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Q9R049 (AMFR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length643 AA.
Sequence statusComplete.
Protein existenceEvidence 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 transferring VCP/p97 from the cytosol to microsomes.

Sequence similarities

Contains 1 CUE domain.

Contains 1 RING-type zinc finger.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
Zinc-finger
   LigandMetal-binding
Nucleotide-binding
Zinc
   Molecular functionLigase
Receptor
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processER-associated ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

aging

Inferred from electronic annotation. Source: Ensembl

cellular process

Traceable author statement Ref.1. Source: MGI

endoplasmic reticulum unfolded protein response

Inferred from electronic annotation. Source: Ensembl

learning or memory

Inferred from electronic annotation. Source: Ensembl

protein oligomerization

Inferred from electronic annotation. Source: Ensembl

protein polyubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentdendrite

Inferred from electronic annotation. Source: Ensembl

growth cone

Inferred from electronic annotation. Source: Ensembl

integral component of endoplasmic reticulum membrane

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of plasma membrane

Inferred from sequence or structural similarity Ref.1. Source: MGI

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

protein complex

Inferred from sequence orthology PubMed 23382219. Source: MGI

   Molecular_functionnucleotide binding

Inferred from electronic annotation. Source: UniProtKB-KW

receptor activity

Inferred from electronic annotation. Source: Ensembl

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

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 643643E3 ubiquitin-protein ligase AMFR
PRO_0000064580

Regions

Transmembrane82 – 10221Helical; Potential
Transmembrane122 – 14221Helical; Potential
Transmembrane186 – 20621Helical; Potential
Transmembrane215 – 23521Helical; Potential
Transmembrane254 – 27421Helical; Potential
Transmembrane276 – 29621Helical; Potential
Transmembrane429 – 44921Helical; Potential
Domain456 – 49843CUE
Zinc finger341 – 37939RING-type
Region614 – 64330VCP/p97-interacting motif (VIM)

Amino acid modifications

Modified residue5161Phosphoserine By similarity
Modified residue5421Phosphoserine Ref.8

Natural variations

Alternative sequence57 – 604Missing in isoform 2.
VSP_008224

Experimental info

Sequence conflict4121R → S in AAD56721. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2003. Version 2.
Checksum: 7119277725982F79

FASTA64373,105
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 22FF6303EEA033F1
Show »

FASTA63972,753

References

« Hide '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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+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.
RefSeqNP_035917.2. NM_011787.2.
UniGeneMm.34641.
Mm.490433.

3D structure databases

ProteinModelPortalQ9R049.
SMRQ9R049. Positions 327-384, 453-504, 574-599.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204722. 3 interactions.
IntActQ9R049. 7 interactions.
MINTMINT-1864613.
STRING10090.ENSMUSP00000052258.

PTM databases

PhosphoSiteQ9R049.

Proteomic databases

PaxDbQ9R049.
PRIDEQ9R049.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000053766; ENSMUSP00000052258; ENSMUSG00000031751. [Q9R049-2]
GeneID23802.
KEGGmmu:23802.

Organism-specific databases

CTD267.
MGIMGI:1345634. Amfr.

Phylogenomic databases

eggNOGCOG5243.
GeneTreeENSGT00530000062938.
HOGENOMHOG000037436.
HOVERGENHBG044694.
InParanoidQ9R049.
KOK10636.
OMAVSEKQHL.
OrthoDBEOG7QRQT8.
PhylomeDBQ9R049.
TreeFamTF320052.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9R049.
BgeeQ9R049.
CleanExMM_AMFR.
GenevestigatorQ9R049.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR026608. Amfr.
IPR003892. CUE.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERPTHR12477:SF4. PTHR12477:SF4. 1 hit.
PfamPF02845. CUE. 1 hit.
PF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTSM00546. CUE. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
PROSITEPS51140. CUE. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAMFR. mouse.
NextBio303423.
PROQ9R049.
SOURCESearch...

Entry information

Entry nameAMFR_MOUSE
AccessionPrimary (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: April 16, 2014
This is version 105 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot