AMFR
entrez
267
canonical
uniprot
Q9UKV5
canonical
ensembl
ENSG00000159461
resolver
ensp
ENSP00000290649
resolver
enst
ENST00000290649
resolver
genesymbol
AMFR
resolver
genesymbol_syn
RNF45
resolver
hgnc
HGNC:463
resolver
uniprot
P26442
resolver
uniprot
Q8IZ70
resolver
uniprot_entry
AMFR_HUMAN
resolver
uniprot_sec
P26442
resolver
uniprot_sec
Q8IZ70
resolver
amino_acid_sequence
MPLLFLERFPWPSLRTYTGLSGLALLGTIISAYRALSQPEAGPGEPDQLTASLQPEPPAPARPSAGGPRARDVAQYLLSDSLFVWVLVNTACCVLMLVAKLIQCIVFGPLRVSERQHLKDKFWNFIFYKFIFIFGVLNVQTVEEVVMWCLWFAGLVFLHLMVQLCKDRFEYLSFSPTTPMSSHGRVLSLLVAMLLSCCGLAAVCSITGYTHGMHTLAFMAAESLLVTVRTAHVILRYVIHLWDLNHEGTWEGKGTYVYYTDFVMELTLLSLDLMHHIHMLLFGNIWLSMASLVIFMQLRYLFHEVQRRIRRHKNYLRVVGNMEARFAVATPEELAVNNDDCAICWDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSLNIADNNRVREEHQGENLDENLVPVAAAEGRPRLNQHNHFFHFDGSRIASWLPSFSVEVMHTTNILGITQASNSQLNAMAHQIQEMFPQVPYHLVLQDLQLTRSVEITTDNILEGRIQVPFPTQRSDSIRPALNSPVERPSSDQEEGETSAQTERVPLDLSPRLEETLDFGEVEVEPSEVEDFEARGSRFSKSADERQRMLVQRKDELLQQARKRFLNKSSEDDAASESFLPSEGASSDPVTLRRRMLAAAAERRLQKQQTS
uniprot
proteins
disease_involvement
DISEASE: Spastic paraplegia 89, autosomal recessive (SPG89) [MIM:620379]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or weakness and stiffness may spread to other parts of the body. SPG89 affected individuals show delayed motor development, abnormal spastic gait, and hyperreflexia of the lower limbs. Some patients may have mildly impaired intellectual development or learning difficulties. SPG89 disease onset is in the first years of life. {ECO:0000269|PubMed:37119330}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.3.2.36
uniprot
proteins
function
FUNCTION: E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins, such as CD3D, CYP3A4, CFTR, INSIG1, SOAT2/ACAT2 and APOB for proteasomal degradation (PubMed:10456327, PubMed:11724934, PubMed:12670940, PubMed:19103148, PubMed:24424410, PubMed:28604676). Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of endoplasmic reticulum-associated degradation (ERAD) (PubMed:10456327, PubMed:11724934, PubMed:19103148, PubMed:24424410). The VCP/p97-AMFR/gp78 complex is involved in the sterol-accelerated ERAD degradation of HMGCR through binding to the HMGCR-INSIG1 complex at the ER membrane (PubMed:16168377, PubMed:22143767). In addition, interaction of AMFR with AUP1 facilitates interaction of AMFR with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase RNF139, leading to sterol-induced HMGCR ubiquitination (PubMed:23223569). The ubiquitinated HMGCR is then released from the ER into the cytosol for subsequent destruction (PubMed:16168377, PubMed:22143767, PubMed:23223569). In addition to ubiquitination on lysine residues, catalyzes ubiquitination on cysteine residues: together with INSIG1, mediates polyubiquitination of SOAT2/ACAT2 at 'Cys-277', leading to its degradation when the lipid levels are low (PubMed:28604676). Catalyzes ubiquitination and subsequent degradation of INSIG1 when cells are depleted of sterols (PubMed:17043353). Mediates polyubiquitination of INSIG2 at 'Cys-215' in some tissues, leading to its degradation (PubMed:31953408). Also regulates ERAD through the ubiquitination of UBL4A a component of the BAG6/BAT3 complex (PubMed:21636303). Also acts as a scaffold protein to assemble a complex that couples ubiquitination, retranslocation and deglycosylation (PubMed:21636303). Mediates tumor invasion and metastasis as a receptor for the GPI/autocrine motility factor (PubMed:10456327). In association with LMBR1L and UBAC2, negatively regulates the canonical Wnt signaling pathway in the lymphocytes by promoting the ubiquitin-mediated degradation of CTNNB1 and Wnt receptors FZD6 and LRP6 (PubMed:31073040). Regulates NF-kappa-B and MAPK signaling pathways by mediating 'Lys-27'-linked polyubiquitination of TAB3 and promoting subsequent TAK1/MAP3K7 activation (PubMed:36593296). Required for proper lipid homeostasis (PubMed:37119330). {ECO:0000269|PubMed:10456327, ECO:0000269|PubMed:11724934, ECO:0000269|PubMed:12670940, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:17043353, ECO:0000269|PubMed:19103148, ECO:0000269|PubMed:21636303, ECO:0000269|PubMed:22143767, ECO:0000269|PubMed:23223569, ECO:0000269|PubMed:24424410, ECO:0000269|PubMed:28604676, ECO:0000269|PubMed:31073040, ECO:0000269|PubMed:31953408, ECO:0000269|PubMed:36593296, ECO:0000269|PubMed:37119330}.
uniprot
proteins
mass_dalton
72996
uniprot
proteins
mutagenesis
MUTAGEN 341..344; /note="CAIC->AAIA: Decreased palmitoylation."; /evidence="ECO:0000269|PubMed:22728137"; MUTAGEN 346; /note="D->A: Abolished binding to TAB3."; /evidence="ECO:0000269|PubMed:36593296"; MUTAGEN 356; /note="C->A: Decreased palmitoylation. No degradation of HMGCR."; /evidence="ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:22728137"; MUTAGEN 364; /note="C->A: Decreased palmitoylation."; /evidence="ECO:0000269|PubMed:22728137"; MUTAGEN 375..378; /note="CPTC->APTA: Decreased palmitoylation."; /evidence="ECO:0000269|PubMed:22728137"; MUTAGEN 379; /note="R->A: Abolished binding to TAB3."; /evidence="ECO:0000269|PubMed:36593296
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:11724934, ECO:0000269|PubMed:16168377}.
uniprot
proteins
post_translational_modification
PTM: Palmitoylation of the RING-type zing finger by ZDHHC6 promotes localization to the peripheral endoplasmic reticulum. {ECO:0000269|PubMed:22728137}.
uniprot
proteins
pubmed
10456327
uniprot
proteins
pubmed
11724934
uniprot
proteins
pubmed
12670940
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16168377
uniprot
proteins
pubmed
16186510
uniprot
proteins
pubmed
1649192
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17043353
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19103148
uniprot
proteins
pubmed
21636303
uniprot
proteins
pubmed
21914798
uniprot
proteins
pubmed
22143767
uniprot
proteins
pubmed
22728137
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23223569
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24424410
uniprot
proteins
pubmed
28604676
uniprot
proteins
pubmed
29184177
uniprot
proteins
pubmed
29275994
uniprot
proteins
pubmed
31073040
uniprot
proteins
pubmed
31953408
uniprot
proteins
pubmed
36593296
uniprot
proteins
pubmed
37119330
uniprot
proteins
pubmed
7626106
uniprot
proteins
sequence_length
643
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:11724934, ECO:0000269|PubMed:22728137, ECO:0000269|PubMed:36593296}; Multi-pass membrane protein {ECO:0000269|PubMed:11724934}. Note=Palmitoylation promotes localization to the peripheral endoplasmic reticulum. {ECO:0000269|PubMed:22728137}.
uniprot
proteins
transmembrane_region
TRANSMEM 82..102; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 122..142; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 145..165; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 186..206; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 215..235; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 276..296; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 429..449; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins