ID AMFR_MOUSE Reviewed; 643 AA. AC Q9R049; Q8K008; Q99LH5; DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 2. DT 27-MAR-2024, entry version 179. DE RecName: Full=E3 ubiquitin-protein ligase AMFR; DE EC=2.3.2.36 {ECO:0000250|UniProtKB:Q9UKV5}; DE AltName: Full=Autocrine motility factor receptor; DE Short=AMF receptor; DE AltName: Full=RING-type E3 ubiquitin transferase AMFR {ECO:0000305}; GN Name=Amfr; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090 {ECO:0000312|EMBL:AAD56721.1}; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Lung, and Testis; 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] (ISOFORM 2). RC STRAIN=FVB/N; TISSUE=Colon, and Mammary gland; 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 FUNCTION. RX PubMed=12650607; DOI=10.1023/a:1022594503657; RA Onishi Y., Tsukada K., Yokota J., Raz A.; RT "Overexpression of autocrine motility factor receptor (AMFR) in NIH3T3 RT fibroblasts induces cell transformation."; RL Clin. Exp. Metastasis 20:51-58(2003). RN [4] RP INTERACTION WITH VCP IN THE VCP/P97-AMFR/GP78 COMPLEX, FUNCTION, RP SUBCELLULAR LOCATION, AND MOTIF VIM. RX PubMed=16987818; DOI=10.1074/jbc.m603355200; RA Ballar P., Shen Y., Yang H., Fang S.; RT "The role of a novel p97/valosin-containing protein-interacting motif of RT gp78 in endoplasmic reticulum-associated degradation."; RL J. Biol. Chem. 281:35359-35368(2006). RN [5] RP INTERACTION WITH NGLY1; PSMC1; SAKS1; RAD23B AND VCP. RX PubMed=16709668; DOI=10.1073/pnas.0602747103; RA Li G., Zhao G., Zhou X., Schindelin H., Lennarz W.J.; RT "The AAA ATPase p97 links peptide N-glycanase to the endoplasmic reticulum- RT associated E3 ligase autocrine motility factor receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 103:8348-8353(2006). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain cortex; RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200; RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., RA Panse C., Schlapbach R., Mansuy I.M.; RT "Qualitative and quantitative analyses of protein phosphorylation in naive RT and stimulated mouse synaptosomal preparations."; RL Mol. Cell. Proteomics 6:283-293(2007). RN [7] RP FUNCTION IN UBIQUITINATION OF MISFOLDED PROTEINS, INTERACTION WITH RNF5, RP AND DOMAIN CUE. RX PubMed=18216283; DOI=10.1091/mbc.e07-06-0601; RA Morito D., Hirao K., Oda Y., Hosokawa N., Tokunaga F., Cyr D.M., Tanaka K., RA Iwai K., Nagata K.; RT "Gp78 cooperates with RMA1 in endoplasmic reticulum-associated degradation RT of CFTRDeltaF508."; RL Mol. Biol. Cell 19:1328-1336(2008). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-542, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Liver, Pancreas, Spleen, RC and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [10] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=22863805; DOI=10.1016/j.cmet.2012.06.014; RA Liu T.F., Tang J.J., Li P.S., Shen Y., Li J.G., Miao H.H., Li B.L., RA Song B.L.; RT "Ablation of gp78 in liver improves hyperlipidemia and insulin resistance RT by inhibiting SREBP to decrease lipid biosynthesis."; RL Cell Metab. 16:213-225(2012). RN [11] RP FUNCTION, AND INTERACTION WITH LMBR1L; UBAC2 AND CTNNB1. 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). 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:16987818, PubMed:18216283). Component CC of a VCP/p97-AMFR/gp78 complex that participates in the final step of CC endoplasmic reticulum-associated degradation (ERAD) (PubMed:16987818, CC PubMed:18216283). The VCP/p97-AMFR/gp78 complex is involved in the CC sterol-accelerated ERAD degradation of HMGCR through binding to the CC HMGCR-INSIG1 complex at the ER membrane (PubMed:22863805). 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 (By similarity). The CC ubiquitinated HMGCR is then released from the ER by the complex into CC the cytosol for subsequent destruction (By similarity). In addition to CC ubiquitination on lysine residues, catalyzes ubiquitination on cysteine CC residues: together with INSIG1, mediates polyubiquitination of CC SOAT2/ACAT2 at 'Cys-277', leading to its degradation when the lipid CC levels are low (By similarity). Catalyzes ubiquitination and subsequent CC degradation of INSIG1 when cells are depleted of sterols (By CC similarity). Mediates polyubiquitination of INSIG2 at 'Cys-215' in some CC tissues, leading to its degradation (By similarity). Also regulates CC ERAD through the ubiquitination of UBL4A a component of the BAG6/BAT3 CC complex (By similarity). Also acts as a scaffold protein to assemble a CC complex that couples ubiquitination, retranslocation and CC deglycosylation (By similarity). Mediates tumor invasion and metastasis CC as a receptor for the GPI/autocrine motility factor (PubMed:12650607). CC In association with LMBR1L and UBAC2, negatively regulates the CC canonical Wnt signaling pathway in the lymphocytes by promoting the CC ubiquitin-mediated degradation of CTNNB1 and Wnt receptors FZD6 and CC LRP6 (PubMed:31073040). Regulates NF-kappa-B and MAPK signaling CC pathways by mediating 'Lys-27'-linked polyubiquitination of TAB3 and CC promoting subsequent TAK1/MAP3K7 activation (By similarity). CC {ECO:0000250|UniProtKB:Q9UKV5, ECO:0000269|PubMed:12650607, CC ECO:0000269|PubMed:16987818, ECO:0000269|PubMed:18216283, CC ECO:0000269|PubMed:22863805, ECO:0000269|PubMed:31073040}. 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:0000250|UniProtKB:Q9UKV5}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Interacts with RNF5. Also forms an ERAD complex containing CC VCP/p97, NGLY1; PSMC1; SAKS1 and RAD23B required for coupling CC retrotranslocation, ubiquitination and deglycosylation. Interacts with CC DERL1. Interacts (through a region distinct from the RING finger) with CC UBE2G2/UBC7. Component of the VCP/p97-AMFR/gp78 complex that enhances CC VCP/p97 binding to polyubiquitinated proteins for their degradation by CC the endoplasmic reticulum-associated degradation (ERAD) pathway. CC Interacts (via the VIM) with VCP/p97. Interacts (via its membrane CC domain) with INSIG1; the interaction initiates the sterol-mediated CC ubiquitination and degradation of HMGCR by the ERAD pathway. Interacts CC with AUP1, UBE2G2 and RNF139/TRC8; interaction with AUP1 facilitates CC interaction of AMFR with ubiquitin-conjugating enzyme UBE2G2 and CC ubiquitin ligase RNF139, leading to sterol-induced ubiquitination of CC HNGCR and its subsequent proteasomal degradation (By similarity). CC Interacts with BAG6. Interacts with USP13 (via UBA 2 domain); the CC interaction is direct (By similarity). Interacts with LMBR1L, UBAC2 and CC CTNNB1 (PubMed:31073040). Interacts with C18orf32 (By similarity). CC {ECO:0000250|UniProtKB:Q9UKV5, ECO:0000269|PubMed:16709668, CC ECO:0000269|PubMed:16987818, ECO:0000269|PubMed:18216283, CC ECO:0000269|PubMed:31073040}. CC -!- INTERACTION: CC Q9R049; Q9JI78: Ngly1; NbExp=5; IntAct=EBI-3648125, EBI-3648128; CC Q9R049; Q01853: Vcp; NbExp=4; IntAct=EBI-3648125, EBI-80597; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:16987818}; Multi-pass membrane protein CC {ECO:0000255}. Note=Palmitoylation promotes localization to the CC peripheral endoplasmic reticulum. {ECO:0000250|UniProtKB:Q9UKV5}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1 {ECO:0000269|PubMed:10456327}; CC IsoId=Q9R049-1; Sequence=Displayed; CC Name=2 {ECO:0000305}; CC IsoId=Q9R049-2; Sequence=VSP_008224; CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, liver, lung, skeletal CC muscle, kidney and testis. Not detected in spleen. CC {ECO:0000269|PubMed:10456327}. CC -!- DOMAIN: The CUE domain is required for recognition of misfolded CC proteins such as mutant CFTR. {ECO:0000269|PubMed:18216283}. 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:16987818}. CC -!- PTM: Palmitoylation of the RING-type zing finger by ZDHHC6 promotes CC localization to the peripheral endoplasmic reticulum. CC {ECO:0000250|UniProtKB:Q9UKV5}. CC -!- DISRUPTION PHENOTYPE: Mice with a conditional deletion in the liver CC display improved hyperlipidemia and insulin resistance: mice show CC elevated energy expenditure and are resistant to diet-induced obesity CC and glucose intolerance (PubMed:22863805). Increased stability of CC Hmgcr, Insig1 and Insig2 and suppression of the SREBP pathway and novo CC lipid biosynthesis (PubMed:22863805). {ECO:0000269|PubMed:22863805}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF124144; AAD56721.1; -; mRNA. DR EMBL; BC003256; AAH03256.1; -; mRNA. DR EMBL; BC034538; AAH34538.1; -; mRNA. DR EMBL; BC040338; AAH40338.1; -; mRNA. DR CCDS; CCDS22533.1; -. [Q9R049-2] DR RefSeq; NP_035917.2; NM_011787.2. [Q9R049-2] DR AlphaFoldDB; Q9R049; -. DR BMRB; Q9R049; -. DR SMR; Q9R049; -. DR BioGRID; 204722; 23. DR CORUM; Q9R049; -. DR IntAct; Q9R049; 6. DR MINT; Q9R049; -. DR STRING; 10090.ENSMUSP00000052258; -. DR iPTMnet; Q9R049; -. DR PhosphoSitePlus; Q9R049; -. DR SwissPalm; Q9R049; -. DR EPD; Q9R049; -. DR jPOST; Q9R049; -. DR MaxQB; Q9R049; -. DR PaxDb; 10090-ENSMUSP00000052258; -. DR ProteomicsDB; 296400; -. [Q9R049-1] DR ProteomicsDB; 296401; -. [Q9R049-2] DR Pumba; Q9R049; -. DR Antibodypedia; 14770; 333 antibodies from 31 providers. DR DNASU; 23802; -. DR Ensembl; ENSMUST00000053766.14; ENSMUSP00000052258.7; ENSMUSG00000031751.15. [Q9R049-2] DR GeneID; 23802; -. DR KEGG; mmu:23802; -. DR AGR; MGI:1345634; -. DR CTD; 267; -. DR MGI; MGI:1345634; Amfr. DR VEuPathDB; HostDB:ENSMUSG00000031751; -. DR eggNOG; KOG0802; Eukaryota. DR GeneTree; ENSGT00940000156482; -. DR HOGENOM; CLU_015061_0_0_1; -. DR InParanoid; Q9R049; -. DR OMA; WAWFTAL; -. DR OrthoDB; 2912447at2759; -. DR PhylomeDB; Q9R049; -. DR TreeFam; TF320052; -. DR Reactome; R-MMU-532668; N-glycan trimming in the ER and Calnexin/Calreticulin cycle. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 23802; 5 hits in 76 CRISPR screens. DR ChiTaRS; Amfr; mouse. DR PRO; PR:Q9R049; -. DR Proteomes; UP000000589; Chromosome 8. DR RNAct; Q9R049; Protein. DR Bgee; ENSMUSG00000031751; Expressed in spermatocyte and 269 other cell types or tissues. DR ExpressionAtlas; Q9R049; baseline and differential. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0030425; C:dendrite; ISO:MGI. DR GO; GO:0036513; C:Derlin-1 retrotranslocation complex; ISO:MGI. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI. DR GO; GO:0030426; C:growth cone; ISO:MGI. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISS:MGI. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central. DR GO; GO:1904288; F:BAT3 complex binding; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW. DR GO; GO:0051087; F:protein-folding chaperone binding; ISO:MGI. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:MGI. DR GO; GO:0038023; F:signaling receptor activity; ISO:MGI. DR GO; GO:0043130; F:ubiquitin binding; IEA:InterPro. DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB. DR GO; GO:1990381; F:ubiquitin-specific protease binding; ISO:MGI. DR GO; GO:0034450; F:ubiquitin-ubiquitin ligase activity; ISO:MGI. DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISO:MGI. 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:0038061; P:non-canonical NF-kappaB signal transduction; ISO:MGI. DR GO; GO:0051865; P:protein autoubiquitination; ISO:MGI. DR GO; GO:0044314; P:protein K27-linked ubiquitination; ISO:MGI. DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISO:MGI. DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB. DR GO; GO:2000638; P:regulation of SREBP signaling pathway; IMP:UniProtKB. DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISS:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISO:MGI. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR CDD; cd14421; CUE_AMFR; 1. DR CDD; cd16455; RING-H2_AMFR; 1. DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR040675; AMFR_Ube2g2-bd. DR InterPro; IPR003892; CUE. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR15067:SF4; E3 UBIQUITIN-PROTEIN LIGASE AMFR; 1. DR PANTHER; PTHR15067; E3 UBIQUITIN-PROTEIN LIGASE RNF8; 1. 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 SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS51140; CUE; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR Genevisible; Q9R049; MM. PE 1: Evidence at protein level; KW Alternative splicing; Endoplasmic reticulum; Lipoprotein; Membrane; KW Metal-binding; Nucleotide-binding; Palmitate; Phosphoprotein; Receptor; KW Reference proteome; Transferase; Transmembrane; Transmembrane helix; KW Ubl conjugation pathway; Wnt signaling pathway; Zinc; Zinc-finger. FT CHAIN 1..643 FT /note="E3 ubiquitin-protein ligase AMFR" FT /id="PRO_0000064580" FT TRANSMEM 82..102 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 122..142 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 254..274 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 504..535 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 598..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:0000250|UniProtKB:Q9UKV5" FT MOD_RES 516 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UKV5" FT MOD_RES 542 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319" FT VAR_SEQ 57..60 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_008224" FT CONFLICT 412 FT /note="R -> S (in Ref. 1; AAD56721)" FT /evidence="ECO:0000305" SQ SEQUENCE 643 AA; 73105 MW; 7119277725982F79 CRC64; MPLLFLERFP WPSLRTYTGL SGLALLGTIV SAYRALSQPE DGSGEPEPLT APLQPEALAP ARLTAGGPRA RDVAQYLLSD SLFVWVLVNT ACCVLMLVAK LIQCIVFGPL RVSERQHLKD KFWNFIFYKF IFIFGVLNVQ TVEEVVMWCL WFAGLVFLHL MVQLCKDRFE YLSFSPTTPM SSHGRVLSLL IAMLLSCCGL AVVCCVTGYT HGMHTLAFMA AESLLVTVRT AHVILRYVIH LWDLNHEGTW EGKGTYVYYT DFVMELALLS LDLMHHIHML LFGNIWLSMA SLVIFMQLRY LFHEVQRRIR RHKNYLRVVG NMEARFAVAT PEELAVNNDD CAICWDSMQA ARKLPCGHLF HNSCLRSWLE QDTSCPTCRM SLNIADGSRA REDHQGENLD ENLVPVAAAE GRPRLNQHNH FFHFDGSRIA SWLPSFSVEV MHTTNILGIT QASNSQLNAM AHQIQEMFPQ VPYHLVLQDL QMTRSVEITT DNILEGRIQV PFPTQRSDSL RPALNSPVER PSPDLEEGEA SVQTERVPLD LSPRLEETLD FSEVELEPIE VEDFEARGSR FSKSADERQR MLVQRKDDLL QQARKRFLNK SSEDDGASER LLPSEGTSSD PVTLRRRMLA AAAERRLQRQ RTT //