Q8N5C8 (TAB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
TGF-beta-activated kinase 1 and MAP3K7-binding protein 3

Alternative name(s):
Mitogen-activated protein kinase kinase kinase 7-interacting protein 3
NF-kappa-B-activating protein 1
TAK1-binding protein 3
Short name=TAB-3
TGF-beta-activated kinase 1-binding protein 3

Gene names

Name:	TAB3
Synonyms:	MAP3K7IP3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	712 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Adapter linking MAP3K7/TAK1 and TRAF6 or TRAF2. Mediator of MAP3K7 activation, respectively in the IL1 and TNF signaling pathways. Plays a role in activation of NF-kappa-B and AP1 transcription factor. Isoform 2 may be an oncogenic factor. Ref.1 Ref.3
Subunit structure	Interacts with TAB1, TAB2, MAP3K7, TRAF2 and TRAF6. The minimal TAB3-containing complex (TAB1-MAP3K7-TAB3) appears not to contain TAB2. However, it seems sensible to consider that TAB2 may also join this complex and may act in a cooperative manner with TAB3. Interacts with WDR34 (via the WD domains). Interacts with RBCK1. Ref.1 Ref.2 Ref.3 Ref.6 Ref.9
Tissue specificity	Widely expressed. Constitutively overexpressed in certain tumor tissues. Isoform 1 is a major transcript while isoform 2 is a minor transcript. Ref.2 Ref.3
Post-translational modification	Ubiquitinated; following IL1 stimulation or TRAF6 overexpression. Ref.1 Phosphorylated at ser-506 by MAPKAPK2 and MAPKAPK3 following IL1 treatment. Ref.1 Ref.2 Ref.7 Ref.8
Sequence similarities	Contains 1 CUE domain. Contains 1 RanBP2-type zinc finger.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	I-kappaB kinase/NF-kappaB cascade Traceable author statement. Source: Reactome JNK cascade Traceable author statement. Source: Reactome MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome MyD88-independent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome activation of MAPK activity Traceable author statement. Source: Reactome innate immune response Traceable author statement. Source: Reactome nucleotide-binding oligomerization domain containing signaling pathway Traceable author statement. Source: Reactome positive regulation of NF-kappaB transcription factor activity Traceable author statement. Source: Reactome stress-activated MAPK cascade Traceable author statement. Source: Reactome toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome endosome membrane Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome
Molecular function	protein binding Inferred from physical interaction Ref.6. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Map3k7	Q62073	2	EBI-359964,EBI-1775345	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8N5C8-1)

Also known as: Tab3a;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8N5C8-2)

Also known as: Tab3b;

The sequence of this isoform differs from the canonical sequence as follows:
     602-629: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 712	712	TGF-beta-activated kinase 1 and MAP3K7-binding protein 3		PRO_0000226972
Regions
	Domain	8 – 51	44	CUE
	Zinc finger	682 – 712	31	RanBP2-type
	Coiled coil	517 – 559	43	Potential
	Compositional bias	152 – 451	300	Pro-rich
	Compositional bias	504 – 509	6	Poly-Ser
	Compositional bias	659 – 662	4	Poly-Ala
Amino acid modifications
	Modified residue	60	1	Phosphoserine Ref.8
	Modified residue	404	1	Phosphothreonine Ref.8
	Modified residue	408	1	Phosphoserine Ref.8
	Modified residue	492	1	Phosphoserine Ref.8
	Modified residue	506	1	Phosphoserine; by MAPKAPK2 and MAPKAPK3 Ref.7
Natural variations
	Alternative sequence	602 – 629	28	Missing in isoform 2.		VSP_017516
	Natural variant	394	1	W → R. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs5927629 [ dbSNP | Ensembl ].		VAR_055294

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Tab3a) [UniParc]. Last modified May 5, 2009. Version 2. Checksum: 591DAC3E74CE9294	FASTA	712	78,683
	10 20 30 40 50 60 MAQSSPQLDI QVLHDLRQRF PEIPEGVVSQ CMLQNNNNLE ACCRALSQES SKYLYMEYHS 70 80 90 100 110 120 PDDNRMNRNR LLHINLGIHS PSSYHPGDGA QLNGGRTLVH SSSDGHIDPQ HAAGKQLICL 130 140 150 160 170 180 VQEPHSAPAV VAATPNYNPF FMNEQNRSAA TPPSQPPQQP SSMQTGMNPS AMQGPSPPPP 190 200 210 220 230 240 PPSYMHIPRY STNPITVTVS QNLPSGQTVP RALQILPQIP SNLYGSPGSI YIRQTSQSSS 250 260 270 280 290 300 GRQTPQSTPW QSSPQGPVPH YSQRPLPVYP HQQNYQPSQY SPKQQQIPQS AYHSPPPSQC 310 320 330 340 350 360 PSPFSSPQHQ VQPSQLGHIF MPPSPSTTPP HPYQQGPPSY QKQGSHSVAY LPYTASSLSK 370 380 390 400 410 420 GSMKKIEITV EPSQRPGTAI NRSPSPISNQ PSPWNQHSLY TATTPPSSSP SRGISSQPKP 430 440 450 460 470 480 PFSVNPVYIT YTQPTGPSCT PSPSPRVIPN PTTVFKITVG RATTENLLNL VDQEERSAAP 490 500 510 520 530 540 EPIQPISVIP GSGGEKGSHK YQRSSSSGSD DYAYTQALLL HQRARMERLA KQLKLEKEEL 550 560 570 580 590 600 ERLKSEVNGM EHDLMQRRLR RVSCTTAIPT PEEMTRLRSM NRQLQINVDC TLKEVDLLQS 610 620 630 640 650 660 RGNFDPKAMN NFYDNIEPGP VVPPKPSKKD SSDPCTIERK ARRISVTSKV QADIHDTQAA 670 680 690 700 710 AADEHRTGST QSPRTQPRDE DYEGAPWNCD SCTFLNHPAL NRCEQCEMPR YT
	Isoform 2 (Tab3b) [UniParc]. Checksum: 56FD54E4E2082928	FASTA	684	75,599
	10 20 30 40 50 60 MAQSSPQLDI QVLHDLRQRF PEIPEGVVSQ CMLQNNNNLE ACCRALSQES SKYLYMEYHS 70 80 90 100 110 120 PDDNRMNRNR LLHINLGIHS PSSYHPGDGA QLNGGRTLVH SSSDGHIDPQ HAAGKQLICL 130 140 150 160 170 180 VQEPHSAPAV VAATPNYNPF FMNEQNRSAA TPPSQPPQQP SSMQTGMNPS AMQGPSPPPP 190 200 210 220 230 240 PPSYMHIPRY STNPITVTVS QNLPSGQTVP RALQILPQIP SNLYGSPGSI YIRQTSQSSS 250 260 270 280 290 300 GRQTPQSTPW QSSPQGPVPH YSQRPLPVYP HQQNYQPSQY SPKQQQIPQS AYHSPPPSQC 310 320 330 340 350 360 PSPFSSPQHQ VQPSQLGHIF MPPSPSTTPP HPYQQGPPSY QKQGSHSVAY LPYTASSLSK 370 380 390 400 410 420 GSMKKIEITV EPSQRPGTAI NRSPSPISNQ PSPWNQHSLY TATTPPSSSP SRGISSQPKP 430 440 450 460 470 480 PFSVNPVYIT YTQPTGPSCT PSPSPRVIPN PTTVFKITVG RATTENLLNL VDQEERSAAP 490 500 510 520 530 540 EPIQPISVIP GSGGEKGSHK YQRSSSSGSD DYAYTQALLL HQRARMERLA KQLKLEKEEL 550 560 570 580 590 600 ERLKSEVNGM EHDLMQRRLR RVSCTTAIPT PEEMTRLRSM NRQLQINVDC TLKEVDLLQS 610 620 630 640 650 660 RDSSDPCTIE RKARRISVTS KVQADIHDTQ AAAADEHRTG STQSPRTQPR DEDYEGAPWN 670 680 CDSCTFLNHP ALNRCEQCEM PRYT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling." Ishitani T., Takaesu G., Ninomiya-Tsuji J., Shibuya H., Gaynor R.B., Matsumoto K. EMBO J. 22:6277-6288(2003) [PubMed: 14633987] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH MAP3K7; TRAF2 AND TRAF6, UBIQUITINATION, PHOSPHORYLATION, FUNCTION, VARIANT ARG-394. Tissue: Kidney.
[2]	"TAB3, a new binding partner of the protein kinase TAK1." Cheung P.C., Nebreda A.R., Cohen P. Biochem. J. 378:27-34(2004) [PubMed: 14670075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, PHOSPHORYLATION, INTERACTION WITH TAB1; TAB2 AND MAP3K7, VARIANT ARG-394.
[3]	"Identification of a human NF-kappaB-activating protein, TAB3." Jin G., Klika A., Callahan M., Faga B., Danzig J., Jiang Z., Li X., Stark G.R., Harrington J., Sherf B. Proc. Natl. Acad. Sci. U.S.A. 101:2028-2033(2004) [PubMed: 14766965] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH MAP3K7 AND TRAF6, TISSUE SPECIFICITY, FUNCTION, VARIANT ARG-394.
[4]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-394. Tissue: Eye.
[6]	"RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-triggered NF-kappaB activation by targeting TAB2/3 for degradation." Tian Y., Zhang Y., Zhong B., Wang Y.Y., Diao F.C., Wang R.P., Zhang M., Chen D.Y., Zhai Z.H., Shu H.B. J. Biol. Chem. 282:16776-16782(2007) [PubMed: 17449468] [Abstract] Cited for: INTERACTION WITH RBCK1.
[7]	"Roles for TAB1 in regulating the IL-1-dependent phosphorylation of the TAB3 regulatory subunit and activity of the TAK1 complex." Mendoza H., Campbell D.G., Burness K., Hastie J., Ronkina N., Shim J.H., Arthur J.S., Davis R.J., Gaestel M., Johnson G.L., Ghosh S., Cohen P. Biochem. J. 409:711-722(2008) [PubMed: 18021073] [Abstract] Cited for: PHOSPHORYLATION AT SER-506.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60; THR-404; SER-408 AND SER-492, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-kappaB activation pathway." Gao D., Wang R., Li B., Yang Y., Zhai Z., Chen D.Y. Cell. Mol. Life Sci. 66:2573-2584(2009) [PubMed: 19521662] [Abstract] Cited for: INTERACTION WITH WDR34.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY437560 mRNA. Translation: AAR06179.1. AY371491 mRNA. Translation: AAQ88279.1. AY331591 mRNA. Translation: AAQ92938.1. AY331592 mRNA. Translation: AAQ92939.1. AC108359 Genomic DNA. No translation available. BC032526 mRNA. Translation: AAH32526.1.
IPI	IPI00166840. IPI00397561.
RefSeq	NP_690000.2. NM_152787.3.
UniGene	Hs.188256.
3D structure databases
ProteinModelPortal	Q8N5C8.
SMR	Q8N5C8. Positions 4-57, 684-712.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8N5C8. 4 interactions.
MINT	MINT-1145071.
STRING	Q8N5C8.
PTM databases
PhosphoSite	Q8N5C8.
Polymorphism databases
DMDM	229462756.
Proteomic databases
PRIDE	Q8N5C8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000288422; ENSP00000288422; ENSG00000157625. ENST00000378930; ENSP00000368212; ENSG00000157625. ENST00000378933; ENSP00000368215; ENSG00000157625.
GeneID	257397.
KEGG	hsa:257397.
UCSC	uc010ngl.1. human.
Organism-specific databases
CTD	257397.
GeneCards	GC0XM030845.
H-InvDB	HIX0016717.
HGNC	HGNC:30681. TAB3.
HPA	HPA034980.
MIM	300480. gene.
neXtProt	NX_Q8N5C8.
PharmGKB	PA145148470. PA165757406.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00530000063642.
HOGENOM	HBG714653.
HOVERGEN	HBG056952.
InParanoid	Q8N5C8.
OMA	QGPVPHY.
OrthoDB	EOG4XD3QR.
PhylomeDB	Q8N5C8.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q8N5C8.
Bgee	Q8N5C8.
CleanEx	HS_MAP3K7IP3.
Genevestigator	Q8N5C8.
GermOnline	ENSG00000157625. Homo sapiens.
Family and domain databases
InterPro	IPR003892. CUE. IPR001876. Znf_RanBP2. [Graphical view]
KO	K12793.
Pfam	PF02845. CUE. 1 hit. [Graphical view]
SMART	SM00546. CUE. 1 hit. SM00547. ZnF_RBZ. 1 hit. [Graphical view]
PROSITE	PS51140. CUE. 1 hit. PS01358. ZF_RANBP2_1. 1 hit. PS50199. ZF_RANBP2_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	93003.
SOURCE	Search...

Entry information

Entry name

TAB3_HUMAN

Accession

Primary (citable) accession number: Q8N5C8
Secondary accession number(s): A6NDD9, Q6VQR0

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 7, 2006
Last sequence update:	May 5, 2009
Last modified:	January 25, 2012
This is version 79 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.