Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P21580

- TNAP3_HUMAN

UniProt

P21580 - TNAP3_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Tumor necrosis factor alpha-induced protein 3

Gene

TNFAIP3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquitinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system. Required for LPS-induced production of proinflammatory cytokines and IFN beta in LPS-tolerized macrophages.12 Publications

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei100 – 1001By similarity
Active sitei103 – 1031Nucleophile1 Publication
Active sitei256 – 2561Proton acceptor1 Publication
Sitei439 – 4402Cleavage; by MALT1

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri381 – 41636A20-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri472 – 50736A20-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri515 – 54834A20-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri601 – 63636A20-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri651 – 68636A20-type 5PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri710 – 74536A20-type 6PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri756 – 79035A20-type 7PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. DNA binding Source: UniProtKB-KW
  2. ligase activity Source: UniProtKB-KW
  3. protease binding Source: BHF-UCL
  4. protein self-association Source: BHF-UCL
  5. ubiquitin binding Source: BHF-UCL
  6. ubiquitin-protein transferase activity Source: UniProtKB
  7. ubiquitin-specific protease activity Source: UniProtKB
  8. ubiquitin thiolesterase activity Source: UniProtKB
  9. zinc ion binding Source: InterPro

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. B-1 B cell homeostasis Source: BHF-UCL
  3. cellular response to hydrogen peroxide Source: UniProtKB
  4. cellular response to lipopolysaccharide Source: BHF-UCL
  5. inflammatory response Source: UniProtKB-KW
  6. innate immune response Source: Reactome
  7. negative regulation of B cell activation Source: BHF-UCL
  8. negative regulation of bone resorption Source: BHF-UCL
  9. negative regulation of CD40 signaling pathway Source: BHF-UCL
  10. negative regulation of endothelial cell apoptotic process Source: BHF-UCL
  11. negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
  12. negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  13. negative regulation of inflammatory response Source: BHF-UCL
  14. negative regulation of innate immune response Source: UniProtKB
  15. negative regulation of interleukin-2 production Source: BHF-UCL
  16. negative regulation of interleukin-6 production Source: BHF-UCL
  17. negative regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  18. negative regulation of osteoclast proliferation Source: BHF-UCL
  19. negative regulation of protein ubiquitination Source: BHF-UCL
  20. negative regulation of smooth muscle cell proliferation Source: BHF-UCL
  21. negative regulation of toll-like receptor 2 signaling pathway Source: BHF-UCL
  22. negative regulation of toll-like receptor 3 signaling pathway Source: BHF-UCL
  23. negative regulation of toll-like receptor 4 signaling pathway Source: BHF-UCL
  24. negative regulation of tumor necrosis factor production Source: BHF-UCL
  25. negative regulation of type I interferon production Source: Reactome
  26. nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Source: Reactome
  27. nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  28. positive regulation of protein catabolic process Source: BHF-UCL
  29. protein deubiquitination Source: BHF-UCL
  30. protein K11-linked deubiquitination Source: UniProtKB
  31. protein K48-linked deubiquitination Source: UniProtKB
  32. protein K48-linked ubiquitination Source: UniProtKB
  33. protein K63-linked deubiquitination Source: UniProtKB
  34. protein oligomerization Source: BHF-UCL
  35. regulation of defense response to virus by host Source: BHF-UCL
  36. regulation of germinal center formation Source: BHF-UCL
  37. regulation of vascular wound healing Source: BHF-UCL
  38. response to molecule of bacterial origin Source: BHF-UCL
  39. tolerance induction to lipopolysaccharide Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Ligase, Protease, Thiol protease

Keywords - Biological processi

Apoptosis, Inflammatory response, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_25271. Negative regulators of RIG-I/MDA5 signaling.
REACT_75776. NOD1/2 Signaling Pathway.
SignaLinkiP21580.

Protein family/group databases

MEROPSiC64.003.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor alpha-induced protein 3 (EC:3.4.19.12, EC:6.3.2.-)
Short name:
TNF alpha-induced protein 3
Alternative name(s):
OTU domain-containing protein 7C
Putative DNA-binding protein A20
Zinc finger protein A20
Cleaved into the following 2 chains:
Gene namesi
Name:TNFAIP3
Synonyms:OTUD7C
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:11896. TNFAIP3.

Subcellular locationi

GO - Cellular componenti

  1. centrosome Source: HPA
  2. cytoplasm Source: HPA
  3. cytosol Source: Reactome
  4. extracellular vesicular exosome Source: UniProt
  5. lysosome Source: UniProtKB-KW
  6. nucleus Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Lysosome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi70 – 701D → A: Minor effect on 'Lys-48' deubiquitinase activity. Strongly reduced 'Lys-63' deubiquitinase activity. 2 Publications
Mutagenesisi97 – 971T → A: Minor effect on 'Lys-48' deubiquitinase activity. 1 Publication
Mutagenesisi100 – 1001D → A: Strongly reduced deubiquitinase activity. 1 Publication
Mutagenesisi103 – 1031C → A: Loss of deubiquitinase activity. 4 Publications
Mutagenesisi103 – 1031C → S: Loss of 'Lys-63' deubiquitinating activity. Down-regulation of TNF-induced NF-kappa-B activity less effective. 4 Publications
Mutagenesisi157 – 1571L → A: Strongly reduced 'Lys-48' deubiquitinase activity. 1 Publication
Mutagenesisi159 – 1591Y → A: Strongly reduced 'Lys-48' deubiquitinase activity. 1 Publication
Mutagenesisi190 – 1901S → A: Strongly reduced 'Lys-48' deubiquitinase activity. 1 Publication
Mutagenesisi192 – 1921E → A: Strongly reduced 'Lys-48' deubiquitinase activity. 1 Publication
Mutagenesisi224 – 2241F → A: Strongly reduced 'Lys-48' deubiquitinase activity. 1 Publication
Mutagenesisi227 – 2271L → A: Strongly reduced 'Lys-48' deubiquitinase activity. 1 Publication
Mutagenesisi256 – 2561H → A: Loss of deubiquitinase activity. 1 Publication
Mutagenesisi521 – 5211C → A: No effect on ubiquitin ligase activity; when associated with A-524. 1 Publication
Mutagenesisi524 – 5241C → A: No effect on ubiquitin ligase activity; when associated with A-521. 1 Publication
Mutagenesisi562 – 5621R → A: Abolishes interactionj with YWHAZ AND YWHAH; no effect on inhibitory activity of TNF-induced NF-kappa-B activation. 1 Publication
Mutagenesisi565 – 5651S → A: Abolishes interactionj with YWHAZ AND YWHAH; no effect on inhibitory activity of TNF-induced NF-kappa-B activation. 1 Publication
Mutagenesisi614 – 6141Y → A: Impairs ubiquitination activity. Loss of down-regulation of NF-kappa-B activity; when associated with A-615 or R-626. 1 Publication
Mutagenesisi615 – 6151F → A: Impairs ubiquitination activity. Loss of down-regulation of NF-kappa-B activity; when associated with A-614. 1 Publication
Mutagenesisi624 – 6241C → A: Marked attenuation of ubiquitin ligase activity and inhibition of RIPK1 degradation; when associated with A-627. 1 Publication
Mutagenesisi626 – 6261L → R: Impairs ubiquitination activity. Loss of down-regulation of NF-kappa-B activity; when associated with A-614. 1 Publication
Mutagenesisi627 – 6271C → A: Marked attenuation of ubiquitin ligase activity and inhibition of RIPK1 degradation; when associated with A-624. 1 Publication
Mutagenesisi770 – 7712FG → AA: Impairs polyubiquitin binding, abolishes inhibition of IKK activation. 1 Publication
Mutagenesisi779 – 7791C → A: Impairs polyubiquitin binding, abolishes inhibition of IKK activation; when associated with A-782. 1 Publication
Mutagenesisi782 – 7821C → A: Impairs polyubiquitin binding, abolishes inhibition of IKK activation; when associated with A-779. 1 Publication

Organism-specific databases

Orphaneti536. Systemic lupus erythematosus.
PharmGKBiPA36593.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 790789Tumor necrosis factor alpha-induced protein 3PRO_0000188791Add
BLAST
Chaini2 – 439438A20p50PRO_0000418127Add
BLAST
Chaini440 – 790351A20p37PRO_0000418128Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication
Modified residuei459 – 4591Phosphoserine1 Publication

Post-translational modificationi

Proteolytically cleaved by MALT1 upon TCR stimulation; disrupts NF-kappa-B inhibitory function and results in increased IL-2 production. It is proposed that only a fraction of TNFAIP3 colocalized with TCR and CBM complex is cleaved, leaving the main TNFAIP3 pool intact.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP21580.
PaxDbiP21580.
PRIDEiP21580.

PTM databases

PhosphoSiteiP21580.

Expressioni

Inductioni

By TNF.

Gene expression databases

BgeeiP21580.
CleanExiHS_TNFAIP3.
ExpressionAtlasiP21580. baseline and differential.
GenevestigatoriP21580.

Organism-specific databases

HPAiHPA002116.

Interactioni

Subunit structurei

Homodimer. Interacts with TNIP1, TAX1BP1 and TRAF2. Interacts with RNF11, ITCH and TAX1BP1 only after TNF stimulation; these interaction are transient and they are lost after 1 hour of stimulation with TNF (By similarity). Interacts with YWHAZ and YWHAH. Interacts with IKBKG; the interaction is induced by TNF stimulation and by polyubiquitin. Interacts with RIPK1. Interacts with UBE2N; the interaction requires TAX1BP1. Interacts with TRAF6; the interaction is inhibited by HTLV-1 protein Tax.By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
IKBKGQ9Y6K94EBI-527670,EBI-81279
RNF11Q9Y3C52EBI-527670,EBI-396669
YwhahP685103EBI-527670,EBI-444641From a different organism.

Protein-protein interaction databases

BioGridi112983. 70 interactions.
DIPiDIP-33804N.
IntActiP21580. 21 interactions.
MINTiMINT-97330.
STRINGi9606.ENSP00000237289.

Structurei

Secondary structure

1
790
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi10 – 134
Helixi15 – 2713
Beta strandi33 – 353
Beta strandi39 – 424
Helixi43 – 453
Beta strandi54 – 563
Helixi58 – 6811
Helixi71 – 799
Beta strandi82 – 843
Beta strandi87 – 893
Beta strandi92 – 954
Helixi103 – 11311
Helixi121 – 13212
Helixi136 – 14712
Helixi164 – 17411
Beta strandi176 – 1783
Beta strandi181 – 1855
Helixi193 – 20311
Beta strandi207 – 2115
Beta strandi231 – 2333
Helixi240 – 2423
Beta strandi248 – 2536
Beta strandi256 – 2638
Beta strandi267 – 2704
Beta strandi272 – 2798
Beta strandi282 – 2854
Helixi293 – 2975
Helixi299 – 3068
Beta strandi309 – 3157
Beta strandi317 – 32913
Helixi337 – 3393
Helixi341 – 35414
Helixi359 – 3613
Beta strandi384 – 3863
Turni398 – 4025
Helixi405 – 4128
Beta strandi604 – 6063
Beta strandi613 – 6153
Helixi618 – 6203
Helixi625 – 63410
Helixi773 – 7753
Helixi780 – 7889

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2EQENMR-A597-631[»]
2EQFNMR-A758-790[»]
2EQGNMR-A381-416[»]
2VFJX-ray3.20A/B/C/D1-366[»]
3DKBX-ray2.50A/B/C/D/E/F1-370[»]
3OJ3X-ray2.50I/J/K/L/M/N/O/P592-635[»]
3OJ4X-ray3.40C/F592-635[»]
3VUWX-ray1.95E/F/G757-789[»]
3VUXX-ray1.70E/F/G757-790[»]
3VUYX-ray1.98D/E/F757-790[»]
3ZJDX-ray1.87A/B1-366[»]
3ZJEX-ray1.84A/B1-366[»]
3ZJFX-ray2.20A/B1-366[»]
3ZJGX-ray1.92A/B1-366[»]
ProteinModelPortaliP21580.
SMRiP21580. Positions 3-362, 382-419, 603-635, 758-790.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21580.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini92 – 263172OTUPROSITE-ProRule annotationAdd
BLAST
Repeati286 – 317321Add
BLAST
Repeati324 – 356332Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni58 – 300243TRAF-bindingAdd
BLAST
Regioni157 – 1593Interaction with ubiquitinCurated
Regioni190 – 1923Interaction with ubiquitinCurated
Regioni224 – 2274Interaction with ubiquitinCurated
Regioni286 – 356712 X approximate repeatsAdd
BLAST
Regioni369 – 775407Interaction with TNIP1By similarityAdd
BLAST
Regioni386 – 45368Interaction with RIPK1Add
BLAST
Regioni605 – 65551Required for proteosomal degradation of UBE2N and UBE2D3, TRAF6 deubiquitination, and TAX1BP1 interaction with UBE2NBy similarityAdd
BLAST
Regioni606 – 790185Sufficient for inhibitory activity of TNF-induced NF-kappa-B activityBy similarityAdd
BLAST
Regioni697 – 79094Required for lysosomal localization and for TRAF2 lysosomal degradationAdd
BLAST

Domaini

The A20-type zinc fingers mediate the ubiquitin ligase activity. The A20-type zinc finger 4 selectively recognizes 'Lys-63'-linked polyubiquitin. The A20-type zinc finger 4-7 are sufficient to bind polyubiquitin.1 Publication
The OTU domain mediates the deubiquitinase activity.1 Publication

Sequence similaritiesi

Belongs to the peptidase C64 family.Curated
Contains 7 A20-type zinc fingers.PROSITE-ProRule annotation
Contains 1 OTU domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri381 – 41636A20-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri472 – 50736A20-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri515 – 54834A20-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri601 – 63636A20-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri651 – 68636A20-type 5PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri710 – 74536A20-type 6PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri756 – 79035A20-type 7PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiNOG248343.
GeneTreeiENSGT00530000062989.
HOGENOMiHOG000133004.
HOVERGENiHBG059260.
InParanoidiP21580.
KOiK11859.
OMAiCETPNCP.
OrthoDBiEOG7JHM57.
PhylomeDBiP21580.
TreeFamiTF323312.

Family and domain databases

InterProiIPR003323. OTU.
IPR002653. Znf_A20.
[Graphical view]
PfamiPF02338. OTU. 1 hit.
PF01754. zf-A20. 6 hits.
[Graphical view]
SMARTiSM00259. ZnF_A20. 7 hits.
[Graphical view]
PROSITEiPS50802. OTU. 1 hit.
PS51036. ZF_A20. 7 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P21580-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAEQVLPQAL YLSNMRKAVK IRERTPEDIF KPTNGIIHHF KTMHRYTLEM
60 70 80 90 100
FRTCQFCPQF REIIHKALID RNIQATLESQ KKLNWCREVR KLVALKTNGD
110 120 130 140 150
GNCLMHATSQ YMWGVQDTDL VLRKALFSTL KETDTRNFKF RWQLESLKSQ
160 170 180 190 200
EFVETGLCYD TRNWNDEWDN LIKMASTDTP MARSGLQYNS LEEIHIFVLC
210 220 230 240 250
NILRRPIIVI SDKMLRSLES GSNFAPLKVG GIYLPLHWPA QECYRYPIVL
260 270 280 290 300
GYDSHHFVPL VTLKDSGPEI RAVPLVNRDR GRFEDLKVHF LTDPENEMKE
310 320 330 340 350
KLLKEYLMVI EIPVQGWDHG TTHLINAAKL DEANLPKEIN LVDDYFELVQ
360 370 380 390 400
HEYKKWQENS EQGRREGHAQ NPMEPSVPQL SLMDVKCETP NCPFFMSVNT
410 420 430 440 450
QPLCHECSER RQKNQNKLPK LNSKPGPEGL PGMALGASRG EAYEPLAWNP
460 470 480 490 500
EESTGGPHSA PPTAPSPFLF SETTAMKCRS PGCPFTLNVQ HNGFCERCHN
510 520 530 540 550
ARQLHASHAP DHTRHLDPGK CQACLQDVTR TFNGICSTCF KRTTAEASSS
560 570 580 590 600
LSTSLPPSCH QRSKSDPSRL VRSPSPHSCH RAGNDAPAGC LSQAARTPGD
610 620 630 640 650
RTGTSKCRKA GCVYFGTPEN KGFCTLCFIE YRENKHFAAA SGKVSPTASR
660 670 680 690 700
FQNTIPCLGR ECGTLGSTMF EGYCQKCFIE AQNQRFHEAK RTEEQLRSSQ
710 720 730 740 750
RRDVPRTTQS TSRPKCARAS CKNILACRSE ELCMECQHPN QRMGPGAHRG
760 770 780 790
EPAPEDPPKQ RCRAPACDHF GNAKCNGYCN ECFQFKQMYG
Length:790
Mass (Da):89,614
Last modified:May 1, 1991 - v1
Checksum:i320AEA97F58D4491
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti125 – 1251A → V.1 Publication
Corresponds to variant rs5029941 [ dbSNP | Ensembl ].
VAR_020447
Natural varianti127 – 1271F → C.1 Publication
Corresponds to variant rs2230926 [ dbSNP | Ensembl ].
VAR_022143
Natural varianti766 – 7661A → P.1 Publication
Corresponds to variant rs5029957 [ dbSNP | Ensembl ].
VAR_029319

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M59465 mRNA. Translation: AAA51550.1.
AK312862 mRNA. Translation: BAG35714.1.
AY248754 Genomic DNA. Translation: AAO61093.1.
AL357060 Genomic DNA. Translation: CAH72937.1.
CH471051 Genomic DNA. Translation: EAW47925.1.
CH471051 Genomic DNA. Translation: EAW47926.1.
BC113871 mRNA. Translation: AAI13872.1.
BC114480 mRNA. Translation: AAI14481.1.
AL157444 mRNA. Translation: CAB75664.1.
CCDSiCCDS5187.1.
PIRiA35797.
RefSeqiNP_001257436.1. NM_001270507.1.
NP_001257437.1. NM_001270508.1.
NP_006281.1. NM_006290.3.
XP_005267176.1. XM_005267119.1.
UniGeneiHs.211600.

Genome annotation databases

EnsembliENST00000237289; ENSP00000237289; ENSG00000118503.
ENST00000612899; ENSP00000481570; ENSG00000118503.
GeneIDi7128.
KEGGihsa:7128.
UCSCiuc003qhr.4. human.

Polymorphism databases

DMDMi112894.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs
Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M59465 mRNA. Translation: AAA51550.1 .
AK312862 mRNA. Translation: BAG35714.1 .
AY248754 Genomic DNA. Translation: AAO61093.1 .
AL357060 Genomic DNA. Translation: CAH72937.1 .
CH471051 Genomic DNA. Translation: EAW47925.1 .
CH471051 Genomic DNA. Translation: EAW47926.1 .
BC113871 mRNA. Translation: AAI13872.1 .
BC114480 mRNA. Translation: AAI14481.1 .
AL157444 mRNA. Translation: CAB75664.1 .
CCDSi CCDS5187.1.
PIRi A35797.
RefSeqi NP_001257436.1. NM_001270507.1.
NP_001257437.1. NM_001270508.1.
NP_006281.1. NM_006290.3.
XP_005267176.1. XM_005267119.1.
UniGenei Hs.211600.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2EQE NMR - A 597-631 [» ]
2EQF NMR - A 758-790 [» ]
2EQG NMR - A 381-416 [» ]
2VFJ X-ray 3.20 A/B/C/D 1-366 [» ]
3DKB X-ray 2.50 A/B/C/D/E/F 1-370 [» ]
3OJ3 X-ray 2.50 I/J/K/L/M/N/O/P 592-635 [» ]
3OJ4 X-ray 3.40 C/F 592-635 [» ]
3VUW X-ray 1.95 E/F/G 757-789 [» ]
3VUX X-ray 1.70 E/F/G 757-790 [» ]
3VUY X-ray 1.98 D/E/F 757-790 [» ]
3ZJD X-ray 1.87 A/B 1-366 [» ]
3ZJE X-ray 1.84 A/B 1-366 [» ]
3ZJF X-ray 2.20 A/B 1-366 [» ]
3ZJG X-ray 1.92 A/B 1-366 [» ]
ProteinModelPortali P21580.
SMRi P21580. Positions 3-362, 382-419, 603-635, 758-790.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112983. 70 interactions.
DIPi DIP-33804N.
IntActi P21580. 21 interactions.
MINTi MINT-97330.
STRINGi 9606.ENSP00000237289.

Protein family/group databases

MEROPSi C64.003.

PTM databases

PhosphoSitei P21580.

Polymorphism databases

DMDMi 112894.

Proteomic databases

MaxQBi P21580.
PaxDbi P21580.
PRIDEi P21580.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000237289 ; ENSP00000237289 ; ENSG00000118503 .
ENST00000612899 ; ENSP00000481570 ; ENSG00000118503 .
GeneIDi 7128.
KEGGi hsa:7128.
UCSCi uc003qhr.4. human.

Organism-specific databases

CTDi 7128.
GeneCardsi GC06P138188.
HGNCi HGNC:11896. TNFAIP3.
HPAi HPA002116.
MIMi 191163. gene.
neXtProti NX_P21580.
Orphaneti 536. Systemic lupus erythematosus.
PharmGKBi PA36593.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG248343.
GeneTreei ENSGT00530000062989.
HOGENOMi HOG000133004.
HOVERGENi HBG059260.
InParanoidi P21580.
KOi K11859.
OMAi CETPNCP.
OrthoDBi EOG7JHM57.
PhylomeDBi P21580.
TreeFami TF323312.

Enzyme and pathway databases

Reactomei REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
REACT_75776. NOD1/2 Signaling Pathway.
SignaLinki P21580.

Miscellaneous databases

ChiTaRSi TNFAIP3. human.
EvolutionaryTracei P21580.
GeneWikii TNFAIP3.
GenomeRNAii 7128.
NextBioi 27895.
PROi P21580.
SOURCEi Search...

Gene expression databases

Bgeei P21580.
CleanExi HS_TNFAIP3.
ExpressionAtlasi P21580. baseline and differential.
Genevestigatori P21580.

Family and domain databases

InterProi IPR003323. OTU.
IPR002653. Znf_A20.
[Graphical view ]
Pfami PF02338. OTU. 1 hit.
PF01754. zf-A20. 6 hits.
[Graphical view ]
SMARTi SM00259. ZnF_A20. 7 hits.
[Graphical view ]
PROSITEi PS50802. OTU. 1 hit.
PS51036. ZF_A20. 7 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein."
    Opipari A.W. Jr., Boguski M.S., Dixit V.M.
    J. Biol. Chem. 265:14705-14708(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Trachea.
  3. SeattleSNPs variation discovery resource
    Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-125; CYS-127 AND PRO-766.
  4. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. 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].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 155-790.
    Tissue: Testis.
  8. "The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation."
    Song H.Y., Rothe M., Goeddel D.V.
    Proc. Natl. Acad. Sci. U.S.A. 93:6721-6725(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TRAF1 AND TRAF2.
  9. "A20 inhibits NF-kappaB activation independently of binding to 14-3-3 proteins."
    De Valck D., Heyninck K., Van Criekinge W., Vandenabeele P., Fiers W., Beyaert R.
    Biochem. Biophys. Res. Commun. 238:590-594(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH YWHAZ AND YWHAH, MUTAGENESIS OF ARG-562 AND SER-565.
  10. "Epstein-Barr virus-encoded latent membrane protein 1 activates the JNK pathway through its extreme C-terminus via a mechanism involving TRADD and TRAF2."
    Eliopoulos A.G., Blake S.M., Floettmann J.E., Rowe M., Young L.S.
    J. Virol. 73:1023-1035(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TRAF2.
  11. "The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases."
    de Valck D., Jin D.-Y., Heyninck K., van de Craen M., Contreras R., Fiers W., Jeang K.-T., Beyaert R.
    Oncogene 18:4182-4190(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TAX1BP1.
  12. "Isolation and characterization of two novel A20-like proteins."
    Evans P.C., Taylor E.R., Coadwell J., Heyninck K., Beyaert R., Kilshaw P.J.
    Biochem. J. 357:617-623(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  13. "Zinc-finger protein A20, a regulator of inflammation and cell survival, has de-ubiquitinating activity."
    Evans P.C., Ovaa H., Hamon M., Kilshaw P.J., Hamm S., Bauer S., Ploegh H.L., Smith T.S.
    Biochem. J. 378:727-734(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF CYS-103.
  14. "De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling."
    Wertz I.E., O'Rourke K.M., Zhou H., Eby M., Aravind L., Seshagiri S., Wu P., Wiesmann C., Baker R., Boone D.L., Ma A., Koonin E.V., Dixit V.M.
    Nature 430:694-699(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DOMAIN OTU, DOMAIN A20-TYPE ZINC-FINGER, MUTAGENESIS OF CYS-103; CYS-521; CYS-524; CYS-624 AND CYS-627.
  15. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
    Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
    Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  16. "ABIN-1 binds to NEMO/IKKgamma and co-operates with A20 in inhibiting NF-kappaB."
    Mauro C., Pacifico F., Lavorgna A., Mellone S., Iannetti A., Acquaviva R., Formisano S., Vito P., Leonardi A.
    J. Biol. Chem. 281:18482-18488(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH IKBKG AND TNIP1.
  17. "T cell antigen receptor stimulation induces MALT1 paracaspase-mediated cleavage of the NF-kappaB inhibitor A20."
    Coornaert B., Baens M., Heyninck K., Bekaert T., Haegman M., Staal J., Sun L., Chen Z.J., Marynen P., Beyaert R.
    Nat. Immunol. 9:263-271(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC CLEAVAGE.
  18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  19. "The zinc finger protein A20 targets TRAF2 to the lysosomes for degradation."
    Li L., Soetandyo N., Wang Q., Ye Y.
    Biochim. Biophys. Acta 1793:346-353(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  20. "The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-kappaB signalling."
    Shembade N., Parvatiyar K., Harhaj N.S., Harhaj E.W.
    EMBO J. 28:513-522(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TAX1BP1; RNF11 AND RIPK1.
  21. "A20 negatively regulates T cell receptor signaling to NF-kappaB by cleaving Malt1 ubiquitin chains."
    Duwel M., Welteke V., Oeckinghaus A., Baens M., Kloo B., Ferch U., Darnay B.G., Ruland J., Marynen P., Krappmann D.
    J. Immunol. 182:7718-7728(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  22. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-459, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  23. Cited for: PROTEOLYTIC CLEAVAGE, SUBCELLULAR LOCATION.
  24. "Direct, noncatalytic mechanism of IKK inhibition by A20."
    Skaug B., Chen J., Du F., He J., Ma A., Chen Z.J.
    Mol. Cell 44:559-571(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH IKBKG, MUTAGENESIS OF 770-PHE-GLY-771; CYS-779 AND CYS-782.
  25. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  26. "OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis."
    Mevissen T.E., Hospenthal M.K., Geurink P.P., Elliott P.R., Akutsu M., Arnaudo N., Ekkebus R., Kulathu Y., Wauer T., El Oualid F., Freund S.M., Ovaa H., Komander D.
    Cell 154:169-184(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY.
  27. "Solution structure of the A20-type zinc finger domains from human tumor necrosis factor, alpha-induced protein 3."
    RIKEN structural genomics initiative (RSGI)
    Submitted (OCT-2007) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 381-790.
  28. "Structure of the A20 OTU domain and mechanistic insights into deubiquitination."
    Komander D., Barford D.
    Biochem. J. 409:77-85(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 1-366, CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF ASP-70; CYS-103 AND HIS-256.
  29. "Molecular basis for the unique deubiquitinating activity of the NF-kappaB inhibitor A20."
    Lin S.C., Chung J.Y., Lamothe B., Rajashankar K., Lu M., Lo Y.C., Lam A.Y., Darnay B.G., Wu H.
    J. Mol. Biol. 376:526-540(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-370, ACTIVE SITE, CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF ASP-70; THR-97; ASP-100; CYS-103; LEU-157; TYR-159; SER-190; GLU-192; PHE-224 AND LEU-227.
  30. "Ubiquitin binding to A20 ZnF4 is required for modulation of NF-kappaB signaling."
    Bosanac I., Wertz I.E., Pan B., Yu C., Kusam S., Lam C., Phu L., Phung Q., Maurer B., Arnott D., Kirkpatrick D.S., Dixit V.M., Hymowitz S.G.
    Mol. Cell 40:548-557(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 592-635 IN COMPLEX WITH UBIQUITIN, X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 592-635 IN COMPLEX WITH UBIQUITIN AND UBE2D1, MUTAGENESIS OF TYR-614; PHE-615 AND LEU-626.

Entry informationi

Entry nameiTNAP3_HUMAN
AccessioniPrimary (citable) accession number: P21580
Secondary accession number(s): B2R767
, E1P588, Q2HIX9, Q5VXQ7, Q9NSR6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: May 1, 1991
Last modified: October 29, 2014
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3