER stress and viral infection.

Other names

DnaJ heat shock protein family member C14DRIP78HDJ3hDj-3LIP6FLJ32792DnaJ protein homolog 3Dopamine receptor-interacting protein of 78 kDaHuman DnaJ protein 3LYST-interacting protein LIP6dnaJ homolog subfamily C member 14DnaJ (Hsp40) homolog subfamily C member 14dnaJ protein homolog 3dopamine receptor interacting proteindnaJ protein 3

For viral replication: DNAJC14 acts as a host cofactor inhibiting viral RNA replication by interfering with viral replication complex assembly (e.g., yellow fever virus), or enhancing protease activity necessary for viral polyprotein processing (e.g., bovine viral diarrhea virus)[2]. For protein trafficking: DNAJC14 diverts misfolded proteins from degradation to unconventional cell-surface secretion through modulation of Hsc70 chaperone activity[1].