Full text data of TAB3
TAB3
(MAP3K7IP3)
[Confidence: low (only semi-automatic identification from reviews)]
TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 (Mitogen-activated protein kinase kinase kinase 7-interacting protein 3; NF-kappa-B-activating protein 1; TAK1-binding protein 3; TAB-3; TGF-beta-activated kinase 1-binding protein 3)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 (Mitogen-activated protein kinase kinase kinase 7-interacting protein 3; NF-kappa-B-activating protein 1; TAK1-binding protein 3; TAB-3; TGF-beta-activated kinase 1-binding protein 3)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q8N5C8
ID TAB3_HUMAN Reviewed; 712 AA.
AC Q8N5C8; A6NDD9; Q6VQR0;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-MAY-2009, sequence version 2.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=TGF-beta-activated kinase 1 and MAP3K7-binding protein 3;
DE AltName: Full=Mitogen-activated protein kinase kinase kinase 7-interacting protein 3;
DE AltName: Full=NF-kappa-B-activating protein 1;
DE AltName: Full=TAK1-binding protein 3;
DE Short=TAB-3;
DE AltName: Full=TGF-beta-activated kinase 1-binding protein 3;
GN Name=TAB3; Synonyms=MAP3K7IP3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH MAP3K7; TRAF2
RP AND TRAF6, UBIQUITINATION, PHOSPHORYLATION, FUNCTION, AND VARIANT
RP ARG-394.
RC TISSUE=Kidney;
RX PubMed=14633987; DOI=10.1093/emboj/cdg605;
RA Ishitani T., Takaesu G., Ninomiya-Tsuji J., Shibuya H., Gaynor R.B.,
RA Matsumoto K.;
RT "Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling.";
RL EMBO J. 22:6277-6288(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY,
RP PHOSPHORYLATION, INTERACTION WITH TAB1; TAB2 AND MAP3K7, AND VARIANT
RP ARG-394.
RX PubMed=14670075; DOI=10.1042/BJ20031794;
RA Cheung P.C., Nebreda A.R., Cohen P.;
RT "TAB3, a new binding partner of the protein kinase TAK1.";
RL Biochem. J. 378:27-34(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH MAP3K7
RP AND TRAF6, TISSUE SPECIFICITY, FUNCTION, AND VARIANT ARG-394.
RX PubMed=14766965; DOI=10.1073/pnas.0307314101;
RA Jin G., Klika A., Callahan M., Faga B., Danzig J., Jiang Z., Li X.,
RA Stark G.R., Harrington J., Sherf B.;
RT "Identification of a human NF-kappaB-activating protein, TAB3.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:2028-2033(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP ARG-394.
RC TISSUE=Eye;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH RBCK1.
RX PubMed=17449468; DOI=10.1074/jbc.M701913200;
RA Tian Y., Zhang Y., Zhong B., Wang Y.Y., Diao F.C., Wang R.P.,
RA Zhang M., Chen D.Y., Zhai Z.H., Shu H.B.;
RT "RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-
RT triggered NF-kappaB activation by targeting TAB2/3 for degradation.";
RL J. Biol. Chem. 282:16776-16782(2007).
RN [7]
RP PHOSPHORYLATION AT SER-506.
RX PubMed=18021073; DOI=10.1042/BJ20071149;
RA Mendoza H., Campbell D.G., Burness K., Hastie J., Ronkina N.,
RA Shim J.H., Arthur J.S., Davis R.J., Gaestel M., Johnson G.L.,
RA Ghosh S., Cohen P.;
RT "Roles for TAB1 in regulating the IL-1-dependent phosphorylation of
RT the TAB3 regulatory subunit and activity of the TAK1 complex.";
RL Biochem. J. 409:711-722(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60; THR-404 AND SER-492,
RP AND MASS SPECTROMETRY.
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 [9]
RP INTERACTION WITH WDR34.
RX PubMed=19521662; DOI=10.1007/s00018-009-0059-6;
RA Gao D., Wang R., Li B., Yang Y., Zhai Z., Chen D.Y.;
RT "WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-
RT induced NF-kappaB activation pathway.";
RL Cell. Mol. Life Sci. 66:2573-2584(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-60, MASS SPECTROMETRY, AND CLEAVAGE OF
RP INITIATOR METHIONINE.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP INTERACTION WITH TRIM5.
RX PubMed=21512573; DOI=10.1038/nature09976;
RA Pertel T., Hausmann S., Morger D., Zueger S., Guerra J., Lascano J.,
RA Reinhard C., Santoni F.A., Uchil P.D., Chatel L., Bisiaux A.,
RA Albert M.L., Strambio-De-Castillia C., Mothes W., Pizzato M.,
RA Gruetter M.G., Luban J.;
RT "TRIM5 is an innate immune sensor for the retrovirus capsid lattice.";
RL Nature 472:361-365(2011).
CC -!- FUNCTION: Adapter linking MAP3K7/TAK1 and TRAF6 or TRAF2. Mediator
CC of MAP3K7 activation, respectively in the IL1 and TNF signaling
CC pathways. Plays a role in activation of NF-kappa-B and AP1
CC transcription factor. Isoform 2 may be an oncogenic factor.
CC -!- SUBUNIT: Interacts with TAB1, TAB2, MAP3K7, TRAF2 and TRAF6. The
CC minimal TAB3-containing complex (TAB1-MAP3K7-TAB3) appears not to
CC contain TAB2. However, it seems sensible to consider that TAB2 may
CC also join this complex and may act in a cooperative manner with
CC TAB3. Interacts with WDR34 (via the WD domains). Interacts with
CC RBCK1. Binds 'Lys-63'-linked polyubiquitin chains. Interacts with
CC TRIM5.
CC -!- INTERACTION:
CC Q14457:BECN1; NbExp=9; IntAct=EBI-359964, EBI-949378;
CC O43318:MAP3K7; NbExp=3; IntAct=EBI-359964, EBI-358684;
CC Q62073:Map3k7 (xeno); NbExp=2; IntAct=EBI-359964, EBI-1775345;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Tab3a;
CC IsoId=Q8N5C8-1; Sequence=Displayed;
CC Name=2; Synonyms=Tab3b;
CC IsoId=Q8N5C8-2; Sequence=VSP_017516;
CC -!- TISSUE SPECIFICITY: Widely expressed. Constitutively overexpressed
CC in certain tumor tissues. Isoform 1 is a major transcript while
CC isoform 2 is a minor transcript.
CC -!- DOMAIN: The RanBP2-type zinc finger (NZF) mediates binding to two
CC consecutive 'Lys-63'-linked ubiquitins (By similarity).
CC -!- PTM: Ubiquitinated; following IL1 stimulation or TRAF6
CC overexpression.
CC -!- PTM: Phosphorylated at Ser-506 by MAPKAPK2 and MAPKAPK3 following
CC IL1 treatment.
CC -!- SIMILARITY: Contains 1 CUE domain.
CC -!- SIMILARITY: Contains 1 RanBP2-type zinc finger.
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DR EMBL; AY437560; AAR06179.1; -; mRNA.
DR EMBL; AY371491; AAQ88279.1; -; mRNA.
DR EMBL; AY331591; AAQ92938.1; -; mRNA.
DR EMBL; AY331592; AAQ92939.1; -; mRNA.
DR EMBL; AC108359; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032526; AAH32526.1; -; mRNA.
DR RefSeq; NP_690000.2; NM_152787.3.
DR RefSeq; XP_005274539.1; XM_005274482.1.
DR RefSeq; XP_005274540.1; XM_005274483.1.
DR UniGene; Hs.188256; -.
DR ProteinModelPortal; Q8N5C8; -.
DR SMR; Q8N5C8; 4-57, 684-712.
DR DIP; DIP-32489N; -.
DR IntAct; Q8N5C8; 9.
DR MINT; MINT-1145071; -.
DR PhosphoSite; Q8N5C8; -.
DR DMDM; 229462756; -.
DR PaxDb; Q8N5C8; -.
DR PRIDE; Q8N5C8; -.
DR Ensembl; ENST00000288422; ENSP00000288422; ENSG00000157625.
DR Ensembl; ENST00000378930; ENSP00000368212; ENSG00000157625.
DR Ensembl; ENST00000378932; ENSP00000368214; ENSG00000157625.
DR Ensembl; ENST00000378933; ENSP00000368215; ENSG00000157625.
DR GeneID; 257397; -.
DR KEGG; hsa:257397; -.
DR UCSC; uc004dcj.3; human.
DR CTD; 257397; -.
DR GeneCards; GC0XM030845; -.
DR H-InvDB; HIX0016717; -.
DR HGNC; HGNC:30681; TAB3.
DR HPA; HPA034980; -.
DR MIM; 300480; gene.
DR neXtProt; NX_Q8N5C8; -.
DR PharmGKB; PA165757406; -.
DR eggNOG; NOG47991; -.
DR HOGENOM; HOG000261646; -.
DR HOVERGEN; HBG056952; -.
DR InParanoid; Q8N5C8; -.
DR KO; K12793; -.
DR OMA; QGPVPHY; -.
DR OrthoDB; EOG776SPP; -.
DR PhylomeDB; Q8N5C8; -.
DR Reactome; REACT_6782; TRAF6 Mediated Induction of proinflammatory cytokines.
DR Reactome; REACT_6900; Immune System.
DR GeneWiki; MAP3K7IP3; -.
DR GenomeRNAi; 257397; -.
DR NextBio; 93003; -.
DR PRO; PR:Q8N5C8; -.
DR ArrayExpress; Q8N5C8; -.
DR Bgee; Q8N5C8; -.
DR CleanEx; HS_MAP3K7IP3; -.
DR Genevestigator; Q8N5C8; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0000187; P:activation of MAPK activity; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB cascade; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0007254; P:JNK cascade; TAS:Reactome.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR GO; GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:Reactome.
DR GO; GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR GO; GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
DR GO; GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
DR GO; GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR InterPro; IPR003892; CUE.
DR InterPro; IPR001876; Znf_RanBP2.
DR Pfam; PF02845; CUE; 1.
DR SMART; SM00546; CUE; 1.
DR SMART; SM00547; ZnF_RBZ; 1.
DR PROSITE; PS51140; CUE; 1.
DR PROSITE; PS01358; ZF_RANBP2_1; 1.
DR PROSITE; PS50199; ZF_RANBP2_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Coiled coil; Complete proteome;
KW Metal-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Ubl conjugation; Zinc; Zinc-finger.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 712 TGF-beta-activated kinase 1 and MAP3K7-
FT binding protein 3.
FT /FTId=PRO_0000226972.
FT DOMAIN 8 51 CUE.
FT ZN_FING 682 712 RanBP2-type.
FT COILED 517 559 Potential.
FT COMPBIAS 152 451 Pro-rich.
FT COMPBIAS 504 509 Poly-Ser.
FT COMPBIAS 659 662 Poly-Ala.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 60 60 Phosphoserine.
FT MOD_RES 404 404 Phosphothreonine.
FT MOD_RES 492 492 Phosphoserine.
FT MOD_RES 506 506 Phosphoserine; by MAPKAPK2 and MAPKAPK3.
FT VAR_SEQ 602 629 Missing (in isoform 2).
FT /FTId=VSP_017516.
FT VARIANT 394 394 W -> R (in dbSNP:rs5927629).
FT /FTId=VAR_055294.
SQ SEQUENCE 712 AA; 78683 MW; 591DAC3E74CE9294 CRC64;
MAQSSPQLDI QVLHDLRQRF PEIPEGVVSQ CMLQNNNNLE ACCRALSQES SKYLYMEYHS
PDDNRMNRNR LLHINLGIHS PSSYHPGDGA QLNGGRTLVH SSSDGHIDPQ HAAGKQLICL
VQEPHSAPAV VAATPNYNPF FMNEQNRSAA TPPSQPPQQP SSMQTGMNPS AMQGPSPPPP
PPSYMHIPRY STNPITVTVS QNLPSGQTVP RALQILPQIP SNLYGSPGSI YIRQTSQSSS
GRQTPQSTPW QSSPQGPVPH YSQRPLPVYP HQQNYQPSQY SPKQQQIPQS AYHSPPPSQC
PSPFSSPQHQ VQPSQLGHIF MPPSPSTTPP HPYQQGPPSY QKQGSHSVAY LPYTASSLSK
GSMKKIEITV EPSQRPGTAI NRSPSPISNQ PSPWNQHSLY TATTPPSSSP SRGISSQPKP
PFSVNPVYIT YTQPTGPSCT PSPSPRVIPN PTTVFKITVG RATTENLLNL VDQEERSAAP
EPIQPISVIP GSGGEKGSHK YQRSSSSGSD DYAYTQALLL HQRARMERLA KQLKLEKEEL
ERLKSEVNGM EHDLMQRRLR RVSCTTAIPT PEEMTRLRSM NRQLQINVDC TLKEVDLLQS
RGNFDPKAMN NFYDNIEPGP VVPPKPSKKD SSDPCTIERK ARRISVTSKV QADIHDTQAA
AADEHRTGST QSPRTQPRDE DYEGAPWNCD SCTFLNHPAL NRCEQCEMPR YT
//
ID TAB3_HUMAN Reviewed; 712 AA.
AC Q8N5C8; A6NDD9; Q6VQR0;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-MAY-2009, sequence version 2.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=TGF-beta-activated kinase 1 and MAP3K7-binding protein 3;
DE AltName: Full=Mitogen-activated protein kinase kinase kinase 7-interacting protein 3;
DE AltName: Full=NF-kappa-B-activating protein 1;
DE AltName: Full=TAK1-binding protein 3;
DE Short=TAB-3;
DE AltName: Full=TGF-beta-activated kinase 1-binding protein 3;
GN Name=TAB3; Synonyms=MAP3K7IP3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH MAP3K7; TRAF2
RP AND TRAF6, UBIQUITINATION, PHOSPHORYLATION, FUNCTION, AND VARIANT
RP ARG-394.
RC TISSUE=Kidney;
RX PubMed=14633987; DOI=10.1093/emboj/cdg605;
RA Ishitani T., Takaesu G., Ninomiya-Tsuji J., Shibuya H., Gaynor R.B.,
RA Matsumoto K.;
RT "Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling.";
RL EMBO J. 22:6277-6288(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY,
RP PHOSPHORYLATION, INTERACTION WITH TAB1; TAB2 AND MAP3K7, AND VARIANT
RP ARG-394.
RX PubMed=14670075; DOI=10.1042/BJ20031794;
RA Cheung P.C., Nebreda A.R., Cohen P.;
RT "TAB3, a new binding partner of the protein kinase TAK1.";
RL Biochem. J. 378:27-34(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH MAP3K7
RP AND TRAF6, TISSUE SPECIFICITY, FUNCTION, AND VARIANT ARG-394.
RX PubMed=14766965; DOI=10.1073/pnas.0307314101;
RA Jin G., Klika A., Callahan M., Faga B., Danzig J., Jiang Z., Li X.,
RA Stark G.R., Harrington J., Sherf B.;
RT "Identification of a human NF-kappaB-activating protein, TAB3.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:2028-2033(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP ARG-394.
RC TISSUE=Eye;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH RBCK1.
RX PubMed=17449468; DOI=10.1074/jbc.M701913200;
RA Tian Y., Zhang Y., Zhong B., Wang Y.Y., Diao F.C., Wang R.P.,
RA Zhang M., Chen D.Y., Zhai Z.H., Shu H.B.;
RT "RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-
RT triggered NF-kappaB activation by targeting TAB2/3 for degradation.";
RL J. Biol. Chem. 282:16776-16782(2007).
RN [7]
RP PHOSPHORYLATION AT SER-506.
RX PubMed=18021073; DOI=10.1042/BJ20071149;
RA Mendoza H., Campbell D.G., Burness K., Hastie J., Ronkina N.,
RA Shim J.H., Arthur J.S., Davis R.J., Gaestel M., Johnson G.L.,
RA Ghosh S., Cohen P.;
RT "Roles for TAB1 in regulating the IL-1-dependent phosphorylation of
RT the TAB3 regulatory subunit and activity of the TAK1 complex.";
RL Biochem. J. 409:711-722(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60; THR-404 AND SER-492,
RP AND MASS SPECTROMETRY.
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 [9]
RP INTERACTION WITH WDR34.
RX PubMed=19521662; DOI=10.1007/s00018-009-0059-6;
RA Gao D., Wang R., Li B., Yang Y., Zhai Z., Chen D.Y.;
RT "WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-
RT induced NF-kappaB activation pathway.";
RL Cell. Mol. Life Sci. 66:2573-2584(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-60, MASS SPECTROMETRY, AND CLEAVAGE OF
RP INITIATOR METHIONINE.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP INTERACTION WITH TRIM5.
RX PubMed=21512573; DOI=10.1038/nature09976;
RA Pertel T., Hausmann S., Morger D., Zueger S., Guerra J., Lascano J.,
RA Reinhard C., Santoni F.A., Uchil P.D., Chatel L., Bisiaux A.,
RA Albert M.L., Strambio-De-Castillia C., Mothes W., Pizzato M.,
RA Gruetter M.G., Luban J.;
RT "TRIM5 is an innate immune sensor for the retrovirus capsid lattice.";
RL Nature 472:361-365(2011).
CC -!- FUNCTION: Adapter linking MAP3K7/TAK1 and TRAF6 or TRAF2. Mediator
CC of MAP3K7 activation, respectively in the IL1 and TNF signaling
CC pathways. Plays a role in activation of NF-kappa-B and AP1
CC transcription factor. Isoform 2 may be an oncogenic factor.
CC -!- SUBUNIT: Interacts with TAB1, TAB2, MAP3K7, TRAF2 and TRAF6. The
CC minimal TAB3-containing complex (TAB1-MAP3K7-TAB3) appears not to
CC contain TAB2. However, it seems sensible to consider that TAB2 may
CC also join this complex and may act in a cooperative manner with
CC TAB3. Interacts with WDR34 (via the WD domains). Interacts with
CC RBCK1. Binds 'Lys-63'-linked polyubiquitin chains. Interacts with
CC TRIM5.
CC -!- INTERACTION:
CC Q14457:BECN1; NbExp=9; IntAct=EBI-359964, EBI-949378;
CC O43318:MAP3K7; NbExp=3; IntAct=EBI-359964, EBI-358684;
CC Q62073:Map3k7 (xeno); NbExp=2; IntAct=EBI-359964, EBI-1775345;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Tab3a;
CC IsoId=Q8N5C8-1; Sequence=Displayed;
CC Name=2; Synonyms=Tab3b;
CC IsoId=Q8N5C8-2; Sequence=VSP_017516;
CC -!- TISSUE SPECIFICITY: Widely expressed. Constitutively overexpressed
CC in certain tumor tissues. Isoform 1 is a major transcript while
CC isoform 2 is a minor transcript.
CC -!- DOMAIN: The RanBP2-type zinc finger (NZF) mediates binding to two
CC consecutive 'Lys-63'-linked ubiquitins (By similarity).
CC -!- PTM: Ubiquitinated; following IL1 stimulation or TRAF6
CC overexpression.
CC -!- PTM: Phosphorylated at Ser-506 by MAPKAPK2 and MAPKAPK3 following
CC IL1 treatment.
CC -!- SIMILARITY: Contains 1 CUE domain.
CC -!- SIMILARITY: Contains 1 RanBP2-type zinc finger.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AY437560; AAR06179.1; -; mRNA.
DR EMBL; AY371491; AAQ88279.1; -; mRNA.
DR EMBL; AY331591; AAQ92938.1; -; mRNA.
DR EMBL; AY331592; AAQ92939.1; -; mRNA.
DR EMBL; AC108359; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032526; AAH32526.1; -; mRNA.
DR RefSeq; NP_690000.2; NM_152787.3.
DR RefSeq; XP_005274539.1; XM_005274482.1.
DR RefSeq; XP_005274540.1; XM_005274483.1.
DR UniGene; Hs.188256; -.
DR ProteinModelPortal; Q8N5C8; -.
DR SMR; Q8N5C8; 4-57, 684-712.
DR DIP; DIP-32489N; -.
DR IntAct; Q8N5C8; 9.
DR MINT; MINT-1145071; -.
DR PhosphoSite; Q8N5C8; -.
DR DMDM; 229462756; -.
DR PaxDb; Q8N5C8; -.
DR PRIDE; Q8N5C8; -.
DR Ensembl; ENST00000288422; ENSP00000288422; ENSG00000157625.
DR Ensembl; ENST00000378930; ENSP00000368212; ENSG00000157625.
DR Ensembl; ENST00000378932; ENSP00000368214; ENSG00000157625.
DR Ensembl; ENST00000378933; ENSP00000368215; ENSG00000157625.
DR GeneID; 257397; -.
DR KEGG; hsa:257397; -.
DR UCSC; uc004dcj.3; human.
DR CTD; 257397; -.
DR GeneCards; GC0XM030845; -.
DR H-InvDB; HIX0016717; -.
DR HGNC; HGNC:30681; TAB3.
DR HPA; HPA034980; -.
DR MIM; 300480; gene.
DR neXtProt; NX_Q8N5C8; -.
DR PharmGKB; PA165757406; -.
DR eggNOG; NOG47991; -.
DR HOGENOM; HOG000261646; -.
DR HOVERGEN; HBG056952; -.
DR InParanoid; Q8N5C8; -.
DR KO; K12793; -.
DR OMA; QGPVPHY; -.
DR OrthoDB; EOG776SPP; -.
DR PhylomeDB; Q8N5C8; -.
DR Reactome; REACT_6782; TRAF6 Mediated Induction of proinflammatory cytokines.
DR Reactome; REACT_6900; Immune System.
DR GeneWiki; MAP3K7IP3; -.
DR GenomeRNAi; 257397; -.
DR NextBio; 93003; -.
DR PRO; PR:Q8N5C8; -.
DR ArrayExpress; Q8N5C8; -.
DR Bgee; Q8N5C8; -.
DR CleanEx; HS_MAP3K7IP3; -.
DR Genevestigator; Q8N5C8; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0000187; P:activation of MAPK activity; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB cascade; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0007254; P:JNK cascade; TAS:Reactome.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR GO; GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:Reactome.
DR GO; GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR GO; GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
DR GO; GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
DR GO; GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR InterPro; IPR003892; CUE.
DR InterPro; IPR001876; Znf_RanBP2.
DR Pfam; PF02845; CUE; 1.
DR SMART; SM00546; CUE; 1.
DR SMART; SM00547; ZnF_RBZ; 1.
DR PROSITE; PS51140; CUE; 1.
DR PROSITE; PS01358; ZF_RANBP2_1; 1.
DR PROSITE; PS50199; ZF_RANBP2_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Coiled coil; Complete proteome;
KW Metal-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Ubl conjugation; Zinc; Zinc-finger.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 712 TGF-beta-activated kinase 1 and MAP3K7-
FT binding protein 3.
FT /FTId=PRO_0000226972.
FT DOMAIN 8 51 CUE.
FT ZN_FING 682 712 RanBP2-type.
FT COILED 517 559 Potential.
FT COMPBIAS 152 451 Pro-rich.
FT COMPBIAS 504 509 Poly-Ser.
FT COMPBIAS 659 662 Poly-Ala.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 60 60 Phosphoserine.
FT MOD_RES 404 404 Phosphothreonine.
FT MOD_RES 492 492 Phosphoserine.
FT MOD_RES 506 506 Phosphoserine; by MAPKAPK2 and MAPKAPK3.
FT VAR_SEQ 602 629 Missing (in isoform 2).
FT /FTId=VSP_017516.
FT VARIANT 394 394 W -> R (in dbSNP:rs5927629).
FT /FTId=VAR_055294.
SQ SEQUENCE 712 AA; 78683 MW; 591DAC3E74CE9294 CRC64;
MAQSSPQLDI QVLHDLRQRF PEIPEGVVSQ CMLQNNNNLE ACCRALSQES SKYLYMEYHS
PDDNRMNRNR LLHINLGIHS PSSYHPGDGA QLNGGRTLVH SSSDGHIDPQ HAAGKQLICL
VQEPHSAPAV VAATPNYNPF FMNEQNRSAA TPPSQPPQQP SSMQTGMNPS AMQGPSPPPP
PPSYMHIPRY STNPITVTVS QNLPSGQTVP RALQILPQIP SNLYGSPGSI YIRQTSQSSS
GRQTPQSTPW QSSPQGPVPH YSQRPLPVYP HQQNYQPSQY SPKQQQIPQS AYHSPPPSQC
PSPFSSPQHQ VQPSQLGHIF MPPSPSTTPP HPYQQGPPSY QKQGSHSVAY LPYTASSLSK
GSMKKIEITV EPSQRPGTAI NRSPSPISNQ PSPWNQHSLY TATTPPSSSP SRGISSQPKP
PFSVNPVYIT YTQPTGPSCT PSPSPRVIPN PTTVFKITVG RATTENLLNL VDQEERSAAP
EPIQPISVIP GSGGEKGSHK YQRSSSSGSD DYAYTQALLL HQRARMERLA KQLKLEKEEL
ERLKSEVNGM EHDLMQRRLR RVSCTTAIPT PEEMTRLRSM NRQLQINVDC TLKEVDLLQS
RGNFDPKAMN NFYDNIEPGP VVPPKPSKKD SSDPCTIERK ARRISVTSKV QADIHDTQAA
AADEHRTGST QSPRTQPRDE DYEGAPWNCD SCTFLNHPAL NRCEQCEMPR YT
//
MIM
300480
*RECORD*
*FIELD* NO
300480
*FIELD* TI
*300480 TAK1-BINDING PROTEIN 3; TAB3
*FIELD* TX
CLONING
By random activation of gene expression (RAGE), Jin et al. (2004)
read moregenerated a limited protein expression library in a transgenic
NF-kappa-B (see 164011) reporter cell line, and the library was selected
for cells that constitutively activated NF-kappa-B. By RT-PCR and
3-prime RACE of one of these clones, they obtained full length TAB3 and
a splice variant that excludes exon 10. They termed the full length
variant TAB3a, and the splice variant TAB3b. TAB3a encodes a deduced
712-amino acid protein that contains an N-terminal CUE domain, a central
coiled-coil region, and a C-terminal zinc finger domain. The CUE domain
is expected to direct self-monoubiquitylation. TAB3b encodes a deduced
684-amino acid protein that lacks 28 amino acids between the coiled-coil
domain and the zinc finger domain. Within their C-terminal zinc finger
domains, TAB3 shares 82% identity with TAB2 (605101). Overall, TAB3
shares 67% identity with X. laevis Tab3. PCR analysis detected both
transcripts in all tissues examined, which included kidney, brain,
prostate, and peripheral blood leukocytes. TAB3b represented 13 to 20%
of the total TAB3 transcripts. RNA dot blot analysis detected expression
in matched normal and tumor cells of testis, skin, and small intestine,
with higher expression in most tumor samples.
GENE FUNCTION
Jin et al. (2004) found that both TAB3a and TAB3b increased expression
from an IL8 (146930) promoter. Overexpression of TAB3 activated both
NF-kappa-B and AP1 (see 165160) transcription factors. The activation of
NF-kappa-B was blocked by an NF-kappa-B inhibitor, and by expression of
dominant negative forms of TNF-alpha (TNFA; 191160)-associated factor-6
(AF6; 159559) and TGF-beta (TGFB; 190180)-activated kinase (AK)
indicating that TAB3 is a constituent of the NF-kappa-B pathway,
functioning upstream of TNFA-AF6 and TGFB-AK. Overexpression of TAB3
resulted in cellular transformation of NIH 3T3 mouse fibroblasts.
Zhang et al. (2012) showed that human TAB2 and TAB3, ubiquitin chain
sensory proteins involved in NF-kappa-B signaling, are directly
inactivated by enteropathogenic E. coli NleE, a conserved bacterial type
III-secreted effector responsible for blocking host NF-kappa-B
signaling. NleE harbored an unprecedented
S-adenosyl-L-methionine-dependent methyltransferase activity that
specifically modified a zinc-coordinating cysteine in the Npl4 zinc
finger (NZF) domains in TAB2 and TAB3. Cysteine-methylated TAB2-NZF and
TAB3-NZF (truncated proteins comprising only the NZF domain) lost the
zinc ion as well as the ubiquitin chain binding activity. Ectopically
expressed or type III secretion system-delivered NleE methylated TAB2
and TAB3 in host cells and diminished their ubiquitin chain binding
activity. Replacement of the NZF domain of TAB3 with the NleE
methylation-insensitive Npl4 NZF domain resulted in NleE-resistant
NF-kappa-B activation. Zhang et al. (2012) postulated that, given the
prevalence of zinc finger motifs and activation of cysteine thiol by
zinc binding, methylation of zinc finger cysteine might regulate other
eukaryotic pathways in addition to NF-kappa-B signaling.
GENE STRUCTURE
Jin et al. (2004) determined that the TAB3 gene contains at least 12
exons. The open reading frame (ORF) begins in exon 6 and ends in exon
12. They predict the possibility of an additional uncharacterized
upstream exon that may contribute to the 5-prime UTR.
MAPPING
Jin et al. (2004) stated that TAB3 maps to chromosome X.
*FIELD* RF
1. Jin, G.; Klika, A.; Callahan, M.; Faga, B.; Danzig, J.; Jiang,
Z.; Li, X.; Stark, G. R.; Harrington, J.; Sherf, B.: Identification
of a human NF-kappa-B-activating protein, TAB3. Proc. Nat. Acad.
Sci. 101: 2029-2033, 2004.
2. Zhang, L.; Ding, X.; Cui, J.; Xu, H.; Chen, J.; Gong, Y.-N.; Hu,
L.; Zhou, Y.; Ge, J.; Lu, Q.; Liu, L.; Chen, S.; Shao, F.: Cysteine
methylation disrupts ubiquitin-chain sensing in NF-kappa-B activation. Nature 481:
204-208, 2012.
*FIELD* CN
Ada Hamosh - updated: 2/7/2012
*FIELD* CD
Patricia A. Hartz: 2/26/2004
*FIELD* ED
alopez: 02/13/2012
terry: 2/7/2012
cwells: 2/26/2004
*RECORD*
*FIELD* NO
300480
*FIELD* TI
*300480 TAK1-BINDING PROTEIN 3; TAB3
*FIELD* TX
CLONING
By random activation of gene expression (RAGE), Jin et al. (2004)
read moregenerated a limited protein expression library in a transgenic
NF-kappa-B (see 164011) reporter cell line, and the library was selected
for cells that constitutively activated NF-kappa-B. By RT-PCR and
3-prime RACE of one of these clones, they obtained full length TAB3 and
a splice variant that excludes exon 10. They termed the full length
variant TAB3a, and the splice variant TAB3b. TAB3a encodes a deduced
712-amino acid protein that contains an N-terminal CUE domain, a central
coiled-coil region, and a C-terminal zinc finger domain. The CUE domain
is expected to direct self-monoubiquitylation. TAB3b encodes a deduced
684-amino acid protein that lacks 28 amino acids between the coiled-coil
domain and the zinc finger domain. Within their C-terminal zinc finger
domains, TAB3 shares 82% identity with TAB2 (605101). Overall, TAB3
shares 67% identity with X. laevis Tab3. PCR analysis detected both
transcripts in all tissues examined, which included kidney, brain,
prostate, and peripheral blood leukocytes. TAB3b represented 13 to 20%
of the total TAB3 transcripts. RNA dot blot analysis detected expression
in matched normal and tumor cells of testis, skin, and small intestine,
with higher expression in most tumor samples.
GENE FUNCTION
Jin et al. (2004) found that both TAB3a and TAB3b increased expression
from an IL8 (146930) promoter. Overexpression of TAB3 activated both
NF-kappa-B and AP1 (see 165160) transcription factors. The activation of
NF-kappa-B was blocked by an NF-kappa-B inhibitor, and by expression of
dominant negative forms of TNF-alpha (TNFA; 191160)-associated factor-6
(AF6; 159559) and TGF-beta (TGFB; 190180)-activated kinase (AK)
indicating that TAB3 is a constituent of the NF-kappa-B pathway,
functioning upstream of TNFA-AF6 and TGFB-AK. Overexpression of TAB3
resulted in cellular transformation of NIH 3T3 mouse fibroblasts.
Zhang et al. (2012) showed that human TAB2 and TAB3, ubiquitin chain
sensory proteins involved in NF-kappa-B signaling, are directly
inactivated by enteropathogenic E. coli NleE, a conserved bacterial type
III-secreted effector responsible for blocking host NF-kappa-B
signaling. NleE harbored an unprecedented
S-adenosyl-L-methionine-dependent methyltransferase activity that
specifically modified a zinc-coordinating cysteine in the Npl4 zinc
finger (NZF) domains in TAB2 and TAB3. Cysteine-methylated TAB2-NZF and
TAB3-NZF (truncated proteins comprising only the NZF domain) lost the
zinc ion as well as the ubiquitin chain binding activity. Ectopically
expressed or type III secretion system-delivered NleE methylated TAB2
and TAB3 in host cells and diminished their ubiquitin chain binding
activity. Replacement of the NZF domain of TAB3 with the NleE
methylation-insensitive Npl4 NZF domain resulted in NleE-resistant
NF-kappa-B activation. Zhang et al. (2012) postulated that, given the
prevalence of zinc finger motifs and activation of cysteine thiol by
zinc binding, methylation of zinc finger cysteine might regulate other
eukaryotic pathways in addition to NF-kappa-B signaling.
GENE STRUCTURE
Jin et al. (2004) determined that the TAB3 gene contains at least 12
exons. The open reading frame (ORF) begins in exon 6 and ends in exon
12. They predict the possibility of an additional uncharacterized
upstream exon that may contribute to the 5-prime UTR.
MAPPING
Jin et al. (2004) stated that TAB3 maps to chromosome X.
*FIELD* RF
1. Jin, G.; Klika, A.; Callahan, M.; Faga, B.; Danzig, J.; Jiang,
Z.; Li, X.; Stark, G. R.; Harrington, J.; Sherf, B.: Identification
of a human NF-kappa-B-activating protein, TAB3. Proc. Nat. Acad.
Sci. 101: 2029-2033, 2004.
2. Zhang, L.; Ding, X.; Cui, J.; Xu, H.; Chen, J.; Gong, Y.-N.; Hu,
L.; Zhou, Y.; Ge, J.; Lu, Q.; Liu, L.; Chen, S.; Shao, F.: Cysteine
methylation disrupts ubiquitin-chain sensing in NF-kappa-B activation. Nature 481:
204-208, 2012.
*FIELD* CN
Ada Hamosh - updated: 2/7/2012
*FIELD* CD
Patricia A. Hartz: 2/26/2004
*FIELD* ED
alopez: 02/13/2012
terry: 2/7/2012
cwells: 2/26/2004