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Protein

E3 ubiquitin-protein ligase AMFR

Gene

AMFR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 regulates ERAD through the ubiquitination of UBL4A a component of the BAG6/BAT3 complex. 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.5 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-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
  • identical protein binding Source: IntAct
  • metal ion binding Source: UniProtKB-KW
  • protein binding, bridging Source: ParkinsonsUK-UCL
  • signaling receptor activity Source: UniProtKB
  • ubiquitin protein ligase activity Source: ParkinsonsUK-UCL
  • ubiquitin-protein transferase activity Source: UniProtKB
  • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL
  • ubiquitin-ubiquitin ligase activity Source: ParkinsonsUK-UCL

GO - Biological processi

  • aging Source: Ensembl
  • endoplasmic reticulum mannose trimming Source: Reactome
  • endoplasmic reticulum unfolded protein response Source: UniProtKB
  • learning or memory Source: Ensembl
  • positive regulation of protein binding Source: ParkinsonsUK-UCL
  • protein autoubiquitination Source: ParkinsonsUK-UCL
  • protein complex oligomerization Source: UniProtKB
  • protein folding Source: Reactome
  • protein K48-linked ubiquitination Source: ParkinsonsUK-UCL
  • protein polyubiquitination Source: UniProtKB
  • signal transduction Source: ProtInc
  • ubiquitin-dependent ERAD pathway Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: UniProtKB

Keywordsi

Molecular functionReceptor, Transferase
Biological processUbl conjugation pathway
LigandMetal-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

EuPathDBiHostDB:ENSG00000159461.14
HGNCiHGNC:463 AMFR
MIMi603243 gene
neXtProtiNX_Q9UKV5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi341 – 344CAIC → AAIA: Decreased palmitoylation. 1 Publication4
Mutagenesisi356C → A: Decreased palmitoylation. No degradation of HMGCR. 2 Publications1
Mutagenesisi364C → A: Decreased palmitoylation. 1 Publication1
Mutagenesisi375 – 378CPTC → APTA: Decreased palmitoylation. 1 Publication4

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

Post-translational modificationi

Palmitoylation of the RING-type zing finger by ZDHHC6 promotes localization to the peripheral endoplasmic reticulum.1 Publication

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiQ9UKV5
MaxQBiQ9UKV5
PaxDbiQ9UKV5
PeptideAtlasiQ9UKV5
PRIDEiQ9UKV5

PTM databases

iPTMnetiQ9UKV5
PhosphoSitePlusiQ9UKV5
SwissPalmiQ9UKV5

Expressioni

Gene expression databases

BgeeiENSG00000159461
CleanExiHS_AMFR
ExpressionAtlasiQ9UKV5 baseline and differential
GenevisibleiQ9UKV5 HS

Organism-specific databases

HPAiCAB026381
HPA029018
HPA077835

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. Interacts with BAG6 (PubMed:21636303). Interacts with USP13 (via UBA 2 domain); the interaction is direct (PubMed:24424410).By similarity6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • chaperone binding Source: ParkinsonsUK-UCL
  • identical protein binding Source: IntAct
  • protein binding, bridging Source: ParkinsonsUK-UCL
  • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi106764, 125 interactors
CORUMiQ9UKV5
DIPiDIP-29060N
IntActiQ9UKV5, 32 interactors
MINTiQ9UKV5
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.

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
OMAiVVMWCLW
OrthoDBiEOG091G06NX
PhylomeDBiQ9UKV5
TreeFamiTF320052

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR003892 CUE
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF02845 CUE, 1 hit
PF13639 zf-RING_2, 1 hit
SMARTiView protein in SMART
SM00546 CUE, 1 hit
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS51140 CUE, 1 hit
PS50089 ZF_RING_2, 1 hit

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 dbSNP:rs373191257Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiAMFR_HUMAN
AccessioniPrimary (citable) accession number: Q9UKV5
Secondary accession number(s): P26442, Q8IZ70
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: June 1, 2003
Last modified: May 23, 2018
This is version 162 of the entry and version 2 of the sequence. See 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

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