Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

AMFR (autocrine motility factor receptor)

Written2011-08Yalcin Erzurumlu, Petek Ballar
Ege University, Faculty of Pharmacy, Biochemistry Department, Bornova, 35100, Izmir, Turkey

(Note : for Links provided by Atlas : click)


Other aliasGP78
LocusID (NCBI) 267
Atlas_Id 627
Location 16q12.2  [Link to chromosome band 16q12]
Location_base_pair Starts at and ends at bp from pter
  AMFR gene genomic location at chromosome 16q12.2 (minus strand).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
AMFR (16q12.2) / ITGAM (16p11.2)AMFR (16q12.2) / PRRC2A (6p21.33)AMFR (16q13) / ITGAM (16p11.2)
PRRC2A (6p21.33) / AMFR (16q12.2)


  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.


Somatic D605V mutation has been reported in breast cancer (Sjöblom et al., 2006). Several SNPs have been found in gp78/AMFR gene both at coding regions and at UTRs and introns. See SNP database at NCBI.

Implicated in

Entity Sarcoma metastasis
Note gp78/AMFR targets KAI1, a known metastasis suppressor protein for ubiquitin mediated proteasomal degradation (Tsai et al., 2007). Thus gp78/AMFR has role in metastasis of human sarcoma. Furthermore, a human sarcoma tissue microarray study documents that tumors with low gp78 expression has higher levels of KAI1 and high gp78 level lower KAI1 expression in tumors (Tsai et al., 2007).
Entity Breast cancer
Note gp78/AMFR expression in gp78 transgenic mammary glands induces mammary gland hyperplasia, increases duct number and network density and shows down-regulation of KAI1 metastasis suppressor (Joshi et al., 2010). Additionally, gp78/AMFR has been identified as one of the most mutated genes in breast cancer (Sjöblom et al., 2006). Consistently, gp78/AMFR is overexpressed in human breast cancer and is negatively associated with patients' clinical outcome (Jiang et al., 2006).
Entity Gastric carcinoma
Note gp78/AMFR expression may be associated with the progression and invasion of gastric carcinoma as well as the prognoses of the patients (Hirono et al., 1996). Furthermore, by using same 3F3A antibody it was reported that gp78/AMFR expression is associated with lymph node metastasis and peritoneal dissemination in gastric carcinoma (Taniguchi et al., 1998).
Entity Colorectal cancer
Note gp78/AMFR expression is correlated high incidence of recurrence of the patients with colorectal cancer (Nakamori et al., 1994).
Entity Melanoma
Note It was showed by using 3F3A antibody that gp78/AMFR protein expression in human melanoma cell lines correlates to their metastatic potential. While in thin tumors weak/heterogenous gp78/AMFR expression predominated, in thick tumors the strong gp78/AMFR expression profile was predominant (Tímár et al., 2002).
Entity Lung cancer
Note Using immunohistochemical staining the gp78/AMFR expression was showed to be associated with histologic type of tumor, mainly in adenocarcinoma (Kara et al., 2001).
Entity Hepatocellular carcinoma
Note The expression of gp78/AMFR significantly increased in hepatocellular carcinoma compared with pericarcinomatous liver tissues. Furthermore, there is a strong correlation between AMFR expression and invasion and metastasis of HCC (Wang et al., 2007).
Entity Bladder carcinoma
Note While in normal urothelium gp78/AMFR is not expressed, its expression is increased in bladder carcinoma specimens (Otto et al., 1994).
Entity Cardiovascular diseases and hypercholesterolemia
Note Accumulation of sterols in ER membranes triggers the binding of HMG CoA reductase, the rate limiting enzyme of cholesterol biosynthesis, to the Insig1-gp78/AMFR complex which is essential for the ubiquitination and proteasomal degradation of HMGCoA-reductase (Goldstein et al., 2006; Jo and DeBose-Boyd, 2010). gp78/AMFR is also the E3 ligase of apolipoprotein B100, the protein component of atherogenic lipoproteins, overproduction of which is a common feature of human dyslipidemia (Liang et al., 2003).
Entity Cystic fibrosis
Note gp78/AMFR degrades mutant cystic fibrosis transmembrane conductance regulator (CFTRΔF508) associated with cystic fibrosis (Ballar et al., 2010; Morito et al., 2008).
Entity Metabolism and disposition of drugs
Note gp78/AMFR participates in proteasomal degradation of CYP3A4, a dominant human liver cytochrome P450 enzyme functioning in the metabolism and disposition of drugs and responsible for many adverse drug-drug interactions (Kim et al., 2010; Pabarcus et al., 2009).
Entity Chronic obstructive pulmonary disease
Note gp78/AMFR expression is increased with the severity of emphysema (Min et al., 2011).
Entity Neurodegenerative diseases
Note gp78/AMFR may play a protective role against mutant huntingtin toxicity. Mutant huntingtin hinders polyubiquitin binding to the cue domain of gp78/AMFR and causes aggregation of ligase (Yang et al., 2010). gp78/AMFR also enhances ubiquitination, degradation, suppression of aggregation of mutant SOD1 associated with amyotrophic lateral sclerosis (ALS), and mutant ataxin-3 associated with Machado-Joseph disease. Furthermore, in spinal cords of ALS mice, gp78/AMFR expression is significantly is up-regulated (Ying et al., 2009).
Entity Alpha-1-antitrypsin deficiency
Note gp78/AMFR targets mutant ATZ (Z-variant alpha-1-antitrypsin) associated with alpha-1-antitrypsin deficiency for the proteasomal degradation and increases its solubility (Shen et al., 2006).


Differential regulation of CFTRDeltaF508 degradation by ubiquitin ligases gp78 and Hrd1.
Ballar P, Ors AU, Yang H, Fang S.
Int J Biochem Cell Biol. 2010 Jan;42(1):167-73. Epub 2009 Oct 12.
PMID 19828134
The role of a novel p97/valosin-containing protein-interacting motif of gp78 in endoplasmic reticulum-associated degradation.
Ballar P, Shen Y, Yang H, Fang S.
J Biol Chem. 2006 Nov 17;281(46):35359-68. Epub 2006 Sep 20.
PMID 16987818
Ufd1 is a cofactor of gp78 and plays a key role in cholesterol metabolism by regulating the stability of HMG-CoA reductase.
Cao J, Wang J, Qi W, Miao HH, Wang J, Ge L, DeBose-Boyd RA, Tang JJ, Li BL, Song BL.
Cell Metab. 2007 Aug;6(2):115-28.
PMID 17681147
The activity of a human endoplasmic reticulum-associated degradation E3, gp78, requires its Cue domain, RING finger, and an E2-binding site.
Chen B, Mariano J, Tsai YC, Chan AH, Cohen M, Weissman AM.
Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):341-6. Epub 2006 Jan 3.
PMID 16407162
Autocrine motility factor receptor: a clinical review.
Chiu CG, St-Pierre P, Nabi IR, Wiseman SM.
Expert Rev Anticancer Ther. 2008 Feb;8(2):207-17. (REVIEW)
PMID 18279062
The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum.
Fang S, Ferrone M, Yang C, Jensen JP, Tiwari S, Weissman AM.
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14422-7. Epub 2001 Nov 27.
PMID 11724934
Protein sensors for membrane sterols.
Goldstein JL, DeBose-Boyd RA, Brown MS.
Cell. 2006 Jan 13;124(1):35-46. (REVIEW)
PMID 16413480
Expression of autocrine motility factor receptor correlates with disease progression in human gastric cancer.
Hirono Y, Fushida S, Yonemura Y, Yamamoto H, Watanabe H, Raz A.
Br J Cancer. 1996 Dec;74(12):2003-7.
PMID 8980404
Expression of autocrine motility factor (AMF) and its receptor, AMFR, in human breast cancer.
Jiang WG, Raz A, Douglas-Jones A, Mansel RE.
J Histochem Cytochem. 2006 Feb;54(2):231-41. Epub 2005 Oct 3.
PMID 16204225
Control of cholesterol synthesis through regulated ER-associated degradation of HMG CoA reductase.
Jo Y, Debose-Boyd RA.
Crit Rev Biochem Mol Biol. 2010 Jun;45(3):185-98. (REVIEW)
PMID 20482385
A role for KAI1 in promotion of cell proliferation and mammary gland hyperplasia by the gp78 ubiquitin ligase.
Joshi B, Li L, Nabi IR.
J Biol Chem. 2010 Mar 19;285(12):8830-9. Epub 2010 Jan 20.
PMID 20089858
Autocrine motility factor receptor expression in patients with stage I non-small cell lung cancer.
Kara M, Ohta Y, Tanaka Y, Oda M, Watanabe Y.
Ann Thorac Surg. 2001 Mar;71(3):944-8.
PMID 11269478
Liver cytochrome P450 3A ubiquitination in vivo by gp78/autocrine motility factor receptor and C terminus of Hsp70-interacting protein (CHIP) E3 ubiquitin ligases: physiological and pharmacological relevance.
Kim SM, Acharya P, Engel JC, Correia MA.
J Biol Chem. 2010 Nov 12;285(46):35866-77. Epub 2010 Sep 6.
PMID 20819951
Multiple modes of interaction of the deglycosylation enzyme, mouse peptide N-glycanase, with the proteasome.
Li G, Zhou X, Zhao G, Schindelin H, Lennarz WJ.
Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15809-14. Epub 2005 Oct 25.
PMID 16249333
Overexpression of the tumor autocrine motility factor receptor Gp78, a ubiquitin protein ligase, results in increased ubiquitinylation and decreased secretion of apolipoprotein B100 in HepG2 cells.
Liang JS, Kim T, Fang S, Yamaguchi J, Weissman AM, Fisher EA, Ginsberg HN.
J Biol Chem. 2003 Jun 27;278(26):23984-8. Epub 2003 Apr 1.
PMID 12670940
Critical role of proteostasis-imbalance in pathogenesis of COPD and severe emphysema.
Min T, Bodas M, Mazur S, Vij N.
J Mol Med (Berl). 2011 Jun;89(6):577-93. Epub 2011 Feb 12.
PMID 21318260
Gp78 cooperates with RMA1 in endoplasmic reticulum-associated degradation of CFTRDeltaF508.
Morito D, Hirao K, Oda Y, Hosokawa N, Tokunaga F, Cyr DM, Tanaka K, Iwai K, Nagata K.
Mol Biol Cell. 2008 Apr;19(4):1328-36. Epub 2008 Jan 23.
PMID 18216283
Cell shape modulation alters glycosylation of a metastatic melanoma cell-surface antigen.
Nabi IR, Raz A.
Int J Cancer. 1987 Sep 15;40(3):396-402.
PMID 3623718
Identification of B16-F1 melanoma autocrine motility-like factor receptor.
Nabi IR, Watanabe H, Raz A.
Cancer Res. 1990 Jan 15;50(2):409-14.
PMID 2153051
Expression of autocrine motility factor receptor in colorectal cancer as a predictor for disease recurrence.
Nakamori S, Watanabe H, Kameyama M, Imaoka S, Furukawa H, Ishikawa O, Sasaki Y, Kabuto T, Raz A.
Cancer. 1994 Oct 1;74(7):1855-62.
PMID 8082090
Inverse relation of E-cadherin and autocrine motility factor receptor expression as a prognostic factor in patients with bladder carcinomas.
Otto T, Birchmeier W, Schmidt U, Hinke A, Schipper J, Rubben H, Raz A.
Cancer Res. 1994 Jun 15;54(12):3120-3.
PMID 8205527
CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases.
Pabarcus MK, Hoe N, Sadeghi S, Patterson C, Wiertz E, Correia MA.
Arch Biochem Biophys. 2009 Mar 1;483(1):66-74. Epub 2008 Dec 10.
PMID 19103148
Proteins of the endoplasmic-reticulum-associated degradation pathway: domain detection and function prediction.
Ponting CP.
Biochem J. 2000 Oct 15;351 Pt 2:527-35.
PMID 11023840
Ubiquitin ligase gp78 increases solubility and facilitates degradation of the Z variant of alpha-1-antitrypsin.
Shen Y, Ballar P, Fang S.
Biochem Biophys Res Commun. 2006 Nov 3;349(4):1285-93. Epub 2006 Sep 7.
PMID 16979136
The autocrine motility factor receptor gene encodes a novel type of seven transmembrane protein.
Shimizu K, Tani M, Watanabe H, Nagamachi Y, Niinaka Y, Shiroishi T, Ohwada S, Raz A, Yokota J.
FEBS Lett. 1999 Aug 6;456(2):295-300.
PMID 10456327
Autocrine motility factor is a growth factor.
Silletti S, Raz A.
Biochem Biophys Res Commun. 1993 Jul 15;194(1):446-57.
PMID 8392842
The consensus coding sequences of human breast and colorectal cancers.
Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE.
Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7.
PMID 16959974
Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase.
Song BL, Sever N, DeBose-Boyd RA.
Mol Cell. 2005 Sep 16;19(6):829-40.
PMID 16168377
The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor, and urokinase-type plasminogen activator receptor.
Taniguchi K, Yonemura Y, Nojima N, Hirono Y, Fushida S, Fujimura T, Miwa K, Endo Y, Yamamoto H, Watanabe H.
Cancer. 1998 Jun 1;82(11):2112-22.
PMID 9610690
Expression and function of the AMF receptor by human melanoma in experimental and clinical systems.
Timar J, Raso E, Dome B, Ladanyi A, Banfalvi T, Gilde K, Raz A.
Clin Exp Metastasis. 2002;19(3):225-32.
PMID 12067203
The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation.
Tsai YC, Mendoza A, Mariano JM, Zhou M, Kostova Z, Chen B, Veenstra T, Hewitt SM, Helman LJ, Khanna C, Weissman AM.
Nat Med. 2007 Dec;13(12):1504-9. Epub 2007 Nov 25.
PMID 18037895
Elevated expression of autocrine motility factor receptor correlates with overexpression of RhoC and indicates poor prognosis in hepatocellular carcinoma.
Wang W, Yang LY, Yang ZL, Peng JX, Yang JQ.
Dig Dis Sci. 2007 Mar;52(3):770-5.
PMID 17265125
Purification of human tumor cell autocrine motility factor and molecular cloning of its receptor.
Watanabe H, Carmi P, Hogan V, Raz T, Silletti S, Nabi IR, Raz A.
J Biol Chem. 1991 Jul 15;266(20):13442-8.
PMID 1649192
Huntingtin interacts with the cue domain of gp78 and inhibits gp78 binding to ubiquitin and p97/VCP.
Yang H, Liu C, Zhong Y, Luo S, Monteiro MJ, Fang S.
PLoS One. 2010 Jan 26;5(1):e8905.
PMID 20126661
Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation.
Ying Z, Wang H, Fan H, Zhu X, Zhou J, Fei E, Wang G.
Hum Mol Genet. 2009 Nov 15;18(22):4268-81. Epub 2009 Aug 6.
PMID 19661182


This paper should be referenced as such :
Erzurumlu, Y ; Ballar, P
AMFR (autocrine motility factor receptor)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(1):25-29.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(16;16)(p11;q12) AMFR/ITGAM

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)267
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
Other databaseH-invDB
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Oct 18 17:28:13 CEST 2018

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us