HOIL1_HUMAN
ID HOIL1_HUMAN Reviewed; 510 AA.
AC Q9BYM8; O95623; Q86SL2; Q96BS3; Q9BYM9;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=RanBP-type and C3HC4-type zinc finger-containing protein 1;
DE EC=2.3.2.31 {ECO:0000269|PubMed:12629548};
DE AltName: Full=HBV-associated factor 4;
DE AltName: Full=Heme-oxidized IRP2 ubiquitin ligase 1;
DE Short=HOIL-1;
DE AltName: Full=Hepatitis B virus X-associated protein 4;
DE AltName: Full=RING finger protein 54;
DE AltName: Full=RING-type E3 ubiquitin transferase HOIL-1 {ECO:0000305};
DE AltName: Full=Ubiquitin-conjugating enzyme 7-interacting protein 3 {ECO:0000303|PubMed:11780052};
GN Name=RBCK1;
GN Synonyms=C20orf18, RNF54, UBCE7IP3, XAP3 {ECO:0000303|PubMed:11780052},
GN XAP4;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH PRKCH AND
RP HEPATITIS B VIRUS/HBV PROTEIN HBX (MICROBIAL INFECTION).
RX PubMed=9195957; DOI=10.1074/jbc.272.26.16482;
RA Cong Y.-S., Yao Y.-L., Yang W.-M., Kuzhandaivelu N., Seto E.;
RT "The hepatitis B virus X-associated protein, XAP3, is a protein kinase C-
RT binding protein.";
RL J. Biol. Chem. 272:16482-16489(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY,
RP PATHWAY, INTERACTION WITH IREB2, AND MUTAGENESIS OF CYS-282 AND CYS-285.
RC TISSUE=Kidney adenocarcinoma;
RX PubMed=12629548; DOI=10.1038/ncb952;
RA Yamanaka K., Ishikawa H., Megumi Y., Tokunaga F., Kanie M., Rouault T.A.,
RA Morishima I., Minato N., Ishimori K., Iwai K.;
RT "Identification of the ubiquitin-protein ligase that recognizes oxidized
RT IRP2.";
RL Nat. Cell Biol. 5:336-340(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Lung, and Placenta;
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 [5]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-330, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mammary epithelium;
RX PubMed=15951569; DOI=10.1074/mcp.m500089-mcp200;
RA Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J.,
RA Lauffenburger D.A., White F.M.;
RT "Time-resolved mass spectrometry of tyrosine phosphorylation sites in the
RT epidermal growth factor receptor signaling network reveals dynamic
RT modules.";
RL Mol. Cell. Proteomics 4:1240-1250(2005).
RN [7]
RP IDENTIFICATION IN THE LUBAC COMPLEX, AND FUNCTION OF THE LUBAC COMPLEX.
RX PubMed=17006537; DOI=10.1038/sj.emboj.7601360;
RA Kirisako T., Kamei K., Murata S., Kato M., Fukumoto H., Kanie M., Sano S.,
RA Tokunaga F., Tanaka K., Iwai K.;
RT "A ubiquitin ligase complex assembles linear polyubiquitin chains.";
RL EMBO J. 25:4877-4887(2006).
RN [8]
RP FUNCTION, AND INTERACTION WITH TAB2; TAB3; MAP3K7; TRAF6 AND RIPK1.
RX PubMed=17449468; DOI=10.1074/jbc.m701913200;
RA Tian Y., Zhang Y., Zhong B., Wang Y.Y., Diao F.C., Wang R.P., Zhang M.,
RA Chen D.Y., Zhai Z.H., Shu H.B.;
RT "RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-
RT triggered NF-kappaB activation by targeting TAB2/3 for degradation.";
RL J. Biol. Chem. 282:16776-16782(2007).
RN [9]
RP FUNCTION, INDUCTION, AND INTERACTION WITH IRF3.
RX PubMed=18711448; DOI=10.1038/cr.2008.277;
RA Zhang M., Tian Y., Wang R.P., Gao D., Zhang Y., Diao F.C., Chen D.Y.,
RA Zhai Z.H., Shu H.B.;
RT "Negative feedback regulation of cellular antiviral signaling by RBCK1-
RT mediated degradation of IRF3.";
RL Cell Res. 18:1096-1104(2008).
RN [10]
RP POLYUBIQUITIN-BINDING, FUNCTION OF THE LUBAC COMPLEX, ASSOCIATION WITH
RP TNF-RSC, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=20005846; DOI=10.1016/j.molcel.2009.10.013;
RA Haas T.L., Emmerich C.H., Gerlach B., Schmukle A.C., Cordier S.M.,
RA Rieser E., Feltham R., Vince J., Warnken U., Wenger T., Koschny R.,
RA Komander D., Silke J., Walczak H.;
RT "Recruitment of the linear ubiquitin chain assembly complex stabilizes the
RT TNF-R1 signaling complex and is required for TNF-mediated gene induction.";
RL Mol. Cell 36:831-844(2009).
RN [11]
RP FUNCTION OF THE LUBAC COMPLEX.
RX PubMed=19136968; DOI=10.1038/ncb1821;
RA Tokunaga F., Sakata S., Saeki Y., Satomi Y., Kirisako T., Kamei K.,
RA Nakagawa T., Kato M., Murata S., Yamaoka S., Yamamoto M., Akira S.,
RA Takao T., Tanaka K., Iwai K.;
RT "Involvement of linear polyubiquitylation of NEMO in NF-kappaB
RT activation.";
RL Nat. Cell Biol. 11:123-132(2009).
RN [12]
RP IDENTIFICATION IN THE LUBAC COMPLEX, AND FUNCTION.
RX PubMed=21455173; DOI=10.1038/nature09816;
RA Gerlach B., Cordier S.M., Schmukle A.C., Emmerich C.H., Rieser E.,
RA Haas T.L., Webb A.I., Rickard J.A., Anderton H., Wong W.W., Nachbur U.,
RA Gangoda L., Warnken U., Purcell A.W., Silke J., Walczak H.;
RT "Linear ubiquitination prevents inflammation and regulates immune
RT signalling.";
RL Nature 471:591-596(2011).
RN [13]
RP IDENTIFICATION IN THE LUBAC COMPLEX, AND FUNCTION.
RX PubMed=21455180; DOI=10.1038/nature09815;
RA Tokunaga F., Nakagawa T., Nakahara M., Saeki Y., Taniguchi M., Sakata S.,
RA Tanaka K., Nakano H., Iwai K.;
RT "SHARPIN is a component of the NF-kappaB-activating linear ubiquitin chain
RT assembly complex.";
RL Nature 471:633-636(2011).
RN [14]
RP IDENTIFICATION IN THE LUBAC COMPLEX, FUNCTION, DOMAIN RANBP2-TYPE, AND
RP UBIQUITIN-BINDING.
RX PubMed=21455181; DOI=10.1038/nature09814;
RA Ikeda F., Deribe Y.L., Skanland S.S., Stieglitz B., Grabbe C.,
RA Franz-Wachtel M., van Wijk S.J., Goswami P., Nagy V., Terzic J.,
RA Tokunaga F., Androulidaki A., Nakagawa T., Pasparakis M., Iwai K.,
RA Sundberg J.P., Schaefer L., Rittinger K., Macek B., Dikic I.;
RT "SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB
RT activity and apoptosis.";
RL Nature 471:637-641(2011).
RN [15]
RP INVOLVEMENT IN PGBM1.
RX PubMed=23104095; DOI=10.1038/ni.2457;
RA Boisson B., Laplantine E., Prando C., Giliani S., Israelsson E., Xu Z.,
RA Abhyankar A., Israel L., Trevejo-Nunez G., Bogunovic D., Cepika A.M.,
RA MacDuff D., Chrabieh M., Hubeau M., Bajolle F., Debre M., Mazzolari E.,
RA Vairo D., Agou F., Virgin H.W., Bossuyt X., Rambaud C., Facchetti F.,
RA Bonnet D., Quartier P., Fournet J.C., Pascual V., Chaussabel D.,
RA Notarangelo L.D., Puel A., Israel A., Casanova J.L., Picard C.;
RT "Immunodeficiency, autoinflammation and amylopectinosis in humans with
RT inherited HOIL-1 and LUBAC deficiency.";
RL Nat. Immunol. 13:1178-1186(2012).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [17]
RP INVOLVEMENT IN PGBM1, AND VARIANTS PGBM1 PRO-18 AND SER-387.
RX PubMed=23798481; DOI=10.1002/ana.23963;
RA Nilsson J., Schoser B., Laforet P., Kalev O., Lindberg C., Romero N.B.,
RA Davila Lopez M., Akman H.O., Wahbi K., Iglseder S., Eggers C., Engel A.G.,
RA Dimauro S., Oldfors A.;
RT "Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1.";
RL Ann. Neurol. 74:914-919(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [19]
RP FUNCTION.
RX PubMed=23708998; DOI=10.1038/nature12296;
RA Rivkin E., Almeida S.M., Ceccarelli D.F., Juang Y.C., Maclean T.A.,
RA Srikumar T., Huang H., Dunham W.H., Fukumura R., Xie G., Gondo Y.,
RA Raught B., Gingras A.C., Sicheri F., Cordes S.P.;
RT "The linear ubiquitin-specific deubiquitinase gumby regulates
RT angiogenesis.";
RL Nature 498:318-324(2013).
RN [20]
RP INTERACTION WITH S.FLEXNERI IPAH1.4 AND IPAH2.5 (MICROBIAL INFECTION).
RX PubMed=27572974; DOI=10.1038/nmicrobiol.2016.84;
RA de Jong M.F., Liu Z., Chen D., Alto N.M.;
RT "Shigella flexneri suppresses NF-kappaB activation by inhibiting linear
RT ubiquitin chain ligation.";
RL Nat. Microbiol. 1:16084-16084(2016).
RN [21]
RP FUNCTION, IDENTIFICATION IN THE LUBAC COMPLEX, AND PATHWAY.
RX PubMed=28481331; DOI=10.1038/nmicrobiol.2017.63;
RA Noad J., von der Malsburg A., Pathe C., Michel M.A., Komander D.,
RA Randow F.;
RT "LUBAC-synthesized linear ubiquitin chains restrict cytosol-invading
RT bacteria by activating autophagy and NF-kappaB.";
RL Nat. Microbiol. 2:17063-17063(2017).
RN [22]
RP STRUCTURE BY NMR OF 194-232.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the ZF-RANBP domain of the protein HBV associated
RT factor.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) OF 37-137, AND INTERACTION WITH
RP RNF31.
RX PubMed=22430200; DOI=10.1038/embor.2012.24;
RA Yagi H., Ishimoto K., Hiromoto T., Fujita H., Mizushima T., Uekusa Y.,
RA Yagi-Utsumi M., Kurimoto E., Noda M., Uchiyama S., Tokunaga F., Iwai K.,
RA Kato K.;
RT "A non-canonical UBA-UBL interaction forms the linear-ubiquitin-chain
RT assembly complex.";
RL EMBO Rep. 13:462-468(2012).
RN [24]
RP STRUCTURE BY NMR OF 51-139.
RX PubMed=22517668; DOI=10.1002/pro.2080;
RA Beasley S.A., Safadi S.S., Barber K.R., Shaw G.S.;
RT "Solution structure of the E3 ligase HOIL-1 Ubl domain.";
RL Protein Sci. 21:1085-1092(2012).
CC -!- FUNCTION: E3 ubiquitin-protein ligase, which accepts ubiquitin from
CC specific E2 ubiquitin-conjugating enzymes, such as UBE2L3/UBCM4, and
CC then transfers it to substrates (PubMed:12629548, PubMed:17449468,
CC PubMed:18711448). Functions as an E3 ligase for oxidized IREB2 and both
CC heme and oxygen are necessary for IREB2 ubiquitination
CC (PubMed:12629548). Promotes ubiquitination of TAB2 and IRF3 and their
CC degradation by the proteasome (PubMed:17449468, PubMed:18711448).
CC Component of the LUBAC complex which conjugates linear ('Met-1'-linked)
CC polyubiquitin chains to substrates and plays a key role in NF-kappa-B
CC activation and regulation of inflammation (PubMed:17006537,
CC PubMed:21455173, PubMed:21455180, PubMed:21455181, PubMed:19136968).
CC LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is
CC involved in activation of the canonical NF-kappa-B and the JNK
CC signaling pathways (PubMed:17006537, PubMed:21455173, PubMed:21455180,
CC PubMed:21455181, PubMed:19136968). Linear ubiquitination mediated by
CC the LUBAC complex interferes with TNF-induced cell death and thereby
CC prevents inflammation (PubMed:17006537, PubMed:21455173,
CC PubMed:21455180, PubMed:21455181). LUBAC is recruited to the TNF-R1
CC signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC
CC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin
CC to IKBKG and possibly other components contributing to the stability of
CC the complex (PubMed:17006537, PubMed:21455173, PubMed:21455180,
CC PubMed:21455181, PubMed:19136968). The LUBAC complex is also involved
CC in innate immunity by conjugating linear polyubiquitin chains at the
CC surface of bacteria invading the cytosol to form the ubiquitin coat
CC surrounding bacteria (PubMed:28481331). LUBAC is not able to initiate
CC formation of the bacterial ubiquitin coat, and can only promote
CC formation of linear polyubiquitins on pre-existing ubiquitin
CC (PubMed:28481331). The bacterial ubiquitin coat acts as an 'eat-me'
CC signal for xenophagy and promotes NF-kappa-B activation
CC (PubMed:28481331). Together with OTULIN, the LUBAC complex regulates
CC the canonical Wnt signaling during angiogenesis (PubMed:23708998).
CC Binds polyubiquitin of different linkage types (PubMed:20005846,
CC PubMed:21455181). {ECO:0000269|PubMed:12629548,
CC ECO:0000269|PubMed:17006537, ECO:0000269|PubMed:17449468,
CC ECO:0000269|PubMed:18711448, ECO:0000269|PubMed:19136968,
CC ECO:0000269|PubMed:20005846, ECO:0000269|PubMed:21455173,
CC ECO:0000269|PubMed:21455180, ECO:0000269|PubMed:21455181,
CC ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:28481331}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.;
CC EC=2.3.2.31; Evidence={ECO:0000269|PubMed:12629548};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:12629548, ECO:0000269|PubMed:28481331}.
CC -!- SUBUNIT: Component of the LUBAC complex (linear ubiquitin chain
CC assembly complex) which consists of SHARPIN, RBCK1 and RNF31
CC (PubMed:17006537, PubMed:21455173, PubMed:21455180, PubMed:21455181,
CC PubMed:28481331, PubMed:22430200). LUBAC has a MW of approximately 600
CC kDa suggesting a heteromultimeric assembly of its subunits
CC (PubMed:17006537, PubMed:21455173, PubMed:21455180, PubMed:21455181).
CC Interacts with beta-I-type (PRKCB1) and zeta-type protein kinase C
CC (PRKCZ) (By similarity). Interacts with UBE2L3 (By similarity).
CC Interacts with PRKCH (PubMed:9195957). Associates with the TNF-R1
CC signaling complex (TNF-RSC) in a stimulation-dependent manner
CC (PubMed:20005846). Interacts with EYA1, TAB2, TAB3, MAP3K7 TRAF6 and
CC RIPK1 (PubMed:17449468). Interacts with IRF3 (PubMed:18711448).
CC {ECO:0000250|UniProtKB:Q62921, ECO:0000250|UniProtKB:Q9WUB0,
CC ECO:0000269|PubMed:17006537, ECO:0000269|PubMed:17449468,
CC ECO:0000269|PubMed:18711448, ECO:0000269|PubMed:20005846,
CC ECO:0000269|PubMed:21455173, ECO:0000269|PubMed:21455180,
CC ECO:0000269|PubMed:21455181, ECO:0000269|PubMed:22430200,
CC ECO:0000269|PubMed:28481331, ECO:0000269|PubMed:9195957}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with IREB2 only in iron-rich
CC conditions. {ECO:0000269|PubMed:12629548}.
CC -!- SUBUNIT: [Isoform 2]: Interacts with IREB2 only in iron-rich
CC conditions. {ECO:0000269|PubMed:12629548}.
CC -!- SUBUNIT: (Microbial infection) Interacts with S.flexneri E3 ubiquitin-
CC protein ligases IpaH1.4 and IpaH2.5, leading to its ubiquitination.
CC {ECO:0000269|PubMed:27572974}.
CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis B virus/HBV
CC protein HBx; this interaction is required to activate transcription of
CC the viral genome. {ECO:0000269|PubMed:9195957}.
CC -!- INTERACTION:
CC Q9BYM8; P54253: ATXN1; NbExp=6; IntAct=EBI-2340624, EBI-930964;
CC Q9BYM8; Q02930-3: CREB5; NbExp=3; IntAct=EBI-2340624, EBI-10192698;
CC Q9BYM8; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-2340624, EBI-744099;
CC Q9BYM8; Q8IVS8: GLYCTK; NbExp=3; IntAct=EBI-2340624, EBI-748515;
CC Q9BYM8; A0A0S2Z4Q4: HGS; NbExp=3; IntAct=EBI-2340624, EBI-16429135;
CC Q9BYM8; P31273: HOXC8; NbExp=3; IntAct=EBI-2340624, EBI-1752118;
CC Q9BYM8; Q9Y6K9: IKBKG; NbExp=9; IntAct=EBI-2340624, EBI-81279;
CC Q9BYM8; Q14005-2: IL16; NbExp=3; IntAct=EBI-2340624, EBI-17178971;
CC Q9BYM8; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-2340624, EBI-2556193;
CC Q9BYM8; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-2340624, EBI-739832;
CC Q9BYM8; O60336: MAPKBP1; NbExp=3; IntAct=EBI-2340624, EBI-947402;
CC Q9BYM8; P41227: NAA10; NbExp=3; IntAct=EBI-2340624, EBI-747693;
CC Q9BYM8; Q9BU61: NDUFAF3; NbExp=3; IntAct=EBI-2340624, EBI-2114801;
CC Q9BYM8; Q9BU61-2: NDUFAF3; NbExp=3; IntAct=EBI-2340624, EBI-10298649;
CC Q9BYM8; P25786: PSMA1; NbExp=3; IntAct=EBI-2340624, EBI-359352;
CC Q9BYM8; Q9BYM8: RBCK1; NbExp=3; IntAct=EBI-2340624, EBI-2340624;
CC Q9BYM8; Q96EP0: RNF31; NbExp=48; IntAct=EBI-2340624, EBI-948111;
CC Q9BYM8; Q9H0F6: SHARPIN; NbExp=26; IntAct=EBI-2340624, EBI-3942966;
CC Q9BYM8; Q8N0S2: SYCE1; NbExp=3; IntAct=EBI-2340624, EBI-6872807;
CC Q9BYM8; Q13148: TARDBP; NbExp=3; IntAct=EBI-2340624, EBI-372899;
CC Q9BYM8; Q96PN8: TSSK3; NbExp=6; IntAct=EBI-2340624, EBI-3918381;
CC Q9BYM8; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-2340624, EBI-9090990;
CC Q9BYM8; P61086: UBE2K; NbExp=3; IntAct=EBI-2340624, EBI-473850;
CC Q9BYM8; P68036: UBE2L3; NbExp=4; IntAct=EBI-2340624, EBI-711173;
CC Q9BYM8; O14933: UBE2L6; NbExp=7; IntAct=EBI-2340624, EBI-2129974;
CC Q9BYM8; P61088: UBE2N; NbExp=2; IntAct=EBI-2340624, EBI-1052908;
CC Q9BYM8; Q96IQ9: ZNF414; NbExp=3; IntAct=EBI-2340624, EBI-744257;
CC Q9BYM8; P09022: Hoxa1; Xeno; NbExp=3; IntAct=EBI-2340624, EBI-3957603;
CC Q9BYM8; Q9JLY0: Socs6; Xeno; NbExp=5; IntAct=EBI-2340624, EBI-8500205;
CC Q9BYM8; Q4VA12: Traf1; Xeno; NbExp=2; IntAct=EBI-2340624, EBI-6116765;
CC Q9BYM8-4; P61086: UBE2K; NbExp=3; IntAct=EBI-25867896, EBI-473850;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=1; Synonyms=HOIL-1L;
CC IsoId=Q9BYM8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BYM8-3; Sequence=VSP_005766;
CC Name=3;
CC IsoId=Q9BYM8-4; Sequence=VSP_005766, VSP_005767, VSP_005768;
CC -!- INDUCTION: By viral transfection. {ECO:0000269|PubMed:18711448}.
CC -!- DOMAIN: The RanBP2-type zinc finger, also called Npl4 zinc finger
CC (NZF), mediates binding to 'Met-1'-linked polyubiquitins.
CC {ECO:0000250|UniProtKB:Q9WUB0}.
CC -!- DOMAIN: The UBL domain mediates association with RNF31 via interaction
CC with its UBA domain. {ECO:0000269|PubMed:21455181}.
CC -!- PTM: Auto-ubiquitinated. Auto-ubiquitination leads to degradation by
CC the proteasome (By similarity). {ECO:0000250|UniProtKB:Q62921}.
CC -!- PTM: Phosphorylated. In vitro, phosphorylation inhibits auto-
CC ubiquitination activity (By similarity).
CC {ECO:0000250|UniProtKB:Q62921}.
CC -!- DISEASE: Polyglucosan body myopathy 1 with or without immunodeficiency
CC (PGBM1) [MIM:615895]: A disease characterized by polyglucosan storage
CC myopathy associated with early-onset progressive muscle weakness and
CC progressive dilated cardiomyopathy, which may necessitate cardiac
CC transplant in severe cases. Some patients present with severe
CC immunodeficiency, invasive bacterial infections and chronic
CC autoinflammation. {ECO:0000269|PubMed:23104095,
CC ECO:0000269|PubMed:23798481}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the RBR family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH15219.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U67322; AAD00162.1; -; mRNA.
DR EMBL; AB107766; BAC75409.1; -; mRNA.
DR EMBL; AL121747; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000983; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC015219; AAH15219.2; ALT_INIT; mRNA.
DR CCDS; CCDS12998.1; -. [Q9BYM8-3]
DR CCDS; CCDS13000.2; -. [Q9BYM8-1]
DR RefSeq; NP_006453.1; NM_006462.5. [Q9BYM8-3]
DR RefSeq; NP_112506.2; NM_031229.3. [Q9BYM8-1]
DR PDB; 2CRC; NMR; -; A=194-232.
DR PDB; 2LGY; NMR; -; A=51-139.
DR PDB; 4DBG; X-ray; 2.71 A; A=37-137.
DR PDB; 7V8E; X-ray; 1.90 A; C/D=53-135.
DR PDBsum; 2CRC; -.
DR PDBsum; 2LGY; -.
DR PDBsum; 4DBG; -.
DR PDBsum; 7V8E; -.
DR AlphaFoldDB; Q9BYM8; -.
DR BMRB; Q9BYM8; -.
DR SMR; Q9BYM8; -.
DR BioGRID; 115862; 148.
DR ComplexPortal; CPX-1877; LUBAC ubiquitin ligase complex.
DR CORUM; Q9BYM8; -.
DR DIP; DIP-47737N; -.
DR IntAct; Q9BYM8; 93.
DR MINT; Q9BYM8; -.
DR STRING; 9606.ENSP00000348632; -.
DR BindingDB; Q9BYM8; -.
DR ChEMBL; CHEMBL4296109; -.
DR iPTMnet; Q9BYM8; -.
DR MetOSite; Q9BYM8; -.
DR PhosphoSitePlus; Q9BYM8; -.
DR BioMuta; RBCK1; -.
DR DMDM; 166214993; -.
DR EPD; Q9BYM8; -.
DR jPOST; Q9BYM8; -.
DR MassIVE; Q9BYM8; -.
DR MaxQB; Q9BYM8; -.
DR PaxDb; Q9BYM8; -.
DR PeptideAtlas; Q9BYM8; -.
DR PRIDE; Q9BYM8; -.
DR ProteomicsDB; 79667; -. [Q9BYM8-1]
DR ProteomicsDB; 79668; -. [Q9BYM8-3]
DR ProteomicsDB; 79669; -. [Q9BYM8-4]
DR Antibodypedia; 6164; 300 antibodies from 27 providers.
DR DNASU; 10616; -.
DR Ensembl; ENST00000353660.7; ENSP00000254960.5; ENSG00000125826.21. [Q9BYM8-3]
DR Ensembl; ENST00000356286.10; ENSP00000348632.6; ENSG00000125826.21. [Q9BYM8-1]
DR GeneID; 10616; -.
DR KEGG; hsa:10616; -.
DR MANE-Select; ENST00000356286.10; ENSP00000348632.6; NM_031229.4; NP_112506.2.
DR UCSC; uc002wdp.5; human. [Q9BYM8-1]
DR CTD; 10616; -.
DR DisGeNET; 10616; -.
DR GeneCards; RBCK1; -.
DR HGNC; HGNC:15864; RBCK1.
DR HPA; ENSG00000125826; Low tissue specificity.
DR MalaCards; RBCK1; -.
DR MIM; 610924; gene.
DR MIM; 615895; phenotype.
DR neXtProt; NX_Q9BYM8; -.
DR OpenTargets; ENSG00000125826; -.
DR Orphanet; 329173; Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis.
DR Orphanet; 397937; Polyglucosan body myopathy type 1.
DR PharmGKB; PA25723; -.
DR VEuPathDB; HostDB:ENSG00000125826; -.
DR eggNOG; KOG1815; Eukaryota.
DR GeneTree; ENSGT00940000161130; -.
DR HOGENOM; CLU_014998_1_0_1; -.
DR InParanoid; Q9BYM8; -.
DR OMA; VKCATWL; -.
DR OrthoDB; 1086223at2759; -.
DR PhylomeDB; Q9BYM8; -.
DR TreeFam; TF323486; -.
DR PathwayCommons; Q9BYM8; -.
DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-HSA-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9BYM8; -.
DR SIGNOR; Q9BYM8; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 10616; 18 hits in 1116 CRISPR screens.
DR ChiTaRS; RBCK1; human.
DR EvolutionaryTrace; Q9BYM8; -.
DR GeneWiki; RBCK1; -.
DR GenomeRNAi; 10616; -.
DR Pharos; Q9BYM8; Tbio.
DR PRO; PR:Q9BYM8; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9BYM8; protein.
DR Bgee; ENSG00000125826; Expressed in right hemisphere of cerebellum and 197 other tissues.
DR ExpressionAtlas; Q9BYM8; baseline and differential.
DR Genevisible; Q9BYM8; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0071797; C:LUBAC complex; IDA:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0140311; F:protein sequestering activity; IDA:GO_Central.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:GO_Central.
DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0051220; P:cytoplasmic sequestering of protein; IDA:GO_Central.
DR GO; GO:0042742; P:defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0060546; P:negative regulation of necroptotic process; IEA:Ensembl.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0097039; P:protein linear polyubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR026261; RBCK1/SHARPIN.
DR InterPro; IPR044066; TRIAD_supradom.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR027370; Znf-RING_LisH.
DR InterPro; IPR001876; Znf_RanBP2.
DR InterPro; IPR036443; Znf_RanBP2_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR22770:SF35; PTHR22770:SF35; 1.
DR Pfam; PF13445; zf-RING_UBOX; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00547; ZnF_RBZ; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF90209; SSF90209; 1.
DR PROSITE; PS51873; TRIAD; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
DR PROSITE; PS01358; ZF_RANBP2_1; 1.
DR PROSITE; PS50199; ZF_RANBP2_2; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Coiled coil;
KW Disease variant; Host-virus interaction; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..510
FT /note="RanBP-type and C3HC4-type zinc finger-containing
FT protein 1"
FT /id="PRO_0000056295"
FT DOMAIN 55..119
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT ZN_FING 193..222
FT /note="RanBP2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT ZN_FING 282..332
FT /note="RING-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 351..411
FT /note="IBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 447..476
FT /note="RING-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 1..270
FT /note="Interaction with TAB2"
FT /evidence="ECO:0000269|PubMed:17449468"
FT REGION 1..220
FT /note="Interaction with IRF3"
FT /evidence="ECO:0000269|PubMed:18711448"
FT REGION 69..131
FT /note="Interaction with RNF31"
FT /evidence="ECO:0000269|PubMed:22430200"
FT REGION 160..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 278..506
FT /note="TRIAD supradomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT COILED 233..261
FT /evidence="ECO:0000255"
FT COMPBIAS 166..192
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 460
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 282
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 285
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 300
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 302
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 305
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 308
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 323
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 332
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 371
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 376
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 391
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 394
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 399
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 402
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 406
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 411
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 447
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 450
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 465
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 468
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 330
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15951569"
FT VAR_SEQ 1..55
FT /note="MDEKTKKAEEMALSLTRAVAGGDEQVAMKCAIWLAEQRVPLSVQLKPEVSPT
FT QDI -> MGTATPDGREDQE (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:12629548,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9195957"
FT /id="VSP_005766"
FT VAR_SEQ 253..272
FT /note="RKQQQQEGNYLQHVQLDQRS -> GVPAGHHPQQPGGGGLLPLH (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_005767"
FT VAR_SEQ 273..510
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_005768"
FT VARIANT 18
FT /note="A -> P (in PGBM1)"
FT /evidence="ECO:0000269|PubMed:23798481"
FT /id="VAR_071385"
FT VARIANT 387
FT /note="N -> S (in PGBM1; dbSNP:rs566912235)"
FT /evidence="ECO:0000269|PubMed:23798481"
FT /id="VAR_071386"
FT MUTAGEN 282
FT /note="C->S: Binds to IREB2 in iron-treated cells. Reversed
FT iron-induced down-regulation of IREB2. No ubiquitination of
FT heme-loaded IREB2; when associated with S-285."
FT /evidence="ECO:0000269|PubMed:12629548"
FT MUTAGEN 285
FT /note="C->S: Binds to IREB2 in iron-treated cells. Reversed
FT iron-induced down-regulation of IREB2. No ubiquitination of
FT heme-loaded IREB2; when associated with S-282."
FT /evidence="ECO:0000269|PubMed:12629548"
FT CONFLICT 236
FT /note="E -> D (in Ref. 2; BAC75409)"
FT /evidence="ECO:0000305"
FT STRAND 55..66
FT /evidence="ECO:0007829|PDB:4DBG"
FT STRAND 69..75
FT /evidence="ECO:0007829|PDB:4DBG"
FT HELIX 81..92
FT /evidence="ECO:0007829|PDB:4DBG"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:4DBG"
FT STRAND 99..103
FT /evidence="ECO:0007829|PDB:4DBG"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:4DBG"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:4DBG"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:4DBG"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:2CRC"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:2CRC"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:2CRC"
SQ SEQUENCE 510 AA; 57572 MW; C6EF957B1F152FF2 CRC64;
MDEKTKKAEE MALSLTRAVA GGDEQVAMKC AIWLAEQRVP LSVQLKPEVS PTQDIRLWVS
VEDAQMHTVT IWLTVRPDMT VASLKDMVFL DYGFPPVLQQ WVIGQRLARD QETLHSHGVR
QNGDSAYLYL LSARNTSLNP QELQRERQLR MLEDLGFKDL TLQPRGPLEP GPPKPGVPQE
PGRGQPDAVP EPPPVGWQCP GCTFINKPTR PGCEMCCRAR PEAYQVPASY QPDEEERARL
AGEEEALRQY QQRKQQQQEG NYLQHVQLDQ RSLVLNTEPA ECPVCYSVLA PGEAVVLREC
LHTFCRECLQ GTIRNSQEAE VSCPFIDNTY SCSGKLLERE IKALLTPEDY QRFLDLGISI
AENRSAFSYH CKTPDCKGWC FFEDDVNEFT CPVCFHVNCL LCKAIHEQMN CKEYQEDLAL
RAQNDVAARQ TTEMLKVMLQ QGEAMRCPQC QIVVQKKDGC DWIRCTVCHT EICWVTKGPR
WGPGGPGDTS GGCRCRVNGI PCHPSCQNCH
