The COP-II complex comprises five highly conserved proteins, among these SEC31A, creating small membrane vesicles that originate from the ER. Budding of these vesicles is essential in the cellular trafficking pathway, through which membrane and luminal cargo proteins are transported from their site of synthesis to other cellular compartments. This machinery assembles hierarchically, driven by the initial recruitment and activation of the small GTPase SAR1, which exists in a soluble cytoplasmic form when in its GDP-bound state. SAR1 is promoted by SEC12, a membrane-bound GEF that catalyzes GDP/GTP exchange. Once tightly anchored into the ER membrane, the active GTP-bound SAR1 recruits the SEC23-SEC24 heterodimer to form the inner “pre-budding” complex, capable of engaging cargo through interactions between SEC24 and multiple ER export motifs. Finally, the SEC13–SEC31A hetero-tetramer is recruited to promote coat polymerization, membrane curvature, and eventually membrane fission. With the full complement of the COP-II complex, the extruded membrane is separated from the ER membrane to form an intact vesicle. Most mammalian COP-II complex subunits have one or more paralogues with partially redundant functions, as the loss of selected copies often results in a genetic disease. The mammalian repertoire consists of two SAR1 paralogs, SAR1A and SAR1B; two SEC23 paralogs, SEC23A and SEC23B; four SEC24 paralogs, SEC24A, SEC24B, SEC24C, and SEC24D; a single SEC13 and two SEC31 paralogs: SEC31A, comprising part of the SEC13/SEC31 hetero-tetramer, and SEC31B. The repertoire of COP-II paralogs available in mammals could contribute to a wide variety of COP-II coats, thus facilitating selective cargo transport in a tissue-specific manner. Alternative splicing could further contribute to the COP-II vesicle and cargo selection diversity. +Associated diseases/phenotypes with mutations in the COP-II complex genes described to date (2021) Yeast COP-II Mammalian COP-II Organism Associated disease/phenotypes OMIM SAR1p SAR1A SAR1B Human Chylomicron retention (CMRD)/Anderson's disease 246700 SEC23p SEC23A Human Cranio-lenticulo-sutural dysplasia (CLSD) 607812 Zebrafish Skeletal and craniofacial development defects SEC23B Human Congenital dyserythropoietic anemia type II (CDAII) 610512 Zebrafish Aberrant erythrocyte development SEC24p SEC24A Arabidopsis thaliana Secretory and Golgi proteins accumulate in ER SEC24B Mice Neural tube defects and craniorachischisis SEC24C Mice Embryonic lethality SEC24D Human Osteogenesis imperfecta-like syndrome 607186 Zebrafish Craniofacial dysmorphology, defects in trafficking of ECM proteins including type II collagen Medaka Skeletal and facial development defects Mice Early embryonic lethality SEC13p SEC13 Zebrafish Defects in proteoglycan deposition cause CLSD-like phenotype SEC31p SEC31A Human<unk>  618615 SEC31B
Halperin-Birk syndrome
Birk-Barel syndrome
Hurler syndrome
Kindler syndrome
Hecht Scott syndrome
ZTTK syndrome
GRACILE syndrome
GAPO syndrome