TNR1A_HUMAN » Tumor necrosis factor receptor superfamily member 1A

TNR1A_HUMAN » Tumor necrosis factor receptor superfamily member 1A
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Topology in Plasma membrane
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cytoplasmic side
TNR1A_HUMAN » Tumor necrosis factor receptor superfamily member 1A » Tumor necrosis factor receptor 1;TNF-R1; Tumor necrosis factor receptor type I;TNF-RI; TNFR-I; p55;p60;
Hydrophobic Thickness 37.2 ± 1.0 Å
Tilt Angle 1 ± 0°
ΔGtransfer -53.8 kcal/mol
ΔGfold -21.3 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 208-236 (206-237)
Pathways

Adipocytokine signaling pathway (KEGG)

Alzheimer's disease (KEGG)

Amyotrophic lateral sclerosis (KEGG)

Apoptosis (Reactome)

Apoptosis (KEGG)

Chagas disease (KEGG)

Cytokine-cytokine receptor interaction (KEGG)

Hepatitis C (KEGG)

Herpes simplex infection (KEGG)

HTLV-I infection (KEGG)

Influenza A (KEGG)

MAPK signaling pathway (KEGG)

NF-kappa B signaling pathway (KEGG)

Osteoclast differentiation (KEGG)

TNF signaling pathway (KEGG)

Toxoplasmosis (KEGG)

Tuberculosis (KEGG)

PDB 1ich (345-455), 1ext (A/B=41-201), 1ft4 (A/B=41-201), 1ncf (A/B=41-201), 1tnr (R=44-182)
OPM none
Complexes

TNR1A:TNR1A_HUMAN

Interactions

ADA17, Complex: ADA17:TNR1A

ATD3A, Complex: TNR1A:ATD3A, PubMed

ATF6A, Complex: ATF6A:TNR1A, PubMed

CALX, Complex: TNR1A:CALX, PubMed

DJB12, Complex: TNR1A:DJB12, PubMed

EGFR, Complex: EGFR:TNR1A, PubMed

ERAP1, Complex: TNR1A:ERAP1, PubMed

ERN1, Complex: TNR1A:ERN1:AGFG1, PubMed

ITA9, Complex: ITA9:TNR1A, PubMed

LRC59, Complex: TNR1A:LRC59, PubMed

MUC1, Complex: MUC1:TNR1A, PubMed

OST48, Complex: TNR1A:OST48, PubMed

SE1L1, Complex: SE1L1:TNR1A, PubMed

SSRD, Complex: SSRD:TNR1A, PubMed

TIM50, Complex: TIM50:TNR1A, PubMed

TNF10, Complex: TR10A:RIPK1:TRAF2:TNF10:TNR1A:TNR6:TRADD:CFLAR

TNFA, Complex: TNR1A:TNFA, PubMed

TNFC, Complex: TNFC:TNR1A, PubMed

TNFL6, Complex: TNFL6:TNR1A, PubMed

TNR1A, Complex: Homodimer of tumor necrosis factor receptor 1A, PDBID: 1EXT

TNR1B, Complex: TNR1A:TNR1B, PubMed

TNR25, Complex: TNR25:TNR1A, PubMed

TNR6, Complex: TNR1A:TNR6, PubMed

TR10B, Complex: TNR1A:TR10B, PubMed

Domains

AA: 44-81, PDBID: 1EXT, Subunit A, Seq Identity:100%, TNFR/NGFR cysteine-rich region

AA: 84-125, PDBID: 1EXT, Subunit A, Seq Identity:100%, TNFR/NGFR cysteine-rich region

AA: 127-166, PDBID: 1EXT, Subunit A, Seq Identity:100%, TNFR/NGFR cysteine-rich region

AA: 356-441, PDBID: 1ICH, Subunit A, Seq Identity:100%, Death domain

UniProt annotation for TNR1A_HUMAN » Tumor necrosis factor receptor superfamily member 1A
FUNCTION: Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate- specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.

SUBUNIT: Binding of TNF to the extracellular domain leads to homotrimerization. The aggregated death domains provide a novel molecular interface that interacts specifically with the death domain of TRADD. Various TRADD-interacting proteins such as TRAFS, RIPK1 and possibly FADD, are recruited to the complex by their association with TRADD. This complex activates at least two distinct signaling cascades, apoptosis and NF-kappa-B signaling. Interacts with BAG4, BRE, FEM1B, GRB2, SQSTM1 and TRPC4AP. Interacts with HCV core protein. Interacts with human cytomegalovirus/HHV-5 protein UL138. Interacts directly with NOL3 (via CARD domain); inhibits TNF-signaling pathway (By similarity).

DOMAIN: The domain that induces A-SMASE is probably identical to the death domain. The N-SMASE activation domain (NSD) is both necessary and sufficient for activation of N-SMASE.

DOMAIN: Both the cytoplasmic membrane-proximal region and the C- terminal region containing the death domain are involved in the interaction with TRPC4AP.

DISEASE: Familial hibernian fever (FHF) OMIM: A hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases. mutations affecting the gene represented in this entry.

DISEASE: Multiple sclerosis 5 (MS5) OMIM: A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheath, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. associated with variations affecting the gene represented in this entry. An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist.

UniProt features for TNR1A_HUMAN » Tumor necrosis factor receptor superfamily member 1A
SIGNAL 1 21
CHAIN 22 455 Tumor necrosis factor receptor superfamily member 1A, membrane form.
CHAIN 41 291 Tumor necrosis factor-binding protein 1.
REPEAT 43 82 TNFR-Cys 1.
REPEAT 83 125 TNFR-Cys 2.
REPEAT 126 166 TNFR-Cys 3.
REPEAT 167 196 TNFR-Cys 4.
DOMAIN 356 441 Death.
REGION 338 348 N-SMase activation domain (NSD).
DISULFID 44 58
DISULFID 59 72
DISULFID 62 81
DISULFID 84 99
DISULFID 102 117
DISULFID 105 125
DISULFID 127 143
DISULFID 146 158
DISULFID 149 166
DISULFID 168 179
DISULFID 182 195
DISULFID 185 191
Amino Acid Sequence for TNR1A_HUMAN » Tumor necrosis factor receptor superfamily member 1A
MGLSTVPDLL LPLVLLELLV GIYPSGVIGL VPHLGDREKR DSVCPQGKYI HPQNNSICCT KCHKGTYLYN DCPGPGQDTD CRECESGSFT ASENHLRHCL SCSKCRKEMG QVEISSCTVD RDTVCGCRKN QYRHYWSENL FQCFNCSLCL NGTVHLSCQE KQNTVCTCHA GFFLRENECV SCSNCKKSLE CTKLCLPQIE NVKGTEDSGT TVLLPLVIFF GLCLLSLLFI GLMYRYQRWK SKLYSIVCGK STPEKEGELE GTTTKPLAPN PSFSPTPGFT PTLGFSPVPS STFTSSSTYT PGDCPNFAAP RREVAPPYQG ADPILATALA SDPIPNPLQK WEDSAHKPQS LDTDDPATLY AVVENVPPLR WKEFVRRLGL SDHEIDRLEL QNGRCLREAQ YSMLATWRRR TPRREATLEL LGRVLRDMDL LGCLEDIEEA LCGPAALPPA PSLLR