TNFRSF1A

Functionⁱ

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.

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Receptor
Biological process	Apoptosis, Host-virus interaction

Enzyme and pathway databases

PathwayCommonsⁱ	P19438
Reactomeⁱ	R-HSA-5357786, TNFR1-induced proapoptotic signaling R-HSA-5357905, Regulation of TNFR1 signaling R-HSA-5357956, TNFR1-induced NFkappaB signaling pathway R-HSA-5626978, TNFR1-mediated ceramide production R-HSA-5669034, TNFs bind their physiological receptors R-HSA-6783783, Interleukin-10 signaling R-HSA-75893, TNF signaling
SIGNORⁱ	P19438

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Tumor necrosis factor receptor superfamily member 1A Alternative name(s): Tumor necrosis factor receptor 1 Short name: TNF-R1 Tumor necrosis factor receptor type I Short name: TNF-RI Short name: TNFR-I p55 p60 CD_antigen: CD120a Cleaved into the following 2 chains: Tumor necrosis factor receptor superfamily member 1A, membrane form Tumor necrosis factor-binding protein 1 Short name: TBPI
Gene namesⁱ	Name:TNFRSF1A Synonyms:TNFAR, TNFR1
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 12

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000067182.7
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:11916, TNFRSF1A
MIMⁱ	191190, gene
neXtProtⁱ	NX_P19438

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	30 – 211	ExtracellularSequence analysisAdd BLAST	182
Transmembraneⁱ	212 – 232	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	233 – 455	CytoplasmicSequence analysisAdd BLAST	223

Keywords - Cellular componentⁱ

Cell membrane, Golgi apparatus, Membrane, Secreted

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Familial hibernian fever (FHF)5 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_019329	51	H → Q in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895254EnsemblClinVar.	1
Natural variantⁱVAR_013410	59	C → R in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895217EnsemblClinVar.	1
Natural variantⁱVAR_019302	59	C → S in FHF. 2 PublicationsCorresponds to variant dbSNP:rs104895223EnsemblClinVar.	1
Natural variantⁱVAR_019303	62	C → G in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895225EnsemblClinVar.	1
Natural variantⁱVAR_013411	62	C → Y in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895218EnsemblClinVar.	1
Natural variantⁱVAR_019330	75	P → L in FHF; may be a polymorphism. 2 PublicationsCorresponds to variant dbSNP:rs4149637EnsemblClinVar.	1
Natural variantⁱVAR_013412	79	T → M in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895219EnsemblClinVar.	1
Natural variantⁱVAR_013413	81	C → F in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895220EnsemblClinVar.	1
Natural variantⁱVAR_019304	99	C → S in FHF. 2 PublicationsCorresponds to variant dbSNP:rs104895228EnsemblClinVar.	1
Natural variantⁱVAR_019331	115	S → G in FHF. 1 Publication	1
Natural variantⁱVAR_013414	117	C → R in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895221EnsemblClinVar.	1
Natural variantⁱVAR_013415	117	C → Y in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895222EnsemblClinVar.	1
Natural variantⁱVAR_019305	121	R → P in FHF. 1 PublicationCorresponds to variant dbSNP:rs4149584EnsemblClinVar.	1
Natural variantⁱVAR_019332	121	R → Q in FHF; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs4149584EnsemblClinVar.	1

Multiple sclerosis 5 (MS5)1 Publication

Disease susceptibility is 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.

Disease descriptionA 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.

Related information in OMIM

Keywords - Diseaseⁱ

Amyloidosis, Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	7132
MalaCards human disease database More...MalaCardsⁱ	TNFRSF1A
MIMⁱ	142680, phenotype 614810, phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000067182
Orphanetⁱ	329967, Intermittent hydrarthrosis 802, NON RARE IN EUROPE: Multiple sclerosis 32960, Tumor necrosis factor receptor 1 associated periodic syndrome
PharmGKBⁱ	PA36609

Miscellaneous databases

Pharosⁱ	P19438, Tchem

Pharosⁱ

P19438, Tchem

Chemistry databases

ChEMBLⁱ	CHEMBL3378
Drug and drug target database More...DrugBankⁱ	DB03507, 6-[3-(4-Morpholinyl)Propyl]-2-(3-Nitrophenyl)-5-Thioxo-5,6,-Dihydro-7h-Thienol[2',3':4,5]Pyrrolo[1,2-C]Imidazol-7-One DB11626, Tasonermin

Polymorphism and mutation databases

BioMutaⁱ	TNFRSF1A
DMDMⁱ	135959

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Length
Signal peptideⁱ	1 – 29	1 PublicationAdd BLAST	29
ChainⁱPRO_0000034543	30 – 455	Tumor necrosis factor receptor superfamily member 1A, membrane formAdd BLAST	426
ChainⁱPRO_0000034544	41 – 201	Tumor necrosis factor-binding protein 1Add BLAST	161

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Disulfide bondⁱ	44 ↔ 58
Glycosylationⁱ	54	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	59 ↔ 72
Disulfide bondⁱ	62 ↔ 81
Disulfide bondⁱ	84 ↔ 99
Disulfide bondⁱ	102 ↔ 117
Disulfide bondⁱ	105 ↔ 125
Disulfide bondⁱ	127 ↔ 143
Glycosylationⁱ	145	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	146 ↔ 158
Disulfide bondⁱ	149 ↔ 166
Glycosylationⁱ	151	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	168 ↔ 179
Disulfide bondⁱ	182 ↔ 195
Disulfide bondⁱ	185 ↔ 191

Post-translational modificationⁱ

The soluble form is produced from the membrane form by proteolytic processing.

Keywords - PTMⁱ

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

EPDⁱ	P19438
jPOSTⁱ	P19438
MassIVEⁱ	P19438
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P19438
PaxDbⁱ	P19438
PeptideAtlas More...PeptideAtlasⁱ	P19438
PRIDEⁱ	P19438
ProteomicsDBⁱ	53659 [P19438-1] 53660 [P19438-2] 53661 [P19438-3] 5939

PTM databases

GlyGenⁱ	P19438, 3 sites
iPTMnetⁱ	P19438
PhosphoSitePlusⁱ	P19438
SwissPalmⁱ	P19438

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000067182, Expressed in tendon of biceps brachii and 237 other tissues
ExpressionAtlasⁱ	P19438, baseline and differential
Genevisibleⁱ	P19438, HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000067182, Low tissue specificity

HPAⁱ

ENSG00000067182, Low tissue specificity

Interactionⁱ

Subunit structureⁱ

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, BABAM2, FEM1B, GRB2, SQSTM1 and TRPC4AP (PubMed:10356400, PubMed:10359574, PubMed:10542291, PubMed:15465831, PubMed:8387891, PubMed:9915703).

Interacts directly with NOL3 (via CARD domain); inhibits TNF-signaling pathway (By similarity).

Interacts with SH3RF2, TRADD and RIPK1. SH3RF2 facilitates the recruitment of RIPK1 and TRADD to TNFRSF1A in a TNF-alpha-dependent process (PubMed:24130170).

By similarity7 Publications

(Microbial infection) Interacts with mumps virus protein SH; this interaction inhibits downstream NF-kappa-B pathway activation.

1 Publication

(Microbial infection) Interacts with HCV core protein.

1 Publication

(Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL138.

1 Publication

(Microbial infection) Interacts with host TNFRSF1A; this interaction leads to the stimulation of both surface expression and shedding of TNFRSF1A.

2 Publications

Binary interactionsⁱ

Hide details

P19438

With	#Exp.	IntAct
GRN [P28799]	4	EBI-299451,EBI-747754
RFK [Q969G6]	4	EBI-299451,EBI-716872
RIPK1 [Q13546]	6	EBI-299451,EBI-358507
TNF [P01375]	15	EBI-299451,EBI-359977
TRADD [Q15628]	13	EBI-299451,EBI-359215
TRAF2 [Q12933]	5	EBI-299451,EBI-355744

TNFRSF1A - isoform 1 [P19438-1]

With	#Exp.	IntAct
RFK [Q969G6]	2	EBI-15795644,EBI-716872
itself	2	EBI-15795644,EBI-15795644

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGRIDⁱ	112986, 183 interactors
CORUMⁱ	P19438
Database of interacting proteins More...DIPⁱ	DIP-407N
IntActⁱ	P19438, 92 interactors
Molecular INTeraction database More...MINTⁱ	P19438
STRINGⁱ	9606.ENSP00000162749

Chemistry databases

BindingDBⁱ

P19438

Miscellaneous databases

RNActⁱ	P19438, protein

RNActⁱ

P19438, protein

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	48 – 50	Combined sources	3
Beta strandⁱ	52 – 54	Combined sources	3
Beta strandⁱ	58 – 60	Combined sources	3
Beta strandⁱ	66 – 70	Combined sources	5
Beta strandⁱ	80 – 83	Combined sources	4
Beta strandⁱ	92 – 94	Combined sources	3
Helixⁱ	107 – 109	Combined sources	3
Beta strandⁱ	112 – 115	Combined sources	4
Beta strandⁱ	124 – 126	Combined sources	3
Beta strandⁱ	131 – 137	Combined sources	7
Beta strandⁱ	140 – 145	Combined sources	6
Beta strandⁱ	152 – 156	Combined sources	5
Beta strandⁱ	160 – 162	Combined sources	3
Beta strandⁱ	165 – 168	Combined sources	4
Beta strandⁱ	172 – 175	Combined sources	4
Beta strandⁱ	178 – 181	Combined sources	4
Helixⁱ	182 – 184	Combined sources	3
Helixⁱ	192 – 195	Combined sources	4
Helixⁱ	357 – 365	Combined sources	9
Helixⁱ	371 – 378	Combined sources	8
Helixⁱ	382 – 391	Combined sources	10
Helixⁱ	396 – 410	Combined sources	15
Helixⁱ	417 – 427	Combined sources	11
Helixⁱ	431 – 441	Combined sources	11

Show more details

3D structure databases

SMRⁱ	P19438
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P19438

EvolutionaryTraceⁱ

P19438

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Repeatⁱ	43 – 82	TNFR-Cys 1Add BLAST	40
Repeatⁱ	83 – 125	TNFR-Cys 2Add BLAST	43
Repeatⁱ	126 – 166	TNFR-Cys 3Add BLAST	41
Repeatⁱ	167 – 196	TNFR-Cys 4Add BLAST	30
Domainⁱ	356 – 441	DeathPROSITE-ProRule annotationAdd BLAST	86

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	338 – 348	N-SMase activation domain (NSD)Add BLAST		11

Domainⁱ

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.

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

Keywords - Domainⁱ

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	ENOG502S050, Eukaryota
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000159540
HOGENOMⁱ	CLU_050864_0_0_1
InParanoidⁱ	P19438
KEGG Orthology (KO) More...KOⁱ	K03158
OMAⁱ	VLCDMDL
Database of Orthologous Groups More...OrthoDBⁱ	976094at2759
PhylomeDBⁱ	P19438
TreeFamⁱ	TF333916

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd08313, Death_TNFR1, 1 hit cd10576, TNFRSF1A, 1 hit
InterProⁱ	View protein in InterPro IPR011029, DEATH-like_dom_sf IPR000488, Death_domain IPR001368, TNFR/NGFR_Cys_rich_reg IPR020419, TNFR_1A IPR033994, TNFRSF1A_death IPR033993, TNFRSF1A_N
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00531, Death, 1 hit PF00020, TNFR_c6, 3 hits
PRINTSⁱ	PR01918, TNFACTORR1A
SMARTⁱ	View protein in SMART SM00005, DEATH, 1 hit SM00208, TNFR, 4 hits
SUPFAMⁱ	SSF47986, SSF47986, 1 hit
PROSITEⁱ	View protein in PROSITE PS50017, DEATH_DOMAIN, 1 hit PS00652, TNFR_NGFR_1, 3 hits PS50050, TNFR_NGFR_2, 3 hits

Sequences (5+)ⁱ

Sequence statusⁱ: Complete.

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

This entry describes 5 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 5 described isoforms and 7 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: P19438-1) [UniParc]FASTA Add to basket

Also known as: FL-TNFR1

This isoform has been chosen as the canonicalⁱ 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
MGLSTVPDLL LPLVLLELLV GIYPSGVIGL VPHLGDREKR DSVCPQGKYI 
        60         70         80         90        100
HPQNNSICCT KCHKGTYLYN DCPGPGQDTD CRECESGSFT ASENHLRHCL 
       110        120        130        140        150
SCSKCRKEMG QVEISSCTVD RDTVCGCRKN QYRHYWSENL FQCFNCSLCL 
       160        170        180        190        200
NGTVHLSCQE KQNTVCTCHA GFFLRENECV SCSNCKKSLE CTKLCLPQIE 
       210        220        230        240        250
NVKGTEDSGT TVLLPLVIFF GLCLLSLLFI GLMYRYQRWK SKLYSIVCGK 
       260        270        280        290        300
STPEKEGELE GTTTKPLAPN PSFSPTPGFT PTLGFSPVPS STFTSSSTYT 
       310        320        330        340        350
PGDCPNFAAP RREVAPPYQG ADPILATALA SDPIPNPLQK WEDSAHKPQS 
       360        370        380        390        400
LDTDDPATLY AVVENVPPLR WKEFVRRLGL SDHEIDRLEL QNGRCLREAQ 
       410        420        430        440        450
YSMLATWRRR TPRREATLEL LGRVLRDMDL LGCLEDIEEA LCGPAALPPA 

PSLLR

Length:455

Mass (Da):50,495

Last modified:February 1, 1991 - v1

Checksum:ⁱ4CEFBA96D03B8225

GO

Isoform 2 (identifier: P19438-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
1-108: Missing.

« Hide

        10         20         30         40         50
MGQVEISSCT VDRDTVCGCR KNQYRHYWSE NLFQCFNCSL CLNGTVHLSC 
        60         70         80         90        100
QEKQNTVCTC HAGFFLRENE CVSCSNCKKS LECTKLCLPQ IENVKGTEDS 
       110        120        130        140        150
GTTVLLPLVI FFGLCLLSLL FIGLMYRYQR WKSKLYSIVC GKSTPEKEGE 
       160        170        180        190        200
LEGTTTKPLA PNPSFSPTPG FTPTLGFSPV PSSTFTSSST YTPGDCPNFA 
       210        220        230        240        250
APRREVAPPY QGADPILATA LASDPIPNPL QKWEDSAHKP QSLDTDDPAT 
       260        270        280        290        300
LYAVVENVPP LRWKEFVRRL GLSDHEIDRL ELQNGRCLRE AQYSMLATWR 
       310        320        330        340 
RRTPRREATL ELLGRVLRDM DLLGCLEDIE EALCGPAALP PAPSLLR

Show »

Length:347

Mass (Da):38,651

Checksum:ⁱ8C629DAF8D7BA515

GO

Isoform 4 (identifier: P19438-4) [UniParc]FASTA Add to basket

Also known as: Delta6-TNFR1

The sequence of this isoform differs from the canonical sequence as follows:
184-455: NCKKSLECTK...ALPPAPSLLR → KHHSAVAPGH...LLHCLWEIDT

« Hide

        10         20         30         40         50
MGLSTVPDLL LPLVLLELLV GIYPSGVIGL VPHLGDREKR DSVCPQGKYI 
        60         70         80         90        100
HPQNNSICCT KCHKGTYLYN DCPGPGQDTD CRECESGSFT ASENHLRHCL 
       110        120        130        140        150
SCSKCRKEMG QVEISSCTVD RDTVCGCRKN QYRHYWSENL FQCFNCSLCL 
       160        170        180        190        200
NGTVHLSCQE KQNTVCTCHA GFFLRENECV SCSKHHSAVA PGHFLWSLPF 
       210        220 
IPPLHWFNVS LPTVEVQALL HCLWEIDT

Note: Disease-associated isoform. Isoform 4 splicing pattern is driven by a variation in the exon 6/intron 6 boundary region that alters exon 6 splicing. Exon 6 skipping introduces a frameshift and the translation of a protein lacking the intracellular, the transmembrane and part of the extracellular domain.Curated

Show »

Length:228

Mass (Da):25,577

Checksum:ⁱA67C489AF6DDBFEC

GO

Isoform 3 (identifier: P19438-3) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
1-232: Missing.

« Hide

        10         20         30         40         50
MYRYQRWKSK LYSIVCGKST PEKEGELEGT TTKPLAPNPS FSPTPGFTPT 
        60         70         80         90        100
LGFSPVPSST FTSSSTYTPG DCPNFAAPRR EVAPPYQGAD PILATALASD 
       110        120        130        140        150
PIPNPLQKWE DSAHKPQSLD TDDPATLYAV VENVPPLRWK EFVRRLGLSD 
       160        170        180        190        200
HEIDRLELQN GRCLREAQYS MLATWRRRTP RREATLELLG RVLRDMDLLG 
       210        220 
CLEDIEEALC GPAALPPAPS LLR

Show »

Length:223

Mass (Da):24,794

Checksum:ⁱ31BDA9ACAEF12FC3

GO

Isoform 5 (identifier: P19438-5) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
184-218: NCKKSLECTKLCLPQIENVKGTEDSGTTVLLPLVI → KVLLCRPGWNAVARSRLTATSASQIQAILLLQPPK
219-455: Missing.

« Hide

        10         20         30         40         50
MGLSTVPDLL LPLVLLELLV GIYPSGVIGL VPHLGDREKR DSVCPQGKYI 
        60         70         80         90        100
HPQNNSICCT KCHKGTYLYN DCPGPGQDTD CRECESGSFT ASENHLRHCL 
       110        120        130        140        150
SCSKCRKEMG QVEISSCTVD RDTVCGCRKN QYRHYWSENL FQCFNCSLCL 
       160        170        180        190        200
NGTVHLSCQE KQNTVCTCHA GFFLRENECV SCSKVLLCRP GWNAVARSRL 
       210 
TATSASQIQA ILLLQPPK

Show »

Length:218

Mass (Da):24,194

Checksum:ⁱFBDD906CEF26F405

GO

Computationally mapped potential isoform sequencesⁱ

There are 7 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

F5H8A6	F5H8A6_HUMAN	Tumor necrosis factor receptor supe... Tumor necrosis factor receptor superfamily member 1A	TNFRSF1A	298	Annotation score:
F5H6V7	F5H6V7_HUMAN	Tumor necrosis factor receptor supe... Tumor necrosis factor receptor superfamily member 1A	TNFRSF1A	254	Annotation score:
F5H061	F5H061_HUMAN	Tumor necrosis factor receptor supe... Tumor necrosis factor receptor superfamily member 1A	TNFRSF1A	412	Annotation score:
F5H6Z2	F5H6Z2_HUMAN	Tumor necrosis factor receptor supe... Tumor necrosis factor receptor superfamily member 1A	TNFRSF1A	118	Annotation score:
F5GWJ4	F5GWJ4_HUMAN	Tumor necrosis factor receptor supe... Tumor necrosis factor receptor superfamily member 1A	TNFRSF1A	122	Annotation score:
F5H4T5	F5H4T5_HUMAN	Tumor necrosis factor receptor supe... Tumor necrosis factor receptor superfamily member 1A	TNFRSF1A	71	Annotation score:
F5H7N1	F5H7N1_HUMAN	Tumor necrosis factor receptor supe... Tumor necrosis factor receptor superfamily member 1A	TNFRSF1A	72	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	13	L → LILPQ in BAG51763 (PubMed:14702039).Curated	1
Sequence conflictⁱ	255	K → E in BAG37891 (PubMed:14702039).Curated	1
Sequence conflictⁱ	286	S → G in BAG51763 (PubMed:14702039).Curated	1
Sequence conflictⁱ	394	R → L in BAF83777 (PubMed:14702039).Curated	1
Sequence conflictⁱ	412	Missing in AAA36756 (PubMed:2170974).Curated	1
Sequence conflictⁱ	443 – 446	GPAA → APP in AAA36756 (PubMed:2170974).Curated	4

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_019329	51	H → Q in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895254EnsemblClinVar.	1
Natural variantⁱVAR_013410	59	C → R in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895217EnsemblClinVar.	1
Natural variantⁱVAR_019302	59	C → S in FHF. 2 PublicationsCorresponds to variant dbSNP:rs104895223EnsemblClinVar.	1
Natural variantⁱVAR_019303	62	C → G in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895225EnsemblClinVar.	1
Natural variantⁱVAR_013411	62	C → Y in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895218EnsemblClinVar.	1
Natural variantⁱVAR_019330	75	P → L in FHF; may be a polymorphism. 2 PublicationsCorresponds to variant dbSNP:rs4149637EnsemblClinVar.	1
Natural variantⁱVAR_013412	79	T → M in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895219EnsemblClinVar.	1
Natural variantⁱVAR_013413	81	C → F in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895220EnsemblClinVar.	1
Natural variantⁱVAR_019304	99	C → S in FHF. 2 PublicationsCorresponds to variant dbSNP:rs104895228EnsemblClinVar.	1
Natural variantⁱVAR_019331	115	S → G in FHF. 1 Publication	1
Natural variantⁱVAR_013414	117	C → R in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895221EnsemblClinVar.	1
Natural variantⁱVAR_013415	117	C → Y in FHF. 1 PublicationCorresponds to variant dbSNP:rs104895222EnsemblClinVar.	1
Natural variantⁱVAR_019305	121	R → P in FHF. 1 PublicationCorresponds to variant dbSNP:rs4149584EnsemblClinVar.	1
Natural variantⁱVAR_019332	121	R → Q in FHF; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs4149584EnsemblClinVar.	1
Natural variantⁱVAR_011813	305	P → T. Corresponds to variant dbSNP:rs1804532Ensembl.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_037154	1 – 232	Missing in isoform 3. 1 PublicationAdd BLAST	232
Alternative sequenceⁱVSP_037153	1 – 108	Missing in isoform 2. 1 PublicationAdd BLAST	108
Alternative sequenceⁱVSP_044949	184 – 455	NCKKS…PSLLR → KHHSAVAPGHFLWSLPFIPP LHWFNVSLPTVEVQALLHCL WEIDT in isoform 4. CuratedAdd BLAST	272
Alternative sequenceⁱVSP_047613	184 – 218	NCKKS…LPLVI → KVLLCRPGWNAVARSRLTAT SASQIQAILLLQPPK in isoform 5. 1 PublicationAdd BLAST	35
Alternative sequenceⁱVSP_047614	219 – 455	Missing in isoform 5. 1 PublicationAdd BLAST	237

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M58286 mRNA Translation: AAA36753.1 M33294 mRNA Translation: AAA03210.1 M63121 mRNA Translation: AAA36754.1 X55313 mRNA Translation: CAA39021.1 M60275 mRNA Translation: AAA36756.1 M75866, M75864, M75865 Genomic DNA Translation: AAA61201.1 AY131997 Genomic DNA Translation: AAM77802.1 AK056611 mRNA Translation: BAG51763.1 AK291088 mRNA Translation: BAF83777.1 AK298729 mRNA Translation: BAG60879.1 AK304517 mRNA Translation: BAG65321.1 AK315509 mRNA Translation: BAG37891.1 EU927389 mRNA Translation: ACH57451.1 AC006057 Genomic DNA No translation available. CH471116 Genomic DNA Translation: EAW88805.1 CH471116 Genomic DNA Translation: EAW88806.1 BC010140 mRNA Translation: AAH10140.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS8542.1 [P19438-1]
PIRⁱ	A38208, GQHUT1
NCBI Reference Sequences More...RefSeqⁱ	NP_001056.1, NM_001065.3 [P19438-1] NP_001333020.1, NM_001346091.1 [P19438-2] NP_001333021.1, NM_001346092.1

Genome annotation databases

Ensemblⁱ	ENST00000162749; ENSP00000162749; ENSG00000067182 [P19438-1] ENST00000366159; ENSP00000380389; ENSG00000067182 [P19438-5]
GeneIDⁱ	7132
KEGGⁱ	hsa:7132
UCSC genome browser More...UCSCⁱ	uc001qnu.4, human [P19438-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P19438	Isoform 3 of Tumor necrosis factor receptor superfamily member 1A		HUMAN		223	UniRef100_P19438
Tumor necrosis factor receptor 1		HUMAN		347
Isoform 2 of Tumor necrosis factor receptor superfamily member 1A		HUMAN		347

Protein	Similar proteins		Species	Score	Length	Source
P19438	Isoform 3 of Tumor necrosis factor receptor superfamily member 1A		HUMAN		223	UniRef90_P19438
Tumor necrosis factor receptor 1		PAPAN		459
Tumor necrosis factor receptor 1		PANPA		455
Tumor necrosis factor receptor 1		COLAP		455
Tumor necrosis factor receptor 1		NOMLE		455
+45
P19438-5	Uncharacterized protein		NOMLE		219	UniRef90_P19438-5
TNF receptor superfamily member 1A		GORGO		218
TNF receptor superfamily member 1A		PANTR		218
Uncharacterized protein		MACFA		218
Uncharacterized protein		MACNE		218
+2

Protein	Similar proteins		Species	Score	Length	Source
P19438	Tumor necrosis factor receptor superfamily member 1A		PIG		461	UniRef50_P19438
Tumor necrosis factor receptor superfamily member 1A		MOUSE		454
Isoform 3 of Tumor necrosis factor receptor superfamily member 1A		HUMAN		223
Tumor necrosis factor receptor 1		PAPAN		459
Tumor necrosis factor receptor 1		MACFA		455
+103
P19438-5	Uncharacterized protein		NOMLE		219	UniRef50_P19438-5
Uncharacterized protein		COLAP		218
TNF receptor superfamily member 1A		GORGO		218
TNF receptor superfamily member 1A		PANTR		218
Uncharacterized protein		MACFA		218
+2

Cross-referencesⁱ

Web resourcesⁱ

INFEVERS

Repertory of FMF and hereditary autoinflammatory disorders mutations

SeattleSNPs

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M58286 mRNA Translation: AAA36753.1 M33294 mRNA Translation: AAA03210.1 M63121 mRNA Translation: AAA36754.1 X55313 mRNA Translation: CAA39021.1 M60275 mRNA Translation: AAA36756.1 M75866, M75864, M75865 Genomic DNA Translation: AAA61201.1 AY131997 Genomic DNA Translation: AAM77802.1 AK056611 mRNA Translation: BAG51763.1 AK291088 mRNA Translation: BAF83777.1 AK298729 mRNA Translation: BAG60879.1 AK304517 mRNA Translation: BAG65321.1 AK315509 mRNA Translation: BAG37891.1 EU927389 mRNA Translation: ACH57451.1 AC006057 Genomic DNA No translation available. CH471116 Genomic DNA Translation: EAW88805.1 CH471116 Genomic DNA Translation: EAW88806.1 BC010140 mRNA Translation: AAH10140.1
CCDSⁱ	CCDS8542.1 [P19438-1]
PIRⁱ	A38208, GQHUT1
RefSeqⁱ	NP_001056.1, NM_001065.3 [P19438-1] NP_001333020.1, NM_001346091.1 [P19438-2] NP_001333021.1, NM_001346092.1

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1EXT	X-ray	1.85	A/B	41-201	[»]
	1FT4	X-ray	2.90	A/B	41-201	[»]
	1ICH	NMR	-	A	345-455	[»]
	1NCF	X-ray	2.25	A/B	41-201	[»]
	1TNR	X-ray	2.85	R	44-182	[»]
SMRⁱ	P19438
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Protein-protein interaction databases

BioGRIDⁱ	112986, 183 interactors
CORUMⁱ	P19438
DIPⁱ	DIP-407N
IntActⁱ	P19438, 92 interactors
MINTⁱ	P19438
STRINGⁱ	9606.ENSP00000162749

Chemistry databases

BindingDBⁱ	P19438
ChEMBLⁱ	CHEMBL3378
DrugBankⁱ	DB03507, 6-[3-(4-Morpholinyl)Propyl]-2-(3-Nitrophenyl)-5-Thioxo-5,6,-Dihydro-7h-Thienol[2',3':4,5]Pyrrolo[1,2-C]Imidazol-7-One DB11626, Tasonermin

PTM databases

GlyGenⁱ	P19438, 3 sites
iPTMnetⁱ	P19438
PhosphoSitePlusⁱ	P19438
SwissPalmⁱ	P19438

Polymorphism and mutation databases

BioMutaⁱ	TNFRSF1A
DMDMⁱ	135959

Proteomic databases

EPDⁱ	P19438
jPOSTⁱ	P19438
MassIVEⁱ	P19438
MaxQBⁱ	P19438
PaxDbⁱ	P19438
PeptideAtlasⁱ	P19438
PRIDEⁱ	P19438
ProteomicsDBⁱ	53659 [P19438-1] 53660 [P19438-2] 53661 [P19438-3] 5939

Protocols and materials databases

ABCDⁱ	P19438, 8 sequenced antibodies
Antibodypediaⁱ	1320, 1415 antibodies
The DNASU plasmid repository More...DNASUⁱ	7132

Genome annotation databases

Ensemblⁱ	ENST00000162749; ENSP00000162749; ENSG00000067182 [P19438-1] ENST00000366159; ENSP00000380389; ENSG00000067182 [P19438-5]
GeneIDⁱ	7132
KEGGⁱ	hsa:7132
UCSCⁱ	uc001qnu.4, human [P19438-1]

Organism-specific databases

CTDⁱ	7132
DisGeNETⁱ	7132
EuPathDBⁱ	HostDB:ENSG00000067182.7
GeneCardsⁱ	TNFRSF1A
HGNCⁱ	HGNC:11916, TNFRSF1A
HPAⁱ	ENSG00000067182, Low tissue specificity
MalaCardsⁱ	TNFRSF1A
MIMⁱ	142680, phenotype 191190, gene 614810, phenotype
neXtProtⁱ	NX_P19438
OpenTargetsⁱ	ENSG00000067182
Orphanetⁱ	329967, Intermittent hydrarthrosis 802, NON RARE IN EUROPE: Multiple sclerosis 32960, Tumor necrosis factor receptor 1 associated periodic syndrome
PharmGKBⁱ	PA36609
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG502S050, Eukaryota
GeneTreeⁱ	ENSGT00940000159540
HOGENOMⁱ	CLU_050864_0_0_1
InParanoidⁱ	P19438
KOⁱ	K03158
OMAⁱ	VLCDMDL
OrthoDBⁱ	976094at2759
PhylomeDBⁱ	P19438
TreeFamⁱ	TF333916

Enzyme and pathway databases

PathwayCommonsⁱ	P19438
Reactomeⁱ	R-HSA-5357786, TNFR1-induced proapoptotic signaling R-HSA-5357905, Regulation of TNFR1 signaling R-HSA-5357956, TNFR1-induced NFkappaB signaling pathway R-HSA-5626978, TNFR1-mediated ceramide production R-HSA-5669034, TNFs bind their physiological receptors R-HSA-6783783, Interleukin-10 signaling R-HSA-75893, TNF signaling
SIGNORⁱ	P19438

Miscellaneous databases

BioGRID-ORCSⁱ	7132, 2 hits in 875 CRISPR screens
ChiTaRSⁱ	TNFRSF1A, human
EvolutionaryTraceⁱ	P19438
GeneWikiⁱ	TNFRSF1A
GenomeRNAiⁱ	7132
Pharosⁱ	P19438, Tchem
Protein Ontology More...PROⁱ	PR:P19438
RNActⁱ	P19438, protein
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000067182, Expressed in tendon of biceps brachii and 237 other tissues
ExpressionAtlasⁱ	P19438, baseline and differential
Genevisibleⁱ	P19438, HS

Family and domain databases

CDDⁱ	cd08313, Death_TNFR1, 1 hit cd10576, TNFRSF1A, 1 hit
InterProⁱ	View protein in InterPro IPR011029, DEATH-like_dom_sf IPR000488, Death_domain IPR001368, TNFR/NGFR_Cys_rich_reg IPR020419, TNFR_1A IPR033994, TNFRSF1A_death IPR033993, TNFRSF1A_N
Pfamⁱ	View protein in Pfam PF00531, Death, 1 hit PF00020, TNFR_c6, 3 hits
PRINTSⁱ	PR01918, TNFACTORR1A
SMARTⁱ	View protein in SMART SM00005, DEATH, 1 hit SM00208, TNFR, 4 hits
SUPFAMⁱ	SSF47986, SSF47986, 1 hit
PROSITEⁱ	View protein in PROSITE PS50017, DEATH_DOMAIN, 1 hit PS00652, TNFR_NGFR_1, 3 hits PS50050, TNFR_NGFR_2, 3 hits
ProtoNetⁱ	Search...
MobiDBⁱ	Search...

Entry informationⁱ

Entry nameⁱ	TNR1A_HUMAN
Accessionⁱ	P19438Primary (citable) accession number: P19438 Secondary accession number(s): A8K4X3 Q9UCA4
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
	Last sequence update:	February 1, 1991
	Last modified:	August 12, 2020
	This is version 245 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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, Direct protein sequencing, Reference proteome

Documents

Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - P19438 (TNR1A_HUMAN)

Your basket is currently empty. i <p>When browsing through different UniProt proteins, you can use the 'basket' to save them, so that you can back to find or analyse them later.<p><a href='/help/basket' target='_top'>More...</a></p>

Tumor necrosis factor receptor superfamily member 1A

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Plasma membrane

Extracellular region or secreted

Golgi apparatus

Extracellular region or secreted

Extracellular region or secreted

Golgi apparatus

Mitochondrion

Plasma Membrane

Other locations

Topology

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Keywords - Diseasei

Organism-specific databases

Miscellaneous databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

P19438

TNFRSF1A - isoform 1 [P19438-1]

GO - Molecular functioni

Protein-protein interaction databases

Chemistry databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Your basket is currently empty. ⁱ

Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ