BIRC2_HUMAN
ID BIRC2_HUMAN Reviewed; 618 AA.
AC Q13490; B4E026; Q16516; Q4TTG0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Baculoviral IAP repeat-containing protein 2;
DE EC=2.3.2.27 {ECO:0000269|PubMed:18082613, ECO:0000269|PubMed:21145488, ECO:0000269|PubMed:21931591, ECO:0000269|PubMed:23453969};
DE AltName: Full=Cellular inhibitor of apoptosis 1;
DE Short=C-IAP1 {ECO:0000303|PubMed:8548810};
DE AltName: Full=IAP homolog B;
DE AltName: Full=Inhibitor of apoptosis protein 2;
DE Short=hIAP-2;
DE Short=hIAP2;
DE AltName: Full=RING finger protein 48;
DE AltName: Full=RING-type E3 ubiquitin transferase BIRC2 {ECO:0000305};
DE AltName: Full=TNFR2-TRAF-signaling complex protein 2;
GN Name=BIRC2; Synonyms=API1, MIHB, RNF48;
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 1).
RX PubMed=8548810; DOI=10.1016/0092-8674(95)90149-3;
RA Rothe M., Pan M.-G., Henzel W.J., Ayres T.M., Goeddel D.V.;
RT "The TNFR2-TRAF signaling complex contains two novel proteins related to
RT baculoviral inhibitor of apoptosis proteins.";
RL Cell 83:1243-1252(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=8552191; DOI=10.1038/379349a0;
RA Liston P., Roy N., Tamai K., Lefebvre C., Baird S., Cherton-Horvat G.,
RA Farahani R., McLean M., Ikeda J., Mackenzie A., Korneluk R.G.;
RT "Suppression of apoptosis in mammalian cells by NAIP and a related family
RT of IAP genes.";
RL Nature 379:349-353(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal liver;
RX PubMed=8643514; DOI=10.1073/pnas.93.10.4974;
RA Uren A.G., Pakusch M., Hawkins C.J., Puls K.L., Vaux D.L.;
RT "Cloning and expression of apoptosis inhibitory protein homologs that
RT function to inhibit apoptosis and/or bind tumor necrosis factor receptor-
RT associated factors.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:4974-4978(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-453; VAL-506 AND
RP SER-549.
RG NIEHS SNPs program;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis, and Uterus;
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 [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BIRC5/SURVIVIN.
RX PubMed=15665297;
RA Samuel T., Okada K., Hyer M., Welsh K., Zapata J.M., Reed J.C.;
RT "cIAP1 Localizes to the nuclear compartment and modulates the cell cycle.";
RL Cancer Res. 65:210-218(2005).
RN [9]
RP FUNCTION IN THE UBIQUITINATION OF MXD1/MAD1, AND CATALYTIC ACTIVITY.
RX PubMed=18082613; DOI=10.1016/j.molcel.2007.10.027;
RA Xu L., Zhu J., Hu X., Zhu H., Kim H.T., LaBaer J., Goldberg A., Yuan J.;
RT "c-IAP1 cooperates with Myc by acting as a ubiquitin ligase for Mad1.";
RL Mol. Cell 28:914-922(2007).
RN [10]
RP REVIEW ON FUNCTION.
RX PubMed=18414036; DOI=10.4161/cc.7.8.5783;
RA Dubrez-Daloz L., Dupoux A., Cartier J.;
RT "IAPs: more than just inhibitors of apoptosis proteins.";
RL Cell Cycle 7:1036-1046(2008).
RN [11]
RP INTERACTION WITH FAS; GSK3B; TNFRSF10A AND TNFRSF10B, AND CLEAVAGE BY
RP CASPASES.
RX PubMed=18846110; DOI=10.1038/cdd.2008.124;
RA Sun M., Song L., Li Y., Zhou T., Jope R.S.;
RT "Identification of an antiapoptotic protein complex at death receptors.";
RL Cell Death Differ. 15:1887-1900(2008).
RN [12]
RP IDENTIFICATION BY 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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP REVIEW ON FUNCTION.
RX PubMed=20888210; DOI=10.1016/j.ceb.2010.08.025;
RA Lopez J., Meier P.;
RT "To fight or die - inhibitor of apoptosis proteins at the crossroad of
RT innate immunity and death.";
RL Curr. Opin. Cell Biol. 22:872-881(2010).
RN [15]
RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE OF THE NEDD8 CONJUGATION
RP PATHWAY, AND CATALYTIC ACTIVITY.
RX PubMed=21145488; DOI=10.1016/j.molcel.2010.11.011;
RA Broemer M., Tenev T., Rigbolt K.T., Hempel S., Blagoev B., Silke J.,
RA Ditzel M., Meier P.;
RT "Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases.";
RL Mol. Cell 40:810-822(2010).
RN [16]
RP REVIEW ON FUNCTION.
RX PubMed=20651737; DOI=10.1038/nrc2889;
RA Gyrd-Hansen M., Meier P.;
RT "IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and
RT cancer.";
RL Nat. Rev. Cancer 10:561-574(2010).
RN [17]
RP REVIEW ON FUNCTION.
RX PubMed=21447281;
RA Damgaard R.B., Gyrd-Hansen M.;
RT "Inhibitor of apoptosis (IAP) proteins in regulation of inflammation and
RT innate immunity.";
RL Discov. Med. 11:221-231(2011).
RN [18]
RP FUNCTION, INTERACTION WITH E2F1 AND TRAF2, AND SUBCELLULAR LOCATION.
RX PubMed=21653699; DOI=10.1074/jbc.m110.191239;
RA Cartier J., Berthelet J., Marivin A., Gemble S., Edmond V., Plenchette S.,
RA Lagrange B., Hammann A., Dupoux A., Delva L., Eymin B., Solary E.,
RA Dubrez L.;
RT "Cellular inhibitor of apoptosis protein-1 (cIAP1) can regulate E2F1
RT transcription factor-mediated control of cyclin transcription.";
RL J. Biol. Chem. 286:26406-26417(2011).
RN [19]
RP ACTIVITY REGULATION, AND INTERACTION WITH USP19.
RX PubMed=21849505; DOI=10.1074/jbc.m111.282020;
RA Mei Y., Hahn A.A., Hu S., Yang X.;
RT "The USP19 deubiquitinase regulates the stability of c-IAP1 and c-IAP2.";
RL J. Biol. Chem. 286:35380-35387(2011).
RN [20]
RP FUNCTION IN THE UBIQUITINATION OF RIPK1; RIPK2; RIPK3 AND RIPK4,
RP INTERACTION WITH RIPK1; RIPK2; RIPK3 AND RIPK4, AND CATALYTIC ACTIVITY.
RX PubMed=21931591; DOI=10.1371/journal.pone.0022356;
RA Bertrand M.J., Lippens S., Staes A., Gilbert B., Roelandt R., De Medts J.,
RA Gevaert K., Declercq W., Vandenabeele P.;
RT "cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin
RT chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).";
RL PLoS ONE 6:E22356-E22356(2011).
RN [21]
RP REVIEW ON FUNCTION.
RX PubMed=22095281; DOI=10.1038/cdd.2011.163;
RA Darding M., Meier P.;
RT "IAPs: guardians of RIPK1.";
RL Cell Death Differ. 19:58-66(2012).
RN [22]
RP FUNCTION IN IKBKE UBIQUITINATION, AND CATALYTIC ACTIVITY.
RX PubMed=23453969; DOI=10.1016/j.celrep.2013.01.031;
RA Zhou A.Y., Shen R.R., Kim E., Lock Y.J., Xu M., Chen Z.J., Hahn W.C.;
RT "IKKepsilon-mediated tumorigenesis requires K63-linked polyubiquitination
RT by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex.";
RL Cell Rep. 3:724-733(2013).
RN [23]
RP INTERACTION WITH HSP90AB1.
RX PubMed=25486457; DOI=10.1016/j.bbamcr.2014.11.026;
RA Synoradzki K., Bieganowski P.;
RT "Middle domain of human Hsp90 isoforms differentially binds Aha1 in human
RT cells and alters Hsp90 activity in yeast.";
RL Biochim. Biophys. Acta 1853:445-452(2015).
RN [24]
RP INTERACTION WITH UBXN1.
RX PubMed=25681446; DOI=10.1074/jbc.m114.631689;
RA Wang Y.B., Tan B., Mu R., Chang Y., Wu M., Tu H.Q., Zhang Y.C., Guo S.S.,
RA Qin X.H., Li T., Li W.H., Li A.L., Zhang X.M., Li H.Y.;
RT "Ubiquitin-associated domain-containing ubiquitin regulatory X (UBX)
RT protein UBXN1 is a negative regulator of nuclear factor kappaB (NF-kappaB)
RT signaling.";
RL J. Biol. Chem. 290:10395-10405(2015).
RN [25]
RP STRUCTURE BY NMR OF 266-363.
RX PubMed=10404221; DOI=10.1038/10701;
RA Hinds M.G., Norton R.S., Vaux D.L., Day C.L.;
RT "Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat.";
RL Nat. Struct. Biol. 6:648-651(1999).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 260-352 IN COMPLEXES WITH ZINC
RP IONS; DIABLO AND CASP9 PEPTIDES, AND SUBUNIT.
RX PubMed=19153467; DOI=10.1107/s0907444908039243;
RA Kulathila R., Vash B., Sage D., Cornell-Kennon S., Wright K., Koehn J.,
RA Stams T., Clark K., Price A.;
RT "The structure of the BIR3 domain of cIAP1 in complex with the N-terminal
RT peptides of SMAC and caspase-9.";
RL Acta Crystallogr. D 65:58-66(2009).
RN [27]
RP STRUCTURE BY NMR OF 435-562, DOMAIN CARD, AND ACTIVITY REGULATION.
RX PubMed=21549626; DOI=10.1016/j.molcel.2011.04.008;
RA Lopez J., John S.W., Tenev T., Rautureau G.J., Hinds M.G., Francalanci F.,
RA Wilson R., Broemer M., Santoro M.M., Day C.L., Meier P.;
RT "CARD-mediated autoinhibition of cIAP1's E3 ligase activity suppresses cell
RT proliferation and migration.";
RL Mol. Cell 42:569-583(2011).
CC -!- FUNCTION: Multi-functional protein which regulates not only caspases
CC and apoptosis, but also modulates inflammatory signaling and immunity,
CC mitogenic kinase signaling, and cell proliferation, as well as cell
CC invasion and metastasis. Acts as an E3 ubiquitin-protein ligase
CC regulating NF-kappa-B signaling and regulates both canonical and non-
CC canonical NF-kappa-B signaling by acting in opposite directions: acts
CC as a positive regulator of the canonical pathway and suppresses
CC constitutive activation of non-canonical NF-kappa-B signaling. The
CC target proteins for its E3 ubiquitin-protein ligase activity include:
CC RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, TRAF2, DIABLO/SMAC,
CC MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO, IKBKE and MXD1/MAD1. Can also
CC function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation
CC pathway, targeting effector caspases for neddylation and inactivation.
CC Acts as an important regulator of innate immune signaling via
CC regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and
CC RIG-I like receptors (RLRs), collectively referred to as pattern
CC recognition receptors (PRRs). Protects cells from spontaneous formation
CC of the ripoptosome, a large multi-protein complex that has the
CC capability to kill cancer cells in a caspase-dependent and caspase-
CC independent manner. Suppresses ripoptosome formation by ubiquitinating
CC RIPK1 and CASP8. Can stimulate the transcriptional activity of E2F1.
CC Plays a role in the modulation of the cell cycle.
CC {ECO:0000269|PubMed:15665297, ECO:0000269|PubMed:18082613,
CC ECO:0000269|PubMed:21145488, ECO:0000269|PubMed:21653699,
CC ECO:0000269|PubMed:21931591, ECO:0000269|PubMed:23453969}.
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:0000269|PubMed:18082613,
CC ECO:0000269|PubMed:21145488, ECO:0000269|PubMed:21931591,
CC ECO:0000269|PubMed:23453969};
CC -!- ACTIVITY REGULATION: The CARD domain inhibits the activation of E3
CC ubiquitin ligase activity by preventing RING domain dimerization and E2
CC ubiquitin donor binding and activation. The CARD domain-mediated
CC autoinhibition of the E3 ubiquitin-protein ligase activity suppresses
CC cell proliferation and migration. USP19 regulates the stability of
CC BIRC2/c-IAP1 by preventing its ubiquitination.
CC {ECO:0000269|PubMed:21549626, ECO:0000269|PubMed:21849505}.
CC -!- SUBUNIT: Interacts with DIABLO/SMAC and with PRSS25; these interactions
CC inhibit apoptotic suppressor activity. Interacts with CASP9. Interacts
CC (via BIR domains) with TRAF2; the interaction is required for IKBKE
CC ubiquitination. Interacts with E2F1, RIPK1, RIPK2, RIPK3, RIPK4,
CC BIRC5/survivin and USP19. HSP90AB1 (PubMed:25486457). Interacts with
CC UBXN1 (PubMed:25681446). Interacts with GSK3B (PubMed:18846110).
CC Interacts with several death receptors, inclusing FAS, TNFRSF10A and
CC TNFRSF10B (PubMed:18846110). Recruited to TNFRSF10B in the absence of
CC receptor stimulation. When TNFRSF10B is stimulated, further recruited
CC to the receptor and cleaved by caspases. Proteolytic fragments remain
CC associated with TNFRSF10B (PubMed:18846110).
CC {ECO:0000269|PubMed:15665297, ECO:0000269|PubMed:18846110,
CC ECO:0000269|PubMed:19153467, ECO:0000269|PubMed:21653699,
CC ECO:0000269|PubMed:21849505, ECO:0000269|PubMed:21931591,
CC ECO:0000269|PubMed:25486457, ECO:0000269|PubMed:25681446}.
CC -!- INTERACTION:
CC Q13490; Q13490: BIRC2; NbExp=4; IntAct=EBI-514538, EBI-514538;
CC Q13490; Q96CA5: BIRC7; NbExp=6; IntAct=EBI-514538, EBI-517623;
CC Q13490; P51451: BLK; NbExp=3; IntAct=EBI-514538, EBI-2105445;
CC Q13490; P51813: BMX; NbExp=3; IntAct=EBI-514538, EBI-696657;
CC Q13490; Q9Y3E2: BOLA1; NbExp=7; IntAct=EBI-514538, EBI-1049556;
CC Q13490; A0A087WZT3: BOLA2B; NbExp=3; IntAct=EBI-514538, EBI-12006120;
CC Q13490; P55210: CASP7; NbExp=2; IntAct=EBI-514538, EBI-523958;
CC Q13490; P55211: CASP9; NbExp=12; IntAct=EBI-514538, EBI-516799;
CC Q13490; Q9NR28: DIABLO; NbExp=5; IntAct=EBI-514538, EBI-517508;
CC Q13490; Q96CJ1: EAF2; NbExp=3; IntAct=EBI-514538, EBI-1245604;
CC Q13490; Q9NQT4: EXOSC5; NbExp=6; IntAct=EBI-514538, EBI-371876;
CC Q13490; Q96CN9: GCC1; NbExp=6; IntAct=EBI-514538, EBI-746252;
CC Q13490; P14136: GFAP; NbExp=3; IntAct=EBI-514538, EBI-744302;
CC Q13490; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-514538, EBI-1055254;
CC Q13490; O60341: KDM1A; NbExp=3; IntAct=EBI-514538, EBI-710124;
CC Q13490; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-514538, EBI-739832;
CC Q13490; P08949: NMB; NbExp=3; IntAct=EBI-514538, EBI-7964376;
CC Q13490; P08949-2: NMB; NbExp=6; IntAct=EBI-514538, EBI-12302085;
CC Q13490; Q96HA8: NTAQ1; NbExp=6; IntAct=EBI-514538, EBI-741158;
CC Q13490; Q9UBU9: NXF1; NbExp=3; IntAct=EBI-514538, EBI-398874;
CC Q13490; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-514538, EBI-1058491;
CC Q13490; Q8N3J5: PPM1K; NbExp=6; IntAct=EBI-514538, EBI-3923368;
CC Q13490; P63000: RAC1; NbExp=2; IntAct=EBI-514538, EBI-413628;
CC Q13490; P40937: RFC5; NbExp=3; IntAct=EBI-514538, EBI-712376;
CC Q13490; Q13546: RIPK1; NbExp=5; IntAct=EBI-514538, EBI-358507;
CC Q13490; O43353: RIPK2; NbExp=3; IntAct=EBI-514538, EBI-358522;
CC Q13490; Q9Y572: RIPK3; NbExp=3; IntAct=EBI-514538, EBI-298250;
CC Q13490; P57078: RIPK4; NbExp=3; IntAct=EBI-514538, EBI-4422308;
CC Q13490; Q06455-2: RUNX1T1; NbExp=3; IntAct=EBI-514538, EBI-11984663;
CC Q13490; Q9Y4C2-2: TCAF1; NbExp=3; IntAct=EBI-514538, EBI-11974855;
CC Q13490; Q9NP84: TNFRSF12A; NbExp=2; IntAct=EBI-514538, EBI-2851995;
CC Q13490; Q13077: TRAF1; NbExp=5; IntAct=EBI-514538, EBI-359224;
CC Q13490; Q12933: TRAF2; NbExp=17; IntAct=EBI-514538, EBI-355744;
CC Q13490; Q9BZW7: TSGA10; NbExp=4; IntAct=EBI-514538, EBI-744794;
CC Q13490-1; Q13490-1: BIRC2; NbExp=4; IntAct=EBI-16127374, EBI-16127374;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Agents that induce
CC either the extrinsic or intrinsic apoptotic pathways promote its
CC redistribution from the nuclear compartment to the cytoplasmic
CC compartment. Associated with the midbody in telophase cells, and found
CC diffusely in the nucleus of interphase cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13490-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13490-2; Sequence=VSP_045314;
CC -!- TISSUE SPECIFICITY: Present in many fetal and adult tissues. Mainly
CC expressed in adult skeletal muscle, thymus, testis, ovary, and
CC pancreas, low or absent in brain and peripheral blood leukocytes.
CC -!- DOMAIN: The BIR domains mediate nuclear localization.
CC {ECO:0000269|PubMed:21549626}.
CC -!- DOMAIN: The CARD domain is necessary to stabilize the protein and
CC inhibit the activation of E3 ubiquitin-protein ligase activity of
CC BIRC2/c-IAP1 by preventing RING domain dimerization and E2 ubiquitin
CC donor binding and activation. {ECO:0000269|PubMed:21549626}.
CC -!- PTM: Auto-ubiquitinated and degraded by the proteasome in apoptotic
CC cells.
CC -!- PTM: Upon stimulation of death receptors, including TNFRSF10B,
CC recruited to receptors and cleaved by caspases. Proteolytic fragments
CC remain associated with the receptors. This cleavage presumably
CC inactivates the protein. {ECO:0000269|PubMed:18846110}.
CC -!- SIMILARITY: Belongs to the IAP family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/birc2/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BIRC2ID795ch11q22.html";
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DR EMBL; L49431; AAC41942.1; -; mRNA.
DR EMBL; U45879; AAC50372.1; -; mRNA.
DR EMBL; U37547; AAC50508.1; -; mRNA.
DR EMBL; AK303197; BAG64288.1; -; mRNA.
DR EMBL; AP000942; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DQ068066; AAY46158.1; -; Genomic_DNA.
DR EMBL; BC016174; AAH16174.1; -; mRNA.
DR EMBL; BC028578; AAH28578.1; -; mRNA.
DR CCDS; CCDS58169.1; -. [Q13490-2]
DR CCDS; CCDS8316.1; -. [Q13490-1]
DR PIR; S68450; S68450.
DR RefSeq; NP_001157.1; NM_001166.4. [Q13490-1]
DR RefSeq; NP_001243092.1; NM_001256163.1. [Q13490-1]
DR RefSeq; NP_001243095.1; NM_001256166.1. [Q13490-2]
DR PDB; 1QBH; NMR; -; A=266-363.
DR PDB; 2L9M; NMR; -; A=435-562.
DR PDB; 3D9T; X-ray; 1.50 A; A/B=260-352.
DR PDB; 3D9U; X-ray; 2.30 A; A=260-352.
DR PDB; 3M1D; X-ray; 2.00 A; A/B=40-119.
DR PDB; 3MUP; X-ray; 2.60 A; A/B/C/D=251-363.
DR PDB; 3OZ1; X-ray; 3.00 A; A/B/C/D=251-363.
DR PDB; 3T6P; X-ray; 1.90 A; A=265-618.
DR PDB; 3UW4; X-ray; 1.79 A; A=266-343.
DR PDB; 4EB9; X-ray; 2.60 A; A/B/C/D=251-363.
DR PDB; 4HY4; X-ray; 1.25 A; A/B=260-352.
DR PDB; 4HY5; X-ray; 1.75 A; A/B=260-352.
DR PDB; 4KMN; X-ray; 1.52 A; A=260-357.
DR PDB; 4LGE; X-ray; 1.55 A; A/B=260-352.
DR PDB; 4LGU; X-ray; 2.00 A; A/B=260-352.
DR PDB; 4MTI; X-ray; 2.15 A; A/B=260-352.
DR PDB; 4MU7; X-ray; 1.79 A; A/B=260-352.
DR PDB; 5M6N; X-ray; 1.80 A; A/B=266-363.
DR PDB; 6EXW; X-ray; 2.20 A; A/C=250-363.
DR PDB; 6HPR; X-ray; 1.70 A; A=556-618.
DR PDB; 6W74; X-ray; 2.11 A; A=260-352.
DR PDB; 6W7O; X-ray; 2.17 A; C/D=260-352.
DR PDB; 6W8I; X-ray; 3.80 A; D/E/F=260-352.
DR PDB; 7QGJ; X-ray; 1.30 A; A/B=175-256.
DR PDBsum; 1QBH; -.
DR PDBsum; 2L9M; -.
DR PDBsum; 3D9T; -.
DR PDBsum; 3D9U; -.
DR PDBsum; 3M1D; -.
DR PDBsum; 3MUP; -.
DR PDBsum; 3OZ1; -.
DR PDBsum; 3T6P; -.
DR PDBsum; 3UW4; -.
DR PDBsum; 4EB9; -.
DR PDBsum; 4HY4; -.
DR PDBsum; 4HY5; -.
DR PDBsum; 4KMN; -.
DR PDBsum; 4LGE; -.
DR PDBsum; 4LGU; -.
DR PDBsum; 4MTI; -.
DR PDBsum; 4MU7; -.
DR PDBsum; 5M6N; -.
DR PDBsum; 6EXW; -.
DR PDBsum; 6HPR; -.
DR PDBsum; 6W74; -.
DR PDBsum; 6W7O; -.
DR PDBsum; 6W8I; -.
DR PDBsum; 7QGJ; -.
DR AlphaFoldDB; Q13490; -.
DR BMRB; Q13490; -.
DR SMR; Q13490; -.
DR BioGRID; 106826; 225.
DR CORUM; Q13490; -.
DR DIP; DIP-33485N; -.
DR IntAct; Q13490; 123.
DR MINT; Q13490; -.
DR STRING; 9606.ENSP00000477613; -.
DR BindingDB; Q13490; -.
DR ChEMBL; CHEMBL5462; -.
DR GuidetoPHARMACOLOGY; 2791; -.
DR MEROPS; I32.002; -.
DR MEROPS; I32.003; -.
DR MEROPS; I32.007; -.
DR CarbonylDB; Q13490; -.
DR iPTMnet; Q13490; -.
DR PhosphoSitePlus; Q13490; -.
DR BioMuta; BIRC2; -.
DR DMDM; 2497238; -.
DR CPTAC; CPTAC-790; -.
DR CPTAC; CPTAC-791; -.
DR EPD; Q13490; -.
DR jPOST; Q13490; -.
DR MassIVE; Q13490; -.
DR MaxQB; Q13490; -.
DR PaxDb; Q13490; -.
DR PeptideAtlas; Q13490; -.
DR PRIDE; Q13490; -.
DR ProteomicsDB; 5644; -.
DR ProteomicsDB; 59484; -. [Q13490-1]
DR Antibodypedia; 1043; 486 antibodies from 41 providers.
DR DNASU; 329; -.
DR Ensembl; ENST00000227758.7; ENSP00000227758.2; ENSG00000110330.10. [Q13490-1]
DR Ensembl; ENST00000530675.5; ENSP00000431723.1; ENSG00000110330.10. [Q13490-2]
DR Ensembl; ENST00000613397.4; ENSP00000477613.1; ENSG00000110330.10. [Q13490-1]
DR GeneID; 329; -.
DR KEGG; hsa:329; -.
DR MANE-Select; ENST00000227758.7; ENSP00000227758.2; NM_001166.5; NP_001157.1.
DR UCSC; uc001pgy.5; human. [Q13490-1]
DR CTD; 329; -.
DR DisGeNET; 329; -.
DR GeneCards; BIRC2; -.
DR HGNC; HGNC:590; BIRC2.
DR HPA; ENSG00000110330; Low tissue specificity.
DR MIM; 601712; gene.
DR neXtProt; NX_Q13490; -.
DR OpenTargets; ENSG00000110330; -.
DR PharmGKB; PA25359; -.
DR VEuPathDB; HostDB:ENSG00000110330; -.
DR eggNOG; KOG1101; Eukaryota.
DR GeneTree; ENSGT00940000154175; -.
DR HOGENOM; CLU_016347_1_1_1; -.
DR InParanoid; Q13490; -.
DR OMA; WCKGVIA; -.
DR OrthoDB; 1340284at2759; -.
DR PhylomeDB; Q13490; -.
DR TreeFam; TF105356; -.
DR PathwayCommons; Q13490; -.
DR Reactome; R-HSA-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-HSA-168927; TICAM1, RIP1-mediated IKK complex recruitment.
DR Reactome; R-HSA-5213460; RIPK1-mediated regulated necrosis.
DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-HSA-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-HSA-5668541; TNFR2 non-canonical NF-kB pathway.
DR Reactome; R-HSA-5675482; Regulation of necroptotic cell death.
DR Reactome; R-HSA-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-937041; IKK complex recruitment mediated by RIP1.
DR SignaLink; Q13490; -.
DR SIGNOR; Q13490; -.
DR BioGRID-ORCS; 329; 90 hits in 1120 CRISPR screens.
DR ChiTaRS; BIRC2; human.
DR EvolutionaryTrace; Q13490; -.
DR GeneWiki; BIRC2; -.
DR GenomeRNAi; 329; -.
DR Pharos; Q13490; Tchem.
DR PRO; PR:Q13490; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q13490; protein.
DR Bgee; ENSG00000110330; Expressed in cartilage tissue and 211 other tissues.
DR ExpressionAtlas; Q13490; baseline and differential.
DR Genevisible; Q13490; HS.
DR GO; GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001741; C:XY body; IEA:Ensembl.
DR GO; GO:0051087; F:chaperone binding; IPI:UniProtKB.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0098770; F:FBXO family protein binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; IMP:UniProtKB.
DR GO; GO:0016740; F:transferase activity; EXP:Reactome.
DR GO; GO:0043130; F:ubiquitin binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; TAS:Reactome.
DR GO; GO:0070266; P:necroptotic process; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0060546; P:negative regulation of necroptotic process; IBA:GO_Central.
DR GO; GO:1902443; P:negative regulation of ripoptosome assembly involved in necroptotic process; IEA:Ensembl.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; TAS:UniProtKB.
DR GO; GO:0001890; P:placenta development; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEP:UniProtKB.
DR GO; GO:1902524; P:positive regulation of protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:1902523; P:positive regulation of protein K63-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:1902527; P:positive regulation of protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IBA:GO_Central.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB.
DR GO; GO:0045595; P:regulation of cell differentiation; TAS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; TAS:UniProtKB.
DR GO; GO:2000116; P:regulation of cysteine-type endopeptidase activity; TAS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; TAS:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; TAS:UniProtKB.
DR GO; GO:0060544; P:regulation of necroptotic process; IMP:UniProtKB.
DR GO; GO:1901222; P:regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0070424; P:regulation of nucleotide-binding oligomerization domain containing signaling pathway; TAS:UniProtKB.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0039535; P:regulation of RIG-I signaling pathway; TAS:UniProtKB.
DR GO; GO:0034121; P:regulation of toll-like receptor signaling pathway; TAS:UniProtKB.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; TAS:Reactome.
DR CDD; cd00022; BIR; 3.
DR CDD; cd14394; UBA_BIRC2_3; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR001370; BIR_rpt.
DR InterPro; IPR041933; BIRC2/BIRC3_UBA.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR Pfam; PF00653; BIR; 3.
DR Pfam; PF00619; CARD; 1.
DR SMART; SM00238; BIR; 3.
DR SMART; SM00114; CARD; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS01282; BIR_REPEAT_1; 3.
DR PROSITE; PS50143; BIR_REPEAT_2; 3.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Apoptosis; Cytoplasm;
KW Metal-binding; Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..618
FT /note="Baculoviral IAP repeat-containing protein 2"
FT /id="PRO_0000122347"
FT REPEAT 46..113
FT /note="BIR 1"
FT REPEAT 184..250
FT /note="BIR 2"
FT REPEAT 269..336
FT /note="BIR 3"
FT DOMAIN 453..543
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT ZN_FING 571..606
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT BINDING 306
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 309
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 326
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 333
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT VAR_SEQ 1..49
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045314"
FT VARIANT 453
FT /note="M -> I (in dbSNP:rs34749508)"
FT /id="VAR_049535"
FT VARIANT 453
FT /note="M -> V (in dbSNP:rs370745983)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_025016"
FT VARIANT 506
FT /note="A -> V (in dbSNP:rs34510872)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_025017"
FT VARIANT 549
FT /note="P -> S (in dbSNP:rs35494784)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_025018"
FT CONFLICT 157
FT /note="S -> P (in Ref. 2; AAC50372)"
FT /evidence="ECO:0000305"
FT CONFLICT 308
FT /note="C -> G (in Ref. 2; AAC50372)"
FT /evidence="ECO:0000305"
FT CONFLICT 414
FT /note="Q -> L (in Ref. 2; AAC50372)"
FT /evidence="ECO:0000305"
FT CONFLICT 514
FT /note="L -> W (in Ref. 2; AAC50372)"
FT /evidence="ECO:0000305"
FT HELIX 43..51
FT /evidence="ECO:0007829|PDB:3M1D"
FT HELIX 52..55
FT /evidence="ECO:0007829|PDB:3M1D"
FT HELIX 64..69
FT /evidence="ECO:0007829|PDB:3M1D"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:3M1D"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:3M1D"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:3M1D"
FT HELIX 99..106
FT /evidence="ECO:0007829|PDB:3M1D"
FT HELIX 111..117
FT /evidence="ECO:0007829|PDB:3M1D"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:4HY4"
FT HELIX 269..274
FT /evidence="ECO:0007829|PDB:4HY4"
FT TURN 275..278
FT /evidence="ECO:0007829|PDB:4HY4"
FT STRAND 279..282
FT /evidence="ECO:0007829|PDB:1QBH"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:4HY4"
FT HELIX 287..292
FT /evidence="ECO:0007829|PDB:4HY4"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:4HY4"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:4HY4"
FT TURN 307..309
FT /evidence="ECO:0007829|PDB:4HY4"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:3D9T"
FT HELIX 322..329
FT /evidence="ECO:0007829|PDB:4HY4"
FT HELIX 334..340
FT /evidence="ECO:0007829|PDB:4HY4"
FT HELIX 342..348
FT /evidence="ECO:0007829|PDB:4HY4"
FT HELIX 355..361
FT /evidence="ECO:0007829|PDB:5M6N"
FT HELIX 389..391
FT /evidence="ECO:0007829|PDB:3T6P"
FT HELIX 394..401
FT /evidence="ECO:0007829|PDB:3T6P"
FT HELIX 406..420
FT /evidence="ECO:0007829|PDB:3T6P"
FT HELIX 427..450
FT /evidence="ECO:0007829|PDB:3T6P"
FT TURN 451..453
FT /evidence="ECO:0007829|PDB:2L9M"
FT HELIX 456..463
FT /evidence="ECO:0007829|PDB:3T6P"
FT HELIX 465..471
FT /evidence="ECO:0007829|PDB:3T6P"
FT HELIX 476..484
FT /evidence="ECO:0007829|PDB:3T6P"
FT STRAND 485..487
FT /evidence="ECO:0007829|PDB:2L9M"
FT HELIX 490..497
FT /evidence="ECO:0007829|PDB:3T6P"
FT HELIX 502..516
FT /evidence="ECO:0007829|PDB:3T6P"
FT HELIX 518..531
FT /evidence="ECO:0007829|PDB:3T6P"
FT HELIX 533..540
FT /evidence="ECO:0007829|PDB:3T6P"
FT HELIX 553..555
FT /evidence="ECO:0007829|PDB:3T6P"
FT HELIX 558..568
FT /evidence="ECO:0007829|PDB:6HPR"
FT TURN 572..574
FT /evidence="ECO:0007829|PDB:6HPR"
FT STRAND 575..578
FT /evidence="ECO:0007829|PDB:6HPR"
FT STRAND 581..584
FT /evidence="ECO:0007829|PDB:6HPR"
FT STRAND 589..591
FT /evidence="ECO:0007829|PDB:6HPR"
FT TURN 593..595
FT /evidence="ECO:0007829|PDB:6HPR"
FT HELIX 596..598
FT /evidence="ECO:0007829|PDB:6HPR"
FT TURN 603..605
FT /evidence="ECO:0007829|PDB:6HPR"
FT STRAND 611..614
FT /evidence="ECO:0007829|PDB:6HPR"
SQ SEQUENCE 618 AA; 69900 MW; C1778D328063586D CRC64;
MHKTASQRLF PGPSYQNIKS IMEDSTILSD WTNSNKQKMK YDFSCELYRM STYSTFPAGV
PVSERSLARA GFYYTGVNDK VKCFCCGLML DNWKLGDSPI QKHKQLYPSC SFIQNLVSAS
LGSTSKNTSP MRNSFAHSLS PTLEHSSLFS GSYSSLSPNP LNSRAVEDIS SSRTNPYSYA
MSTEEARFLT YHMWPLTFLS PSELARAGFY YIGPGDRVAC FACGGKLSNW EPKDDAMSEH
RRHFPNCPFL ENSLETLRFS ISNLSMQTHA ARMRTFMYWP SSVPVQPEQL ASAGFYYVGR
NDDVKCFCCD GGLRCWESGD DPWVEHAKWF PRCEFLIRMK GQEFVDEIQG RYPHLLEQLL
STSDTTGEEN ADPPIIHFGP GESSSEDAVM MNTPVVKSAL EMGFNRDLVK QTVQSKILTT
GENYKTVNDI VSALLNAEDE KREEEKEKQA EEMASDDLSL IRKNRMALFQ QLTCVLPILD
NLLKANVINK QEHDIIKQKT QIPLQARELI DTILVKGNAA ANIFKNCLKE IDSTLYKNLF
VDKNMKYIPT EDVSGLSLEE QLRRLQEERT CKVCMDKEVS VVFIPCGHLV VCQECAPSLR
KCPICRGIIK GTVRTFLS
