RC3H2_MOUSE
ID RC3H2_MOUSE Reviewed; 1187 AA.
AC P0C090; A2AVP5;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Roquin-2;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q9HBD1};
DE AltName: Full=Membrane-associated nucleic acid-binding protein;
DE AltName: Full=RING finger and CCCH-type zinc finger domain-containing protein 2;
DE AltName: Full=RING-type E3 ubiquitin transferase Roquin-2 {ECO:0000305};
GN Name=Rc3h2; Synonyms=Mnab;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, and Kidney;
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 [3]
RP FUNCTION, AND INTERACTION WITH CCR4-NOT COMPLEX.
RX PubMed=23663784; DOI=10.1016/j.cell.2013.04.016;
RA Leppek K., Schott J., Reitter S., Poetz F., Hammond M.C., Stoecklin G.;
RT "Roquin promotes constitutive mRNA decay via a conserved class of stem-loop
RT recognition motifs.";
RL Cell 153:869-881(2013).
RN [4]
RP FUNCTION, INTERACTION WITH EDC4, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=23583643; DOI=10.1016/j.immuni.2012.12.004;
RA Vogel K.U., Edelmann S.L., Jeltsch K.M., Bertossi A., Heger K., Heinz G.A.,
RA Zoller J., Warth S.C., Hoefig K.P., Lohs C., Neff F., Kremmer E.,
RA Schick J., Repsilber D., Geerlof A., Blum H., Wurst W., Heikenwalder M.,
RA Schmidt-Supprian M., Heissmeyer V.;
RT "Roquin paralogs 1 and 2 redundantly repress the Icos and Ox40 costimulator
RT mRNAs and control follicular helper T cell differentiation.";
RL Immunity 38:655-668(2013).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=23583642; DOI=10.1016/j.immuni.2013.01.011;
RA Pratama A., Ramiscal R.R., Silva D.G., Das S.K., Athanasopoulos V.,
RA Fitch J., Botelho N.K., Chang P.P., Hu X., Hogan J.J., Mana P., Bernal D.,
RA Korner H., Yu D., Goodnow C.C., Cook M.C., Vinuesa C.G.;
RT "Roquin-2 shares functions with its paralog Roquin-1 in the repression of
RT mRNAs controlling T follicular helper cells and systemic inflammation.";
RL Immunity 38:669-680(2013).
RN [6]
RP REVIEW.
RX PubMed=23550652; DOI=10.1111/imr.12056;
RA Heissmeyer V., Vogel K.U.;
RT "Molecular control of Tfh-cell differentiation by Roquin family proteins.";
RL Immunol. Rev. 253:273-289(2013).
RN [7]
RP DISRUPTION PHENOTYPE, FUNCTION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=25282160; DOI=10.1038/ni.3008;
RA Jeltsch K.M., Hu D., Brenner S., Zoeller J., Heinz G.A., Nagel D.,
RA Vogel K.U., Rehage N., Warth S.C., Edelmann S.L., Gloury R., Martin N.,
RA Lohs C., Lech M., Stehklein J.E., Geerlof A., Kremmer E., Weber A.,
RA Anders H.J., Schmitz I., Schmidt-Supprian M., Fu M., Holtmann H.,
RA Krappmann D., Ruland J., Kallies A., Heikenwalder M., Heissmeyer V.;
RT "Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their
RT cooperatively repressed targets to promote T(H)17 differentiation.";
RL Nat. Immunol. 15:1079-1089(2014).
RN [8]
RP FUNCTION.
RX PubMed=25697406; DOI=10.1038/ncomms7253;
RA Srivastava M., Duan G., Kershaw N.J., Athanasopoulos V., Yeo J.H., Ose T.,
RA Hu D., Brown S.H., Jergic S., Patel H.R., Pratama A., Richards S.,
RA Verma A., Jones E.Y., Heissmeyer V., Preiss T., Dixon N.E., Chong M.M.,
RA Babon J.J., Vinuesa C.G.;
RT "Roquin binds microRNA-146a and Argonaute2 to regulate microRNA
RT homeostasis.";
RL Nat. Commun. 6:6253-6253(2015).
CC -!- FUNCTION: Post-transcriptional repressor of mRNAs containing a
CC conserved stem loop motif, called constitutive decay element (CDE),
CC which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID,
CC NFKBIZ, PPP1R10, TNF and in many more mRNAs. Binds to CDE and promotes
CC mRNA deadenylation and degradation. This process does not involve
CC miRNAs (PubMed:23663784). In follicular helper T (Tfh) cells, represses
CC of ICOS and TNFRSF4 expression, thus preventing spontaneous Tfh cell
CC differentiation, germinal center B-cell differentiation in the absence
CC of immunization and autoimmunity. In resting or LPS-stimulated
CC macrophages, controls inflammation by suppressing TNF expression. Also
CC recognizes CDE in its own mRNA and in that of paralogous RC3H1,
CC possibly leading to feedback loop regulation (PubMed:23583643,
CC PubMed:23583642). Inhibits cooperatively with ZC3H12A the
CC differentiation of helper T cells Th17 in lungs. They repress target
CC mRNA encoding the Th17 cell-promoting factors IL6, ICOS, REL, IRF4,
CC NFKBID and NFKBIZ. The cooperation requires RNA-binding by RC3H1 and
CC the nuclease activity of ZC3H12A (PubMed:25282160). miRNA-binding
CC protein that regulates microRNA homeostasis. Enhances DICER-mediated
CC processing of pre-MIR146a but reduces mature MIR146a levels through an
CC increase of 3' end uridylation. Both inhibits ICOS mRNA expression and
CC they may act together to exert the suppression (PubMed:25697406). Acts
CC as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2B, UBE2D2, UBE2E2,
CC UBE2E3, UBE2G2, UBE2K and UBE2Q2 and produces polyubiquitin chains.
CC Shows the strongest activity when paired with UBE2N:UBE2V1 or
CC UBE2N:UBE2V2 E2 complexes and generate both short and long
CC polyubiquitin chains. Involved in the ubiquitination of MAP3K5 (By
CC similarity). Able to interact with double-stranded RNA (dsRNA).
CC {ECO:0000250|UniProtKB:Q9HBD1, ECO:0000269|PubMed:23583642,
CC ECO:0000269|PubMed:23583643, ECO:0000269|PubMed:23663784,
CC ECO:0000269|PubMed:25282160, ECO:0000269|PubMed:25697406}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q9HBD1};
CC -!- ACTIVITY REGULATION: Binding to dsRNA, but not CDE RNA, crosstalks with
CC the E3 ubiquitin ligase activity and may inhibit ubiquitination.
CC {ECO:0000250|UniProtKB:Q9HBD1}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q9HBD1}.
CC -!- SUBUNIT: Interacts with EDC4 (PubMed:23583643). Interacts with CCR4-NOT
CC deadenylase complex (PubMed:23663784). Interacts with MAP3K5; the
CC interaction is probably stimulus-dependent (By similarity).
CC {ECO:0000250|UniProtKB:Q9HBD1, ECO:0000269|PubMed:23583643,
CC ECO:0000269|PubMed:23663784}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000269|PubMed:23583642}.
CC Note=During stress, such as that induced by arsenite, localizes to
CC cytosolic stress granules. Localization to stress granules, but not to
CC P-bodies, depends upon the RING-type zinc finger.
CC -!- TISSUE SPECIFICITY: Highest levels in lymph node and thymus and
CC slightly lesser amounts in brain, lung, and spleen (at protein level).
CC Very weak expression in heart, muscle, and kidney (at protein level).
CC Expressed in CD4(+) helper T-cells (at protein level).
CC {ECO:0000269|PubMed:23583643}.
CC -!- DOMAIN: The RING-type zinc finger is required for proper localization
CC to stress granules, but not to P-bodies. {ECO:0000269|PubMed:23583642}.
CC -!- DOMAIN: The ROQ region is required for CDE RNA-binding. Has 2 separate
CC RNA-binding sites, one for CDE RNA and the other for dsRNA
CC (PubMed:23663784). It may also be involved in localization to stress
CC granules (By similarity). {ECO:0000250|UniProtKB:Q4VGL6,
CC ECO:0000269|PubMed:23663784}.
CC -!- DOMAIN: HEPN (higher eukaryotes and prokaryotes nucleotide-binding) are
CC observed in both N- and C-terminal sides of ROQ domain with 3D
CC structure even if they are poredcted on the basis of sequence.
CC {ECO:0000250|UniProtKB:Q9HBD1}.
CC -!- PTM: Proteolytically cleaved by MALT1 in activated CD4(+) T cells;
CC cleavage at Arg-509 is critical for promoting RC3H1 degradation in
CC response to T-cell receptor (TCR) stimulation, and hence is necessary
CC for prolonging the stability of a set of mRNAs controlling Th17 cell
CC differentiation. {ECO:0000269|PubMed:25282160}.
CC -!- DISRUPTION PHENOTYPE: Mutant animals are born at Mendelian ratio, but
CC very few reach adulthood, a large proportion die within the first days
CC after birth. Lethality can be rescued by changing the genetic
CC background from C57BL/6 to outbred NMRI, on which mutant animals appear
CC healthy and fertile, although smaller. Immune cell homeostasis is
CC normal (PubMed:23583643). However, Mice lacking both Rc3h1 and Rc3h2
CC genes in CD4(+) T-cells develop lymphadenopathy and splenomegaly with
CC increased spleen weight and cellularity, already at young age. They
CC show a prominent lung pathology with a progressive reduction in the
CC alveolar space concomitant with inflammation. They show an average
CC survival of 130 days. CD4(+) T-cells of these mutants show a pronounced
CC bias toward Th17 differentiation (PubMed:23583643, PubMed:25282160).
CC {ECO:0000269|PubMed:23583643, ECO:0000269|PubMed:25282160}.
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DR EMBL; AL929572; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS38116.1; -.
DR RefSeq; NP_001094061.1; NM_001100591.1.
DR RefSeq; XP_006498187.1; XM_006498124.3.
DR AlphaFoldDB; P0C090; -.
DR SMR; P0C090; -.
DR BioGRID; 235547; 2.
DR IntAct; P0C090; 38.
DR STRING; 10090.ENSMUSP00000097721; -.
DR iPTMnet; P0C090; -.
DR PhosphoSitePlus; P0C090; -.
DR MaxQB; P0C090; -.
DR PaxDb; P0C090; -.
DR PRIDE; P0C090; -.
DR ProteomicsDB; 255165; -.
DR Antibodypedia; 30358; 63 antibodies from 15 providers.
DR Ensembl; ENSMUST00000100143; ENSMUSP00000097721; ENSMUSG00000075376.
DR Ensembl; ENSMUST00000112936; ENSMUSP00000108558; ENSMUSG00000075376.
DR GeneID; 319817; -.
DR KEGG; mmu:319817; -.
DR UCSC; uc008jmq.1; mouse.
DR CTD; 54542; -.
DR MGI; MGI:2442789; Rc3h2.
DR VEuPathDB; HostDB:ENSMUSG00000075376; -.
DR eggNOG; KOG3161; Eukaryota.
DR GeneTree; ENSGT00940000157685; -.
DR InParanoid; P0C090; -.
DR OMA; GTEHVEN; -.
DR OrthoDB; 1009668at2759; -.
DR PhylomeDB; P0C090; -.
DR TreeFam; TF317698; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 319817; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Rc3h2; mouse.
DR PRO; PR:P0C090; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P0C090; protein.
DR Bgee; ENSMUSG00000075376; Expressed in rostral migratory stream and 242 other tissues.
DR ExpressionAtlas; P0C090; baseline and differential.
DR Genevisible; P0C090; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0010494; C:cytoplasmic stress granule; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0000932; C:P-body; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0003725; F:double-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003729; F:mRNA binding; IDA:MGI.
DR GO; GO:0035613; F:RNA stem-loop binding; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0001782; P:B cell homeostasis; IGI:MGI.
DR GO; GO:0060173; P:limb development; IMP:MGI.
DR GO; GO:0048286; P:lung alveolus development; IMP:MGI.
DR GO; GO:0048535; P:lymph node development; IGI:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; IMP:UniProtKB.
DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IBA:GO_Central.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IDA:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IDA:MGI.
DR GO; GO:2000628; P:regulation of miRNA metabolic process; IMP:UniProtKB.
DR GO; GO:0048536; P:spleen development; IGI:MGI.
DR GO; GO:0043029; P:T cell homeostasis; IGI:MGI.
DR GO; GO:0042098; P:T cell proliferation; IGI:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0061470; P:T follicular helper cell differentiation; IGI:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR032670; RC3H2.
DR InterPro; IPR041523; ROQ_II.
DR InterPro; IPR027370; Znf-RING_LisH.
DR InterPro; IPR000571; Znf_CCCH.
DR InterPro; IPR036855; Znf_CCCH_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR13139:SF2; PTHR13139:SF2; 1.
DR Pfam; PF18386; ROQ_II; 1.
DR Pfam; PF00642; zf-CCCH; 1.
DR Pfam; PF13445; zf-RING_UBOX; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00356; ZnF_C3H1; 1.
DR SUPFAM; SSF90229; SSF90229; 1.
DR PROSITE; PS50103; ZF_C3H1; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Metal-binding; Phosphoprotein; Reference proteome; Repressor;
KW RNA-binding; Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..1187
FT /note="Roquin-2"
FT /id="PRO_0000055969"
FT ZN_FING 14..54
FT /note="RING-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 410..438
FT /note="C3H1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 91..170
FT /note="HEPN-N"
FT /evidence="ECO:0000250|UniProtKB:Q9HBD1"
FT REGION 171..325
FT /note="ROQ"
FT /evidence="ECO:0000250|UniProtKB:Q9HBD1"
FT REGION 326..396
FT /note="HEPN-C"
FT /evidence="ECO:0000250|UniProtKB:Q9HBD1"
FT REGION 527..571
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 640..677
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 14
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q4VGL6"
FT BINDING 17
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q4VGL6"
FT BINDING 33
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q4VGL6"
FT BINDING 35
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q4VGL6"
FT BINDING 38
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q4VGL6"
FT BINDING 50
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q4VGL6"
FT BINDING 53
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q4VGL6"
FT SITE 509
FT /note="Cleavage; by MALT1"
FT /evidence="ECO:0000250|UniProtKB:Q4VGL6"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HBD1"
FT MOD_RES 806
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HBD1"
FT MOD_RES 981
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HBD1"
FT MOD_RES 1115
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HBD1"
SQ SEQUENCE 1187 AA; 131295 MW; 2C73E8F430649669 CRC64;
MPVQAAQWTE FLSCPICYNE FDENVHKPIS LGCSHTVCKT CLNKLHRKAC PFDQTAINTD
IDVLPVNFAL LQLVGAQVPD HQSIKLSNLG ENKHYEVAKK CVEDLALYLK PLSGGKGVAS
LNQSALSRPM QRKLVTLVNC QLVEEEGRVR AMRAARSLGE RTVTELILQH QNPQQLSANL
WAAVRARGCQ FLGPAMQEEA LKLVLLALED GSALSRKVLV LFVVQRLEPR FPQASKTSIG
HVVQLLYRAS CFKVTKRDED SSLMQLKEEF RSYEALRREH DAQIVHIAME AGLRISPEQW
SSLLYGDLAH KSHMQSIIDK LQSPESFAKS VQELTIVLQR TGDPANLNRL RPHLELLANI
DPNPDAVSPT WEQLENAMVA VKTVVHGLVD FIQNYSRKGH ETPQPQPNSK YKTSMCRDLR
QQGGCPRGTN CTFAHSQEEL EKYRLRNKKM SATVRTFPLL NKVGVNSTVT TTAGNVISVI
GSTETTGKIV ASTNGISNTE SSVSQLIPRG TDSAVRTLET VKKVGKVGTN AQNAGPSAES
VSENKIGSPP KTPVSNAAAT SAGPSNFGTE LNSLPPKSSP FLTRVPVYPQ HSESIQYFQD
PRTQIPFEVP QYPQTGYYPP PPTVPAGVTP CVPRFVRSSN VPESSLPPAS MPYADHYSTF
SPRDRMNSSP YQPPPPQQYG PVPPVPSGMY APVYDSRRIW RPAMYQRDDI IRSNSLPPMD
VMHSSVYQTS LRERYNSLDG YYSVACQPPN DPRTTVPLPR EPCGHLKTSC EEQLRRKPDQ
WTQYHTQKTP VSSTLPVATQ SPTPPSPLFS VDFRSDFSES VSGAKFEEDH LSHYSPWSCG
TIGSCINAID SEPKDVIANS NAVLMDLDSG DVKRRVHLFE AQRRTKEEDP IIPFSDGPII
SKWGAISRSS RTGYHTTDPV QATASQGSAT KPISVSDYVP YVNAVDSRWS SYGNDATSSA
HYIERDRFIV TDLSGHRKHS STGDLLSIEL QQAKSNSLLL QREANALAMQ QKWNSLDEGR
HLTLNLLSKE IELRNGENDY TEDTVDTKPD RDIELELSAL DTDEPDGQSE QIEEILDIQL
GISSQNDQLL NGTAVENGHP AQQHQKDPGK PKRQSLGEDH VILEEQKPIL PVTSCFSQPR
PMSISSASCL PITTSVSVGN LILKTHVMSE DKNDFLKPIA NGKMVNS
