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Q9R049

- AMFR_MOUSE

UniProt

Q9R049 - AMFR_MOUSE

Protein

E3 ubiquitin-protein ligase AMFR

Gene

Amfr

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 2 (01 Jun 2003)
      Previous versions | rss
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    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 similarity

    Pathwayi

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri341 – 37939RING-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. ligase activity Source: UniProtKB-KW
    2. nucleotide binding Source: UniProtKB-KW
    3. protein binding Source: IntAct
    4. receptor activity Source: Ensembl
    5. ubiquitin-protein transferase activity Source: UniProtKB
    6. zinc ion binding Source: InterPro

    GO - Biological processi

    1. aging Source: Ensembl
    2. cellular process Source: MGI
    3. endoplasmic reticulum unfolded protein response Source: Ensembl
    4. ER-associated ubiquitin-dependent protein catabolic process Source: UniProtKB
    5. learning or memory Source: Ensembl
    6. protein oligomerization Source: Ensembl
    7. protein polyubiquitination Source: UniProtKB

    Keywords - Molecular functioni

    Ligase, Receptor

    Keywords - Biological processi

    Ubl conjugation pathway

    Keywords - Ligandi

    Metal-binding, Nucleotide-binding, Zinc

    Enzyme and pathway databases

    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    E3 ubiquitin-protein ligase AMFR (EC:6.3.2.-)
    Alternative name(s):
    Autocrine motility factor receptor
    Short name:
    AMF receptor
    Gene namesi
    Name:Amfr
    OrganismiMus musculus (Mouse)Imported
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 8

    Organism-specific databases

    MGIiMGI:1345634. Amfr.

    Subcellular locationi

    GO - Cellular componenti

    1. dendrite Source: Ensembl
    2. growth cone Source: Ensembl
    3. integral component of endoplasmic reticulum membrane Source: UniProtKB
    4. integral component of plasma membrane Source: MGI
    5. neuronal cell body Source: Ensembl
    6. nucleus Source: Ensembl
    7. protein complex Source: MGI

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 643643E3 ubiquitin-protein ligase AMFRPRO_0000064580Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei516 – 5161PhosphoserineBy similarity
    Modified residuei542 – 5421Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ9R049.
    PRIDEiQ9R049.

    PTM databases

    PhosphoSiteiQ9R049.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    ArrayExpressiQ9R049.
    BgeeiQ9R049.
    CleanExiMM_AMFR.
    GenevestigatoriQ9R049.

    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

    Protein-protein interaction databases

    BioGridi204722. 3 interactions.
    IntActiQ9R049. 7 interactions.
    MINTiMINT-1864613.
    STRINGi10090.ENSMUSP00000052258.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9R049.
    SMRiQ9R049. Positions 327-384, 453-504, 574-599.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei82 – 10221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei122 – 14221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei186 – 20621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei215 – 23521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei254 – 27421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei276 – 29621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei429 – 44921HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini456 – 49843CUEPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni614 – 64330VCP/p97-interacting motif (VIM)Add
    BLAST

    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.CuratedPROSITE-ProRule annotation
    Contains 1 RING-type zinc finger.CuratedPROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri341 – 37939RING-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Transmembrane, Transmembrane helix, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG5243.
    GeneTreeiENSGT00530000062938.
    HOGENOMiHOG000037436.
    HOVERGENiHBG044694.
    InParanoidiQ9R049.
    KOiK10636.
    OMAiNTACCFL.
    OrthoDBiEOG7QRQT8.
    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. Align

    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

    MPLLFLERFP WPSLRTYTGL SGLALLGTIV SAYRALSQPE DGSGEPEPLT    50
    APLQPEALAP ARLTAGGPRA RDVAQYLLSD SLFVWVLVNT ACCVLMLVAK 100
    LIQCIVFGPL RVSERQHLKD KFWNFIFYKF IFIFGVLNVQ TVEEVVMWCL 150
    WFAGLVFLHL MVQLCKDRFE YLSFSPTTPM SSHGRVLSLL IAMLLSCCGL 200
    AVVCCVTGYT HGMHTLAFMA AESLLVTVRT AHVILRYVIH LWDLNHEGTW 250
    EGKGTYVYYT DFVMELALLS LDLMHHIHML LFGNIWLSMA SLVIFMQLRY 300
    LFHEVQRRIR RHKNYLRVVG NMEARFAVAT PEELAVNNDD CAICWDSMQA 350
    ARKLPCGHLF HNSCLRSWLE QDTSCPTCRM SLNIADGSRA REDHQGENLD 400
    ENLVPVAAAE GRPRLNQHNH FFHFDGSRIA SWLPSFSVEV MHTTNILGIT 450
    QASNSQLNAM AHQIQEMFPQ VPYHLVLQDL QMTRSVEITT DNILEGRIQV 500
    PFPTQRSDSL RPALNSPVER PSPDLEEGEA SVQTERVPLD LSPRLEETLD 550
    FSEVELEPIE VEDFEARGSR FSKSADERQR MLVQRKDDLL QQARKRFLNK 600
    SSEDDGASER LLPSEGTSSD PVTLRRRMLA AAAERRLQRQ RTT 643
    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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti412 – 4121R → S in AAD56721. (PubMed:10456327)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei57 – 604Missing in isoform 2. 1 PublicationVSP_008224

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF124144 mRNA. Translation: AAD56721.1 .
    BC003256 mRNA. Translation: AAH03256.1 .
    BC034538 mRNA. Translation: AAH34538.1 .
    BC040338 mRNA. Translation: AAH40338.1 .
    CCDSi CCDS22533.1. [Q9R049-2 ]
    RefSeqi NP_035917.2. NM_011787.2. [Q9R049-2 ]
    UniGenei Mm.34641.
    Mm.490433.

    3D structure databases

    ProteinModelPortali Q9R049.
    SMRi Q9R049. Positions 327-384, 453-504, 574-599.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204722. 3 interactions.
    IntActi Q9R049. 7 interactions.
    MINTi MINT-1864613.
    STRINGi 10090.ENSMUSP00000052258.

    PTM databases

    PhosphoSitei Q9R049.

    Proteomic databases

    PaxDbi Q9R049.
    PRIDEi Q9R049.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000053766 ; ENSMUSP00000052258 ; ENSMUSG00000031751 . [Q9R049-2 ]
    GeneIDi 23802.
    KEGGi mmu:23802.

    Organism-specific databases

    CTDi 267.
    MGIi MGI:1345634. Amfr.

    Phylogenomic databases

    eggNOGi COG5243.
    GeneTreei ENSGT00530000062938.
    HOGENOMi HOG000037436.
    HOVERGENi HBG044694.
    InParanoidi Q9R049.
    KOi K10636.
    OMAi NTACCFL.
    OrthoDBi EOG7QRQT8.
    PhylomeDBi Q9R049.
    TreeFami TF320052.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .

    Miscellaneous databases

    ChiTaRSi AMFR. mouse.
    NextBioi 303423.
    PROi Q9R049.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9R049.
    Bgeei Q9R049.
    CleanExi MM_AMFR.
    Genevestigatori Q9R049.

    Family and domain databases

    Gene3Di 3.30.40.10. 1 hit.
    InterProi IPR003892. CUE.
    IPR001841. Znf_RING.
    IPR013083. Znf_RING/FYVE/PHD.
    [Graphical view ]
    Pfami PF02845. CUE. 1 hit.
    PF13639. zf-RING_2. 1 hit.
    [Graphical view ]
    SMARTi SM00546. CUE. 1 hit.
    SM00184. RING. 1 hit.
    [Graphical view ]
    PROSITEi PS51140. CUE. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: Lung1 Publication and Testis1 Publication.
    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/N1 Publication.
      Tissue: Colon1 Publication and Mammary gland1 Publication.
    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].

    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: October 1, 2014
    This is version 110 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

    External Data

    Dasty 3