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 08-NOV-2023, entry version 228. 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; DOI=10.1158/0008-5472.210.65.1; 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: BOLA2-SMG1P6; 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="https://atlasgeneticsoncology.org/gene/795/BIRC2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 PDB; 8DSF; X-ray; 1.50 A; A/B/C/D=260-352. DR PDB; 8DSO; X-ray; 2.33 A; D=260-352. 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 PDBsum; 8DSF; -. DR PDBsum; 8DSO; -. DR AlphaFoldDB; Q13490; -. DR BMRB; Q13490; -. DR SMR; Q13490; -. DR BioGRID; 106826; 233. DR CORUM; Q13490; -. DR DIP; DIP-33485N; -. DR IntAct; Q13490; 124. 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 GlyGen; Q13490; 2 sites, 1 O-linked glycan (2 sites). 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; 9606-ENSP00000477613; -. DR PeptideAtlas; Q13490; -. DR ProteomicsDB; 5644; -. DR ProteomicsDB; 59484; -. [Q13490-1] DR Pumba; Q13490; -. DR Antibodypedia; 1043; 496 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 AGR; HGNC:590; -. 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; FQRLTCV; -. DR OrthoDB; 383715at2759; -. 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-5357786; TNFR1-induced proapoptotic signaling. DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. DR Reactome; R-HSA-5357956; TNFR1-induced NF-kappa-B 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; 96 hits in 1199 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:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0001741; C:XY body; IEA:Ensembl. 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:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0051087; F:protein-folding chaperone binding; IPI:UniProtKB. 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:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; TAS:Reactome. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. 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:non-canonical NF-kappaB signal transduction; TAS:UniProtKB. DR GO; GO:0001890; P:placenta development; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; 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 non-canonical NF-kappaB signal transduction; 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; cd08329; CARD_BIRC2_BIRC3; 1. DR CDD; cd16713; RING-HC_BIRC2_3_7; 1. DR CDD; cd14394; UBA_BIRC2_3; 1. DR Gene3D; 1.10.533.10; Death Domain, Fas; 1. DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 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 PANTHER; PTHR10044; INHIBITOR OF APOPTOSIS; 1. DR Pfam; PF00653; BIR; 3. DR Pfam; PF00619; CARD; 1. DR Pfam; PF13920; zf-C3HC4_3; 1. DR SMART; SM00238; BIR; 3. DR SMART; SM00114; CARD; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF47986; DEATH domain; 1. DR SUPFAM; SSF57924; Inhibitor of apoptosis (IAP) repeat; 3. 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 184..188 FT /evidence="ECO:0007829|PDB:7QGJ" FT STRAND 197..199 FT /evidence="ECO:0007829|PDB:7QGJ" FT HELIX 201..206 FT /evidence="ECO:0007829|PDB:7QGJ" FT STRAND 209..211 FT /evidence="ECO:0007829|PDB:7QGJ" FT STRAND 218..220 FT /evidence="ECO:0007829|PDB:7QGJ" FT TURN 221..223 FT /evidence="ECO:0007829|PDB:7QGJ" FT HELIX 236..243 FT /evidence="ECO:0007829|PDB:7QGJ" FT HELIX 248..251 FT /evidence="ECO:0007829|PDB:7QGJ" 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 //