Skip Header

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

Tumor necrosis factor alpha-induced protein 3

Gene

TNFAIP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
Active sitei100By similarity1
Active sitei103Nucleophile1 Publication1
Active sitei256Proton acceptor1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri381 – 416A20-type 1PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri472 – 507A20-type 2PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri515 – 548A20-type 3PROSITE-ProRule annotationAdd BLAST34
Zinc fingeri601 – 636A20-type 4PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri651 – 686A20-type 5PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri710 – 745A20-type 6PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri756 – 790A20-type 7PROSITE-ProRule annotationAdd BLAST35

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • K63-linked polyubiquitin binding Source: GO_Central
  • ligase activity Source: UniProtKB-KW
  • protease binding Source: BHF-UCL
  • protein self-association Source: BHF-UCL
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • ubiquitin binding Source: BHF-UCL
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

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

BioCyciZFISH:ENSG00000118503-MONOMER.
ReactomeiR-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-5357786. TNFR1-induced proapoptotic signaling.
R-HSA-5357905. Regulation of TNFR1 signaling.
R-HSA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.
SignaLinkiP21580.
SIGNORiP21580.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:11896. TNFAIP3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • lysosome Source: UniProtKB-SubCell
  • nucleus Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Lysosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

Autoinflammatory syndrome, familial, Behcet-like (AISBL)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant, autoinflammatory disorder with early onset, characterized by ulceration of mucosal surfaces, particularly in the oral and genital areas. Additional variable features include skin rash, uveitis, and polyarthritis.
See also OMIM:616744
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076302243C → Y in AISBL; increases inflammatory cytokine secretion; increases NF-kappaB signaling. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi70D → A: Minor effect on 'Lys-48' deubiquitinase activity. Strongly reduced 'Lys-63' deubiquitinase activity. 2 Publications1
Mutagenesisi97T → A: Minor effect on 'Lys-48' deubiquitinase activity. 1 Publication1
Mutagenesisi100D → A: Strongly reduced deubiquitinase activity. 1 Publication1
Mutagenesisi103C → A: Loss of deubiquitinase activity. 4 Publications1
Mutagenesisi103C → S: Loss of 'Lys-63' deubiquitinating activity. Down-regulation of TNF-induced NF-kappa-B activity less effective. 4 Publications1
Mutagenesisi157L → A: Strongly reduced 'Lys-48' deubiquitinase activity. 1 Publication1
Mutagenesisi159Y → A: Strongly reduced 'Lys-48' deubiquitinase activity. 1 Publication1
Mutagenesisi190S → A: Strongly reduced 'Lys-48' deubiquitinase activity. 1 Publication1
Mutagenesisi192E → A: Strongly reduced 'Lys-48' deubiquitinase activity. 1 Publication1
Mutagenesisi224F → A: Strongly reduced 'Lys-48' deubiquitinase activity. 1 Publication1
Mutagenesisi227L → A: Strongly reduced 'Lys-48' deubiquitinase activity. 1 Publication1
Mutagenesisi256H → A: Loss of deubiquitinase activity. 1 Publication1
Mutagenesisi521C → A: No effect on ubiquitin ligase activity; when associated with A-524. 1 Publication1
Mutagenesisi524C → A: No effect on ubiquitin ligase activity; when associated with A-521. 1 Publication1
Mutagenesisi562R → A: Abolishes interactionj with YWHAZ AND YWHAH; no effect on inhibitory activity of TNF-induced NF-kappa-B activation. 1 Publication1
Mutagenesisi565S → A: Abolishes interactionj with YWHAZ AND YWHAH; no effect on inhibitory activity of TNF-induced NF-kappa-B activation. 1 Publication1
Mutagenesisi614Y → A: Impairs ubiquitination activity. Loss of down-regulation of NF-kappa-B activity; when associated with A-615 or R-626. 1 Publication1
Mutagenesisi615F → A: Impairs ubiquitination activity. Loss of down-regulation of NF-kappa-B activity; when associated with A-614. 1 Publication1
Mutagenesisi624C → A: Marked attenuation of ubiquitin ligase activity and inhibition of RIPK1 degradation; when associated with A-627. 1 Publication1
Mutagenesisi626L → R: Impairs ubiquitination activity. Loss of down-regulation of NF-kappa-B activity; when associated with A-614. 1 Publication1
Mutagenesisi627C → A: Marked attenuation of ubiquitin ligase activity and inhibition of RIPK1 degradation; when associated with A-624. 1 Publication1
Mutagenesisi770 – 771FG → AA: Impairs polyubiquitin binding, abolishes inhibition of IKK activation. 1 Publication2
Mutagenesisi779C → A: Impairs polyubiquitin binding, abolishes inhibition of IKK activation; when associated with A-782. 1 Publication1
Mutagenesisi782C → A: Impairs polyubiquitin binding, abolishes inhibition of IKK activation; when associated with A-779. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi7128.
MIMi616744. phenotype.
OpenTargetsiENSG00000118503.
Orphaneti536. Systemic lupus erythematosus.
PharmGKBiPA36593.

Polymorphism and mutation databases

BioMutaiTNFAIP3.
DMDMi112894.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001887912 – 790Tumor necrosis factor alpha-induced protein 3Add BLAST789
ChainiPRO_00004181272 – 439A20p50Add BLAST438
ChainiPRO_0000418128440 – 790A20p37Add BLAST351

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei459PhosphoserineCombined sources1
Modified residuei575PhosphoserineCombined sources1
Modified residuei645PhosphoserineCombined sources1

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei439 – 440Cleavage; by MALT12

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP21580.
MaxQBiP21580.
PaxDbiP21580.
PeptideAtlasiP21580.
PRIDEiP21580.

PTM databases

iPTMnetiP21580.
PhosphoSitePlusiP21580.

Expressioni

Inductioni

By TNF.

Gene expression databases

BgeeiENSG00000118503.
CleanExiHS_TNFAIP3.
ExpressionAtlasiP21580. baseline and differential.
GenevisibleiP21580. HS.

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
itself3EBI-527670,EBI-527670
ARRDC3Q96B675EBI-527670,EBI-2875665
IKBKGQ9Y6K94EBI-527670,EBI-81279
RNF11Q9Y3C52EBI-527670,EBI-396669
TNIP1Q150256EBI-527670,EBI-357849
TNIP3Q96KP63EBI-527670,EBI-2509913
TRAF2Q129335EBI-527670,EBI-355744
TRIM23P364065EBI-527670,EBI-740098
YwhahP685103EBI-527670,EBI-444641From a different organism.

GO - Molecular functioni

  • K63-linked polyubiquitin binding Source: GO_Central
  • protease binding Source: BHF-UCL
  • protein self-association Source: BHF-UCL
  • ubiquitin binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi112983. 91 interactors.
DIPiDIP-33804N.
IntActiP21580. 31 interactors.
MINTiMINT-97330.
STRINGi9606.ENSP00000237289.

Structurei

Secondary structure

1790
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi10 – 13Combined sources4
Helixi15 – 27Combined sources13
Beta strandi33 – 35Combined sources3
Beta strandi39 – 42Combined sources4
Helixi43 – 45Combined sources3
Beta strandi54 – 56Combined sources3
Helixi58 – 68Combined sources11
Helixi71 – 79Combined sources9
Beta strandi82 – 84Combined sources3
Beta strandi87 – 89Combined sources3
Beta strandi92 – 95Combined sources4
Helixi103 – 113Combined sources11
Helixi121 – 132Combined sources12
Helixi136 – 147Combined sources12
Helixi164 – 174Combined sources11
Beta strandi176 – 178Combined sources3
Beta strandi181 – 185Combined sources5
Helixi193 – 203Combined sources11
Beta strandi207 – 211Combined sources5
Beta strandi231 – 233Combined sources3
Helixi240 – 242Combined sources3
Beta strandi248 – 253Combined sources6
Beta strandi256 – 263Combined sources8
Beta strandi267 – 270Combined sources4
Beta strandi272 – 279Combined sources8
Beta strandi282 – 285Combined sources4
Helixi293 – 297Combined sources5
Helixi299 – 306Combined sources8
Beta strandi309 – 315Combined sources7
Beta strandi317 – 329Combined sources13
Helixi337 – 339Combined sources3
Helixi341 – 354Combined sources14
Helixi359 – 361Combined sources3
Beta strandi384 – 386Combined sources3
Turni398 – 402Combined sources5
Helixi405 – 412Combined sources8
Beta strandi604 – 606Combined sources3
Beta strandi613 – 615Combined sources3
Helixi618 – 620Combined sources3
Helixi625 – 634Combined sources10
Helixi773 – 775Combined sources3
Helixi780 – 788Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4ZRHX-ray2.70A/B/C/D/E/F1-366[»]
4ZS5X-ray3.20A/B/C/D/E/F1-366[»]
5DODX-ray2.50A/B/C/D/E/F1-366[»]
5LRXX-ray2.85A/C/E/F1-366[»]
ProteinModelPortaliP21580.
SMRiP21580.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21580.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini92 – 263OTUPROSITE-ProRule annotationAdd BLAST172
Repeati286 – 3171Add BLAST32
Repeati324 – 3562Add BLAST33

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni58 – 300TRAF-bindingAdd BLAST243
Regioni157 – 159Interaction with ubiquitinCurated3
Regioni190 – 192Interaction with ubiquitinCurated3
Regioni224 – 227Interaction with ubiquitinCurated4
Regioni286 – 3562 X approximate repeatsAdd BLAST71
Regioni369 – 775Interaction with TNIP1By similarityAdd BLAST407
Regioni386 – 453Interaction with RIPK11 PublicationAdd BLAST68
Regioni605 – 655Required for proteosomal degradation of UBE2N and UBE2D3, TRAF6 deubiquitination, and TAX1BP1 interaction with UBE2NBy similarityAdd BLAST51
Regioni606 – 790Sufficient for inhibitory activity of TNF-induced NF-kappa-B activityBy similarityAdd BLAST185
Regioni697 – 790Required for lysosomal localization and for TRAF2 lysosomal degradationAdd BLAST94

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)DescriptionActionsGraphical viewLength
Zinc fingeri381 – 416A20-type 1PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri472 – 507A20-type 2PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri515 – 548A20-type 3PROSITE-ProRule annotationAdd BLAST34
Zinc fingeri601 – 636A20-type 4PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri651 – 686A20-type 5PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri710 – 745A20-type 6PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri756 – 790A20-type 7PROSITE-ProRule annotationAdd BLAST35

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IQZK. Eukaryota.
ENOG41117NJ. LUCA.
GeneTreeiENSGT00530000062989.
HOGENOMiHOG000133004.
HOVERGENiHBG059260.
InParanoidiP21580.
KOiK11859.
OMAiETTAMKC.
OrthoDBiEOG091G01QE.
PhylomeDBiP21580.
TreeFamiTF323312.

Family and domain databases

InterProiIPR033478. A20.
IPR003323. OTU_dom.
IPR002653. Znf_A20.
[Graphical view]
PANTHERiPTHR13367:SF3. PTHR13367:SF3. 1 hit.
PfamiPF02338. OTU. 1 hit.
PF01754. zf-A20. 4 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)DescriptionActionsGraphical viewLength
Natural variantiVAR_020447125A → V.1 PublicationCorresponds to variant rs5029941dbSNPEnsembl.1
Natural variantiVAR_022143127F → C.1 PublicationCorresponds to variant rs2230926dbSNPEnsembl.1
Natural variantiVAR_076302243C → Y in AISBL; increases inflammatory cytokine secretion; increases NF-kappaB signaling. 1 Publication1
Natural variantiVAR_029319766A → P.1 PublicationCorresponds to variant rs5029957dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
XP_011534397.1. XM_011536095.1.
UniGeneiHs.211600.

Genome annotation databases

EnsembliENST00000237289; ENSP00000237289; ENSG00000118503.
ENST00000612899; ENSP00000481570; ENSG00000118503.
GeneIDi7128.
KEGGihsa:7128.
UCSCiuc003qhr.5. human.

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:
EMBLi
GenBanki
DDBJi
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.
XP_011534397.1. XM_011536095.1.
UniGeneiHs.211600.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4ZRHX-ray2.70A/B/C/D/E/F1-366[»]
4ZS5X-ray3.20A/B/C/D/E/F1-366[»]
5DODX-ray2.50A/B/C/D/E/F1-366[»]
5LRXX-ray2.85A/C/E/F1-366[»]
ProteinModelPortaliP21580.
SMRiP21580.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112983. 91 interactors.
DIPiDIP-33804N.
IntActiP21580. 31 interactors.
MINTiMINT-97330.
STRINGi9606.ENSP00000237289.

Protein family/group databases

MEROPSiC64.003.

PTM databases

iPTMnetiP21580.
PhosphoSitePlusiP21580.

Polymorphism and mutation databases

BioMutaiTNFAIP3.
DMDMi112894.

Proteomic databases

EPDiP21580.
MaxQBiP21580.
PaxDbiP21580.
PeptideAtlasiP21580.
PRIDEiP21580.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000237289; ENSP00000237289; ENSG00000118503.
ENST00000612899; ENSP00000481570; ENSG00000118503.
GeneIDi7128.
KEGGihsa:7128.
UCSCiuc003qhr.5. human.

Organism-specific databases

CTDi7128.
DisGeNETi7128.
GeneCardsiTNFAIP3.
HGNCiHGNC:11896. TNFAIP3.
HPAiHPA002116.
MIMi191163. gene.
616744. phenotype.
neXtProtiNX_P21580.
OpenTargetsiENSG00000118503.
Orphaneti536. Systemic lupus erythematosus.
PharmGKBiPA36593.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IQZK. Eukaryota.
ENOG41117NJ. LUCA.
GeneTreeiENSGT00530000062989.
HOGENOMiHOG000133004.
HOVERGENiHBG059260.
InParanoidiP21580.
KOiK11859.
OMAiETTAMKC.
OrthoDBiEOG091G01QE.
PhylomeDBiP21580.
TreeFamiTF323312.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000118503-MONOMER.
ReactomeiR-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-5357786. TNFR1-induced proapoptotic signaling.
R-HSA-5357905. Regulation of TNFR1 signaling.
R-HSA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.
SignaLinkiP21580.
SIGNORiP21580.

Miscellaneous databases

ChiTaRSiTNFAIP3. human.
EvolutionaryTraceiP21580.
GeneWikiiTNFAIP3.
GenomeRNAii7128.
PROiP21580.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118503.
CleanExiHS_TNFAIP3.
ExpressionAtlasiP21580. baseline and differential.
GenevisibleiP21580. HS.

Family and domain databases

InterProiIPR033478. A20.
IPR003323. OTU_dom.
IPR002653. Znf_A20.
[Graphical view]
PANTHERiPTHR13367:SF3. PTHR13367:SF3. 1 hit.
PfamiPF02338. OTU. 1 hit.
PF01754. zf-A20. 4 hits.
[Graphical view]
SMARTiSM00259. ZnF_A20. 7 hits.
[Graphical view]
PROSITEiPS50802. OTU. 1 hit.
PS51036. ZF_A20. 7 hits.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 177 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.