According to hg38/GRCh38-Dec_2013:(GRCh38)
- Start: chr20: 35542029 bp from pter
- End: chr20:35557634 bp from pter
- Size: 15606 bases
- Orientation: forward strand.

Two alternatively spliced transcript variants encoding different isoforms have been demonstrated for this gene.
Isoform 1 transcript is 1383 bases (RefSeq: NM_198398.1), which is comprised of 14 exons and coding the longer isoform (Figure 2).
Isoform 2 represents the shorter 1368 bases, RefSeq: NM_015966.2, which is comprised of 13 exons and coding the shorter isoform (Figure 2). The open reading frame (ORF) is shifted because the variant is not spliced. Therefore, compared to isoform 1 the protein is shorter.

No observed pseudogenes.

Human ERGIC3 protein is a type II transmembrane protein containing two external membrane areas (1~19, 368~383), two transmembrane areas (20~42, 341~362), as well as a endoplasmic reticulum lumen area (43~344) from amino acid residues (figure 3). Human ERGIC3 consists of 383 amino acid with the molecular mass 43.2 kD and the value of theoretical isoelectric point 5.68, (Geng et al., 2014). ERGIC3 protein contains two conserved domains, ERGIC_N and COPIIcoated_ERV (figure 3) which are localized to the early secretory pathway and are involved in protein maturation and processing in the endoplasmic reticulum and/or sorting into COPII vesicles for transport to the Golgi (Otte et al., 2001). There are 2 glycosylation sites in the N241, N266 (figure 3).

388 aa (Accession: NM_198398.1, NP_938408 ) isoform 1; 383 aa (Accession: NM_015966.2, NP_057050.1). isoform 2. ERGIC3 belongs to the family of the ER vesicle (Erv) proteins (Otte et al., 2001). ERGIC3 interacts with ERGIC2 (Welsh et al., 2006) and ERGIC1 (Breuza et al., 2004) and forms a heterotrimeric protein complex. Both isoforms contain ERGIC_N domain and COPIIcoated_ERV domain (figure 3) which is conserved from fungi to humans. ERGIC3 works in close on junction with ERGIC2 and together they form a complex which cycles between the endoplasmic reticulum and cis-Golgi network. Both are integral membrane proteins with two membrane spanning segments each, short N- and C-terminal tails expose to the cytosol, and large central luminal domains (figure 3) (Welsh et al., 2006).

In normal human tissues, ERGIC3 is found in some epitheial cells such as liver, pancreas, stomach, intestine, and so on, but is undetected in lung, cerebral cortex, cerebellum, heart, spleen, thymus, muscle (Lin, 2014). In human tumor tissues, ERGIC3 is highly expressed in lung cancer, hepatocellular carcinoma, pancreatic carcinoma, gastric carcinoma, colon cancer, esophagus cancer, but is negative in osteosarcoma, chondrosarcoma, and fibrosarcoma by immunohistochemical (IHC) staining (Lin, 2014). In addtion, ERGIC3 is highly expressed in the spinal cord and kidney of mouse (Nishikawa et al., 2007).

ERGIC3 mainly localizes to endoplasmic reticulum, endoplasmic reticulum-golgi intermediate compartment (ERGIC) and cis-Golgi network, (Breuza et al., 2004; Orci et al., 2003; Wu et al., 2013).

The precise function of ERGIC3 is presently unclear, especially in mammal cells. There is a strong interaction between ERGIC3 and ERGIC2 so as to form a heteromer complex which exerting its biological function. The complex may be involved in : 1) the sorting of some secretory molecules during vesiclar transport (Belden and Barlowe, 2001; Otte and Barlowe, 2004) due to the hydrophobic signals present on both C-terminal tails of the ERGIC3-ERGIC2 complex control sorting into COPII vesicles for anterograde transport, and retrieval from the Golgi is mediated by a COPI binding KKxx motif on ERGIC3 (Otte and Barlowe, 2002) ; 2) protein folding and glycoprotein processing in the endoplasmic reticulum and cis- Golgi network (Nishikawa et al., 2007; Welsh et al., 2006). Glucosidase II is not transported into COPII vesicles in vitro as well as cells lacking a cycling ERGIC3-ERGIC2 complex have a mild glycoprotein processing defect and a partial loss of glucosidase (Leah, 2006) inhibiting endoplasmic reticulum stress (ERS)-induced cell death by tunicamycin in HEK-293 cells (Nishikawa et al., 2007).

ERGIC3 is highly conserved in species. The amino acid sequence is at least 98% among 8 vertebrates, human, pongo, macaca, ailuropoda, myotis, bovini, mus, heterocephalus. There is only one change in amino acid (T164) between human and pongo, 2 changes in amino acid (T112, W170) between human and macaca (Geng et al., 2014).

No observed mutation sites.