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Protein

E3 ubiquitin-protein ligase AMFR

Gene

AMFR

Organism
Homo sapiens (Human)
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 as a receptor for the GPI/autocrine motility factor.4 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.2 Publications

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

  • BAT3 complex binding Source: ParkinsonsUK-UCL
  • chaperone binding Source: ParkinsonsUK-UCL
  • protein binding, bridging Source: ParkinsonsUK-UCL
  • receptor activity Source: UniProtKB
  • ubiquitin protein ligase activity Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase activity involved in ERAD pathway Source: ParkinsonsUK-UCL
  • ubiquitin-protein transferase activity Source: UniProtKB
  • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL
  • ubiquitin-ubiquitin ligase activity Source: ParkinsonsUK-UCL
  • zinc ion binding Source: InterPro

GO - Biological processi

  • aging Source: Ensembl
  • endoplasmic reticulum unfolded protein response Source: UniProtKB
  • ERAD pathway Source: ParkinsonsUK-UCL
  • ER-associated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • learning or memory Source: Ensembl
  • movement of cell or subcellular component Source: ProtInc
  • positive regulation of protein binding Source: ParkinsonsUK-UCL
  • protein autoubiquitination Source: ParkinsonsUK-UCL
  • protein K48-linked ubiquitination Source: ParkinsonsUK-UCL
  • protein oligomerization Source: UniProtKB
  • protein polyubiquitination Source: UniProtKB
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
  • signal transduction Source: ProtInc
  • ubiquitin-dependent protein catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Receptor, Transferase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi2.3.2.B10. 2681.
ReactomeiR-HSA-532668. N-glycan trimming in the ER and Calnexin/Calreticulin cycle.
R-HSA-901032. ER Quality Control Compartment (ERQC).
SIGNORiQ9UKV5.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase AMFR (EC:2.3.2.272 Publications)
Alternative name(s):
Autocrine motility factor receptor
Short name:
AMF receptor
RING finger protein 45
RING-type E3 ubiquitin transferase AMFRCurated
gp78
Gene namesi
Name:AMFR
Synonyms:RNF45
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:463. AMFR.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei82 – 102HelicalSequence analysisAdd BLAST21
Transmembranei122 – 142HelicalSequence analysisAdd BLAST21
Transmembranei145 – 165HelicalSequence analysisAdd BLAST21
Transmembranei186 – 206HelicalSequence analysisAdd BLAST21
Transmembranei215 – 235HelicalSequence analysisAdd BLAST21
Transmembranei276 – 296HelicalSequence analysisAdd BLAST21
Transmembranei429 – 449HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

  • dendrite Source: Ensembl
  • Derlin-1 retrotranslocation complex Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB
  • growth cone Source: Ensembl
  • Hrd1p ubiquitin ligase ERAD-M complex Source: GO_Central
  • integral component of endoplasmic reticulum membrane Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • neuronal cell body Source: Ensembl
  • nucleus Source: Ensembl
  • perinuclear region of cytoplasm Source: ParkinsonsUK-UCL
  • protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi356C → G: No degradation of HMGCR. 1 Publication1

Organism-specific databases

DisGeNETi267.
OpenTargetsiENSG00000159461.
PharmGKBiPA24768.

Polymorphism and mutation databases

BioMutaiAMFR.
DMDMi34922250.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000645791 – 643E3 ubiquitin-protein ligase AMFRAdd BLAST643

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei516PhosphoserineCombined sources1
Modified residuei523PhosphoserineCombined sources1
Modified residuei542PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UKV5.
MaxQBiQ9UKV5.
PaxDbiQ9UKV5.
PeptideAtlasiQ9UKV5.
PRIDEiQ9UKV5.

PTM databases

iPTMnetiQ9UKV5.
PhosphoSitePlusiQ9UKV5.

Expressioni

Gene expression databases

BgeeiENSG00000159461.
CleanExiHS_AMFR.
ExpressionAtlasiQ9UKV5. baseline and differential.
GenevisibleiQ9UKV5. HS.

Organism-specific databases

HPAiCAB026381.
HPA029018.

Interactioni

Subunit structurei

Interacts with RNF5. Also forms an ERAD complex containing VCP/p97, NGLY1; PSMC1; SAKS1 AND RAD23B required for coupling retrotranslocation, ubiquitination and deglycosylation (By similarity). Interacts with DRL1. Interacts (through a region distinct from the RING finger) with UBE2G2/UBC7. 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 (via its membrane domain) with INSIG1; the interaction initiates the sterol-mediated ubiquitination and degradation of HMGCR by the ERAD pathway.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ERLIN2O949058EBI-1046367,EBI-4400770
INSIG1O155032EBI-1046367,EBI-6252425
UBE2G2P6060418EBI-1046367,EBI-1051028
VCPP550728EBI-1046367,EBI-355164

GO - Molecular functioni

  • BAT3 complex binding Source: ParkinsonsUK-UCL
  • chaperone binding Source: ParkinsonsUK-UCL
  • protein binding, bridging Source: ParkinsonsUK-UCL
  • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi106764. 121 interactors.
DIPiDIP-29060N.
IntActiQ9UKV5. 25 interactors.
MINTiMINT-2821880.
STRINGi9606.ENSP00000290649.

Structurei

Secondary structure

1643
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi332 – 337Combined sources6
Beta strandi342 – 344Combined sources3
Beta strandi351 – 353Combined sources3
Beta strandi355 – 357Combined sources3
Beta strandi359 – 361Combined sources3
Helixi362 – 369Combined sources8
Beta strandi376 – 378Combined sources3
Helixi456 – 467Combined sources12
Helixi473 – 483Combined sources11
Helixi486 – 494Combined sources9
Helixi575 – 599Combined sources25
Helixi625 – 637Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EJSNMR-A452-502[»]
2LVNNMR-C453-504[»]
2LVONMR-C453-504[»]
2LVPNMR-C453-504[»]
2LVQNMR-D453-504[»]
2LXHNMR-C313-393[»]
2LXPNMR-B574-600[»]
C327-384[»]
3FSHX-ray2.76C574-601[»]
3H8KX-ray1.80B573-600[»]
3TIWX-ray1.80C/D622-640[»]
4G3OX-ray1.60A456-498[»]
4LADX-ray2.30B313-393[»]
B574-600[»]
ProteinModelPortaliQ9UKV5.
SMRiQ9UKV5.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UKV5.

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)1 PublicationAdd BLAST19

Domaini

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.
HOGENOMiHOG000172151.
HOVERGENiHBG044694.
InParanoidiQ9UKV5.
KOiK10636.
OMAiGTWESKG.
OrthoDBiEOG091G06NX.
PhylomeDBiQ9UKV5.
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]

Sequencei

Sequence statusi: Complete.

Q9UKV5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPLLFLERFP WPSLRTYTGL SGLALLGTII SAYRALSQPE AGPGEPDQLT
60 70 80 90 100
ASLQPEPPAP ARPSAGGPRA RDVAQYLLSD SLFVWVLVNT ACCVLMLVAK
110 120 130 140 150
LIQCIVFGPL RVSERQHLKD KFWNFIFYKF IFIFGVLNVQ TVEEVVMWCL
160 170 180 190 200
WFAGLVFLHL MVQLCKDRFE YLSFSPTTPM SSHGRVLSLL VAMLLSCCGL
210 220 230 240 250
AAVCSITGYT HGMHTLAFMA AESLLVTVRT AHVILRYVIH LWDLNHEGTW
260 270 280 290 300
EGKGTYVYYT DFVMELTLLS LDLMHHIHML LFGNIWLSMA SLVIFMQLRY
310 320 330 340 350
LFHEVQRRIR RHKNYLRVVG NMEARFAVAT PEELAVNNDD CAICWDSMQA
360 370 380 390 400
ARKLPCGHLF HNSCLRSWLE QDTSCPTCRM SLNIADNNRV REEHQGENLD
410 420 430 440 450
ENLVPVAAAE GRPRLNQHNH FFHFDGSRIA SWLPSFSVEV MHTTNILGIT
460 470 480 490 500
QASNSQLNAM AHQIQEMFPQ VPYHLVLQDL QLTRSVEITT DNILEGRIQV
510 520 530 540 550
PFPTQRSDSI RPALNSPVER PSSDQEEGET SAQTERVPLD LSPRLEETLD
560 570 580 590 600
FGEVEVEPSE VEDFEARGSR FSKSADERQR MLVQRKDELL QQARKRFLNK
610 620 630 640
SSEDDAASES FLPSEGASSD PVTLRRRMLA AAAERRLQKQ QTS
Length:643
Mass (Da):72,996
Last modified:June 1, 2003 - v2
Checksum:i8782324609C0E62A
GO

Sequence cautioni

The sequence AAA36671 differs from that shown. Several sequencing errors.Curated
The sequence AAA79362 differs from that shown. Reason: Frameshift at positions 355, 388, 411, 487, 537, 583 and 632.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti406V → D in AAA79362 (PubMed:7626106).Curated1
Sequence conflicti491D → V in AAA79362 (PubMed:7626106).Curated1
Sequence conflicti500V → L in AAA79362 (PubMed:7626106).Curated1
Sequence conflicti614S → L in AAD56722 (PubMed:10456327).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035790605D → V in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs373191257dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF124145 mRNA. Translation: AAD56722.1.
BC069197 mRNA. Translation: AAH69197.1.
L35233 mRNA. Translation: AAA79362.1. Frameshift.
M63175 mRNA. Translation: AAA36671.1. Sequence problems.
CCDSiCCDS10758.1.
PIRiA39877.
RefSeqiNP_001135.3. NM_001144.5.
NP_001310441.1. NM_001323512.1.
UniGeneiHs.295137.

Genome annotation databases

EnsembliENST00000290649; ENSP00000290649; ENSG00000159461.
GeneIDi267.
KEGGihsa:267.
UCSCiuc002eiy.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF124145 mRNA. Translation: AAD56722.1.
BC069197 mRNA. Translation: AAH69197.1.
L35233 mRNA. Translation: AAA79362.1. Frameshift.
M63175 mRNA. Translation: AAA36671.1. Sequence problems.
CCDSiCCDS10758.1.
PIRiA39877.
RefSeqiNP_001135.3. NM_001144.5.
NP_001310441.1. NM_001323512.1.
UniGeneiHs.295137.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EJSNMR-A452-502[»]
2LVNNMR-C453-504[»]
2LVONMR-C453-504[»]
2LVPNMR-C453-504[»]
2LVQNMR-D453-504[»]
2LXHNMR-C313-393[»]
2LXPNMR-B574-600[»]
C327-384[»]
3FSHX-ray2.76C574-601[»]
3H8KX-ray1.80B573-600[»]
3TIWX-ray1.80C/D622-640[»]
4G3OX-ray1.60A456-498[»]
4LADX-ray2.30B313-393[»]
B574-600[»]
ProteinModelPortaliQ9UKV5.
SMRiQ9UKV5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106764. 121 interactors.
DIPiDIP-29060N.
IntActiQ9UKV5. 25 interactors.
MINTiMINT-2821880.
STRINGi9606.ENSP00000290649.

PTM databases

iPTMnetiQ9UKV5.
PhosphoSitePlusiQ9UKV5.

Polymorphism and mutation databases

BioMutaiAMFR.
DMDMi34922250.

Proteomic databases

EPDiQ9UKV5.
MaxQBiQ9UKV5.
PaxDbiQ9UKV5.
PeptideAtlasiQ9UKV5.
PRIDEiQ9UKV5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000290649; ENSP00000290649; ENSG00000159461.
GeneIDi267.
KEGGihsa:267.
UCSCiuc002eiy.4. human.

Organism-specific databases

CTDi267.
DisGeNETi267.
GeneCardsiAMFR.
HGNCiHGNC:463. AMFR.
HPAiCAB026381.
HPA029018.
MIMi603243. gene.
neXtProtiNX_Q9UKV5.
OpenTargetsiENSG00000159461.
PharmGKBiPA24768.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0802. Eukaryota.
COG5243. LUCA.
GeneTreeiENSGT00530000062938.
HOGENOMiHOG000172151.
HOVERGENiHBG044694.
InParanoidiQ9UKV5.
KOiK10636.
OMAiGTWESKG.
OrthoDBiEOG091G06NX.
PhylomeDBiQ9UKV5.
TreeFamiTF320052.

Enzyme and pathway databases

UniPathwayiUPA00143.
BRENDAi2.3.2.B10. 2681.
ReactomeiR-HSA-532668. N-glycan trimming in the ER and Calnexin/Calreticulin cycle.
R-HSA-901032. ER Quality Control Compartment (ERQC).
SIGNORiQ9UKV5.

Miscellaneous databases

ChiTaRSiAMFR. human.
EvolutionaryTraceiQ9UKV5.
GeneWikiiAMFR.
GenomeRNAii267.
PROiQ9UKV5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000159461.
CleanExiHS_AMFR.
ExpressionAtlasiQ9UKV5. baseline and differential.
GenevisibleiQ9UKV5. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q9UKV5
Secondary accession number(s): P26442, Q8IZ70
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: June 1, 2003
Last modified: November 30, 2016
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.