DBLOH_HUMAN
ID DBLOH_HUMAN Reviewed; 239 AA.
AC Q9NR28; B2RDQ0; Q6W3F3; Q96LV0; Q9BT11; Q9HAV6;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Diablo IAP-binding mitochondrial protein {ECO:0000312|HGNC:HGNC:21528};
DE AltName: Full=Diablo homolog, mitochondrial {ECO:0000312|HGNC:HGNC:21528};
DE AltName: Full=Direct IAP-binding protein with low pI {ECO:0000312|HGNC:HGNC:21528};
DE AltName: Full=Second mitochondria-derived activator of caspase {ECO:0000303|PubMed:10929711};
DE Short=Smac {ECO:0000303|PubMed:10929711};
DE Flags: Precursor;
GN Name=DIABLO {ECO:0000312|HGNC:HGNC:21528};
GN Synonyms=SMAC {ECO:0000312|HGNC:HGNC:21528};
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), PARTIAL PROTEIN SEQUENCE, FUNCTION,
RP AND TISSUE SPECIFICITY.
RX PubMed=10929711; DOI=10.1016/s0092-8674(00)00008-8;
RA Du C., Fang M., Li Y., Li L., Wang X.;
RT "Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase
RT activation by eliminating IAP inhibition.";
RL Cell 102:33-42(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND CHARACTERIZATION.
RX PubMed=10950947; DOI=10.1074/jbc.c000533200;
RA Srinivasula S.M., Datta P., Fan X.J., Fernandes-Alnemri T., Huang Z.,
RA Alnemri E.S.;
RT "Molecular determinants of the caspase-promoting activity of Smac/DIABLO
RT and its role in the death receptor pathway.";
RL J. Biol. Chem. 275:36152-36157(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=14523016; DOI=10.1074/jbc.m308036200;
RA Fu J., Jin Y., Arend L.J.;
RT "Smac3, a novel Smac/DIABLO splicing variant, attenuates the stability and
RT apoptosis-inhibiting activity of X-linked inhibitor of apoptosis protein.";
RL J. Biol. Chem. 278:52660-52672(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Stomach;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle, 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 [7]
RP FUNCTION, AND INTERACTION WITH BIRC6/BRUCE.
RX PubMed=15200957; DOI=10.1016/j.molcel.2004.05.018;
RA Bartke T., Pohl C., Pyrowolakis G., Jentsch S.;
RT "Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin
RT ligase.";
RL Mol. Cell 14:801-811(2004).
RN [8]
RP UBIQUITINATION BY BIRC7/LIVIN, AND INTERACTION WITH BIRC7/LIVIN.
RX PubMed=16729033; DOI=10.1038/sj.cdd.4401959;
RA Ma L., Huang Y., Song Z., Feng S., Tian X., Du W., Qiu X., Heese K., Wu M.;
RT "Livin promotes Smac/DIABLO degradation by ubiquitin-proteasome pathway.";
RL Cell Death Differ. 13:2079-2088(2006).
RN [9]
RP INTERACTION WITH XIAP.
RX PubMed=21695558; DOI=10.1007/s10495-011-0622-0;
RA Bornstein B., Gottfried Y., Edison N., Shekhtman A., Lev T., Glaser F.,
RA Larisch S.;
RT "ARTS binds to a distinct domain in XIAP-BIR3 and promotes apoptosis by a
RT mechanism that is different from other IAP-antagonists.";
RL Apoptosis 16:869-881(2011).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP INTERACTION WITH BIRC5/SURVIVIN.
RX PubMed=21536684; DOI=10.1074/jbc.m111.237586;
RA Pavlyukov M.S., Antipova N.V., Balashova M.V., Vinogradova T.V.,
RA Kopantzev E.P., Shakhparonov M.I.;
RT "Survivin monomer plays an essential role in apoptosis regulation.";
RL J. Biol. Chem. 286:23296-23307(2011).
RN [12]
RP INTERACTION WITH AREL1.
RX PubMed=23479728; DOI=10.1074/jbc.m112.436113;
RA Kim J.B., Kim S.Y., Kim B.M., Lee H., Kim I., Yun J., Jo Y., Oh T., Jo Y.,
RA Chae H.D., Shin D.Y.;
RT "Identification of a novel anti-apoptotic E3 ubiquitin ligase that
RT ubiquitinates antagonists of inhibitor of apoptosis proteins SMAC, HtrA2,
RT and ARTS.";
RL J. Biol. Chem. 288:12014-12021(2013).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 56-239, AND SUBUNIT.
RX PubMed=10972280; DOI=10.1038/35022514;
RA Chai J., Du C., Wu J.W., Kyin S., Wang X., Shi Y.;
RT "Structural and biochemical basis of apoptotic activation by Smac/DIABLO.";
RL Nature 406:855-862(2000).
RN [16]
RP STRUCTURE BY NMR OF 56-64 IN COMPLEX WITH XIAP.
RX PubMed=11140637; DOI=10.1038/35050006;
RA Liu Z., Sun C., Olejniczak E.T., Meadows R.P., Betz S.F., Oost T.,
RA Herrmann J., Wu J.C., Fesik S.W.;
RT "Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain.";
RL Nature 408:1004-1008(2000).
RN [17] {ECO:0007744|PDB:3D9U}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 56-61, AND INTERACTION WITH
RP BIRC2.
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 [18]
RP VARIANT DFNA64 LEU-126, AND CHARACTERIZATION OF DFNA64 LEU-126.
RX PubMed=21722859; DOI=10.1016/j.ajhg.2011.05.027;
RA Cheng J., Zhu Y., He S., Lu Y., Chen J., Han B., Petrillo M.,
RA Wrzeszczynski K.O., Yang S., Dai P., Zhai S., Han D., Zhang M.Q., Li W.,
RA Liu X., Li H., Chen Z.Y., Yuan H.;
RT "Functional mutation of SMAC/DIABLO, encoding a mitochondrial proapoptotic
RT protein, causes human progressive hearing loss DFNA64.";
RL Am. J. Hum. Genet. 89:56-66(2011).
CC -!- FUNCTION: Promotes apoptosis by activating caspases in the cytochrome
CC c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of
CC inhibitor of apoptosis proteins (IAP). Inhibits the activity of
CC BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates
CC the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by
CC promoting XIAP/BIRC4 ubiquitination and degradation through the
CC ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4
CC interacting with processed caspase-9 and promotes caspase-3 activation.
CC Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4
CC abundance. {ECO:0000269|PubMed:10929711, ECO:0000269|PubMed:14523016,
CC ECO:0000269|PubMed:15200957}.
CC -!- SUBUNIT: Homodimer (PubMed:10972280). Interacts with BEX3 (By
CC similarity). Interacts with BIRC2/c-IAP1 (via BIR3 domain)
CC (PubMed:19153467). Interacts with BIRC6/bruce (PubMed:15200957).
CC Interacts with BIRC7/livin (PubMed:16729033). Interacts with XIAP/BIRC4
CC (via BIR3 domain) (PubMed:21695558, PubMed:11140637). Interacts with
CC the monomeric and dimeric form of BIRC5/survivin (PubMed:21536684).
CC Interacts with AREL1 (via HECT domain); in the cytoplasm following
CC induction of apoptosis (PubMed:23479728).
CC {ECO:0000250|UniProtKB:Q9JIQ3, ECO:0000269|PubMed:10972280,
CC ECO:0000269|PubMed:11140637, ECO:0000269|PubMed:15200957,
CC ECO:0000269|PubMed:16729033, ECO:0000269|PubMed:19153467,
CC ECO:0000269|PubMed:21536684, ECO:0000269|PubMed:21695558,
CC ECO:0000269|PubMed:23479728}.
CC -!- INTERACTION:
CC Q9NR28; Q6RW13-2: AGTRAP; NbExp=6; IntAct=EBI-517508, EBI-11522760;
CC Q9NR28; P55056: APOC4; NbExp=3; IntAct=EBI-517508, EBI-18302142;
CC Q9NR28; Q15041: ARL6IP1; NbExp=9; IntAct=EBI-517508, EBI-714543;
CC Q9NR28; P27449: ATP6V0C; NbExp=3; IntAct=EBI-517508, EBI-721179;
CC Q9NR28; Q13490: BIRC2; NbExp=5; IntAct=EBI-517508, EBI-514538;
CC Q9NR28; O15392: BIRC5; NbExp=2; IntAct=EBI-517508, EBI-518823;
CC Q9NR28; Q96CA5: BIRC7; NbExp=6; IntAct=EBI-517508, EBI-517623;
CC Q9NR28; Q8IZR5-2: CMTM4; NbExp=3; IntAct=EBI-517508, EBI-17278014;
CC Q9NR28; Q9GZP9: DERL2; NbExp=3; IntAct=EBI-517508, EBI-7962814;
CC Q9NR28; Q6ZPD8: DGAT2L6; NbExp=3; IntAct=EBI-517508, EBI-12831978;
CC Q9NR28; Q96LJ7: DHRS1; NbExp=3; IntAct=EBI-517508, EBI-746300;
CC Q9NR28; Q08426: EHHADH; NbExp=3; IntAct=EBI-517508, EBI-2339219;
CC Q9NR28; Q8N9I5: FADS6; NbExp=3; IntAct=EBI-517508, EBI-3943864;
CC Q9NR28; Q9Y680: FKBP7; NbExp=3; IntAct=EBI-517508, EBI-3918971;
CC Q9NR28; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-517508, EBI-18053395;
CC Q9NR28; Q5XKP0: MICOS13; NbExp=3; IntAct=EBI-517508, EBI-1053887;
CC Q9NR28; O95563: MPC2; NbExp=3; IntAct=EBI-517508, EBI-719403;
CC Q9NR28; Q15390: MTFR1; NbExp=3; IntAct=EBI-517508, EBI-724207;
CC Q9NR28; Q05655: PRKCD; NbExp=4; IntAct=EBI-517508, EBI-704279;
CC Q9NR28; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-517508, EBI-17589229;
CC Q9NR28; Q96LZ7: RMDN2; NbExp=3; IntAct=EBI-517508, EBI-2806908;
CC Q9NR28; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-517508, EBI-8652744;
CC Q9NR28; Q8WV19: SFT2D1; NbExp=3; IntAct=EBI-517508, EBI-2854842;
CC Q9NR28; Q9BYT1: SLC17A9; NbExp=3; IntAct=EBI-517508, EBI-3940816;
CC Q9NR28; Q8N2U9: SLC66A2; NbExp=3; IntAct=EBI-517508, EBI-3907610;
CC Q9NR28; Q9H169-2: STMN4; NbExp=3; IntAct=EBI-517508, EBI-20117546;
CC Q9NR28; P08247: SYP; NbExp=3; IntAct=EBI-517508, EBI-9071725;
CC Q9NR28; Q9NPL8: TIMMDC1; NbExp=3; IntAct=EBI-517508, EBI-6268651;
CC Q9NR28; P98170: XIAP; NbExp=9; IntAct=EBI-517508, EBI-517127;
CC Q9NR28-1; P98170: XIAP; NbExp=4; IntAct=EBI-15490322, EBI-517127;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14523016}.
CC Note=Released into the cytosol when cells undergo apoptosis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9NR28-1; Sequence=Displayed;
CC Name=2; Synonyms=Diablo-S;
CC IsoId=Q9NR28-2; Sequence=VSP_004397;
CC Name=3; Synonyms=SMAC3;
CC IsoId=Q9NR28-3; Sequence=VSP_042785;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest expression in
CC testis. Expression is also high in heart, liver, kidney, spleen,
CC prostate and ovary. Low in brain, lung, thymus and peripheral blood
CC leukocytes. Isoform 3 is ubiquitously expressed.
CC {ECO:0000269|PubMed:10929711, ECO:0000269|PubMed:14523016}.
CC -!- DOMAIN: The mature N-terminus mediates interaction with XIAP/BIRC4.
CC -!- PTM: Ubiquitinated by BIRC7/livin. {ECO:0000269|PubMed:16729033}.
CC -!- DISEASE: Deafness, autosomal dominant, 64 (DFNA64) [MIM:614152]: A form
CC of non-syndromic sensorineural hearing loss. Sensorineural deafness
CC results from damage to the neural receptors of the inner ear, the nerve
CC pathways to the brain, or the area of the brain that receives sound
CC information. {ECO:0000269|PubMed:21722859}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
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DR EMBL; AF262240; AAF87716.1; -; mRNA.
DR EMBL; AY313210; AAQ86939.1; -; mRNA.
DR EMBL; AK024768; BAB14994.1; -; mRNA.
DR EMBL; AK057778; BAB71568.1; -; mRNA.
DR EMBL; AK315629; BAG37997.1; -; mRNA.
DR EMBL; AF298770; AAG22077.1; -; mRNA.
DR EMBL; AC048338; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004417; AAH04417.1; -; mRNA.
DR EMBL; BC011909; AAH11909.1; -; mRNA.
DR CCDS; CCDS9228.1; -. [Q9NR28-1]
DR CCDS; CCDS9229.1; -. [Q9NR28-3]
DR RefSeq; NP_001265231.1; NM_001278302.1.
DR RefSeq; NP_001265232.1; NM_001278303.1.
DR RefSeq; NP_001265233.1; NM_001278304.1. [Q9NR28-2]
DR RefSeq; NP_001265271.1; NM_001278342.1. [Q9NR28-3]
DR RefSeq; NP_063940.1; NM_019887.5. [Q9NR28-1]
DR RefSeq; NP_620308.1; NM_138930.3. [Q9NR28-2]
DR PDB; 1FEW; X-ray; 2.20 A; A=56-239.
DR PDB; 1G3F; NMR; -; B=56-64.
DR PDB; 1G73; X-ray; 2.00 A; A/B=56-217.
DR PDB; 1OXQ; X-ray; 2.30 A; F=56-64.
DR PDB; 1TW6; X-ray; 1.71 A; C/D=56-64.
DR PDB; 1XB0; X-ray; 2.20 A; G/H/I/J/K/L=56-62.
DR PDB; 1XB1; X-ray; 2.70 A; G/H/I/J/K/L=56-62.
DR PDB; 3D9U; X-ray; 2.30 A; B=56-61.
DR PDB; 3UIH; X-ray; 2.40 A; P/Q=56-70.
DR PDB; 3UIJ; X-ray; 2.70 A; P/Q=56-70.
DR PDB; 4TX5; X-ray; 1.80 A; A/B=56-239.
DR PDB; 6JX6; X-ray; 2.81 A; A/B/C/D=56-239.
DR PDBsum; 1FEW; -.
DR PDBsum; 1G3F; -.
DR PDBsum; 1G73; -.
DR PDBsum; 1OXQ; -.
DR PDBsum; 1TW6; -.
DR PDBsum; 1XB0; -.
DR PDBsum; 1XB1; -.
DR PDBsum; 3D9U; -.
DR PDBsum; 3UIH; -.
DR PDBsum; 3UIJ; -.
DR PDBsum; 4TX5; -.
DR PDBsum; 6JX6; -.
DR AlphaFoldDB; Q9NR28; -.
DR SMR; Q9NR28; -.
DR BioGRID; 121157; 227.
DR DIP; DIP-27627N; -.
DR IntAct; Q9NR28; 71.
DR MINT; Q9NR28; -.
DR STRING; 9606.ENSP00000398495; -.
DR DrugBank; DB12695; Phenethyl Isothiocyanate.
DR MoonDB; Q9NR28; Predicted.
DR GlyGen; Q9NR28; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NR28; -.
DR MetOSite; Q9NR28; -.
DR PhosphoSitePlus; Q9NR28; -.
DR BioMuta; DIABLO; -.
DR DMDM; 18203316; -.
DR EPD; Q9NR28; -.
DR jPOST; Q9NR28; -.
DR MassIVE; Q9NR28; -.
DR MaxQB; Q9NR28; -.
DR PaxDb; Q9NR28; -.
DR PeptideAtlas; Q9NR28; -.
DR PRIDE; Q9NR28; -.
DR ProteomicsDB; 82262; -. [Q9NR28-1]
DR ProteomicsDB; 82263; -. [Q9NR28-2]
DR ProteomicsDB; 82264; -. [Q9NR28-3]
DR TopDownProteomics; Q9NR28-1; -. [Q9NR28-1]
DR TopDownProteomics; Q9NR28-2; -. [Q9NR28-2]
DR TopDownProteomics; Q9NR28-3; -. [Q9NR28-3]
DR Antibodypedia; 1070; 720 antibodies from 45 providers.
DR DNASU; 56616; -.
DR Ensembl; ENST00000353548.11; ENSP00000320343.6; ENSG00000184047.20. [Q9NR28-3]
DR Ensembl; ENST00000464942.7; ENSP00000442360.2; ENSG00000184047.20. [Q9NR28-1]
DR Ensembl; ENST00000650715.1; ENSP00000499058.1; ENSG00000184047.20. [Q9NR28-1]
DR GeneID; 56616; -.
DR KEGG; hsa:56616; -.
DR MANE-Select; ENST00000464942.7; ENSP00000442360.2; NM_001371333.1; NP_001358262.1.
DR UCSC; uc010tab.4; human. [Q9NR28-1]
DR CTD; 56616; -.
DR DisGeNET; 56616; -.
DR GeneCards; DIABLO; -.
DR HGNC; HGNC:21528; DIABLO.
DR HPA; ENSG00000184047; Low tissue specificity.
DR MalaCards; DIABLO; -.
DR MIM; 605219; gene.
DR MIM; 614152; phenotype.
DR neXtProt; NX_Q9NR28; -.
DR OpenTargets; ENSG00000184047; -.
DR Orphanet; 90635; Autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR PharmGKB; PA134945044; -.
DR VEuPathDB; HostDB:ENSG00000184047; -.
DR eggNOG; ENOG502RA48; Eukaryota.
DR GeneTree; ENSGT00390000007237; -.
DR HOGENOM; CLU_098879_0_0_1; -.
DR InParanoid; Q9NR28; -.
DR OMA; MAALRTW; -.
DR PhylomeDB; Q9NR28; -.
DR TreeFam; TF102048; -.
DR PathwayCommons; Q9NR28; -.
DR Reactome; R-HSA-111457; Release of apoptotic factors from the mitochondria.
DR Reactome; R-HSA-111463; SMAC (DIABLO) binds to IAPs.
DR Reactome; R-HSA-111464; SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes.
DR Reactome; R-HSA-111469; SMAC, XIAP-regulated apoptotic response.
DR Reactome; R-HSA-9627069; Regulation of the apoptosome activity.
DR SignaLink; Q9NR28; -.
DR SIGNOR; Q9NR28; -.
DR BioGRID-ORCS; 56616; 15 hits in 1079 CRISPR screens.
DR ChiTaRS; DIABLO; human.
DR EvolutionaryTrace; Q9NR28; -.
DR GeneWiki; Diablo_homolog; -.
DR GenomeRNAi; 56616; -.
DR Pharos; Q9NR28; Tbio.
DR PRO; PR:Q9NR28; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9NR28; protein.
DR Bgee; ENSG00000184047; Expressed in right testis and 102 other tissues.
DR ExpressionAtlas; Q9NR28; baseline and differential.
DR Genevisible; Q9NR28; HS.
DR GO; GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005758; C:mitochondrial intermembrane space; TAS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; TAS:UniProtKB.
DR GO; GO:0008635; P:activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; TAS:ProtInc.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:UniProtKB.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IBA:GO_Central.
DR GO; GO:0051402; P:neuron apoptotic process; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:UniProtKB.
DR DisProt; DP01619; -.
DR InterPro; IPR009062; Smac/DIABLO-like_sf.
DR InterPro; IPR015142; Smac_DIABLO.
DR PANTHER; PTHR32247; PTHR32247; 1.
DR Pfam; PF09057; Smac_DIABLO; 1.
DR SUPFAM; SSF46984; SSF46984; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Deafness;
KW Direct protein sequencing; Disease variant; Mitochondrion;
KW Non-syndromic deafness; Reference proteome; Transit peptide;
KW Ubl conjugation.
FT TRANSIT 1..55
FT /note="Mitochondrion"
FT CHAIN 56..239
FT /note="Diablo IAP-binding mitochondrial protein"
FT /id="PRO_0000021072"
FT REGION 217..239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 56..60
FT /note="IAP-binding"
FT VAR_SEQ 1..60
FT /note="MAALKSWLSRSVTSFFRYRQCLCVPVVANFKKRCFSELIRPWHKTVTIGFGV
FT TLCAVPIA -> MKSDFYF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10950947"
FT /id="VSP_004397"
FT VAR_SEQ 62..105
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14523016"
FT /id="VSP_042785"
FT VARIANT 126
FT /note="S -> L (in DFNA64; does not increase apoptotic
FT activity compared to wild-type; enhances the degradation of
FT mutant and wild-type protein via heterodimerization; cells
FT expressing the mutant protein show increased susceptibility
FT to calcium-induced loss of mitochondrial potential compared
FT to wild-type, indicating increased sensitivity to
FT mitochondrial stress and suggestive of mitochondrial
FT dysfunction; dbSNP:rs387906893)"
FT /evidence="ECO:0000269|PubMed:21722859"
FT /id="VAR_066487"
FT CONFLICT 32
FT /note="K -> E (in Ref. 4; BAB71568)"
FT /evidence="ECO:0000305"
FT CONFLICT 44
FT /note="K -> R (in Ref. 4; BAB14994)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="E -> K (in Ref. 4; BAB71568)"
FT /evidence="ECO:0000305"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:1XB0"
FT HELIX 71..120
FT /evidence="ECO:0007829|PDB:4TX5"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:1FEW"
FT HELIX 126..173
FT /evidence="ECO:0007829|PDB:4TX5"
FT HELIX 177..239
FT /evidence="ECO:0007829|PDB:4TX5"
SQ SEQUENCE 239 AA; 27131 MW; 70C2AE0DC654D031 CRC64;
MAALKSWLSR SVTSFFRYRQ CLCVPVVANF KKRCFSELIR PWHKTVTIGF GVTLCAVPIA
QKSEPHSLSS EALMRRAVSL VTDSTSTFLS QTTYALIEAI TEYTKAVYTL TSLYRQYTSL
LGKMNSEEED EVWQVIIGAR AEMTSKHQEY LKLETTWMTA VGLSEMAAEA AYQTGADQAS
ITARNHIQLV KLQVEEVHQL SRKAETKLAE AQIEELRQKT QEEGEERAES EQEAYLRED
