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Protein

E3 ubiquitin-protein ligase AMFR

Gene

Amfr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity2 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri341 – 379RING-typePROSITE-ProRule annotationAdd BLAST39

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor, Transferase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-532668. N-glycan trimming in the ER and Calnexin/Calreticulin cycle.
R-MMU-901032. ER Quality Control Compartment (ERQC).
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase AMFR (EC:2.3.2.27By similarity)
Alternative name(s):
Autocrine motility factor receptor
Short name:
AMF receptor
RING-type E3 ubiquitin transferase AMFRCurated
Gene namesi
Name:Amfr
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1345634. Amfr.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei82 – 102HelicalSequence analysisAdd BLAST21
Transmembranei122 – 142HelicalSequence analysisAdd BLAST21
Transmembranei186 – 206HelicalSequence analysisAdd BLAST21
Transmembranei215 – 235HelicalSequence analysisAdd BLAST21
Transmembranei254 – 274HelicalSequence analysisAdd BLAST21
Transmembranei276 – 296HelicalSequence analysisAdd BLAST21
Transmembranei429 – 449HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000645801 – 643E3 ubiquitin-protein ligase AMFRAdd BLAST643

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei516PhosphoserineBy similarity1
Modified residuei542PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9R049.
PRIDEiQ9R049.

PTM databases

iPTMnetiQ9R049.
PhosphoSitePlusiQ9R049.
SwissPalmiQ9R049.

Expressioni

Tissue specificityi

Expressed in heart, brain, liver, lung, skeletal muscle, kidney and testis. Not detected in spleen.1 Publication

Gene expression databases

BgeeiENSMUSG00000031751.
CleanExiMM_AMFR.
ExpressionAtlasiQ9R049. baseline and differential.
GenevisibleiQ9R049. MM.

Interactioni

Subunit structurei

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.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Ngly1Q9JI785EBI-3648125,EBI-3648128
VcpQ018534EBI-3648125,EBI-80597

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204722. 4 interactors.
IntActiQ9R049. 7 interactors.
MINTiMINT-1864613.
STRINGi10090.ENSMUSP00000052258.

Structurei

3D structure databases

ProteinModelPortaliQ9R049.
SMRiQ9R049.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini456 – 498CUEPROSITE-ProRule annotationAdd BLAST43

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni622 – 640VCP/p97-interacting motif (VIM)By similarityAdd BLAST19

Domaini

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 similaritiesi

Contains 1 CUE domain.PROSITE-ProRule annotationCurated
Contains 1 RING-type zinc finger.PROSITE-ProRule annotationCurated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri341 – 379RING-typePROSITE-ProRule annotationAdd BLAST39

Keywords - Domaini

Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiKOG0802. Eukaryota.
COG5243. LUCA.
GeneTreeiENSGT00530000062938.
HOGENOMiHOG000037436.
HOVERGENiHBG044694.
InParanoidiQ9R049.
KOiK10636.
OMAiGTWESKG.
PhylomeDBiQ9R049.
TreeFamiTF320052.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR003892. CUE.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF02845. CUE. 1 hit.
PF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTiSM00546. CUE. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS51140. CUE. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q9R049-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPLLFLERFP WPSLRTYTGL SGLALLGTIV SAYRALSQPE DGSGEPEPLT
60 70 80 90 100
APLQPEALAP ARLTAGGPRA RDVAQYLLSD SLFVWVLVNT ACCVLMLVAK
110 120 130 140 150
LIQCIVFGPL RVSERQHLKD KFWNFIFYKF IFIFGVLNVQ TVEEVVMWCL
160 170 180 190 200
WFAGLVFLHL MVQLCKDRFE YLSFSPTTPM SSHGRVLSLL IAMLLSCCGL
210 220 230 240 250
AVVCCVTGYT HGMHTLAFMA AESLLVTVRT AHVILRYVIH LWDLNHEGTW
260 270 280 290 300
EGKGTYVYYT DFVMELALLS LDLMHHIHML LFGNIWLSMA SLVIFMQLRY
310 320 330 340 350
LFHEVQRRIR RHKNYLRVVG NMEARFAVAT PEELAVNNDD CAICWDSMQA
360 370 380 390 400
ARKLPCGHLF HNSCLRSWLE QDTSCPTCRM SLNIADGSRA REDHQGENLD
410 420 430 440 450
ENLVPVAAAE GRPRLNQHNH FFHFDGSRIA SWLPSFSVEV MHTTNILGIT
460 470 480 490 500
QASNSQLNAM AHQIQEMFPQ VPYHLVLQDL QMTRSVEITT DNILEGRIQV
510 520 530 540 550
PFPTQRSDSL RPALNSPVER PSPDLEEGEA SVQTERVPLD LSPRLEETLD
560 570 580 590 600
FSEVELEPIE VEDFEARGSR FSKSADERQR MLVQRKDDLL QQARKRFLNK
610 620 630 640
SSEDDGASER LLPSEGTSSD PVTLRRRMLA AAAERRLQRQ RTT
Length:643
Mass (Da):73,105
Last modified:June 1, 2003 - v2
Checksum:i7119277725982F79
GO
Isoform 2Curated (identifier: Q9R049-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.Curated
Show »
Length:639
Mass (Da):72,753
Checksum:i22FF6303EEA033F1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti412R → S in AAD56721 (PubMed:10456327).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00822457 – 60Missing in isoform 2. 1 Publication4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF124144 mRNA. Translation: AAD56721.1.
BC003256 mRNA. Translation: AAH03256.1.
BC034538 mRNA. Translation: AAH34538.1.
BC040338 mRNA. Translation: AAH40338.1.
CCDSiCCDS22533.1. [Q9R049-2]
RefSeqiNP_035917.2. NM_011787.2. [Q9R049-2]
UniGeneiMm.34641.
Mm.490433.

Genome annotation databases

EnsembliENSMUST00000053766; ENSMUSP00000052258; ENSMUSG00000031751. [Q9R049-2]
GeneIDi23802.
KEGGimmu:23802.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF124144 mRNA. Translation: AAD56721.1.
BC003256 mRNA. Translation: AAH03256.1.
BC034538 mRNA. Translation: AAH34538.1.
BC040338 mRNA. Translation: AAH40338.1.
CCDSiCCDS22533.1. [Q9R049-2]
RefSeqiNP_035917.2. NM_011787.2. [Q9R049-2]
UniGeneiMm.34641.
Mm.490433.

3D structure databases

ProteinModelPortaliQ9R049.
SMRiQ9R049.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204722. 4 interactors.
IntActiQ9R049. 7 interactors.
MINTiMINT-1864613.
STRINGi10090.ENSMUSP00000052258.

PTM databases

iPTMnetiQ9R049.
PhosphoSitePlusiQ9R049.
SwissPalmiQ9R049.

Proteomic databases

PaxDbiQ9R049.
PRIDEiQ9R049.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000053766; ENSMUSP00000052258; ENSMUSG00000031751. [Q9R049-2]
GeneIDi23802.
KEGGimmu:23802.

Organism-specific databases

CTDi267.
MGIiMGI:1345634. Amfr.

Phylogenomic databases

eggNOGiKOG0802. Eukaryota.
COG5243. LUCA.
GeneTreeiENSGT00530000062938.
HOGENOMiHOG000037436.
HOVERGENiHBG044694.
InParanoidiQ9R049.
KOiK10636.
OMAiGTWESKG.
PhylomeDBiQ9R049.
TreeFamiTF320052.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-532668. N-glycan trimming in the ER and Calnexin/Calreticulin cycle.
R-MMU-901032. ER Quality Control Compartment (ERQC).

Miscellaneous databases

ChiTaRSiAmfr. mouse.
PROiQ9R049.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031751.
CleanExiMM_AMFR.
ExpressionAtlasiQ9R049. baseline and differential.
GenevisibleiQ9R049. MM.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR003892. CUE.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF02845. CUE. 1 hit.
PF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTiSM00546. CUE. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS51140. CUE. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAMFR_MOUSE
AccessioniPrimary (citable) accession number: Q9R049
Secondary accession number(s): Q8K008, Q99LH5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: June 1, 2003
Last modified: November 30, 2016
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.