AMFR_HUMAN
ID AMFR_HUMAN Reviewed; 643 AA.
AC Q9UKV5; P26442; Q8IZ70;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=E3 ubiquitin-protein ligase AMFR;
DE EC=2.3.2.36 {ECO:0000269|PubMed:28604676, ECO:0000269|PubMed:31953408};
DE AltName: Full=Autocrine motility factor receptor {ECO:0000303|PubMed:10456327};
DE Short=AMF receptor {ECO:0000303|PubMed:10456327};
DE AltName: Full=RING finger protein 45;
DE AltName: Full=gp78 {ECO:0000303|PubMed:11724934};
GN Name=AMFR {ECO:0000303|PubMed:10456327, ECO:0000312|HGNC:HGNC:463};
GN Synonyms=RNF45 {ECO:0000312|HGNC:HGNC:463};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000312|EMBL:AAD56722.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=10456327; DOI=10.1016/s0014-5793(99)00966-7;
RA Shimizu K., Tani M., Watanabe H., Nagamachi Y., Niinaka Y., Shiroishi T.,
RA Ohwada S., Raz A., Yokota J.;
RT "The autocrine motility factor receptor gene encodes a novel type of seven
RT transmembrane protein.";
RL FEBS Lett. 456:295-300(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 358-643.
RC TISSUE=Placenta;
RX PubMed=7626106; DOI=10.1006/bbrc.1995.2031;
RA Huang B., Xie Y., Raz A.;
RT "Identification of an upstream region that controls the transcription of
RT the human autocrine motility factor receptor.";
RL Biochem. Biophys. Res. Commun. 212:727-742(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 520-643.
RX PubMed=1649192; DOI=10.1016/s0021-9258(18)98859-9;
RA Watanabe H., Carmi P., Hogan V., Raz T., Silletti S., Nabi I.R., Raz A.;
RT "Purification of human tumor cell autocrine motility factor and molecular
RT cloning of its receptor.";
RL J. Biol. Chem. 266:13442-13448(1991).
RN [5]
RP FUNCTION AS A UBIQUITIN LIGASE, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP UBE2G2.
RX PubMed=11724934; DOI=10.1073/pnas.251401598;
RA Fang S., Ferrone M., Yang C., Jensen J.P., Tiwari S., Weissman A.M.;
RT "The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein
RT ligase implicated in degradation from the endoplasmic reticulum.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:14422-14427(2001).
RN [6]
RP FUNCTION IN UBIQUITINATION OF APOB.
RX PubMed=12670940; DOI=10.1074/jbc.m302683200;
RA Liang J.S., Kim T., Fang S., Yamaguchi J., Weissman A.M., Fisher E.A.,
RA Ginsberg H.N.;
RT "Overexpression of the tumor autocrine motility factor receptor, gp78, a
RT ubiquitin protein ligase (E3), results in increased ubiquitinylation and
RT decreased secretion of apolipoprotein B100 in Hep G2 cells.";
RL J. Biol. Chem. 278:23984-23988(2003).
RN [7]
RP INTERACTION WITH INSIG1 AND VCP, FUNCTION, AND MUTAGENESIS OF CYS-356.
RX PubMed=16168377; DOI=10.1016/j.molcel.2005.08.009;
RA Song B.L., Sever N., DeBose-Boyd R.A.;
RT "Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and
RT couples sterol-regulated ubiquitination to degradation of HMG CoA
RT reductase.";
RL Mol. Cell 19:829-840(2005).
RN [8]
RP INTERACTION WITH DERL1 AND VCP.
RX PubMed=16186510; DOI=10.1073/pnas.0505006102;
RA Ye Y., Shibata Y., Kikkert M., van Voorden S., Wiertz E., Rapoport T.A.;
RT "Recruitment of the p97 ATPase and ubiquitin ligases to the site of
RT retrotranslocation at the endoplasmic reticulum membrane.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:14132-14138(2005).
RN [9]
RP FUNCTION.
RX PubMed=17043353; DOI=10.1074/jbc.m608999200;
RA Lee J.N., Song B., DeBose-Boyd R.A., Ye J.;
RT "Sterol-regulated degradation of Insig-1 mediated by the membrane-bound
RT ubiquitin ligase gp78.";
RL J. Biol. Chem. 281:39308-39315(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-516, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP FUNCTION.
RX PubMed=19103148; DOI=10.1016/j.abb.2008.12.001;
RA Pabarcus M.K., Hoe N., Sadeghi S., Patterson C., Wiertz E., Correia M.A.;
RT "CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor
RT receptor, AMFR) and CHIP E3 ligases.";
RL Arch. Biochem. Biophys. 483:66-74(2009).
RN [12]
RP FUNCTION, AND INTERACTION WITH BAG6.
RX PubMed=21636303; DOI=10.1016/j.molcel.2011.05.010;
RA Wang Q., Liu Y., Soetandyo N., Baek K., Hegde R., Ye Y.;
RT "A ubiquitin ligase-associated chaperone holdase maintains polypeptides in
RT soluble states for proteasome degradation.";
RL Mol. Cell 42:758-770(2011).
RN [13]
RP FUNCTION, AND INTERACTION WITH INSIG1.
RX PubMed=22143767; DOI=10.1073/pnas.1112831108;
RA Jo Y., Lee P.C., Sguigna P.V., DeBose-Boyd R.A.;
RT "Sterol-induced degradation of HMG CoA reductase depends on interplay of
RT two Insigs and two ubiquitin ligases, gp78 and Trc8.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:20503-20508(2011).
RN [14]
RP SUBCELLULAR LOCATION, PALMITOYLATION, AND MUTAGENESIS OF 341-CYS--CYS-344;
RP CYS-356; CYS-364 AND 375-CYS--CYS-378.
RX PubMed=22728137; DOI=10.1016/j.febslet.2012.06.011;
RA Fairbank M., Huang K., El-Husseini A., Nabi I.R.;
RT "RING finger palmitoylation of the endoplasmic reticulum Gp78 E3 ubiquitin
RT ligase.";
RL FEBS Lett. 586:2488-2493(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-542, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP FUNCTION, AND INTERACTION WITH AUP1; RNF139 AND UBE2G2.
RX PubMed=23223569; DOI=10.1091/mbc.e12-07-0564;
RA Jo Y., Hartman I.Z., DeBose-Boyd R.A.;
RT "Ancient ubiquitous protein-1 mediates sterol-induced ubiquitination of 3-
RT hydroxy-3-methylglutaryl CoA reductase in lipid droplet-associated
RT endoplasmic reticulum membranes.";
RL Mol. Biol. Cell 24:169-183(2013).
RN [17]
RP FUNCTION, AND INTERACTION WITH USP13.
RX PubMed=24424410; DOI=10.7554/elife.01369;
RA Liu Y., Soetandyo N., Lee J.G., Liu L., Xu Y., Clemons W.M. Jr., Ye Y.;
RT "USP13 antagonizes gp78 to maintain functionality of a chaperone in ER-
RT associated degradation.";
RL Elife 3:E01369-E01369(2014).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-523, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP INTERACTION WITH C18ORF32.
RX PubMed=29275994; DOI=10.1016/j.devcel.2017.11.020;
RA Bersuker K., Peterson C.W.H., To M., Sahl S.J., Savikhin V., Grossman E.A.,
RA Nomura D.K., Olzmann J.A.;
RT "A Proximity Labeling Strategy Provides Insights into the Composition and
RT Dynamics of Lipid Droplet Proteomes.";
RL Dev. Cell 44:97-112(2018).
RN [20]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=28604676; DOI=10.1038/ncb3551;
RA Wang Y.J., Bian Y., Luo J., Lu M., Xiong Y., Guo S.Y., Yin H.Y., Lin X.,
RA Li Q., Chang C.C.Y., Chang T.Y., Li B.L., Song B.L.;
RT "Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2
RT through competitive oxidation.";
RL Nat. Cell Biol. 19:808-819(2017).
RN [21]
RP ERRATUM OF PUBMED:28604676.
RX PubMed=29184177; DOI=10.1038/ncb3651;
RA Wang Y.J., Bian Y., Luo J., Lu M., Xiong Y., Guo S.Y., Yong H., Lin X.,
RA Li Q., Chang C.C.Y., Chang T.Y., Li B.L., Song B.L.;
RT "Corrigendum: Cholesterol and fatty acids regulate cysteine ubiquitylation
RT of ACAT2 through competitive oxidation.";
RL Nat. Cell Biol. 19:1441-1441(2017).
RN [22]
RP FUNCTION, AND INTERACTION WITH LMBR1L.
RX PubMed=31073040; DOI=10.1126/science.aau0812;
RA Choi J.H., Zhong X., McAlpine W., Liao T.C., Zhang D., Fang B., Russell J.,
RA Ludwig S., Nair-Gill E., Zhang Z., Wang K.W., Misawa T., Zhan X., Choi M.,
RA Wang T., Li X., Tang M., Sun Q., Yu L., Murray A.R., Moresco E.M.Y.,
RA Beutler B.;
RT "LMBR1L regulates lymphopoiesis through Wnt/beta-catenin signaling.";
RL Science 364:0-0(2019).
RN [23]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31953408; DOI=10.1038/s41467-019-14231-w;
RA Zhou Z.S., Li M.X., Liu J., Jiao H., Xia J.M., Shi X.J., Zhao H., Chu L.,
RA Liu J., Qi W., Luo J., Song B.L.;
RT "Competitive oxidation and ubiquitylation on the evolutionarily conserved
RT cysteine confer tissue-specific stabilization of Insig-2.";
RL Nat. Commun. 11:379-379(2020).
RN [24]
RP STRUCTURE BY NMR OF 452-502.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RSGI RUH-076, a human CUE domain.";
RL Submitted (SEP-2007) to the PDB data bank.
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 622-640 IN COMPLEX WITH VCP, AND
RP VIM MOTIF.
RX PubMed=21914798; DOI=10.1074/jbc.m111.274506;
RA Hanzelmann P., Schindelin H.;
RT "The structural and functional basis of the p97/valosin-containing protein
RT (VCP)-interacting motif (VIM): mutually exclusive binding of cofactors to
RT the N-terminal domain of p97.";
RL J. Biol. Chem. 286:38679-38690(2011).
RN [26]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-605.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates the
CC polyubiquitination of lysine and cysteine residues on target proteins,
CC such as CD3D, CYP3A4, CFTR, INSIG1, SOAT2/ACAT2 and APOB for
CC proteasomal degradation (PubMed:10456327, PubMed:11724934,
CC PubMed:12670940, PubMed:19103148, PubMed:24424410, PubMed:28604676).
CC Component of a VCP/p97-AMFR/gp78 complex that participates in the final
CC step of endoplasmic reticulum-associated degradation (ERAD)
CC (PubMed:10456327, PubMed:11724934, PubMed:19103148, PubMed:24424410).
CC The VCP/p97-AMFR/gp78 complex is involved in the sterol-accelerated
CC ERAD degradation of HMGCR through binding to the HMGCR-INSIG1 complex
CC at the ER membrane (PubMed:16168377, PubMed:22143767). In addition,
CC interaction of AMFR with AUP1 facilitates interaction of AMFR with
CC ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase RNF139,
CC leading to sterol-induced HMGCR ubiquitination (PubMed:23223569). The
CC ubiquitinated HMGCR is then released from the ER into the cytosol for
CC subsequent destruction (PubMed:16168377, PubMed:22143767,
CC PubMed:23223569). In addition to ubiquitination on lysine residues,
CC catalyzes ubiquitination on cysteine residues: together with INSIG1,
CC mediates polyubiquitination of SOAT2/ACAT2 at 'Cys-277', leading to its
CC degradation when the lipid levels are low (PubMed:28604676). Catalyzes
CC ubiquitination and subsequent degradation of INSIG1 when cells are
CC depleted of sterols (PubMed:17043353). Mediates polyubiquitination of
CC INSIG2 at 'Cys-215' in some tissues, leading to its degradation
CC (PubMed:31953408). Also regulates ERAD through the ubiquitination of
CC UBL4A a component of the BAG6/BAT3 complex (PubMed:21636303). Also acts
CC as a scaffold protein to assemble a complex that couples
CC ubiquitination, retranslocation and deglycosylation (PubMed:21636303).
CC Mediates tumor invasion and metastasis as a receptor for the
CC GPI/autocrine motility factor (PubMed:10456327). In association with
CC LMBR1L and UBAC2, negatively regulates the canonical Wnt signaling
CC pathway in the lymphocytes by promoting the ubiquitin-mediated
CC degradation of CTNNB1 and Wnt receptors FZD6 and LRP6
CC (PubMed:31073040). {ECO:0000269|PubMed:10456327,
CC ECO:0000269|PubMed:11724934, ECO:0000269|PubMed:12670940,
CC ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:17043353,
CC ECO:0000269|PubMed:19103148, ECO:0000269|PubMed:21636303,
CC ECO:0000269|PubMed:22143767, ECO:0000269|PubMed:23223569,
CC ECO:0000269|PubMed:24424410, ECO:0000269|PubMed:28604676,
CC ECO:0000269|PubMed:31073040, ECO:0000269|PubMed:31953408}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine +
CC [acceptor protein]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + [acceptor protein]-S-ubiquitinyl-L-cysteine.; EC=2.3.2.36;
CC Evidence={ECO:0000269|PubMed:28604676, ECO:0000269|PubMed:31953408};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:11724934, ECO:0000269|PubMed:16168377}.
CC -!- SUBUNIT: Interacts with RNF5 (By similarity). Also forms an ERAD
CC complex containing VCP/p97, NGLY1; PSMC1; SAKS1 AND RAD23B required for
CC coupling retrotranslocation, ubiquitination and deglycosylation (By
CC similarity). Interacts with DERL1 (PubMed:16186510). Interacts (through
CC a region distinct from the RING finger) with UBE2G2/UBC7
CC (PubMed:11724934). Component of the VCP/p97-AMFR/gp78 complex that
CC enhances VCP/p97 binding to polyubiquitinated proteins for their
CC degradation by the endoplasmic reticulum-associated degradation (ERAD)
CC pathway (By similarity). Interacts (via the VIM) with VCP/p97
CC (PubMed:16168377, PubMed:16186510). Interacts (via its membrane domain)
CC with INSIG1; the interaction initiates the sterol-mediated
CC ubiquitination and degradation of HMGCR by the ERAD pathway
CC (PubMed:16168377, PubMed:22143767). Interacts with AUP1, UBE2G2 and
CC RNF139/TRC8; interaction with AUP1 facilitates interaction of AMFR with
CC ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase RNF139,
CC leading to sterol-induced ubiquitination of HMGCR and its subsequent
CC proteasomal degradation (PubMed:23223569). Interacts with BAG6
CC (PubMed:21636303). Interacts with USP13 (via UBA 2 domain); the
CC interaction is direct (PubMed:24424410). Interacts with LMBR1L
CC (PubMed:31073040). Interacts with UBAC2 and CTNNB1 (By similarity).
CC Interacts with C18orf32 (PubMed:29275994).
CC {ECO:0000250|UniProtKB:Q9R049, ECO:0000269|PubMed:11724934,
CC ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16186510,
CC ECO:0000269|PubMed:21636303, ECO:0000269|PubMed:21914798,
CC ECO:0000269|PubMed:22143767, ECO:0000269|PubMed:23223569,
CC ECO:0000269|PubMed:24424410, ECO:0000269|PubMed:29275994,
CC ECO:0000305|PubMed:31073040}.
CC -!- INTERACTION:
CC Q9UKV5; Q9UKV5: AMFR; NbExp=11; IntAct=EBI-1046367, EBI-1046367;
CC Q9UKV5; O75477: ERLIN1; NbExp=2; IntAct=EBI-1046367, EBI-359299;
CC Q9UKV5; O94905: ERLIN2; NbExp=10; IntAct=EBI-1046367, EBI-4400770;
CC Q9UKV5; O15503: INSIG1; NbExp=2; IntAct=EBI-1046367, EBI-6252425;
CC Q9UKV5; Q9BVT8: TMUB1; NbExp=2; IntAct=EBI-1046367, EBI-11425701;
CC Q9UKV5; P60604: UBE2G2; NbExp=21; IntAct=EBI-1046367, EBI-1051028;
CC Q9UKV5; P55072: VCP; NbExp=12; IntAct=EBI-1046367, EBI-355164;
CC Q9UKV5; P60605: Ube2g2; Xeno; NbExp=10; IntAct=EBI-1046367, EBI-9108745;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11724934, ECO:0000269|PubMed:22728137}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:11724934}. Note=Palmitoylation
CC promotes localization to the peripheral endoplasmic reticulum.
CC {ECO:0000269|PubMed:22728137}.
CC -!- DOMAIN: The CUE domain is required for recognition of misfolded
CC proteins such as mutant CFTR. {ECO:0000250|UniProtKB:Q9R049}.
CC -!- DOMAIN: The VCP/p97-interacting motif (VIM) is sufficient for binding
CC VCP/p97 to form a complex capable of transferring VCP/p97 from the
CC cytosol to microsomes. {ECO:0000269|PubMed:21914798}.
CC -!- PTM: Palmitoylation of the RING-type zing finger by ZDHHC6 promotes
CC localization to the peripheral endoplasmic reticulum.
CC {ECO:0000269|PubMed:22728137}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA36671.1; Type=Miscellaneous discrepancy; Note=Several sequencing errors.; Evidence={ECO:0000305};
CC Sequence=AAA79362.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/AMFRID627ch16q12.html";
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DR EMBL; AF124145; AAD56722.1; -; mRNA.
DR EMBL; BC069197; AAH69197.1; -; mRNA.
DR EMBL; L35233; AAA79362.1; ALT_FRAME; mRNA.
DR EMBL; M63175; AAA36671.1; ALT_SEQ; mRNA.
DR CCDS; CCDS10758.1; -.
DR PIR; A39877; A39877.
DR RefSeq; NP_001135.3; NM_001144.5.
DR RefSeq; NP_001310441.1; NM_001323512.1.
DR PDB; 2EJS; NMR; -; A=452-502.
DR PDB; 2LVN; NMR; -; C=453-504.
DR PDB; 2LVO; NMR; -; C=453-504.
DR PDB; 2LVP; NMR; -; C=453-504.
DR PDB; 2LVQ; NMR; -; D=453-504.
DR PDB; 2LXH; NMR; -; C=313-393.
DR PDB; 2LXP; NMR; -; B=574-600, C=327-384.
DR PDB; 3FSH; X-ray; 2.76 A; C=574-601.
DR PDB; 3H8K; X-ray; 1.80 A; B=573-600.
DR PDB; 3TIW; X-ray; 1.80 A; C/D=622-640.
DR PDB; 4G3O; X-ray; 1.60 A; A=456-498.
DR PDB; 4LAD; X-ray; 2.30 A; B=313-393, B=574-600.
DR PDBsum; 2EJS; -.
DR PDBsum; 2LVN; -.
DR PDBsum; 2LVO; -.
DR PDBsum; 2LVP; -.
DR PDBsum; 2LVQ; -.
DR PDBsum; 2LXH; -.
DR PDBsum; 2LXP; -.
DR PDBsum; 3FSH; -.
DR PDBsum; 3H8K; -.
DR PDBsum; 3TIW; -.
DR PDBsum; 4G3O; -.
DR PDBsum; 4LAD; -.
DR AlphaFoldDB; Q9UKV5; -.
DR BMRB; Q9UKV5; -.
DR SMR; Q9UKV5; -.
DR BioGRID; 106764; 244.
DR CORUM; Q9UKV5; -.
DR DIP; DIP-29060N; -.
DR IntAct; Q9UKV5; 73.
DR MINT; Q9UKV5; -.
DR STRING; 9606.ENSP00000290649; -.
DR TCDB; 8.A.183.1.1; the rela-associated inhibitor (rai) family.
DR iPTMnet; Q9UKV5; -.
DR PhosphoSitePlus; Q9UKV5; -.
DR SwissPalm; Q9UKV5; -.
DR BioMuta; AMFR; -.
DR DMDM; 34922250; -.
DR EPD; Q9UKV5; -.
DR jPOST; Q9UKV5; -.
DR MassIVE; Q9UKV5; -.
DR MaxQB; Q9UKV5; -.
DR PaxDb; Q9UKV5; -.
DR PeptideAtlas; Q9UKV5; -.
DR PRIDE; Q9UKV5; -.
DR ProteomicsDB; 54350; -.
DR ProteomicsDB; 84893; -.
DR Antibodypedia; 14770; 299 antibodies from 31 providers.
DR DNASU; 267; -.
DR Ensembl; ENST00000290649.10; ENSP00000290649.5; ENSG00000159461.15.
DR GeneID; 267; -.
DR KEGG; hsa:267; -.
DR MANE-Select; ENST00000290649.10; ENSP00000290649.5; NM_001144.6; NP_001135.3.
DR UCSC; uc002eiy.4; human.
DR CTD; 267; -.
DR DisGeNET; 267; -.
DR GeneCards; AMFR; -.
DR HGNC; HGNC:463; AMFR.
DR HPA; ENSG00000159461; Low tissue specificity.
DR MIM; 603243; gene.
DR neXtProt; NX_Q9UKV5; -.
DR OpenTargets; ENSG00000159461; -.
DR PharmGKB; PA24768; -.
DR VEuPathDB; HostDB:ENSG00000159461; -.
DR eggNOG; KOG0802; Eukaryota.
DR GeneTree; ENSGT00940000156482; -.
DR HOGENOM; CLU_015061_0_0_1; -.
DR InParanoid; Q9UKV5; -.
DR OMA; WAWFTAL; -.
DR OrthoDB; 897451at2759; -.
DR PhylomeDB; Q9UKV5; -.
DR TreeFam; TF320052; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; Q9UKV5; -.
DR Reactome; R-HSA-532668; N-glycan trimming in the ER and Calnexin/Calreticulin cycle.
DR Reactome; R-HSA-901032; ER Quality Control Compartment (ERQC).
DR SignaLink; Q9UKV5; -.
DR SIGNOR; Q9UKV5; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 267; 30 hits in 1113 CRISPR screens.
DR ChiTaRS; AMFR; human.
DR EvolutionaryTrace; Q9UKV5; -.
DR GeneWiki; AMFR; -.
DR GenomeRNAi; 267; -.
DR Pharos; Q9UKV5; Tbio.
DR PRO; PR:Q9UKV5; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9UKV5; protein.
DR Bgee; ENSG00000159461; Expressed in stromal cell of endometrium and 198 other tissues.
DR ExpressionAtlas; Q9UKV5; baseline and differential.
DR Genevisible; Q9UKV5; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0036513; C:Derlin-1 retrotranslocation complex; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IEA:GOC.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0030426; C:growth cone; IEA:Ensembl.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:1904288; F:BAT3 complex binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051087; F:chaperone binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0038023; F:signaling receptor activity; IPI:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IEA:InterPro.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:1990381; F:ubiquitin-specific protease binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0034450; F:ubiquitin-ubiquitin ligase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:1904380; P:endoplasmic reticulum mannose trimming; TAS:Reactome.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IMP:UniProtKB.
DR GO; GO:0007611; P:learning or memory; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:2000638; P:regulation of SREBP signaling pathway; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 3.30.40.10; -; 1.
DR IDEAL; IID00226; -.
DR InterPro; IPR040675; AMFR_Ube2g2-bd.
DR InterPro; IPR003892; CUE.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF02845; CUE; 1.
DR Pfam; PF18442; G2BR; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00546; CUE; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS51140; CUE; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endoplasmic reticulum; Lipoprotein; Membrane; Metal-binding;
KW Palmitate; Phosphoprotein; Receptor; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix; Ubl conjugation pathway;
KW Wnt signaling pathway; Zinc; Zinc-finger.
FT CHAIN 1..643
FT /note="E3 ubiquitin-protein ligase AMFR"
FT /id="PRO_0000064579"
FT TRANSMEM 82..102
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 145..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 186..206
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 215..235
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 276..296
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 429..449
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 456..498
FT /note="CUE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00468"
FT ZN_FING 341..379
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 39..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 504..579
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 596..624
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 622..640
FT /note="VCP/p97-interacting motif (VIM)"
FT /evidence="ECO:0000269|PubMed:21914798"
FT COMPBIAS 504..521
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 561..579
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 516
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 523
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 542
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 605
FT /note="D -> V (in a breast cancer sample; somatic mutation;
FT dbSNP:rs373191257)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035790"
FT MUTAGEN 341..344
FT /note="CAIC->AAIA: Decreased palmitoylation."
FT /evidence="ECO:0000269|PubMed:22728137"
FT MUTAGEN 356
FT /note="C->A: Decreased palmitoylation. No degradation of
FT HMGCR."
FT /evidence="ECO:0000269|PubMed:16168377,
FT ECO:0000269|PubMed:22728137"
FT MUTAGEN 364
FT /note="C->A: Decreased palmitoylation."
FT /evidence="ECO:0000269|PubMed:22728137"
FT MUTAGEN 375..378
FT /note="CPTC->APTA: Decreased palmitoylation."
FT /evidence="ECO:0000269|PubMed:22728137"
FT CONFLICT 406
FT /note="V -> D (in Ref. 3; AAA79362)"
FT /evidence="ECO:0000305"
FT CONFLICT 491
FT /note="D -> V (in Ref. 3; AAA79362)"
FT /evidence="ECO:0000305"
FT CONFLICT 500
FT /note="V -> L (in Ref. 3; AAA79362)"
FT /evidence="ECO:0000305"
FT CONFLICT 614
FT /note="S -> L (in Ref. 1; AAD56722)"
FT /evidence="ECO:0000305"
FT HELIX 332..337
FT /evidence="ECO:0007829|PDB:2LXH"
FT STRAND 342..344
FT /evidence="ECO:0007829|PDB:4LAD"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:4LAD"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:2LXH"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:4LAD"
FT HELIX 362..369
FT /evidence="ECO:0007829|PDB:4LAD"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:4LAD"
FT HELIX 456..467
FT /evidence="ECO:0007829|PDB:4G3O"
FT HELIX 473..483
FT /evidence="ECO:0007829|PDB:4G3O"
FT HELIX 486..494
FT /evidence="ECO:0007829|PDB:4G3O"
FT HELIX 575..599
FT /evidence="ECO:0007829|PDB:3H8K"
FT HELIX 625..637
FT /evidence="ECO:0007829|PDB:3TIW"
SQ SEQUENCE 643 AA; 72996 MW; 8782324609C0E62A CRC64;
MPLLFLERFP WPSLRTYTGL SGLALLGTII SAYRALSQPE AGPGEPDQLT ASLQPEPPAP
ARPSAGGPRA RDVAQYLLSD SLFVWVLVNT ACCVLMLVAK LIQCIVFGPL RVSERQHLKD
KFWNFIFYKF IFIFGVLNVQ TVEEVVMWCL WFAGLVFLHL MVQLCKDRFE YLSFSPTTPM
SSHGRVLSLL VAMLLSCCGL AAVCSITGYT HGMHTLAFMA AESLLVTVRT AHVILRYVIH
LWDLNHEGTW EGKGTYVYYT DFVMELTLLS LDLMHHIHML LFGNIWLSMA SLVIFMQLRY
LFHEVQRRIR RHKNYLRVVG NMEARFAVAT PEELAVNNDD CAICWDSMQA ARKLPCGHLF
HNSCLRSWLE QDTSCPTCRM SLNIADNNRV REEHQGENLD ENLVPVAAAE GRPRLNQHNH
FFHFDGSRIA SWLPSFSVEV MHTTNILGIT QASNSQLNAM AHQIQEMFPQ VPYHLVLQDL
QLTRSVEITT DNILEGRIQV PFPTQRSDSI RPALNSPVER PSSDQEEGET SAQTERVPLD
LSPRLEETLD FGEVEVEPSE VEDFEARGSR FSKSADERQR MLVQRKDELL QQARKRFLNK
SSEDDAASES FLPSEGASSD PVTLRRRMLA AAAERRLQKQ QTS
