TNR5_HUMAN
ID TNR5_HUMAN Reviewed; 277 AA.
AC P25942; E1P5S9; Q53GN5; Q5JY15; Q5U007; Q7M4Q8; Q86YK5; Q9BYU0;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 241.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 5;
DE AltName: Full=B-cell surface antigen CD40;
DE AltName: Full=Bp50;
DE AltName: Full=CD40L receptor;
DE AltName: Full=CDw40;
DE AltName: CD_antigen=CD40;
DE Flags: Precursor;
GN Name=CD40; Synonyms=TNFRSF5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM I).
RX PubMed=2475341; DOI=10.1002/j.1460-2075.1989.tb03521.x;
RA Stamenkovic I., Clark E.A., Seed B.;
RT "A B-lymphocyte activation molecule related to the nerve growth factor
RT receptor and induced by cytokines in carcinomas.";
RL EMBO J. 8:1403-1410(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM II).
RX PubMed=11172023; DOI=10.1073/pnas.98.4.1751;
RA Tone M., Tone Y., Fairchild P.J., Wykes M., Waldmann H.;
RT "Regulation of CD40 function by its isoforms generated through alternative
RT splicing.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:1751-1756(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM I).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM I).
RC TISSUE=Kidney;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-124 AND ALA-227.
RG NIEHS SNPs program;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B.,
RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O.,
RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I.,
RA Nickerson D.A.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM I).
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-223 (ISOFORM I).
RC TISSUE=Leukocyte;
RA He X., Xu L., Zeng Y.;
RT "Transcripts of CD40 isoform in peripheral mononuclear cells.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP PROTEIN SEQUENCE OF 21-50, SUBUNIT, AND VARIANTS GLN-26; GLY-35 AND THR-39.
RC TISSUE=Lymphoma, and Urinary bladder carcinoma;
RX PubMed=2463309;
RA Braesch-Andersen S., Paulie S., Koho H., Nika H., Aspenstroem P.,
RA Perlmann P.;
RT "Biochemical characteristics and partial amino acid sequence of the
RT receptor-like human B cell and carcinoma antigen CDw40.";
RL J. Immunol. 142:562-567(1989).
RN [12]
RP PROTEIN SEQUENCE OF 21-35.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [13]
RP PROTEIN SEQUENCE OF 21-30.
RX PubMed=11676606; DOI=10.1006/prep.2001.1501;
RA Khandekar S.S., Silverman C., Wells-Marani J., Bacon A.M., Birrell H.,
RA Brigham-Burke M., DeMarini D.J., Jonak Z.L., Camilleri P.,
RA Fishman-Lobell J.;
RT "Determination of carbohydrate structures N-linked to soluble CD154 and
RT characterization of the interactions of CD40 with CD154 expressed in Pichia
RT pastoris and Chinese hamster ovary cells.";
RL Protein Expr. Purif. 23:301-310(2001).
RN [14]
RP INTERACTION WITH TRAF3.
RX PubMed=7530216; DOI=10.1016/0014-5793(94)01406-q;
RA Sato T., Irie S., Reed J.C.;
RT "A novel member of the TRAF family of putative signal transducing proteins
RT binds to the cytosolic domain of CD40.";
RL FEBS Lett. 358:113-118(1995).
RN [15]
RP INTERACTION WITH TRAF3.
RX PubMed=7533327; DOI=10.1126/science.7533327;
RA Cheng G., Cleary A.M., Ye Z.S., Hong D.I., Lederman S., Baltimore D.;
RT "Involvement of CRAF1, a relative of TRAF, in CD40 signaling.";
RL Science 267:1494-1498(1995).
RN [16]
RP INTERACTION WITH TRAF1; TRAF2; TRAF3 AND TRAF5.
RX PubMed=9718306; DOI=10.1021/bi981067q;
RA Pullen S.S., Miller H.G., Everdeen D.S., Dang T.T., Crute J.J., Kehry M.R.;
RT "CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions:
RT regulation of CD40 signaling through multiple TRAF binding sites and TRAF
RT hetero-oligomerization.";
RL Biochemistry 37:11836-11845(1998).
RN [17]
RP INTERACTION WITH TRAF5.
RX PubMed=9511754; DOI=10.1016/s0378-1119(97)00616-1;
RA Mizushima S., Fujita M., Ishida T., Azuma S., Kato K., Hirai M., Otsuka M.,
RA Yamamoto T., Inoue J.;
RT "Cloning and characterization of a cDNA encoding the human homolog of tumor
RT necrosis factor receptor-associated factor 5 (TRAF5).";
RL Gene 207:135-140(1998).
RN [18]
RP INTERACTION WITH TRAF6.
RX PubMed=9432981; DOI=10.1084/jem.187.2.237;
RA Kashiwada M., Shirakata Y., Inoue J., Nakano H., Okazaki K., Okumura K.,
RA Yamamoto T., Nagaoka H., Takemori T.;
RT "Tumor necrosis factor receptor-associated factor 6 (TRAF6) stimulates
RT extracellular signal-regulated kinase (ERK) activity in CD40 signaling
RT along a ras-independent pathway.";
RL J. Exp. Med. 187:237-244(1998).
RN [19]
RP FUNCTION.
RX PubMed=31331973; DOI=10.4049/jimmunol.1801630;
RA Takada Y.K., Yu J., Shimoda M., Takada Y.;
RT "Integrin Binding to the Trimeric Interface of CD40L Plays a Critical Role
RT in CD40/CD40L Signaling.";
RL J. Immunol. 203:1383-1391(2019).
RN [20]
RP 3D-STRUCTURE MODELING OF 24-144.
RX PubMed=9037712;
RX DOI=10.1002/(sici)1097-0134(199701)27:1<59::aid-prot7>3.0.co;2-i;
RA Bajorath J., Aruffo A.;
RT "Construction and analysis of a detailed three-dimensional model of the
RT ligand binding domain of the human B cell receptor CD40.";
RL Proteins 27:59-70(1997).
RN [21]
RP 3D-STRUCTURE MODELING OF 26-186 IN COMPLEX WITH CD40LG.
RX PubMed=9605317; DOI=10.1002/pro.5560070506;
RA Singh J., Garber E., van Vlijmen H., Karpsusas M., Hsu Y.-M., Zheng Z.,
RA Naismith J.H., Thomas D.;
RT "The role of polar interactions in the molecular recognition of CD40L with
RT its receptor CD40.";
RL Protein Sci. 7:1124-1135(1998).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 247-266 IN COMPLEX WITH TRAF3.
RX PubMed=10984535; DOI=10.1073/pnas.97.19.10395;
RA Ni C.Z., Welsh K., Leo E., Chiou C.K., Wu H., Reed J.C., Ely K.R.;
RT "Molecular basis for CD40 signaling mediated by TRAF3.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:10395-10399(2000).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 178-195 IN COMPLEX WITH TRAF3.
RX PubMed=12005438; DOI=10.1016/s0969-2126(02)00733-5;
RA Li C., Ni C.Z., Havert M.L., Cabezas E., He J., Kaiser D., Reed J.C.,
RA Satterthwait A.C., Cheng G., Ely K.R.;
RT "Downstream regulator TANK binds to the CD40 recognition site on TRAF3.";
RL Structure 10:403-411(2002).
RN [24]
RP VARIANT HIGM3 ARG-83.
RX PubMed=11675497; DOI=10.1073/pnas.221456898;
RA Ferrari S., Giliani S., Insalaco A., Al-Ghonaium A., Soresina A.R.,
RA Loubser M., Avanzini M.A., Marconi M., Badolato R., Ugazio A.G., Levy Y.,
RA Catalan N., Durandy A., Tbakhi A., Notarangelo L.D., Plebani A.;
RT "Mutations of CD40 gene cause an autosomal recessive form of
RT immunodeficiency with hyper IgM.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12614-12619(2001).
RN [25]
RP VARIANT HIGM3 GLY-37.
RX PubMed=26545377; DOI=10.1007/s00251-015-0878-6;
RA Ouadani H., Ben-Mustapha I., Ben-ali M., Ben-khemis L., Largueche B.,
RA Boussoffara R., Maalej S., Fetni I., Hassayoun S., Mahfoudh A.,
RA Mellouli F., Yalaoui S., Masmoudi H., Bejaoui M., Barbouche M.R.;
RT "Novel and recurrent AID mutations underlie prevalent autosomal recessive
RT form of HIGM in consanguineous patients.";
RL Immunogenetics 68:19-28(2016).
CC -!- FUNCTION: Receptor for TNFSF5/CD40LG (PubMed:31331973). Transduces
CC TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and
CC B cells, leading to induction of immunoglobulin secretion (By
CC similarity). {ECO:0000250|UniProtKB:P27512,
CC ECO:0000269|PubMed:31331973}.
CC -!- SUBUNIT: Monomer and homodimer. The variant form found in the bladder
CC carcinoma cell line Hu549 does not form homodimers. Interacts with
CC TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6. Interacts with TRAF6 and MAP3K8;
CC the interaction is required for ERK activation.
CC {ECO:0000269|PubMed:10984535, ECO:0000269|PubMed:12005438,
CC ECO:0000269|PubMed:2463309, ECO:0000269|PubMed:7530216,
CC ECO:0000269|PubMed:7533327, ECO:0000269|PubMed:9432981,
CC ECO:0000269|PubMed:9511754, ECO:0000269|PubMed:9718306}.
CC -!- INTERACTION:
CC P25942; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-525714, EBI-11522780;
CC P25942; Q9NX76: CMTM6; NbExp=3; IntAct=EBI-525714, EBI-1054315;
CC P25942; Q8NBI2: CYB561A3; NbExp=3; IntAct=EBI-525714, EBI-10269179;
CC P25942; Q5J5C9: DEFB121; NbExp=3; IntAct=EBI-525714, EBI-10244198;
CC P25942; Q15125: EBP; NbExp=3; IntAct=EBI-525714, EBI-3915253;
CC P25942; Q9Y5U4: INSIG2; NbExp=3; IntAct=EBI-525714, EBI-8503746;
CC P25942; P21145: MAL; NbExp=3; IntAct=EBI-525714, EBI-3932027;
CC P25942; Q6N075: MFSD5; NbExp=3; IntAct=EBI-525714, EBI-3920969;
CC P25942; P30301: MIP; NbExp=3; IntAct=EBI-525714, EBI-8449636;
CC P25942; P60201-2: PLP1; NbExp=3; IntAct=EBI-525714, EBI-12188331;
CC P25942; Q9BRI3: SLC30A2; NbExp=3; IntAct=EBI-525714, EBI-8644112;
CC P25942; Q99726: SLC30A3; NbExp=3; IntAct=EBI-525714, EBI-10294651;
CC P25942; Q96H72: SLC39A13; NbExp=3; IntAct=EBI-525714, EBI-10287091;
CC P25942; P30825: SLC7A1; NbExp=3; IntAct=EBI-525714, EBI-4289564;
CC P25942; Q96CP7: TLCD1; NbExp=3; IntAct=EBI-525714, EBI-11337932;
CC P25942; Q6UX40: TMEM107; NbExp=3; IntAct=EBI-525714, EBI-12845616;
CC P25942; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-525714, EBI-10694905;
CC P25942; Q9BVK8: TMEM147; NbExp=3; IntAct=EBI-525714, EBI-348587;
CC P25942; Q12933: TRAF2; NbExp=17; IntAct=EBI-525714, EBI-355744;
CC P25942; Q13114: TRAF3; NbExp=3; IntAct=EBI-525714, EBI-357631;
CC P25942; Q9Y4K3: TRAF6; NbExp=2; IntAct=EBI-525714, EBI-359276;
CC P25942; B2RUR8: Otud7b; Xeno; NbExp=2; IntAct=EBI-525714, EBI-3454264;
CC -!- SUBCELLULAR LOCATION: [Isoform I]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform II]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=I;
CC IsoId=P25942-1; Sequence=Displayed;
CC Name=II;
CC IsoId=P25942-2; Sequence=VSP_006472, VSP_006473;
CC -!- TISSUE SPECIFICITY: B-cells and in primary carcinomas.
CC -!- DISEASE: Immunodeficiency with hyper-IgM 3 (HIGM3) [MIM:606843]: A rare
CC immunodeficiency syndrome characterized by normal or elevated serum IgM
CC levels with absence of IgG, IgA, and IgE. It results in a profound
CC susceptibility to bacterial infections. {ECO:0000269|PubMed:11675497,
CC ECO:0000269|PubMed:26545377}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- WEB RESOURCE: Name=CD40base; Note=CD40 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/CD40base/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tnfrsf5/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CD40 entry;
CC URL="https://en.wikipedia.org/wiki/CD40";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X60592; CAA43045.1; -; mRNA.
DR EMBL; AJ300189; CAC29424.1; -; mRNA.
DR EMBL; BT019901; AAV38704.1; -; mRNA.
DR EMBL; AK222896; BAD96616.1; -; mRNA.
DR EMBL; AY504960; AAR84238.1; -; Genomic_DNA.
DR EMBL; EF064754; ABK41937.1; -; Genomic_DNA.
DR EMBL; AL035662; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75758.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75760.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75762.1; -; Genomic_DNA.
DR EMBL; BC012419; AAH12419.1; -; mRNA.
DR EMBL; AY225405; AAO43990.1; -; mRNA.
DR CCDS; CCDS13393.1; -. [P25942-1]
DR CCDS; CCDS13394.1; -. [P25942-2]
DR PIR; B60771; B60771.
DR PIR; S04460; A60771.
DR RefSeq; NP_001241.1; NM_001250.5. [P25942-1]
DR RefSeq; NP_001289682.1; NM_001302753.1.
DR RefSeq; NP_001309351.1; NM_001322422.1.
DR RefSeq; NP_690593.1; NM_152854.3. [P25942-2]
DR PDB; 1CZZ; X-ray; 2.70 A; D/E=250-258.
DR PDB; 1D00; X-ray; 2.00 A; I/J/K/L/M/N/O/P=250-254.
DR PDB; 1FLL; X-ray; 3.50 A; X/Y=246-266.
DR PDB; 1LB6; X-ray; 1.80 A; B=230-236.
DR PDB; 3QD6; X-ray; 3.50 A; R/S/T/U=21-190.
DR PDB; 5DMI; X-ray; 3.69 A; A=23-193.
DR PDB; 5DMJ; X-ray; 2.79 A; A/D/F=23-193.
DR PDB; 5IHL; X-ray; 3.30 A; A/D/F/H=23-193.
DR PDB; 6FAX; X-ray; 2.99 A; R=21-193.
DR PDB; 6PE8; X-ray; 2.84 A; T/U=21-193.
DR PDB; 6PE9; X-ray; 3.13 A; G/I/J/U/V=21-193.
DR PDB; 7P3I; X-ray; 2.29 A; A/C=21-193.
DR PDBsum; 1CZZ; -.
DR PDBsum; 1D00; -.
DR PDBsum; 1FLL; -.
DR PDBsum; 1LB6; -.
DR PDBsum; 3QD6; -.
DR PDBsum; 5DMI; -.
DR PDBsum; 5DMJ; -.
DR PDBsum; 5IHL; -.
DR PDBsum; 6FAX; -.
DR PDBsum; 6PE8; -.
DR PDBsum; 6PE9; -.
DR PDBsum; 7P3I; -.
DR AlphaFoldDB; P25942; -.
DR SASBDB; P25942; -.
DR SMR; P25942; -.
DR BioGRID; 107396; 152.
DR DIP; DIP-3014N; -.
DR ELM; P25942; -.
DR IntAct; P25942; 28.
DR STRING; 9606.ENSP00000361359; -.
DR BindingDB; P25942; -.
DR ChEMBL; CHEMBL1250358; -.
DR DrugBank; DB12589; Dacetuzumab.
DR DrugBank; DB06360; Lucatumumab.
DR GuidetoPHARMACOLOGY; 1874; -.
DR GlyConnect; 1866; 2 N-Linked glycans (1 site).
DR GlyGen; P25942; 2 sites, 2 N-linked glycans (1 site).
DR iPTMnet; P25942; -.
DR PhosphoSitePlus; P25942; -.
DR BioMuta; CD40; -.
DR DMDM; 116000; -.
DR EPD; P25942; -.
DR jPOST; P25942; -.
DR MassIVE; P25942; -.
DR MaxQB; P25942; -.
DR PaxDb; P25942; -.
DR PeptideAtlas; P25942; -.
DR PRIDE; P25942; -.
DR ProteomicsDB; 54302; -. [P25942-1]
DR ProteomicsDB; 54303; -. [P25942-2]
DR ABCD; P25942; 38 sequenced antibodies.
DR Antibodypedia; 3736; 2664 antibodies from 52 providers.
DR CPTC; P25942; 3 antibodies.
DR DNASU; 958; -.
DR Ensembl; ENST00000372276.7; ENSP00000361350.3; ENSG00000101017.14. [P25942-2]
DR Ensembl; ENST00000372285.8; ENSP00000361359.3; ENSG00000101017.14. [P25942-1]
DR GeneID; 958; -.
DR KEGG; hsa:958; -.
DR MANE-Select; ENST00000372285.8; ENSP00000361359.3; NM_001250.6; NP_001241.1.
DR UCSC; uc002xrg.2; human. [P25942-1]
DR CTD; 958; -.
DR DisGeNET; 958; -.
DR GeneCards; CD40; -.
DR HGNC; HGNC:11919; CD40.
DR HPA; ENSG00000101017; Low tissue specificity.
DR MalaCards; CD40; -.
DR MIM; 109535; gene.
DR MIM; 606843; phenotype.
DR neXtProt; NX_P25942; -.
DR OpenTargets; ENSG00000101017; -.
DR Orphanet; 101090; Hyper-IgM syndrome type 3.
DR PharmGKB; PA36612; -.
DR VEuPathDB; HostDB:ENSG00000101017; -.
DR eggNOG; ENOG502S5TQ; Eukaryota.
DR GeneTree; ENSGT00940000161464; -.
DR HOGENOM; CLU_052667_4_0_1; -.
DR InParanoid; P25942; -.
DR OMA; CQPGEKL; -.
DR OrthoDB; 1038336at2759; -.
DR PhylomeDB; P25942; -.
DR TreeFam; TF331157; -.
DR PathwayCommons; P25942; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. [P25942-1]
DR Reactome; R-HSA-5668541; TNFR2 non-canonical NF-kB pathway. [P25942-1]
DR Reactome; R-HSA-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway. [P25942-1]
DR SignaLink; P25942; -.
DR SIGNOR; P25942; -.
DR BioGRID-ORCS; 958; 11 hits in 1078 CRISPR screens.
DR ChiTaRS; CD40; human.
DR EvolutionaryTrace; P25942; -.
DR GeneWiki; CD40_(protein); -.
DR GenomeRNAi; 958; -.
DR Pharos; P25942; Tchem.
DR PRO; PR:P25942; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P25942; protein.
DR Bgee; ENSG00000101017; Expressed in lymph node and 166 other tissues.
DR ExpressionAtlas; P25942; baseline and differential.
DR Genevisible; P25942; HS.
DR GO; GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL.
DR GO; GO:0009986; C:cell surface; HDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL.
DR GO; GO:0003823; F:antigen binding; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0042113; P:B cell activation; IBA:GO_Central.
DR GO; GO:0019724; P:B cell mediated immunity; IEA:Ensembl.
DR GO; GO:0042100; P:B cell proliferation; NAS:UniProtKB.
DR GO; GO:0023035; P:CD40 signaling pathway; IDA:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:BHF-UCL.
DR GO; GO:0071347; P:cellular response to interleukin-1; IBA:GO_Central.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IBA:GO_Central.
DR GO; GO:0042832; P:defense response to protozoan; IBA:GO_Central.
DR GO; GO:0051607; P:defense response to virus; IBA:GO_Central.
DR GO; GO:0002768; P:immune response-regulating cell surface receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0030168; P:platelet activation; NAS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IBA:GO_Central.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IMP:BHF-UCL.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IDA:BHF-UCL.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:BHF-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEP:UniProtKB.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IBA:GO_Central.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; IBA:GO_Central.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IMP:BHF-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:BHF-UCL.
DR GO; GO:0090037; P:positive regulation of protein kinase C signaling; IMP:BHF-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:BHF-UCL.
DR GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR GO; GO:0034341; P:response to interferon-gamma; IBA:GO_Central.
DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; IBA:GO_Central.
DR CDD; cd13407; TNFRSF5; 1.
DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg.
DR InterPro; IPR020435; TNFR_5.
DR InterPro; IPR034021; TNFRSF5_N.
DR Pfam; PF00020; TNFR_c6; 1.
DR PRINTS; PR01922; TNFACTORR5.
DR SMART; SM00208; TNFR; 4.
DR PROSITE; PS00652; TNFR_NGFR_1; 1.
DR PROSITE; PS50050; TNFR_NGFR_2; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane;
KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW Immunity; Membrane; Receptor; Reference proteome; Repeat; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:11676606,
FT ECO:0000269|PubMed:15340161, ECO:0000269|PubMed:2463309"
FT CHAIN 21..277
FT /note="Tumor necrosis factor receptor superfamily member 5"
FT /id="PRO_0000034559"
FT TOPO_DOM 21..193
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 194..215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 216..277
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 25..60
FT /note="TNFR-Cys 1"
FT REPEAT 61..103
FT /note="TNFR-Cys 2"
FT REPEAT 104..144
FT /note="TNFR-Cys 3"
FT REPEAT 145..187
FT /note="TNFR-Cys 4"
FT REGION 223..277
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 26..37
FT DISULFID 38..51
FT DISULFID 41..59
FT DISULFID 62..77
FT DISULFID 83..103
FT DISULFID 105..119
FT DISULFID 111..116
FT DISULFID 125..143
FT VAR_SEQ 166..203
FT /note="SCETKDLVVQQAGTNKTDVVCGPQDRLRALVVIPIIFG -> RSPGSAESPG
FT GDPHHLRDPVCHPLGAGLYQKGGQEANQ (in isoform II)"
FT /evidence="ECO:0000303|PubMed:11172023"
FT /id="VSP_006472"
FT VAR_SEQ 204..277
FT /note="Missing (in isoform II)"
FT /evidence="ECO:0000303|PubMed:11172023"
FT /id="VSP_006473"
FT VARIANT 26
FT /note="C -> Q (in bladder carcinoma cell line Hu549;
FT requires 2 nucleotide substitutions)"
FT /evidence="ECO:0000269|PubMed:2463309"
FT /id="VAR_039301"
FT VARIANT 35
FT /note="S -> G (in bladder carcinoma cell line Hu549;
FT dbSNP:rs750234130)"
FT /evidence="ECO:0000269|PubMed:2463309"
FT /id="VAR_039302"
FT VARIANT 37
FT /note="C -> G (in HIGM3)"
FT /evidence="ECO:0000269|PubMed:26545377"
FT /id="VAR_077569"
FT VARIANT 39
FT /note="S -> T (in bladder carcinoma cell line Hu549)"
FT /evidence="ECO:0000269|PubMed:2463309"
FT /id="VAR_039303"
FT VARIANT 83
FT /note="C -> R (in HIGM3; dbSNP:rs28931586)"
FT /evidence="ECO:0000269|PubMed:11675497"
FT /id="VAR_013628"
FT VARIANT 124
FT /note="S -> L (in dbSNP:rs11569321)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_018751"
FT VARIANT 227
FT /note="P -> A (in dbSNP:rs11086998)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_018752"
FT CONFLICT 112
FT /note="T -> A (in Ref. 4; BAD96616)"
FT /evidence="ECO:0000305"
FT TURN 28..30
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 33..37
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 45..49
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:3QD6"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:5DMJ"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 89..93
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 102..108
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 129..133
FT /evidence="ECO:0007829|PDB:6PE8"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:6PE8"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:6PE8"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:5DMJ"
FT STRAND 234..237
FT /evidence="ECO:0007829|PDB:1LB6"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:1FLL"
SQ SEQUENCE 277 AA; 30619 MW; BC8776EC2C4A5680 CRC64;
MVRLPLQCVL WGCLLTAVHP EPPTACREKQ YLINSQCCSL CQPGQKLVSD CTEFTETECL
PCGESEFLDT WNRETHCHQH KYCDPNLGLR VQQKGTSETD TICTCEEGWH CTSEACESCV
LHRSCSPGFG VKQIATGVSD TICEPCPVGF FSNVSSAFEK CHPWTSCETK DLVVQQAGTN
KTDVVCGPQD RLRALVVIPI IFGILFAILL VLVFIKKVAK KPTNKAPHPK QEPQEINFPD
DLPGSNTAAP VQETLHGCQP VTQEDGKESR ISVQERQ
