BIRC6
entrez
57448
canonical
uniprot
Q9NR09
canonical
ensembl
ENSG00000115760
resolver
ensp
ENSP00000393596
resolver
ensp
ENSP00000515025
resolver
ensp
ENSP00000515026
resolver
enst
ENST00000421745
resolver
enst
ENST00000700518
resolver
enst
ENST00000700519
resolver
genesymbol
BIRC6
resolver
genesymbol_syn
KIAA1289
resolver
hgnc
HGNC:13516
resolver
uniprot
A0A8V8TQB4
resolver
uniprot
A0A8V8TR92
resolver
uniprot
Q9ULD1
resolver
uniprot_entry
A0A8V8TQB4_HUMAN
resolver
uniprot_entry
A0A8V8TR92_HUMAN
resolver
uniprot_entry
BIRC6_HUMAN
resolver
uniprot_sec
Q9ULD1
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by DIABLO/SMAC, which competes for the substrate-binding sites on BIRC6 (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). BIRC6 inhibits caspases and protease by ubiquitination but BIRC6 itself is subjected to protease cleavage by CASP3, CASP6, CASP7, CASP9 and HTRA2 by protease cleavage (PubMed:15200957, PubMed:36758104, PubMed:36758105). {ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758105, ECO:0000269|PubMed:36758106}.
uniprot
proteins
amino_acid_sequence
MVTGGGAAPPGTVTEPLPSVIVLSAGRKMAAAAAAASGPGCSSAAGAGAAGVSEWLVLRDGCMHCDADGLHSLSYHPALNAILAVTSRGTIKVIDGTSGATLQASALSAKPGGQVKCQYISAVDKVIFVDDYAVGCRKDLNGILLLDTALQTPVSKQDDVVQLELPVTEAQQLLSACLEKVDISSTEGYDLFITQLKDGLKNTSHETAANHKVAKWATVTFHLPHHVLKSIASAIVNELKKINQNVAALPVASSVMDRLSYLLPSARPELGVGPGRSVDRSLMYSEANRRETFTSWPHVGYRWAQPDPMAQAGFYHQPASSGDDRAMCFTCSVCLVCWEPTDEPWSEHERHSPNCPFVKGEHTQNVPLSVTLATSPAQFPCTDGTDRISCFGSGSCPHFLAAATKRGKICIWDVSKLMKVHLKFEINAYDPAIVQQLILSGDPSSGVDSRRPTLAWLEDSSSCSDIPKLEGDSDDLLEDSDSEEHSRSDSVTGHTSQKEAMEVSLDITALSILQQPEKLQWEIVANVLEDTVKDLEELGANPCLTNSKSEKTKEKHQEQHNIPFPCLLAGGLLTYKSPATSPISSNSHRSLDGLSRTQGESISEQGSTDNESCTNSELNSPLVRRTLPVLLLYSIKESDEKAGKIFSQMNNIMSKSLHDDGFTVPQIIEMELDSQEQLLLQDPPVTYIQQFADAAANLTSPDSEKWNSVFPKPGTLVQCLRLPKFAEEENLCIDSITPCADGIHLLVGLRTCPVESLSAINQVEALNNLNKLNSALCNRRKGELESNLAVVNGANISVIQHESPADVQTPLIIQPEQRNVSGGYLVLYKMNYATRIVTLEEEPIKIQHIKDPQDTITSLILLPPDILDNREDDCEEPIEDMQLTSKNGFEREKTSDISTLGHLVITTQGGYVKILDLSNFEILAKVEPPKKEGTEEQDTFVSVIYCSGTDRLCACTKGGELHFLQIGGTCDDIDEADILVDGSLSKGIEPSSEGSKPLSNPSSPGISGVDLLVDQPFTLEILTSLVELTRFETLTPRFSATVPPCWVEVQQEQQQRRHPQHLHQQHHGDAAQHTRTWKLQTDSNSWDEHVFELVLPKACMVGHVDFKFVLNSNITNIPQIQVTLLKNKAPGLGKVNALNIEVEQNGKPSLVDLNEEMQHMDVEESQCLRLCPFLEDHKEDILCGPVWLASGLDLSGHAGMLTLTSPKLVKGMAGGKYRSFLIHVKAVNERGTEEICNGGMRPVVRLPSLKHQSNKGYSLASLLAKVAAGKEKSSNVKNENTSGTRKSENLRGCDLLQEVSVTIRRFKKTSISKERVQRCAMLQFSEFHEKLLNTLCRKTDDGQITEHAQSLVLDTLCWLAGVHSNGPGSSKEGNENLLSKTRKFLSDIVRVCFFEAGRSIAHKCARFLALCISNGKCDPCQPAFGPVLLKALLDNMSFLPAATTGGSVYWYFVLLNYVKDEDLAGCSTACASLLTAVSRQLQDRLTPMEALLQTRYGLYSSPFDPVLFDLEMSGSSCKNVYNSSIGVQSDEIDLSDVLSGNGKVSSCTAAEGSFTSLTGLLEVEPLHFTCVSTSDGTRIERDDAMSSFGVTPAVGGLSSGTVGEASTALSSAAQVALQSLSHAMASAEQQLQVLQEKQQQLLKLQQQKAKLEAKLHQTTAAAAAAASAVGPVHNSVPSNPVAAPGFFIHPSDVIPPTPKTTPLFMTPPLTPPNEAVSVVINAELAQLFPGSVIDPPAVNLAAHNKNSNKSRMNPLGSGLALAISHASHFLQPPPHQSIIIERMHSGARRFVTLDFGRPILLTDVLIPTCGDLASLSIDIWTLGEEVDGRRLVVATDISTHSLILHDLIPPPVCRFMKITVIGRYGSTNARAKIPLGFYYGHTYILPWESELKLMHDPLKGEGESANQPEIDQHLAMMVALQEDIQCRYNLACHRLETLLQSIDLPPLNSANNAQYFLRKPDKAVEEDSRVFSAYQDCIQLQLQLNLAHNAVQRLKVALGASRKMLSETSNPEDLIQTSSTEQLRTIIRYLLDTLLSLLHASNGHSVPAVLQSTFHAQACEELFKHLCISGTPKIRLHTGLLLVQLCGGERWWGQFLSNVLQELYNSEQLLIFPQDRVFMLLSCIGQRSLSNSGVLESLLNLLDNLLSPLQPQLPMHRRTEGVLDIPMISWVVMLVSRLLDYVATVEDEAAAAKKPLNGNQWSFINNNLHTQSLNRSSKGSSSLDRLYSRKIRKQLVHHKQQLNLLKAKQKALVEQMEKEKIQSNKGSSYKLLVEQAKLKQATSKHFKDLIRLRRTAEWSRSNLDTEVTTAKESPEIEPLPFTLAHERCISVVQKLVLFLLSMDFTCHADLLLFVCKVLARIANATRPTIHLCEIVNEPQLERLLLLLVGTDFNRGDISWGGAWAQYSLTCMLQDILAGELLAPVAAEAMEEGTVGDDVGATAGDSDDSLQQSSVQLLETIDEPLTHDITGAPPLSSLEKDKEIDLELLQDLMEVDIDPLDIDLEKDPLAAKVFKPISSTWYDYWGADYGTYNYNPYIGGLGIPVAKPPANTEKNGSQTVSVSVSQALDARLEVGLEQQAELMLKMMSTLEADSILQALTNTSPTLSQSPTGTDDSLLGGLQAANQTSQLIIQLSSVPMLNVCFNKLFSMLQVHHVQLESLLQLWLTLSLNSSSTGNKENGADIFLYNANRIPVISLNQASITSFLTVLAWYPNTLLRTWCLVLHSLTLMTNMQLNSGSSSAIGTQESTAHLLVSDPNLIHVLVKFLSGTSPHGTNQHSPQVGPTATQAMQEFLTRLQVHLSSTCPQIFSEFLLKLIHILSTERGAFQTGQGPLDAQVKLLEFTLEQNFEVVSVSTISAVIESVTFLVHHYITCSDKVMSRSGSDSSVGARACFGGLFANLIRPGDAKAVCGEMTRDQLMFDLLKLVNILVQLPLSGNREYSARVSVTTNTTDSVSDEEKVSGGKDGNGSSTSVQGSPAYVADLVLANQQIMSQILSALGLCNSSAMAMIIGASGLHLTKHENFHGGLDAISVGDGLFTILTTLSKKASTVHMMLQPILTYMACGYMGRQGSLATCQLSEPLLWFILRVLDTSDALKAFHDMGGVQLICNNMVTSTRAIVNTARSMVSTIMKFLDSGPNKAVDSTLKTRILASEPDNAEGIHNFAPLGTITSSSPTAQPAEVLLQATPPHRRARSAAWSYIFLPEEAWCDLTIHLPAAVLLKEIHIQPHLASLATCPSSVSVEVSADGVNMLPLSTPVVTSGLTYIKIQLVKAEVASAVCLRLHRPRDASTLGLSQIKLLGLTAFGTTSSATVNNPFLPSEDQVSKTSIGWLRLLHHCLTHISDLEGMMASAAAPTANLLQTCAALLMSPYCGMHSPNIEVVLVKIGLQSTRIGLKLIDILLRNCAASGSDPTDLNSPLLFGRLNGLSSDSTIDILYQLGTTQDPGTKDRIQALLKWVSDSARVAAMKRSGRMNYMCPNSSTVEYGLLMPSPSHLHCVAAILWHSYELLVEYDLPALLDQELFELLFNWSMSLPCNMVLKKAVDSLLCSMCHVHPNYFSLLMGWMGITPPPVQCHHRLSMTDDSKKQDLSSSLTDDSKNAQAPLALTESHLATLASSSQSPEAIKQLLDSGLPSLLVRSLASFCFSHISSSESIAQSIDISQDKLRRHHVPQQCNKMPITADLVAPILRFLTEVGNSHIMKDWLGGSEVNPLWTALLFLLCHSGSTSGSHNLGAQQTSARSASLSSAATTGLTTQQRTAIENATVAFFLQCISCHPNNQKLMAQVLCELFQTSPQRGNLPTSGNISGFIRRLFLQLMLEDEKVTMFLQSPCPLYKGRINATSHVIQHPMYGAGHKFRTLHLPVSTTLSDVLDRVSDTPSITAKLISEQKDDKEKKNHEEKEKVKAENGFQDNYSVVVASGLKSQSKRAVSATPPRPPSRRGRTIPDKIGSTSGAEAANKIITVPVFHLFHKLLAGQPLPAEMTLAQLLTLLYDRKLPQGYRSIDLTVKLGSRVITDPSLSKTDSYKRLHPEKDHGDLLASCPEDEALTPGDECMDGILDESLLETCPIQSPLQVFAGMGGLALIAERLPMLYPEVIQQVSAPVVTSTTQEKPKDSDQFEWVTIEQSGELVYEAPETVAAEPPPIKSAVQTMSPIPAHSLAAFGLFLRLPGYAEVLLKERKHAQCLLRLVLGVTDDGEGSHILQSPSANVLPTLPFHVLRSLFSTTPLTTDDGVLLRRMALEIGALHLILVCLSALSHHSPRVPNSSVNQTEPQVSSSHNPTSTEEQQLYWAKGTGFGTGSTASGWDVEQALTKQRLEEEHVTCLLQVLASYINPVSSAVNGEAQSSHETRGQNSNALPSVLLELLSQSCLIPAMSSYLRNDSVLDMARHVPLYRALLELLRAIASCAAMVPLLLPLSTENGEEEEEQSECQTSVGTLLAKMKTCVDTYTNRLRSKRENVKTGVKPDASDQEPEGLTLLVPDIQKTAEIVYAATTSLRQANQEKKLGEYSKKAAMKPKPLSVLKSLEEKYVAVMKKLQFDTFEMVSEDEDGKLGFKVNYHYMSQVKNANDANSAARARRLAQEAVTLSTSLPLSSSSSVFVRCDEERLDIMKVLITGPADTPYANGCFEFDVYFPQDYPSSPPLVNLETTGGHSVRFNPNLYNDGKVCLSILNTWHGRPEEKWNPQTSSFLQVLVSVQSLILVAEPYFNEPGYERSRGTPSGTQSSREYDGNIRQATVKWAMLEQIRNPSPCFKEVIHKHFYLKRVEIMAQCEEWIADIQQYSSDKRVGRTMSHHAAALKRHTAQLREELLKLPCPEGLDPDTDDAPEVCRATTGAEETLMHDQVKPSSSKELPSDFQL
uniprot
proteins
ec_number
2.3.2.24
uniprot
proteins
function
FUNCTION: Anti-apoptotic protein known as inhibitor of apoptosis (IAP) which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase (PubMed:14765125, PubMed:15200957, PubMed:18329369). Unlike most IAPs, does not contain a RING domain and it is not a RING-type E3 ligase (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Instead acts as a dual E2/E3 enzyme that combines ubiquitin conjugating (E2) and ubiquitin ligase (E3) activities in a single polypeptide (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitination is mediated by a non-canonical E1 ubiquitin activating enzyme UBA6 (PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitinates CASP3, CASP7 and CASP9 and inhibits their caspase activity; also ubiquitinates their procaspases but to a weaker extent (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitinates pro-apoptotic factors DIABLO/SMAC and HTRA2 (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). DIABLO/SMAC antagonizes the caspase inhibition activity of BIRC6 by competing for the same binding sites as the caspases (PubMed:18329369, PubMed:36758106). Ubiquitinates the autophagy protein MAP1LC3B; this activity is also inhibited by DIABLO/SMAC (PubMed:36758105). Important regulator for the final stages of cytokinesis (PubMed:18329369). Crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification (PubMed:18329369). {ECO:0000269|PubMed:14765125, ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:18329369, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758105, ECO:0000269|PubMed:36758106}.
uniprot
proteins
mass_dalton
530269
uniprot
proteins
mutagenesis
MUTAGEN 328; /note="C->S: Impairs ubiquitination of CASP3, CASP7 and HTRA2 mutant 'A-306'; when associated with S-331. Abolishes interaction with DIABLO/SMAC and impairs ubiquitination of DIABLO/SMAC; when associated with S-331 and 1616-A--A-1666 del."; /evidence="ECO:0000269|PubMed:36758104"; MUTAGEN 331; /note="C->S: Impairs ubiquitination of CASP3, CASP7 and HTRA2 mutant 'A-306'; when associated with S-328. Abolishes interaction with DIABLO/SMAC and impairs ubiquitination of DIABLO/SMAC; when associated with S-328 and 1616-A--A-1666 del."; /evidence="ECO:0000269|PubMed:36758104"; MUTAGEN 342; /note="D->A: Abolishes interaction with CASP3 and the caspase inhibition activity on CASP3. Impairs interaction with CASP7 and abolishes the caspase inhibition activity on CASP7. Abolishes interaction with CASP9. Abolishes interaction with monomeric DIABLO/SMAC 'D-81' mutant. Abolishes interaction with N-degron peptide from DIABLO/SMAC."; /evidence="ECO:0000269|PubMed:36758105, ECO:0000269|PubMed:36758106"; MUTAGEN 342; /note="D->Q: Fails to ubiquitinate N-degron peptide from HTRA2. Impairs DIABLO/SMAC inhibition on the ubiquitination of MAP1LC3B by BIRC6. Enhances ubiquitination of DIABLO/SMAC. Impairs interaction with DIABLO/SMAC; when associated with H-351. Severely impairs DIABLO/SMAC inhibition on the ubiquitination of MAP1LC3B by BIRC6; when associated with 2228-S--T-2295 del and 3190-A--A-3193. Enhances ubiquitination of DIABLO/SMAC; when associated with 2228-S--T-2295 del and 3190-A--A-3193."; /evidence="ECO:0000269|PubMed:36758105"; MUTAGEN 351; /note="H->D: Impairs interaction with CASP3 and abolishes the caspase inhibition activity on CASP3. Impairs interaction with CASP7 but has little effect on the caspase inhibition activity on CASP7. Impairs interaction with CASP9. Impairs interaction with monomeric DIABLO/SMAC 'D-81' mutant. Impairs interaction with N-degron peptide from DIABLO/SMAC. Impairs interaction with DIABLO/SMAC; when associated with A-342."; /evidence="ECO:0000269|PubMed:36758105, ECO:0000269|PubMed:36758106"; MUTAGEN 1616..1666; /note="Missing: Slightly impairs interaction with DIABLO/SMAC. Abolishes interaction with DIABLO/SMAC and impairs ubiquitination of DIABLO/SMAC; when associated with S-328 and S-331."; /evidence="ECO:0000269|PubMed:36758104"; MUTAGEN 2228..2295; /note="Missing: Impairs DIABLO/SMAC inhibition on the ubiquitination of MAP1LC3B by BIRC6. Enhances ubiquitination of DIABLO/SMAC. Severely impairs DIABLO/SMAC inhibition on the ubiquitination of MAP1LC3B by BIRC6; when associated with Q-342 and 3190-A--A-3193. Enhances ubiquitination of DIABLO/SMAC; when associated with Q-342 and 3190-A--A-3193."; /evidence="ECO:0000269|PubMed:36758105"; MUTAGEN 3189..3193; /note="HRRAR->AAAAA: Impairs interaction with monomeric DIABLO/SMAC 'D-81' mutant."; /evidence="ECO:0000269|PubMed:36758106"; MUTAGEN 3189..3193; /note="HRRAR->DDDDD: Impairs interaction with CASP7 and mildly impairs the caspase inhibition activity on CASP7. Impairs interaction with monomeric DIABLO/SMAC 'D-81' mutant. Impairs interaction with DIABLO/SMAC; when associated with A-342. Abolishes interaction with monomeric DIABLO/SMAC 'D-81' mutant; when associated with A-342."; /evidence="ECO:0000269|PubMed:36758106"; MUTAGEN 3190..3193; /note="RRAR->AAAA: No effect on DIABLO/SMAC inhibition on the ubiquitination of MAP1LC3B by BIRC6. No effect on ubiquitination of DIABLO/SMAC. Severely impairs DIABLO/SMAC inhibition on the ubiquitination of MAP1LC3B by BIRC6; when associated with Q-342 and 2228-S--T-2295 del. Enhances ubiquitination of DIABLO/SMAC; when associated with Q-342 and 2228-S--T-2295 del."; /evidence="ECO:0000269|PubMed:36758105"; MUTAGEN 4094..4145; /note="Missing: Impairs MAP1LC3B ubiquitination without disrupting HTRA2 ubiquitination."; /evidence="ECO:0000269|PubMed:36758105"; MUTAGEN 4666; /note="C->A: Catalytically inactive; fails to autoubiquitinate in the presence of UBA6."; /evidence="ECO:0000269|PubMed:36758105
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated; mediated by RNF41 E3 ligase and leads to proteasomal degradation, impairing inhibition of apoptosis (PubMed:14765125). Deubiquitinated by USP8/UBPY (PubMed:18329369). Autoubiquitinated; mediated by E1 ubiquitin activating enzyme UBA6 (PubMed:36758104, PubMed:36758105, PubMed:36758106). {ECO:0000269|PubMed:14765125, ECO:0000269|PubMed:18329369, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758105, ECO:0000269|PubMed:36758106}.; PTM: Proteolytically cleaved. Acts as substrate for CASP3, CASP6, CASP7, CASP9 and HTRA2. {ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758105}.
uniprot
proteins
protein_family
BIRC6 family
uniprot
proteins
pubmed
10544019
uniprot
proteins
pubmed
10574462
uniprot
proteins
pubmed
12168954
uniprot
proteins
pubmed
14765125
uniprot
proteins
pubmed
15200957
uniprot
proteins
pubmed
15340445
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18329369
uniprot
proteins
pubmed
18414036
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22496338
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
36758104
uniprot
proteins
pubmed
36758105
uniprot
proteins
pubmed
36758106
uniprot
proteins
sequence_length
4857
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane {ECO:0000269|PubMed:18329369}. Endosome {ECO:0000269|PubMed:18329369}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:18329369}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:18329369}. Midbody, Midbody ring {ECO:0000269|PubMed:18329369}. Note=Exhibits cell cycle-dependent localization. Concentrates in a pericentriolar compartment in interphase, moves partially to spindle poles in metaphase, and finally localizes to the spindle midzone and the midbody in telophase and during cytokinesis. On the midbody, localizes to the midbody ring, also called Flemming body (PubMed:18329369). In interphase cells, localizes to the trans-Golgi network membrane and endosomes. During cytokinesis, a fraction moves to the midzone where it specifically arrives at the midbody ring. After abscission completion, travels with the midbody remnant into one daughter cell, and remains bound to it until a new midbody ring is formed during the next cell division (PubMed:18329369). {ECO:0000269|PubMed:18329369}.
uniprot
proteins