AMFR_MOUSE
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 03-AUG-2022, entry version 170.
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, and
RC 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). {ECO:0000250|UniProtKB:Q9UKV5,
CC ECO:0000269|PubMed:12650607, ECO:0000269|PubMed:16987818,
CC ECO:0000269|PubMed:18216283, ECO:0000269|PubMed:22863805,
CC 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}.
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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; 19.
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; Q9R049; -.
DR PRIDE; Q9R049; -.
DR ProteomicsDB; 296400; -. [Q9R049-1]
DR ProteomicsDB; 296401; -. [Q9R049-2]
DR Antibodypedia; 14770; 299 antibodies from 31 providers.
DR DNASU; 23802; -.
DR Ensembl; ENSMUST00000053766; ENSMUSP00000052258; ENSMUSG00000031751. [Q9R049-2]
DR GeneID; 23802; -.
DR KEGG; mmu:23802; -.
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 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 71 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 265 other tissues.
DR ExpressionAtlas; Q9R049; baseline and differential.
DR Genevisible; Q9R049; MM.
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; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0030426; C:growth cone; IEA:Ensembl.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:MGI.
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; ISO: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:0051087; F:chaperone 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: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; ISO:MGI.
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:0007568; P:aging; IEA:Ensembl.
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:0032092; P:positive regulation of protein binding; ISO:MGI.
DR GO; GO:0051865; P:protein autoubiquitination; 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:0016567; P:protein ubiquitination; IBA:GO_Central.
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 Gene3D; 3.30.40.10; -; 1.
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 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
