Uni-Prot
UniProt Knowledgebase Release 2017_01 consists of:
UniProtKB/Swiss-Prot Release 2017_01 of 18-Jan-2017
UniProtKB/TrEMBL Release 2017_01 of 18-Jan-2017
An Example of Uni-Prot entry
ID TNFA_HUMAN STANDARD; PRT; 233 AA.
AC P01375; O43647; Q9P1Q2; Q9UIV3;
DT 21-JUL-1986 (Rel. 01, Created)
DT 21-JUL-1986 (Rel. 01, Last sequence update)
DT 01-FEB-2005 (Rel. 46, Last annotation update)
DE Tumor necrosis factor precursor (TNF-alpha) (Tumor necrosis factor
DE ligand superfamily member 2) (TNF-a) (Cachectin).
GN Name=TNF; Synonyms=TNFA, TNFSF2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=87217060; PubMed=3555974;
RA Nedospasov S.A., Shakhov A.N., Turetskaya R.L., Mett V.A.,
RA Azizov M.M., Georgiev G.P., Korobko V.G., Dobrynin V.N.,
RA Filippov S.A., Bystrov N.S., Boldyreva E.F., Chuvpilo S.A.,
RA Chumakov A.M., Shingarova L.N., Ovchinnikov Y.A.;
RT "Tandem arrangement of genes coding for tumor necrosis factor (TNF-
RT alpha) and lymphotoxin (TNF-beta) in the human genome.";
RL Cold Spring Harb. Symp. Quant. Biol. 51:611-624(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=85086244; PubMed=6392892;
RA Pennica D., Nedwin G.E., Hayflick J.S., Seeburg P.H., Derynck R.,
RA Palladino M.A., Kohr W.J., Aggarwal B.B., Goeddel D.V.;
RT "Human tumour necrosis factor: precursor structure, expression and
RT homology to lymphotoxin.";
RL Nature 312:724-729(1984).
RN [3]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=85137898; PubMed=3883195;
RA Shirai T., Yamaguchi H., Ito H., Todd C.W., Wallace R.B.;
RT "Cloning and expression in Escherichia coli of the gene for human
RT tumour necrosis factor.";
RL Nature 313:803-806(1985).
RN [4]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=86016093; PubMed=2995927;
RA Nedwin G.E., Naylor S.L., Sakaguchi A.Y., Smith D.H.,
RA Jarrett-Nedwin J., Pennica D., Goeddel D.V., Gray P.W.;
RT "Human lymphotoxin and tumor necrosis factor genes: structure,
RT homology and chromosomal localization.";
RL Nucleic Acids Res. 13:6361-6373(1985).
RN [5]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=85142190; PubMed=3856324;
RA Wang A.M., Creasey A.A., Ladner M.B., Lin L.S., Strickler J.,
RA van Arsdell J.N., Yamamoto R., Mark D.F.;
RT "Molecular cloning of the complementary DNA for human tumor necrosis
RT factor.";
RL Science 228:149-154(1985).
RN [6]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=86030296; PubMed=3932069;
RA Marmenout A., Fransen L., Tavernier J., van der Heyden J., Tizard R.,
RA Kawashima E., Shaw A., Johnson M.J., Semon D., Mueller R.,
RA Ruysschaert M.R., van Vliet A., Fiers W.;
RT "Molecular cloning and expression of human tumor necrosis factor and
RT comparison with mouse tumor necrosis factor.";
RL Eur. J. Biochem. 152:515-522(1985).
RN [7]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=93272029; PubMed=8499947;
RA Iris F.J.M., Bougueleret L., Prieur S., Caterina D., Primas G.,
RA Perrot V., Jurka J., Rodriguez-Tome P., Claverie J.-M., Dausset J.,
RA Cohen D.;
RT "Dense Alu clustering and a potential new member of the NF kappa B
RT family within a 90 kilobase HLA class III segment.";
RL Nat. Genet. 3:137-145(1993).
RN [8]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=99218514; PubMed=10202016;
RA Neville M.J., Campbell R.D.;
RT "A new member of the Ig superfamily and a V-ATPase G subunit are among
RT the predicted products of novel genes close to the TNF locus in the
RT human MHC.";
RL J. Immunol. 162:4745-4754(1999).
RN [9]
RP NUCLEOTIDE SEQUENCE.
RA Rowen L., Madan A., Qin S., Shaffer T., James R., Ratcliffe A.,
RA Abbasi N., Dickhoff R., Loretz C., Madan A., Dors M., Young J.,
RA Lasky S., Hood L.;
RT "Sequence of the human major histocompatibility complex class III
RT region.";
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Shiina S., Tamiya G., Oka A., Inoko H.;
RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE.
RA Shiina T., Ota M., Katsuyama Y., Hashimoto N., Inoko H.;
RT "Genome diversity in HLA: a new strategy for detection of genetic
RT polymorphisms in expressed genes within the HLA class III and class I
RT regions.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE.
RA Rieder M.J., Carrington D.P., Chung M.-W., Lee K.L., Poel C.L., Yi Q.,
RA Nickerson D.A.;
RT "SeattleSNPs. NHLBI HL66682 program for genomic applications, UW-
RT FHCRC, Seattle, WA (URL: http://pga.gs.washington.edu).";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE, AND VARIANT LEU-84.
RA Rieder M.J., Livingston R.J., Daniels M.R., Montoya M.A., Chung M.-W.,
RA Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D.,
RA Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Blood;
RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [15]
RP NUCLEOTIDE SEQUENCE OF 77-233.
RA Jang J.S., Kim B.E.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [16]
RP NUCLEOTIDE SEQUENCE OF 84-214.
RC TISSUE=Prostatic carcinoma;
RA Shao C., Yan W., Zhu F., Yue W., Chai Y., Zhao Z., Wang C.;
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [17]
RP PHOSPHORYLATION (MEMBRANE FORM).
RX MEDLINE=96170872; PubMed=8597870;
RA Pocsik E., Duda E., Wallach D.;
RT "Phosphorylation of the 26 kDa TNF precursor in monocytic cells and in
RT transfected HeLa cells.";
RL J. Inflamm. 45:152-160(1995).
RN [18]
RP PHOSPHORYLATION BY CK1, AND DEPHOSPHORYLATION.
RX MEDLINE=99221647; PubMed=10205166; DOI=10.1093/emboj/18.8.2119;
RA Watts A.D., Hunt N.H., Wanigasekara Y., Bloomfield G., Wallach D.,
RA Roufogalis B.D., Chaudhri G.;
RT "A casein kinase I motif present in the cytoplasmic domain of members
RT of the tumour necrosis factor ligand family is implicated in 'reverse
RT signalling'.";
RL EMBO J. 18:2119-2126(1999).
RN [19]
RP MUTAGENESIS.
RX MEDLINE=91184128; PubMed=2009860;
RA Ostade X.V., Tavernier J., Prange T., Fiers W.;
RT "Localization of the active site of human tumour necrosis factor
RT (hTNF) by mutational analysis.";
RL EMBO J. 10:827-836(1991).
RN [20]
RP MYRISTOYLATION.
RX MEDLINE=93018820; PubMed=1402651;
RA Stevenson F.T., Bursten S.L., Locksley R.M., Lovett D.H.;
RT "Myristyl acylation of the tumor necrosis factor alpha precursor on
RT specific lysine residues.";
RL J. Exp. Med. 176:1053-1062(1992).
RN [21]
RP CLEAVAGE BY ADAM17.
RX MEDLINE=97186575; PubMed=9034191;
RA Moss M.L., Jin S.-L.C., Milla M.E., Burkhart W., Carter H.L.,
RA Chen W.-J., Clay W.C., Didsbury J.R., Hassler D., Hoffman C.R.,
RA Kost T.A., Lambert M.H., Leesnitzer M.A., McCauley P., McGeehan G.,
RA Mitchell J., Moyer M., Pahel G., Rocque W., Overton L.K., Schoenen F.,
RA Seaton T., Su J.-L., Warner J., Willard D., Becherer J.D.;
RT "Cloning of a disintegrin metalloproteinase that processes precursor
RT tumour-necrosis factor-alpha.";
RL Nature 385:733-736(1997).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
RX MEDLINE=89159409; PubMed=2922050; DOI=10.1038/338225a0;
RA Jones E.Y., Stuart D.I., Walker N.P.;
RT "Structure of tumour necrosis factor.";
RL Nature 338:225-228(1989).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
RX MEDLINE=91193276; PubMed=1964681;
RA Jones E.Y., Stuart D.I., Walker N.P.;
RT "The structure of tumour necrosis factor -- implications for
RT biological function.";
RL J. Cell Sci. Suppl. 13:11-18(1990).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
RX MEDLINE=90008932; PubMed=2551905;
RA Eck M.J., Sprang S.R.;
RT "The structure of tumor necrosis factor-alpha at 2.6-A resolution.
RT Implications for receptor binding.";
RL J. Biol. Chem. 264:17595-17605(1989).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ARG-107.
RX MEDLINE=98147459; PubMed=9488135; DOI=10.1093/protein/10.10.1101;
RA Reed C., Fu Z.Q., Wu J., Xue Y.N., Harrison R.W., Chen M.J.,
RA Weber I.T.;
RT "Crystal structure of TNF-alpha mutant R31D with greater affinity for
RT receptor R1 compared with R2.";
RL Protein Eng. 10:1101-1107(1997).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF MUTANT M3S.
RX MEDLINE=98113178; PubMed=9442056; DOI=10.1074/jbc.273.4.2153;
RA Cha S.S., Kim J.S., Cho H.S., Shin N.K., Jeong W., Shin H.C.,
RA Kim Y.J., Hahn J.H., Oh B.H.;
RT "High resolution crystal structure of a human tumor necrosis factor-
RT alpha mutant with low systemic toxicity.";
RL J. Biol. Chem. 273:2153-2160(1998).
CC -!- FUNCTION: Cytokine that binds to TNFRSF1A/TNFR1 and
CC TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can
CC induce cell death of certain tumor cell lines. It is potent
CC pyrogen causing fever by direct action or by stimulation of
CC interleukin 1 secretion and is implicated in the induction of
CC cachexia, Under certain conditions it can stimulate cell
CC proliferation and induce cell differentiation.
CC -!- SUBUNIT: Homotrimer.
CC -!- INTERACTION:
CC P19438:tnfrsf1a; NbExp=1; IntAct=EBI-359977, EBI-299451;
CC P20333:tnfrsf1b; NbExp=1; IntAct=EBI-359977, EBI-358983;
CC -!- SUBCELLULAR LOCATION: Type II membrane protein. Also exists as an
CC extracellular soluble form.
CC -!- PTM: The soluble form derives from the membrane form by
CC proteolytic processing.
CC -!- PTM: The membrane form, but not the soluble form, is
CC phosphorylated on serine residues. Dephosphorylation of the
CC membrane form ocurrs by binding to soluble TNFRSF1A/TNFR1.
CC -!- DISEASE: Cachexia accompanies a variety of diseases, including
CC cancer and infection, and is characterized by general ill health
CC and malnutrition.
CC -!- SIMILARITY: Belongs to the tumor necrosis factor family.
CC -!- CAUTION: Ref.8 sequence differs from that shown due to erroneous
CC gene model prediction.
CC -!- CAUTION: Ref.15 sequence differs from that shown due to
CC frameshifts in positions 91 and 157.
CC --------------------------------------------------------------------------
CC This Swiss-Prot entry is copyright. It is produced through a collaboration
CC between the Swiss Institute of Bioinformatics and the EMBL outstation -
CC the European Bioinformatics Institute. There are no restrictions on its
CC use as long as its content is in no way modified and this statement is not
CC removed.
CC --------------------------------------------------------------------------
DR EMBL; M16441; AAA61200.1; -.
DR EMBL; X02910; CAA26669.1; -.
DR EMBL; X01394; CAA25650.1; -.
DR EMBL; M10988; AAA61198.1; -.
DR EMBL; M26331; AAA36758.1; -.
DR EMBL; Z15026; CAA78745.1; -.
DR EMBL; Y14768; CAA75070.1; ALT_SEQ.
DR EMBL; AF129756; AAD18091.1; -.
DR EMBL; AP000505; BAB63396.1; -.
DR EMBL; AB088112; BAC54944.1; -.
DR EMBL; AY066019; AAL47581.1; -.
DR EMBL; AY214167; AAO21132.1; -.
DR EMBL; BC028148; AAH28148.1; -.
DR EMBL; AF043342; AAC03542.1; -.
DR EMBL; AF098751; AAF71992.1; ALT_FRAME.
DR PIR; A93585; QWHUN.
DR PDB; 1A8M; X-ray; A/B/C=77-233.
DR PDB; 1TNF; X-ray; A/B/C=77-233.
DR PDB; 2TUN; X-ray; A/B/C/D/E/F=77-233.
DR PDB; 4TSV; X-ray; A=84-233.
DR PDB; 5TSW; X-ray; A/B/C/D/E/F=84-233.
DR IntAct; P01375; -.
DR GlycoSuiteDB; P01375; -.
DR Genew; HGNC:11892; TNF.
DR H-InvDB; HIX0005719; -.
DR MIM; 191160; -.
DR GO; GO:0005625; C:soluble fraction; TAS.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; TAS.
DR GO; GO:0006916; P:anti-apoptosis; TAS.
DR GO; GO:0006915; P:apoptosis; TAS.
DR GO; GO:0007159; P:leukocyte cell adhesion; TAS.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; TAS.
DR GO; GO:0009615; P:response to virus; TAS.
DR GO; GO:0007165; P:signal transduction; TAS.
DR InterPro; IPR006053; TNF_abc.
DR InterPro; IPR006052; TNF_family.
DR InterPro; IPR008983; TNF_like.
DR InterPro; IPR003636; TNF_subf.
DR Pfam; PF00229; TNF; 1.
DR PRINTS; PR01234; TNECROSISFCT.
DR ProDom; PD002012; TNF_subf; 1.
DR SMART; SM00207; TNF; 1.
DR PROSITE; PS00251; TNF_1; 1.
DR PROSITE; PS50049; TNF_2; 1.
KW 3D-structure; Cytokine; Lipoprotein; Myristate; Phosphorylation;
KW Polymorphism; Signal-anchor; Transmembrane.
FT CHAIN 1 233 Tumor necrosis factor, membrane form.
FT CHAIN 77 233 Tumor necrosis factor, soluble form.
FT DOMAIN 1 35 Cytoplasmic (Potential).
FT TRANSMEM 36 56 Signal-anchor for type II membrane
FT protein (Potential).
FT DOMAIN 57 233 Extracellular (Potential).
FT SITE 76 77 Cleavage (by ADAM17).
FT MOD_RES 2 2 Phosphoserine (by CK1).
FT LIPID 19 19 N6-myristoyl lysine.
FT LIPID 20 20 N6-myristoyl lysine.
FT DISULFID 145 177
FT VARIANT 84 84 P -> L.
FT /FTId=VAR_019378.
FT VARIANT 94 94 A -> T (in dbSNP:1800620).
FT /FTId=VAR_011927.
FT MUTAGEN 105 105 L->S: Low activity.
FT MUTAGEN 108 108 R->W: Biologically inactive.
FT MUTAGEN 112 112 L->F: Biologically inactive.
FT MUTAGEN 160 160 A->V: Biologically inactive.
FT MUTAGEN 162 162 S->F: Biologically inactive.
FT MUTAGEN 167 167 V->A,D: Biologically inactive.
FT MUTAGEN 222 222 E->K: Biologically inactive.
FT CONFLICT 63 63 F -> S (in Ref. 5).
FT CONFLICT 84 86 PSD -> VNR (in Ref. 16).
FT CONFLICT 183 183 E -> R (in Ref. 15).
FT STRAND 89 94
FT TURN 96 97
FT TURN 99 100
FT STRAND 104 105
FT TURN 109 110
FT STRAND 112 114
FT TURN 115 116
FT STRAND 118 120
FT TURN 121 122
FT STRAND 123 125
FT STRAND 130 143
FT STRAND 152 159
FT TURN 161 163
FT STRAND 166 174
FT STRAND 189 202
FT TURN 204 205
FT STRAND 207 212
FT HELIX 215 217
FT STRAND 218 218
FT TURN 223 224
FT STRAND 227 231
SQ SEQUENCE 233 AA; 25644 MW; 3DF90F96C9031FFE CRC64;
MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLI VAGATTLFCL LHFGVIGPQR
EEFPRDLSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG QLQWLNRRAN ALLANGVELR
DNQLVVPSEG LYLIYSQVLF KGQGCPSTHV LLTHTISRIA VSYQTKVNLL SAIKSPCQRE
TPEGAEAKPW YEPIYLGGVF QLEKGDRLSA EINRPDYLDF AESGQVYFGI IAL
//