E3 ubiquitin-protein ligase AMFR (EC 2.3.2.36) (Autocrine motility factor receptor) (AMF receptor) (RING finger protein 45) (gp78)
1_MPLLF 6_ LERFP 11_ WPSLR 16_ TYTGL 21_ SGLAL 26_ LGTII 31_ SAYRA 36_ LSQPE 41_ AGPGE 46_ PDQLT 51_ ASLQP 56_ EPPAP 61_ ARPSA 66_ GGPRA 71_ RDVAQ 76_ YLLSD 81_ SLFVW 86_ VLVNT 91_ ACCVL 96_ MLVAK 101_ LIQCI 106_ VFGPL 111_ RVSER 116_ QHLKD 121_ KFWNF 126_ IFYKF 131_ IFIFG 136_ VLNVQ 141_ TVEEV 146_ VMWCL 151_ WFAGL 156_ VFLHL 161_ MVQLC 166_ KDRFE 171_ YLSFS 176_ PTTPM 181_ SSHGR 186_ VLSLL 191_ VAMLL 196_ SCCGL 201_ AAVCS 206_ ITGYT 211_ HGMHT 216_ LAFMA 221_ AESLL 226_ VTVRT 231_ AHVIL 236_ RYVIH 241_ LWDLN 246_ HEGTW 251_ EGKGT 256_ YVYYT 261_ DFVME 266_ LTLLS 271_ LDLMH 276_ HIHML 281_ LFGNI 286_ WLSMA 291_ SLVIF 296_ MQLRY 301_ LFHEV 306_ QRRIR 311_ RHKNY 316_ LRVVG 321_ NMEAR 326_ FAVAT 331_ PEELA 336_ VNNDD 341_ CAICW 346_ DSMQA 351_ ARKLP 356_ CGHLF 361_ HNSCL 366_ RSWLE 371_ QDTSC 376_ PTCRM 381_ SLNIA 386_ DNNRV 391_ REEHQ 396_ GENLD 401_ ENLVP 406_ VAAAE 411_ GRPRL 416_ NQHNH 421_ FFHFD 426_ GSRIA 431_ SWLPS 436_ FSVEV 441_ MHTTN 446_ ILGIT 451_ QASNS 456_ QLNAM 461_ AHQIQ 466_ EMFPQ 471_ VPYHL 476_ VLQDL 481_ QLTRS 486_ VEITT 491_ DNILE 496_ GRIQV 501_ PFPTQ 506_ RSDSI 511_ RPALN 516_ SPVER 521_ PSSDQ 526_ EEGET 531_ SAQTE 536_ RVPLD 541_ LSPRL 546_ EETLD 551_ FGEVE 556_ VEPSE 561_ VEDFE 566_ ARGSR 571_ FSKSA 576_ DERQR 581_ MLVQR 586_ KDELL 591_ QQARK 596_ RFLNK 601_ SSEDD 606_ AASES 611_ FLPSE 616_ GASSD 621_ PVTLR 626_ RRMLA 631_ AAAER 636_RLQKQ
1: 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)