TNFA_HUMAN » Tumor necrosis factor

TNFA_HUMAN » Tumor necrosis factor
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
TNFA_HUMAN » Tumor necrosis factor » Cachectin;TNF-alpha;Tumor necrosis factor ligand superfamily member 2;TNF-a;
Hydrophobic Thickness 35.2 ± 3.4 Å
Tilt Angle 22 ± 0°
ΔGtransfer -26.4 kcal/mol
ΔGfold -16.4 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome, HMDB
Topology In
TM Segments 31-56 (24-56)
Pathways

Adipocytokine signaling pathway (KEGG)

African trypanosomiasis (KEGG)

Allograft rejection (KEGG)

Alzheimer's disease (KEGG)

Amoebiasis (KEGG)

Amyotrophic lateral sclerosis (KEGG)

Antigen processing and presentation (KEGG)

Apoptosis (KEGG)

Apoptosis (Reactome)

Asthma (KEGG)

Chagas disease (KEGG)

Cytokine-cytokine receptor interaction (KEGG)

Dilated cardiomyopathy (KEGG)

Fc epsilon RI signaling pathway (KEGG)

Graft-versus-host disease (KEGG)

Hematopoietic cell lineage (KEGG)

Hepatitis B (KEGG)

Hepatitis C (KEGG)

Herpes simplex infection (KEGG)

HTLV-I infection (KEGG)

Hypertrophic cardiomyopathy (KEGG)

Influenza A (KEGG)

Legionellosis (KEGG)

Leishmaniasis (KEGG)

Malaria (KEGG)

MAPK signaling pathway (KEGG)

mTOR signaling pathway (KEGG)

Natural killer cell mediated cytotoxicity (KEGG)

NF-kappa B signaling pathway (KEGG)

NOD-like receptor signaling pathway (KEGG)

Osteoclast differentiation (KEGG)

Pertussis (KEGG)

Proteoglycans in cancer (KEGG)

Rheumatoid arthritis (KEGG)

RIG-I-like receptor signaling pathway (KEGG)

Systemic lupus erythematosus (KEGG)

T cell receptor signaling pathway (KEGG)

TGF-beta signaling pathway (KEGG)

TNF signaling pathway (KEGG)

Toll-like receptor signaling pathway (KEGG)

Toxoplasmosis (KEGG)

Tuberculosis (KEGG)

Type I diabetes mellitus (KEGG)

Type II diabetes mellitus (KEGG)

PDB 3alq (A/B...=77-233), 2tun (A/B...=77-233), 3it8 (A/B...=82-233), 5tsw (A/B...=84-233), 4twt (A/B/C/D=77-233), 2az5 (A/B/C/D=86-233), 2e7a (A/B/C=77-233), 1a8m (A/B/C=77-233), 1tnf (A/B/C=77-233), 2zpx (A/B/C=77-233), 2zjc (A/B/C=77-233), 3wd5 (A=77-233), 4tsv (A=84-233), 4g3y (C=77-233), 3l9j (T=85-233)
OPM none
Complexes

TNR1B:TNFA_HUMAN

TNFA:TNFA_HUMAN

Interactions

ADA17, Complex: TNFA:ADA17, PubMed

ADAM9, Complex: ADAM9:TNFA, PubMed

CSF1, Complex: CSF1:TNFA, PubMed

LAMP2, Complex: TNFA:LAMP2

PTPRZ, Complex: TNFA:PTPRZ

TNFA, Complex: Homotrimer of tumor necrosis factor alpha, PDBID: 2E7A

TNR1A, Complex: TRADD:TNR1A:TNFA:TRAF2:RIPK1

TNR1B, Complex: TNR1B:TNFA, PDBID: 3alq, PubMed

TNR3, Complex: TNFA:TNR3, PubMed

TNR6, Complex: TNFA:TNR6, PubMed

Domains

AA: 102-233, PDBID: 1A8M, Subunit A, Seq Identity:100%, TNF(Tumour Necrosis Factor) family

UniProt annotation for TNFA_HUMAN » Tumor necrosis factor
FUNCTION: Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key "Ser-418" residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed).

FUNCTION: The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.

SUBUNIT: Homotrimer. Interacts with SPPL2B.

DISEASE: Psoriatic arthritis (PSORAS) OMIM: An inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis). associated with variations affecting the gene represented in this entry.

UniProt features for TNFA_HUMAN » Tumor necrosis factor
CHAIN 1 233 Tumor necrosis factor, membrane form.
CHAIN 1 39 Intracellular domain 1.
CHAIN 1 35 Intracellular domain 2.
CHAIN 50 ? C-domain 1.
CHAIN 52 ? C-domain 2.
CHAIN 77 233 Tumor necrosis factor, soluble form.
SITE 35 36 Cleavage; by SPPL2A or SPPL2B.
SITE 39 40 Cleavage; by SPPL2A or SPPL2B.
SITE 49 50 Cleavage; by SPPL2A or SPPL2B.
SITE 51 52 Cleavage; by SPPL2A or SPPL2B.
SITE 76 77 Cleavage; by ADAM17.
DISULFID 145 177
Amino Acid Sequence for TNFA_HUMAN » Tumor necrosis factor
MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLI VAGATTLFCL LHFGVIGPQR EEFPRDLSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG QLQWLNRRAN ALLANGVELR DNQLVVPSEG LYLIYSQVLF KGQGCPSTHV LLTHTISRIA VSYQTKVNLL SAIKSPCQRE TPEGAEAKPW YEPIYLGGVF QLEKGDRLSA EINRPDYLDF AESGQVYFGI IAL