Q9R049 (AMFR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase AMFR
EC=6.3.2.-

Alternative name(s):
Autocrine motility factor receptor
Short name=AMF receptor

Gene names

Name:

Amfr

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	643 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 ubiquitin-protein ligase that mediates the polyubiquitination of a number of proteins such as CD3D, CYP3A4, CFTR and APOB for proteasomal degradation. Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of endoplasmic reticulum-associated degradation (ERAD). The VCP/p97-AMFR/gp78 complex is involved in the sterol-accelerated ERAD degradation of HMGCR through binding to the HMGCR-INSIG complex at the ER membrane and initiating ubiquitination of HMGCR. The ubiquitinated HMGCR is then released from the ER by the complex into the cytosol for subsequent destruction. Also acts as a scaffold protein to assemble a complex that couples ubiquitination, retranslocation and deglycosylation. Mediates tumor invasion and metastasis By similarity. Ref.3 Ref.4 Ref.7
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts (through a region distinct from the RING finger) with UBE2G2/UBC7. Interacts with DRL1. Interacts (via the VIM) with VCP/p97. Interacts (via its membrane domain) with INSIG1; the interaction initiates the sterol-mediated ubiquitination and degradation of HMGCR by the ERAD pathway By similarity. Component of the VCP/p97-AMFR/gp78 complex that enhances VCP/p97 binding to polyubiquitinated proteins for their degradation by the endoplasmic reticulum-associated degradation (ERAD) pathway. Interacts (via the VIM) with VCP/p97. Interacts with RNF5. Also forms an ERAD complex containing VCP/p97, NGLY1; PSMC1; SAKS1 AND RAD23B required for coupling retrotranslocation, ubiquitination and deglycosylation. Ref.4 Ref.5 Ref.7
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein By similarity Ref.4.
Tissue specificity	Expressed in heart, brain, liver, lung, skeletal muscle, kidney and testis. Not detected in spleen. Ref.1
Domain	The CUE domain is required for recognition of misfolded proteins such as mutant CFTR. The VCP/p97-interacting motif (VIM) is sufficient for binding VCP/p97 to form a complex capable of transfering VCP/p97 from the cytosol to microsomes.
Sequence similarities	Contains 1 CUE domain. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix Zinc-finger
Ligand	Metal-binding Nucleotide-binding Zinc
Molecular function	Ligase Receptor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ER-associated protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB endoplasmic reticulum unfolded protein response Inferred from electronic annotation. Source: Compara protein oligomerization Inferred from electronic annotation. Source: Compara protein polyubiquitination Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	integral to endoplasmic reticulum membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to plasma membrane Inferred from sequence or structural similarity Ref.1. Source: MGI
Molecular_function	nucleotide binding Inferred from electronic annotation. Source: UniProtKB-KW receptor activity Inferred from electronic annotation. Source: Compara ubiquitin-protein ligase activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ngly1	Q9JI78	5	EBI-3648125,EBI-3648128
Vcp	Q01853	4	EBI-3648125,EBI-80597

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.1 (identifier: Q9R049-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9R049-2)

The sequence of this isoform differs from the canonical sequence as follows:
     57-60: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 643	643	E3 ubiquitin-protein ligase AMFR		PRO_0000064580
Regions
	Transmembrane	82 – 102	21	Helical; Potential
	Transmembrane	122 – 142	21	Helical; Potential
	Transmembrane	186 – 206	21	Helical; Potential
	Transmembrane	215 – 235	21	Helical; Potential
	Transmembrane	254 – 274	21	Helical; Potential
	Transmembrane	276 – 296	21	Helical; Potential
	Transmembrane	429 – 449	21	Helical; Potential
	Domain	456 – 498	43	CUE
	Zinc finger	341 – 379	39	RING-type
	Region	614 – 643	30	VCP/p97-interacting motif (VIM)
Amino acid modifications
	Modified residue	516	1	Phosphoserine By similarity
	Modified residue	542	1	Phosphoserine Ref.6 Ref.8
Natural variations
	Alternative sequence	57 – 60	4	Missing in isoform 2.		VSP_008224
Experimental info
	Sequence conflict	412	1	R → S in AAD56721. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2003. Version 2. Checksum: 7119277725982F79	FASTA	643	73,105
	10 20 30 40 50 60 MPLLFLERFP WPSLRTYTGL SGLALLGTIV SAYRALSQPE DGSGEPEPLT APLQPEALAP 70 80 90 100 110 120 ARLTAGGPRA RDVAQYLLSD SLFVWVLVNT ACCVLMLVAK LIQCIVFGPL RVSERQHLKD 130 140 150 160 170 180 KFWNFIFYKF IFIFGVLNVQ TVEEVVMWCL WFAGLVFLHL MVQLCKDRFE YLSFSPTTPM 190 200 210 220 230 240 SSHGRVLSLL IAMLLSCCGL AVVCCVTGYT HGMHTLAFMA AESLLVTVRT AHVILRYVIH 250 260 270 280 290 300 LWDLNHEGTW EGKGTYVYYT DFVMELALLS LDLMHHIHML LFGNIWLSMA SLVIFMQLRY 310 320 330 340 350 360 LFHEVQRRIR RHKNYLRVVG NMEARFAVAT PEELAVNNDD CAICWDSMQA ARKLPCGHLF 370 380 390 400 410 420 HNSCLRSWLE QDTSCPTCRM SLNIADGSRA REDHQGENLD ENLVPVAAAE GRPRLNQHNH 430 440 450 460 470 480 FFHFDGSRIA SWLPSFSVEV MHTTNILGIT QASNSQLNAM AHQIQEMFPQ VPYHLVLQDL 490 500 510 520 530 540 QMTRSVEITT DNILEGRIQV PFPTQRSDSL RPALNSPVER PSPDLEEGEA SVQTERVPLD 550 560 570 580 590 600 LSPRLEETLD FSEVELEPIE VEDFEARGSR FSKSADERQR MLVQRKDDLL QQARKRFLNK 610 620 630 640 SSEDDGASER LLPSEGTSSD PVTLRRRMLA AAAERRLQRQ RTT
	Isoform 2 [UniParc]. Checksum: 22FF6303EEA033F1	FASTA	639	72,753
	10 20 30 40 50 60 MPLLFLERFP WPSLRTYTGL SGLALLGTIV SAYRALSQPE DGSGEPEPLT APLQPEARLT 70 80 90 100 110 120 AGGPRARDVA QYLLSDSLFV WVLVNTACCV LMLVAKLIQC IVFGPLRVSE RQHLKDKFWN 130 140 150 160 170 180 FIFYKFIFIF GVLNVQTVEE VVMWCLWFAG LVFLHLMVQL CKDRFEYLSF SPTTPMSSHG 190 200 210 220 230 240 RVLSLLIAML LSCCGLAVVC CVTGYTHGMH TLAFMAAESL LVTVRTAHVI LRYVIHLWDL 250 260 270 280 290 300 NHEGTWEGKG TYVYYTDFVM ELALLSLDLM HHIHMLLFGN IWLSMASLVI FMQLRYLFHE 310 320 330 340 350 360 VQRRIRRHKN YLRVVGNMEA RFAVATPEEL AVNNDDCAIC WDSMQAARKL PCGHLFHNSC 370 380 390 400 410 420 LRSWLEQDTS CPTCRMSLNI ADGSRAREDH QGENLDENLV PVAAAEGRPR LNQHNHFFHF 430 440 450 460 470 480 DGSRIASWLP SFSVEVMHTT NILGITQASN SQLNAMAHQI QEMFPQVPYH LVLQDLQMTR 490 500 510 520 530 540 SVEITTDNIL EGRIQVPFPT QRSDSLRPAL NSPVERPSPD LEEGEASVQT ERVPLDLSPR 550 560 570 580 590 600 LEETLDFSEV ELEPIEVEDF EARGSRFSKS ADERQRMLVQ RKDDLLQQAR KRFLNKSSED 610 620 630 DGASERLLPS EGTSSDPVTL RRRMLAAAAE RRLQRQRTT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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. 456:295-300(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Lung and Testis.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: FVB/N. Tissue: Colon and Mammary gland.
[3]	"Overexpression of autocrine motility factor receptor (AMFR) in NIH3T3 fibroblasts induces cell transformation." Onishi Y., Tsukada K., Yokota J., Raz A. Clin. Exp. Metastasis 20:51-58(2003) [PubMed] [Europe PMC] [Abstract] Cited for: ROLE IN METASTASIS.
[4]	"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. 281:35359-35368(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VCP IN THE VCP/P97-AMFR/GP78 COMPLEX, FUNCTION, SUBCELLULAR LOCATION.
[5]	"The AAA ATPase p97 links peptide N-glycanase to the endoplasmic reticulum-associated E3 ligase autocrine motility factor receptor." Li G., Zhao G., Zhou X., Schindelin H., Lennarz W.J. Proc. Natl. Acad. Sci. U.S.A. 103:8348-8353(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NGLY1; PSMC1; SAKS1; RAD23B AND VCP.
[6]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-542, MASS SPECTROMETRY. Tissue: Brain cortex.
[7]	"Gp78 cooperates with RMA1 in endoplasmic reticulum-associated degradation of CFTRDeltaF508." Morito D., Hirao K., Oda Y., Hosokawa N., Tokunaga F., Cyr D.M., Tanaka K., Iwai K., Nagata K. Mol. Biol. Cell 19:1328-1336(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN UBIQUITINATION OF MISFOLDED PROTEINS, INTERACTION WITH RNF5.
[8]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-542, MASS SPECTROMETRY. Tissue: Macrophage.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF124144 mRNA. Translation: AAD56721.1. BC003256 mRNA. Translation: AAH03256.1. BC034538 mRNA. Translation: AAH34538.1. BC040338 mRNA. Translation: AAH40338.1.
IPI	IPI00319880. IPI00351315.
RefSeq	NP_035917.2. NM_011787.2.
UniGene	Mm.34641. Mm.490390. Mm.490433.
3D structure databases
ProteinModelPortal	Q9R049.
SMR	Q9R049. Positions 332-382, 453-504, 574-600.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9R049. 5 interactions.
STRING	10090.ENSMUSP00000052258.
PTM databases
PhosphoSite	Q9R049.
Proteomic databases
PaxDb	Q9R049.
PRIDE	Q9R049.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000053766; ENSMUSP00000052258; ENSMUSG00000031751.
GeneID	23802.
KEGG	mmu:23802.
Organism-specific databases
CTD	267.
MGI	MGI:1345634. Amfr.
Phylogenomic databases
eggNOG	COG5243.
GeneTree	ENSGT00530000062938.
HOGENOM	HOG000037436.
HOVERGEN	HBG044694.
InParanoid	Q9R049.
KO	K10636.
OMA	YTDFIME.
OrthoDB	EOG4DJJW8.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q9R049.
Bgee	Q9R049.
CleanEx	MM_AMFR.
Genevestigator	Q9R049.
GermOnline	ENSMUSG00000031751. Mus musculus.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR026608. Amfr. IPR003892. CUE. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
PANTHER	PTHR12477:SF4. PTHR12477:SF4. 1 hit.
Pfam	PF02845. CUE. 1 hit. PF13639. zf-RING_2. 1 hit. [Graphical view]
SMART	SM00546. CUE. 1 hit. SM00184. RING. 1 hit. [Graphical view]
PROSITE	PS51140. CUE. 1 hit. PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	AMFR. mouse.
NextBio	303423.
SOURCE	Search...

Entry information

Entry name

AMFR_MOUSE

Accession

Primary (citable) accession number: Q9R049
Secondary accession number(s): Q8K008, Q99LH5

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2003
Last sequence update:	June 1, 2003
Last modified:	May 1, 2013
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program