AMFR (autocrine motility factor receptor)

Alias (NCBI)	GP78
	RNF45
HGNC (Hugo)	AMFR
HGNC Alias symb	RNF45
	gp78
LocusID (NCBI)	267
Atlas_Id	627
Location	16q12.2  [Link to chromosome band 16q12]
Location_base_pair	Starts at 56361452 and ends at 56425545 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping AMFR.png]
	AMFR gene genomic location at chromosome 16q12.2 (minus strand).

	A. The alignment of AMFR mRNA to its genomic sequence. B. AMFR mRNA and its amino acid coding.
Description	The AMFR gene spans 64081 bases on minus strand. The DNA of AMFR consists of 14 exons and the coding sequence starts in the first exon.
Transcription	The AMFR gene has two transcripts. One of these transcripts is 2249 bp long and is a processed transcript with no protein product. 3598 bp long second AMFR transcript is a protein coding transcript (accession number: NM_001144). The DNA has been cloned in 1999 (Shimizu et al., 1999).

	A schematic representation of the domain structure.
Description	AMFR belongs to the family of RING-Finger ubiquitin ligases. The complete protein contains 643 amino acids. The calculated molecular weight of AMFR is 73,0 kDa. AMFR was originally isolated as a membrane glycoprotein from murine melanoma cells and was implicated in cell migration (Nabi and Raz, 1987). Subsequently, gp78/AMFR was identified as the tumor autocrine motility factor receptor mediating tumor invasion and metastasis (Nabi et al., 1990). A monoclonal antibody named 3F3A was generated against this protein and first sequence reported for human gp78/AMFR was in 1991 using this antibody (Watanabe et al., 1991). However, the protein product was only 321 amino acids (Watanabe et al., 1991). A sequence giving 643 amino acids protein product was cloned in 1999 (Shimizu et al., 1999). gp78/AMFR has five to seven transmembrane domains according to different softwares like SACS MEMSAT and SOSUI. The protein has a long cytoplasmic tail composed of around 350 amino acids (Shimizu et al., 1999). Besides conveying E3 activity the multifunctional cytoplasmic tail is responsible for interaction with polyubiquitin, ubiquitin conjugating enzyme, p97/VCP and Ufd1. The RING finger domain of gp78/AMFR residing between amino acids 341 and 383 is a RING-H2 type domain containing two His residues in positions 4 and 5 (Fang et al., 2001). The Cue domain of gp78/AMFR residing between amino acids 456 and 497 is responsible for polyubiquitin binding and has been identified by having homologous sequences of yeast protein Cue1p (Ponting, 2000). The p97/VCP-interacting motif of gp78/AMFR consists of C-terminal amino acid residues between 614-643 and it is sufficient to bind to p97/VCP protein (Ballar et al., 2006). gp78/AMFR binds to its ubiquitin conjugating enzyme via a region called UBE2G2 binding region (G2BR) and this region is resides between amino acids 579 and 600 (Chen et al., 2006). Additionally, gp78/AMFR interacts directly with Ufd1 through residues 383-497 (Cao et al., 2007) and with INSIGs through its transmembrane domains (Song et al., 2005).
Expression	gp78/AMFR is relatively ubiquitously expressed in normal human cells, especially highly in liver, heart and lung. Northern blot analysis detected a 3.5-kb AMFR transcript in mouse heart, brain, lung, liver, skeletal muscle, kidney, and testis, but not in spleen (Shimizu et al., 1999). gp78/AMFR is overexpressed in certain malignant tumors and human cancers of the lung, gastrointestinal tract, breast, liver, thymus, and skin (Chiu et al., 2008; Sjöblom et al., 2006; Tsai et al., 2007; Joshi et al., 2010).
Localisation	Endoplasmic reticulum membrane, multi-pass transmembrane protein (Fang et al., 2001).
Function	In 2001, it has been reported that gp78/AMFR possesses ubiquitin ligase (E3) activity (Fang et al., 2001) and can ubiquitinate both itself and other proteins for proteasomal degradation. gp78/AMFR is a member of multiprotein complex functioning in endoplasmic reticulum associated degradation (ERAD). gp78/AMFR not only functions as an E3 during ERAD but also couples retrotranslocation and deglycosylation to ubiquitination (Ballar et al., 2006; Li et al., 2005).
Homology	Homologues have been found in various species like bovine, chimpanzee (99.8 % homology), chicken, zebra fish, rat, C. elegans and mouse. gp78/AMFR shares 94.7 % of homology with murine gp78/AMFR.

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