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Protein

Tumor necrosis factor alpha-induced protein 8

Gene

TNFAIP8

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

Functioni

Acts as a negative mediator of apoptosis and may play a role in tumor progression. Suppresses the TNF-mediated apoptosis by inhibiting caspase-8 activity but not the processing of procaspase-8, subsequently resulting in inhibition of BID cleavage and caspase-3 activation.3 Publications

GO - Molecular functioni

  • cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: UniProtKB

GO - Biological processi

  • defense response to Gram-positive bacterium Source: Ensembl
  • interleukin-1 beta production Source: Ensembl
  • negative regulation of apoptotic process Source: ProtInc
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: GOC
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor alpha-induced protein 8
Short name:
TNF alpha-induced protein 8
Alternative name(s):
Head and neck tumor and metastasis-related protein
MDC-3.13
NF-kappa-B-inducible DED-containing protein
Short name:
NDED
SCC-S2
TNF-induced protein GG2-1
Gene namesi
Name:TNFAIP8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:17260. TNFAIP8.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134957136.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 198198Tumor necrosis factor alpha-induced protein 8PRO_0000285718Add
BLAST

Proteomic databases

MaxQBiO95379.
PaxDbiO95379.
PRIDEiO95379.

Expressioni

Tissue specificityi

Expressed at high levels in the spleen, lymph node, thymus, thyroid, bone marrow and placenta. Expressed at high levels both in various tumor tissues, unstimulated and cytokine-activated cultured cells. Expressed at low levels in the spinal cord, ovary, lung, adrenal glands, heart, brain, testis and skeletal muscle.3 Publications

Developmental stagei

Expressed at high levels in the fetal liver, lung and kidney.1 Publication

Inductioni

By nuclear factor-KB (NF-KB) and TNF. Induction by TNF depends upon activation of NF-KB.2 Publications

Gene expression databases

BgeeiO95379.
CleanExiHS_TNFAIP8.
ExpressionAtlasiO95379. baseline and differential.
GenevisibleiO95379. HS.

Organism-specific databases

HPAiHPA054434.
HPA057089.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
INO80EQ8NBZ03EBI-1049336,EBI-769401
MED4Q9NPJ64EBI-1049336,EBI-394607
PLEKHF2Q9H8W44EBI-1049336,EBI-742388
PRR13Q9NZ813EBI-1049336,EBI-740924
SDCBPO005603EBI-1049336,EBI-727004
TIFAQ96CG33EBI-1049336,EBI-740711

Protein-protein interaction databases

BioGridi117344. 20 interactions.
IntActiO95379. 6 interactions.
MINTiMINT-1473332.
STRINGi9606.ENSP00000421848.

Structurei

3D structure databases

ProteinModelPortaliO95379.
SMRiO95379. Positions 15-196.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili49 – 8335Sequence AnalysisAdd
BLAST

Sequence similaritiesi

Belongs to the TNFAIP8 family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiNOG81900.
GeneTreeiENSGT00390000003488.
HOGENOMiHOG000007708.
HOVERGENiHBG053286.
InParanoidiO95379.
OMAiGRIDEVF.
OrthoDBiEOG7P5T2H.
PhylomeDBiO95379.
TreeFamiTF323415.

Family and domain databases

InterProiIPR008477. DUF758.
[Graphical view]
PANTHERiPTHR12757. PTHR12757. 1 hit.
PfamiPF05527. DUF758. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95379-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MHSEAEESKE VATDVFNSKN LAVQAQKKIL GKMVSKSIAT TLIDDTSSEV
60 70 80 90 100
LDELYRVTRE YTQNKKEAEK IIKNLIKTVI KLAILYRNNQ FNQDELALME
110 120 130 140 150
KFKKKVHQLA MTVVSFHQVD YTFDRNVLSR LLNECREMLH QIIQRHLTAK
160 170 180 190
SHGRVNNVFD HFSDCEFLAA LYNPFGNFKP HLQKLCDGIN KMLDEENI
Length:198
Mass (Da):23,003
Last modified:May 1, 1999 - v1
Checksum:iD9B8F6FCF9AFC2C3
GO
Isoform 2 (identifier: O95379-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: MHSEAEESKE → MA

Show »
Length:190
Mass (Da):22,048
Checksum:i0DCD250217A1209C
GO
Isoform 3 (identifier: O95379-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-11: MHSEAEESKEV → M

Show »
Length:188
Mass (Da):21,877
Checksum:i60452EC0A684F535
GO
Isoform 4 (identifier: O95379-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: MHSEAEESKE → MTLPRYCEVVLLIAHGEKMLKL

Note: No experimental confirmation available.
Show »
Length:210
Mass (Da):24,385
Checksum:i44DE8FBED9290476
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti151 – 1511S → C.
Corresponds to variant rs3203922 [ dbSNP | Ensembl ].
VAR_032047

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1111MHSEAEESKEV → M in isoform 3. 3 PublicationsVSP_024898Add
BLAST
Alternative sequencei1 – 1010MHSEAEESKE → MA in isoform 2. 2 PublicationsVSP_024899
Alternative sequencei1 – 1010MHSEAEESKE → MTLPRYCEVVLLIAHGEKML KL in isoform 4. 1 PublicationVSP_054827

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF070671 mRNA. Translation: AAC83229.1.
AF099935 mRNA. Translation: AAC72975.1.
AF099936 mRNA. Translation: AAC72976.1.
CR457137 mRNA. Translation: CAG33418.1.
AK001850 mRNA. Translation: BAG50983.1.
AK001931 mRNA. Translation: BAG50994.1.
AK301281 mRNA. Translation: BAH13449.1.
AC008475 Genomic DNA. No translation available.
AC027320 Genomic DNA. No translation available.
AC035144 Genomic DNA. No translation available.
CH471086 Genomic DNA. Translation: EAW48914.1.
BC005352 mRNA. Translation: AAH05352.1.
BC007014 mRNA. Translation: AAH07014.1.
AF098933 mRNA. Translation: AAF29435.1.
CCDSiCCDS47257.1. [O95379-3]
CCDS47258.1. [O95379-1]
CCDS68933.1. [O95379-4]
RefSeqiNP_001071122.1. NM_001077654.2. [O95379-3]
NP_001273742.1. NM_001286813.1. [O95379-1]
NP_001273743.1. NM_001286814.1. [O95379-4]
NP_001273744.1. NM_001286815.1.
NP_001273746.1. NM_001286817.1.
NP_055165.2. NM_014350.3. [O95379-1]
UniGeneiHs.618488.
Hs.656274.

Genome annotation databases

EnsembliENST00000274456; ENSP00000274456; ENSG00000145779. [O95379-3]
ENST00000503646; ENSP00000421848; ENSG00000145779. [O95379-1]
ENST00000504771; ENSP00000422245; ENSG00000145779. [O95379-1]
ENST00000513374; ENSP00000427424; ENSG00000145779. [O95379-4]
GeneIDi25816.
KEGGihsa:25816.
UCSCiuc003ksg.3. human. [O95379-3]
uc003ksi.3. human. [O95379-1]
uc011cwf.2. human.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF070671 mRNA. Translation: AAC83229.1.
AF099935 mRNA. Translation: AAC72975.1.
AF099936 mRNA. Translation: AAC72976.1.
CR457137 mRNA. Translation: CAG33418.1.
AK001850 mRNA. Translation: BAG50983.1.
AK001931 mRNA. Translation: BAG50994.1.
AK301281 mRNA. Translation: BAH13449.1.
AC008475 Genomic DNA. No translation available.
AC027320 Genomic DNA. No translation available.
AC035144 Genomic DNA. No translation available.
CH471086 Genomic DNA. Translation: EAW48914.1.
BC005352 mRNA. Translation: AAH05352.1.
BC007014 mRNA. Translation: AAH07014.1.
AF098933 mRNA. Translation: AAF29435.1.
CCDSiCCDS47257.1. [O95379-3]
CCDS47258.1. [O95379-1]
CCDS68933.1. [O95379-4]
RefSeqiNP_001071122.1. NM_001077654.2. [O95379-3]
NP_001273742.1. NM_001286813.1. [O95379-1]
NP_001273743.1. NM_001286814.1. [O95379-4]
NP_001273744.1. NM_001286815.1.
NP_001273746.1. NM_001286817.1.
NP_055165.2. NM_014350.3. [O95379-1]
UniGeneiHs.618488.
Hs.656274.

3D structure databases

ProteinModelPortaliO95379.
SMRiO95379. Positions 15-196.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117344. 20 interactions.
IntActiO95379. 6 interactions.
MINTiMINT-1473332.
STRINGi9606.ENSP00000421848.

Proteomic databases

MaxQBiO95379.
PaxDbiO95379.
PRIDEiO95379.

Protocols and materials databases

DNASUi25816.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000274456; ENSP00000274456; ENSG00000145779. [O95379-3]
ENST00000503646; ENSP00000421848; ENSG00000145779. [O95379-1]
ENST00000504771; ENSP00000422245; ENSG00000145779. [O95379-1]
ENST00000513374; ENSP00000427424; ENSG00000145779. [O95379-4]
GeneIDi25816.
KEGGihsa:25816.
UCSCiuc003ksg.3. human. [O95379-3]
uc003ksi.3. human. [O95379-1]
uc011cwf.2. human.

Organism-specific databases

CTDi25816.
GeneCardsiGC05P118604.
H-InvDBHIX0005115.
HGNCiHGNC:17260. TNFAIP8.
HPAiHPA054434.
HPA057089.
MIMi612111. gene.
neXtProtiNX_O95379.
PharmGKBiPA134957136.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG81900.
GeneTreeiENSGT00390000003488.
HOGENOMiHOG000007708.
HOVERGENiHBG053286.
InParanoidiO95379.
OMAiGRIDEVF.
OrthoDBiEOG7P5T2H.
PhylomeDBiO95379.
TreeFamiTF323415.

Miscellaneous databases

ChiTaRSiTNFAIP8. human.
GeneWikiiTNFAIP8.
GenomeRNAii25816.
NextBioi35480121.
PROiO95379.
SOURCEiSearch...

Gene expression databases

BgeeiO95379.
CleanExiHS_TNFAIP8.
ExpressionAtlasiO95379. baseline and differential.
GenevisibleiO95379. HS.

Family and domain databases

InterProiIPR008477. DUF758.
[Graphical view]
PANTHERiPTHR12757. PTHR12757. 1 hit.
PfamiPF05527. DUF758. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Vascular endothelial genes that are responsive to tumor necrosis factor-alpha in vitro are expressed in atherosclerotic lesions, including inhibitor of apoptosis protein-1, stannin, and two novel genes."
    Horrevoets A.J.G., Fontijn R.D., van Zonneveld A.J., de Vries C.J.M., ten Cate J.W., Pannekoek H.
    Blood 93:3418-3431(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY.
    Tissue: Umbilical vein.
  2. "Identification of cellular factors involved in the differentiation of dendritic cells."
    Nietfeld W., Meyerhans A.F.
    Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
  3. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  4. "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] (ISOFORMS 1; 3 AND 4).
    Tissue: Placenta.
  5. "The DNA sequence and comparative analysis of human chromosome 5."
    Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
    , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
    Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Tissue: Stomach.
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "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 1).
    Tissue: Brain and Urinary bladder.
  8. "Identification of a novel tumor necrosis factor-alpha-inducible gene, SCC-S2, containing the consensus sequence of a death effector domain of fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein."
    Kumar D., Whiteside T.L., Kasid U.
    J. Biol. Chem. 275:2973-2978(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 99-198 (ISOFORM 3), IDENTIFICATION, FUNCTION, INDUCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    Tissue: Heart.
  9. "Nuclear factor-kappa B-inducible death effector domain-containing protein suppresses tumor necrosis factor-mediated apoptosis by inhibiting caspase-8 activity."
    You Z., Ouyang H., Lopatin D., Polver P.J., Wang C.-Y.
    J. Biol. Chem. 276:26398-26404(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  10. "Expression of SCC-S2, an antiapoptotic molecule, correlates with enhanced proliferation and tumorigenicity of MDA-MB 435 cells."
    Kumar D., Gokhale P., Broustas C., Chakravarty D., Ahmad I., Kasid U.
    Oncogene 23:612-616(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiTFIP8_HUMAN
AccessioniPrimary (citable) accession number: O95379
Secondary accession number(s): B3KMH1
, B3KMI2, B7Z713, Q9P1Q1, Q9UER5, Q9UP47
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: May 1, 1999
Last modified: June 24, 2015
This is version 108 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.