Q99K90 (TAB2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
TGF-beta-activated kinase 1 and MAP3K7-binding protein 2

Alternative name(s):
Mitogen-activated protein kinase kinase kinase 7-interacting protein 2
TAK1-binding protein 2
Short name=TAB-2
TGF-beta-activated kinase 1-binding protein 2

Gene names

Name:	Tab2
Synonyms:	Kiaa0733, Map3k7ip2

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	693 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Adapter linking MAP3K7/TAK1 and TRAF6. Promotes MAP3K7 activation in the IL1 signaling pathway. The binding of 'Lys-63'-linked polyubiquitin chains to TAB2 promotes autophosphorylation of MAP3K7 at 'Thr-187' By similarity. Regulates the IL1-mediated translocation of NCOR1 out of the nucleus. Involved in heart development By similarity. Ref.1 Ref.6
Subunit structure	Interacts with MAP3K7 and TRAF6. Identified in the TRIKA2 complex composed of MAP3K7, TAB1 and TAB2. Binds 'Lys-63'-linked polyubiquitin chains. Interacts with NCOR1 and HDAC3 to form a ternary complex. Interacts (via C-terminal) with NUMBL (via PTB domain). Interacts (via the C-terminus) with WDR34 (via WD domains). Interacts with RBCK1 By similarity. Ref.6
Subcellular location	Nucleus. Cytoplasm › cytosol. Note: Cytoplasmic when activated. Following IL1 stimulation, localized in the to cytosol. Ref.1
Tissue specificity	Widely expressed. Ref.1
Post-translational modification	Ubiquitinated; following IL1 stimulation or TRAF6 overexpression. Ubiquitination involves RBCK1 leading to7 proteasomal degradation By similarity. Phosphorylated Probable. Ref.1 Ref.5
Sequence similarities	Contains 1 CUE domain. Contains 1 RanBP2-type zinc finger.
Sequence caution	The sequence BAC40772.1 differs from that shown. Reason: Frameshift at positions 62, 72, 152 and 275.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Domain	Coiled coil Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	heart development Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	K63-linked polyubiquitin binding Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Map3k7	Q62073	5	EBI-1775124,EBI-1775345

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 693

693

TGF-beta-activated kinase 1 and MAP3K7-binding protein 2

PRO_0000225696

Regions

Domain

8 – 51

44

CUE

Zinc finger

663 – 693

31

RanBP2-type

Region

675 – 685

11

Interaction with polyubiquitin

Coiled coil

532 – 619

88

Potential

Amino acid modifications

Modified residue

372

1

Phosphoserine By similarity

Modified residue

450

1

Phosphoserine Ref.5

Experimental info

Mutagenesis

674

1

T → A: Loss of interaction with 'Lys-63'-linked ubiquitin. Ref.6

Mutagenesis

675

1

F → A: Loss of interaction with 'Lys-63'-linked ubiquitin. Ref.6

Mutagenesis

678

1

H → Q: Loss of interaction with 'Lys-63'-linked ubiquitin. Ref.6

Mutagenesis

681

1

L → T: Loss of interaction with 'Lys-63'-linked ubiquitin. Ref.6

Mutagenesis

685

1

E → V: Loss of interaction with 'Lys-63'-linked ubiquitin. Ref.6

Mutagenesis

686

1

Q → I or M: Confers ability to bind monoubiquitin and polyubiquitin, irrespective of the type of linkage. Ref.6

Sequence conflict

183

1

P → T in BAE28166. Ref.3

Sequence conflict

476

1

V → F in BAC40772. Ref.3

Sequence conflict

580

1

S → L in BAE28166. Ref.3

Secondary structure

1

.

.

.

.

.

693

Helix Strand Turn

Details...

Turn

671 – 673

3

Turn

685 – 687

3

Sequences

	Sequence		Length	Mass (Da)
	Q99K90 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 810F17CBE6F80BA8	FASTA	693	76,442
	10 20 30 40 50 60 MAQGSHQIDF QVLHDLRQKF PEVPEVVVSR CMLQNNNNLD ACCAVLSQES TRYLYGEGDL 70 80 90 100 110 120 NFSDESGISG LRNHMTSLNL DLQSQNVYHH GREGSRVNGS RTLTHSVSDG QLHGGQSNNE 130 140 150 160 170 180 LFQQEPQTAP AQVPQGFNVF GMPSTSGASN STPHLGFHLG SKGTSNLSQQ TPRFNPIMVT 190 200 210 220 230 240 LAPNIQTGRS TPTSLHIHGV PPPVLNSPQG NSIYIRPYIT TPSGTARQTQ QHSGWVSQFN 250 260 270 280 290 300 PMNPQQAYQP SQPGPWTTYP ASNPLPHTST QQPNQQGHQT SHVYMPISSP TTPQPPTIHS 310 320 330 340 350 360 SGSSQSSAHS QYNIQNISTG PRKNQIEIKL EPPQRNSSSK LRSSGPRTAS TSSLVNSQTL 370 380 390 400 410 420 NRNQPTVYIA ASPPNTDEMI SRSQPKVYIS ANATAGDEQG MRNQPTLFIS TNSGPSAASR 430 440 450 460 470 480 NMSGQVSMGP AFIHHHPPKS RVLGGNSATS PRVVVTQPNT KYTFKITVSP NKPPAVSPGV 490 500 510 520 530 540 VSPTFELTNL LNHPDHYVET ENIQHLTDPA LAHVDRISEA RKLSMGSDDA AYTQALLVHQ 550 560 570 580 590 600 KARMERLQRE LEMQKKKLDK LKSEVNEMEN NLTRRRLKRS NSISQIPSLE EMQQLRSCNR 610 620 630 640 650 660 QLQIDIDCLT KEIDLFQARG PHFNPSAIHN FYDNIGFVGP VPPKPKDQRS TIKAPKTQDA 670 680 690 EDEEGAQWNC TACTFLNHPA LIRCEQCEMP RHF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein." Baek S.H., Ohgi K.A., Rose D.W., Koo E.H., Glass C.K., Rosenfeld M.G. Cell 110:55-67(2002) [PubMed: 12150997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, PHOSPHORYLATION, SUBCELLULAR LOCATION, FUNCTION. Tissue: Brain.
[2]	"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]. Strain: Czech II and FVB/N. Tissue: Mammary tumor.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-595. Strain: C57BL/6J and NOD.
[4]	"Prediction of the coding sequences of mouse homologues of KIAA gene: I. The complete nucleotide sequences of 100 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Hara Y., Nagase T., Ohara O., Koga H. DNA Res. 9:179-188(2002) [PubMed: 12465718] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-693. Tissue: Embryonic tail.
[5]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450, MASS SPECTROMETRY. Tissue: Liver.
[6]	"Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by NZF domains of TAB2 and TAB3." Sato Y., Yoshikawa A., Yamashita M., Yamagata A., Fukai S. EMBO J. 28:3903-3909(2009) [PubMed: 19927120] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.18 ANGSTROMS) OF 665-693 IN COMPLEX WITH ZINC IONS AND 'LYS-63'-LINKED UBIQUITIN, FUNCTION, LINKAGE-SPECIFIC INTERACTION WITH UBIQUITIN, SUBUNIT, MUTAGENESIS OF THR-674; PHE-675; HIS-678; LEU-681; GLU-685 AND GLN-686.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY093701 mRNA. Translation: AAM10487.1.
BC004072 mRNA. Translation: AAH04072.1.
BC004813 mRNA. Translation: AAH04813.1.
AK089164 mRNA. Translation: BAC40772.1. Frameshift.
AK147830 mRNA. Translation: BAE28166.1.
AB093262 mRNA. Translation: BAC41446.1.

IPI

IPI00115639.

RefSeq

NP_619608.1. NM_138667.3.

UniGene

Mm.193041.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3A9J	X-ray	1.18	C	665-693	[»]

ProteinModelPortal

Q99K90.

SMR

Q99K90. Positions 5-70, 665-693.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q99K90. 1 interaction.

STRING

Q99K90.

PTM databases

PhosphoSite

Q99K90.

Proteomic databases

PRIDE

Q99K90.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000146444; ENSMUSP00000121266; ENSMUSG00000015755.

GeneID

68652.

KEGG

mmu:68652.

UCSC

uc007eir.2. mouse.

Organism-specific databases

CTD

23118.

MGI

MGI:1915902. Tab2.

Rouge

Search...

Phylogenomic databases

eggNOG

roNOG10023.

GeneTree

ENSGT00530000063642.

HOGENOM

HBG714653.

HOVERGEN

HBG056952.

InParanoid

Q99K90.

OMA

LQSQNVY.

OrthoDB

EOG41JZBR.

PhylomeDB

Q99K90.

Gene expression databases

ArrayExpress

Q99K90.

Bgee

Q99K90.

Genevestigator

Q99K90.

GermOnline

ENSMUSG00000015755. Mus musculus.

Family and domain databases

InterPro

IPR003892. CUE.
IPR001876. Znf_RanBP2.
[Graphical view]

KO

K04404.

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

327630.

SOURCE

Search...

Entry information

Entry name

TAB2_MOUSE

Accession

Primary (citable) accession number: Q99K90
Secondary accession number(s): Q3UGP1 , Q8BTP4, Q8CHD3, Q99KP4

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 7, 2006
Last sequence update:	June 1, 2001
Last modified:	November 16, 2011
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program