Q92844 (TANK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
TRAF family member-associated NF-kappa-B activator

Alternative name(s):
TRAF-interacting protein
Short name=I-TRAF

Gene names

Name:	TANK
Synonyms:	ITRAF, TRAF2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	425 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a regulator of TRAF function by maintaining them in a latent state. Overexpression inhibits TRAF2-mediated NF-kappa-B activation signaled by CD40, TNFR1 and TNFR2. Blocks TRAF2 binding to LMP1 and inhibits LMP1-mediated NF-kappa-B activation. May be involved in I-kappa-B-kinase (IKK) regulation; may function as an adapter for kinases such as TBK1 or IKBKE that can modulate IKK activity. Ref.9
Subunit structure	Interacts with TBK1 (via TRAF-C domain). Interacts with TRAF1 (via TRAF-C domain). Interacts with TRAF2 (via TRAF-C domain); the interaction is disrupted by the phosphorylation of TANK by IKBKE. Interacts with TRAF3 (via TRAF-C domain); the interaction with TRAF3 is weaker than the interactions with TRAF1 and TRAF3. Interacts with IKBKG; the interaction is enhanced by IKBKE and TBK1. Part of a ternary complex consisting of TANK, IKBKB and IKBKG. Ref.7 Ref.8 Ref.9
Subcellular location	Cytoplasm.
Tissue specificity	Ubiquitous.
Post-translational modification	Phosphorylated by IKBKE. Ref.8
Sequence similarities	Contains 1 C2H2-type zinc finger.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	I-kappaB kinase/NF-kappaB cascade Inferred from electronic annotation. Source: Compara innate immune response Traceable author statement. Source: Reactome signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APBA3	O96018	2	EBI-356349,EBI-6115839
PLK1	P53350	3	EBI-356349,EBI-476768
TBK1	Q9UHD2	3	EBI-356349,EBI-356402
TRAF2	Q12933	3	EBI-356349,EBI-355744
TRAF3	Q13114	3	EBI-356349,EBI-357631

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: Q92844-1)

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 Short (identifier: Q92844-2)

The sequence of this isoform differs from the canonical sequence as follows:
     111-117: RRQEVSS → DIASAES
     118-425: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q92844-3)

The sequence of this isoform differs from the canonical sequence as follows:
     111-119: RRQEVSSPR → DIASAESSI
     120-425: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 425

425

TRAF family member-associated NF-kappa-B activator

PRO_0000072427

Regions

Zinc finger

394 – 420

27

C2H2-type

Region

172 – 191

20

TRAF family member interaction

Amino acid modifications

Modified residue

126

1

Phosphoserine Ref.12

Modified residue

129

1

Phosphoserine Ref.10 Ref.11 Ref.12

Modified residue

341

1

Phosphoserine Ref.12

Modified residue

354

1

Phosphoserine Ref.12

Modified residue

357

1

Phosphoserine Ref.11 Ref.12

Natural variations

Alternative sequence

111 – 119

9

RRQEVSSPR → DIASAESSI in isoform 3.

VSP_043702

Alternative sequence

111 – 117

7

RRQEVSS → DIASAES in isoform Short.

VSP_004442

Alternative sequence

118 – 425

308

Missing in isoform Short.

VSP_004443

Alternative sequence

120 – 425

306

Missing in isoform 3.

VSP_043703

Natural variant

292

1

G → R.
Corresponds to variant rs10183668 [ dbSNP | Ensembl ].

VAR_051409

Natural variant

358

1

P → L.
Corresponds to variant rs2229759 [ dbSNP | Ensembl ].

VAR_051410

Natural variant

394

1

R → Q.
Corresponds to variant rs3769969 [ dbSNP | Ensembl ].

VAR_051411

Experimental info

Mutagenesis

182

1

Q → A: Abolishes interaction with TRAF2 and TRAF3. Ref.14

Mutagenesis

184

1

T → A: Abolishes interaction with TRAF2 and TRAF3. Ref.14

Mutagenesis

185

1

D → A: Abolishes interaction with TRAF2; greatly diminishes interaction with TRAF3. Ref.14

Mutagenesis

188

1

D → A: Diminishes interaction with TRAF2 and TRAF3. Ref.14

Mutagenesis

194

1

F → A: Diminishes interaction with TRAF2 and TRAF3. Ref.14

Sequence conflict

83

1

E → D in AAC50681. Ref.1

Sequence conflict

88

1

N → T in AAC50681. Ref.1

Sequence conflict

92

1

D → A in AAC50681. Ref.1

Sequence conflict

142

1

F → S in AAC50681. Ref.1

Sequence conflict

195

1

K → T in AAC50681. Ref.1

Sequence conflict

226

1

F → L in AAC50681. Ref.1

Sequence conflict

303

1

L → P in AAC50770. Ref.2

Secondary structure

1

.

.

.

425

Helix Strand Turn

Details...

Beta strand

191 – 193

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified April 3, 2007. Version 2. Checksum: 718D30CF03EB27FF	FASTA	425	47,816
	10 20 30 40 50 60 MDKNIGEQLN KAYEAFRQAC MDRDSAVKEL QQKTENYEQR IREQQEQLSL QQTIIDKLKS 70 80 90 100 110 120 QLLLVNSTQD NNYGCVPLLE DSETRKNNLT LDQPQDKVIS GIAREKLPKV RRQEVSSPRK 130 140 150 160 170 180 ETSARSLGSP LLHERGNIEK TFWDLKEEFH KICMLAKAQK DHLSKLNIPD TATETQCSVP 190 200 210 220 230 240 IQCTDKTDKQ EALFKPQAKD DINRGAPSIT SVTPRGLCRD EEDTSFESLS KFNVKFPPMD 250 260 270 280 290 300 NDSTFLHSTP ERPGILSPAT SEAVCQEKFN MEFRDNPGNF VKTEETLFEI QGIDPIASAI 310 320 330 340 350 360 QNLKTTDKTK PSNLVNTCIR TTLDRAACLP PGDHNALYVN SFPLLDPSDA PFPSLDSPGK 370 380 390 400 410 420 AIRGPQQPIW KPFPNQDSDS VVLSGTDSEL HIPRVCEFCQ AVFPPSITSR GDFLRHLNSH FNGET
	Isoform Short [UniParc]. Checksum: 22A8BEC63333011C	FASTA	117	13,426
	10 20 30 40 50 60 MDKNIGEQLN KAYEAFRQAC MDRDSAVKEL QQKTENYEQR IREQQEQLSL QQTIIDKLKS 70 80 90 100 110 QLLLVNSTQD NNYGCVPLLE DSETRKNNLT LDQPQDKVIS GIAREKLPKV DIASAES
	Isoform 3 [UniParc]. Checksum: 61E5B2A8BEC63333	FASTA	119	13,626
	10 20 30 40 50 60 MDKNIGEQLN KAYEAFRQAC MDRDSAVKEL QQKTENYEQR IREQQEQLSL QQTIIDKLKS 70 80 90 100 110 QLLLVNSTQD NNYGCVPLLE DSETRKNNLT LDQPQDKVIS GIAREKLPKV DIASAESSI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction." Rothe M., Xiong J., Shu H.-B., Williamson K., Goddard A., Goeddel D.V. Proc. Natl. Acad. Sci. U.S.A. 93:8241-8246(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[2]	"Tumor necrosis factor receptor associated factor 2 is a mediator of NF-kappa B activation by latent infection membrane protein 1, the Epstein-Barr virus transforming protein." Kaye K.M., Devergne O., Harada J.N., Izumi K.M., Yalamanchili R., Kieff E., Mosialos G. Proc. Natl. Acad. Sci. U.S.A. 93:11085-11090(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT). Tissue: Placenta.
[7]	"NF-kB activation by a signaling complex containing TRAF2, TANK, and TBK1, a novel IKK-related kinase." Pomerantz J.L., Baltimore D. EMBO J. 18:6694-6704(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TBK1. Tissue: Spleen.
[8]	"NF-kappaB activation through IKK-i-dependent I-TRAF/TANK phosphorylation." Nomura F., Kawai T., Nakanishi K., Akira S. Genes Cells 5:191-202(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TRAF2, PHOSPHORYLATION BY IKBKE.
[9]	"Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases." Chariot A., Leonardi A., Muller J., Bonif M., Brown K., Siebenlist U. J. Biol. Chem. 277:37029-37036(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH IKBKG AND IKBKB.
[10]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129 AND SER-357, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126; SER-129; SER-341; SER-354 AND SER-357, MASS SPECTROMETRY.
[13]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[14]	"Downstream regulator TANK binds to the CD40 recognition site on TRAF3." Li C., Ni C.Z., Havert M.L., Cabezas E., He J., Kaiser D., Reed J.C., Satterthwait A.C., Cheng G., Ely K.R. Structure 10:403-411(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 174-194 IN COMPLEX WITH TRAF3, MUTAGENESIS OF GLN-182; THR-184; ASP-185; ASP-188 AND PHE-194.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U59863 mRNA. Translation: AAC50681.1.
U63830 mRNA. Translation: AAC50770.1.
BT009855 mRNA. Translation: AAP88857.1.
AC009299 Genomic DNA. No translation available.
AC009313 Genomic DNA. No translation available.
CH471058 Genomic DNA. Translation: EAX11374.1.
CH471058 Genomic DNA. Translation: EAX11375.1.
CH471058 Genomic DNA. Translation: EAX11377.1.
BC003388 mRNA. Translation: AAH03388.1.

IPI

IPI00299166.
IPI00375988.

RefSeq

NP_001186064.1. NM_001199135.1.
NP_004171.2. NM_004180.2.
NP_597841.1. NM_133484.1.

UniGene

Hs.132257.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KZZ	X-ray	3.50	B	177-187	[»]
1L0A	X-ray	2.90	B	178-195	[»]

ProteinModelPortal

Q92844.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-27516N.

IntAct

Q92844. 24 interactions.

MINT

MINT-111947.

STRING

9606.ENSP00000259075.

PTM databases

PhosphoSite

Q92844.

Polymorphism databases

DMDM

143811466.

Proteomic databases

PaxDb

Q92844.

PeptideAtlas

Q92844.

PRIDE

Q92844.

Protocols and materials databases

DNASU

10010.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000259075; ENSP00000259075; ENSG00000136560.
ENST00000392749; ENSP00000376505; ENSG00000136560.
ENST00000403609; ENSP00000385983; ENSG00000136560.
ENST00000457476; ENSP00000415276; ENSG00000136560.

GeneID

10010.

KEGG

hsa:10010.

UCSC

uc002ubq.1. human.
uc002ubr.2. human.

Organism-specific databases

CTD

10010.

GeneCards

GC02P161957.

HGNC

HGNC:11562. TANK.

HPA

CAB010345.

MIM

603893. gene.

neXtProt

NX_Q92844.

PharmGKB

PA36330.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG44252.

HOGENOM

HOG000231816.

HOVERGEN

HBG019299.

InParanoid

Q92844.

KO

K12650.

OMA

ETQCSVP.

OrthoDB

EOG45757G.

PhylomeDB

Q92844.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

SignaLink

Q92844.

Gene expression databases

ArrayExpress

Q92844.

Bgee

Q92844.

CleanEx

HS_TANK.
HS_TRAF2.

Genevestigator

Q92844.

GermOnline

ENSG00000136560. Homo sapiens.

Family and domain databases

InterPro

IPR024581. TBD.
[Graphical view]

Pfam

PF12845. TBD. 1 hit.
[Graphical view]

PROSITE

PS00028. ZINC_FINGER_C2H2_1. False negative.
PS50157. ZINC_FINGER_C2H2_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TANK. human.

EvolutionaryTrace

Q92844.

GenomeRNAi

10010.

NextBio

37817.

SOURCE

Search...

Entry information

Entry name

TANK_HUMAN

Accession

Primary (citable) accession number: Q92844
Secondary accession number(s): D3DPB5, Q7Z4J6, Q92885

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	April 3, 2007
Last modified:	May 29, 2013
This is version 129 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.