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 27-MAR-2024, entry version 250. 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>3.3.co;2-z; 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; 153. 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 GlyCosmos; P25942; 2 sites, 2 glycans. DR GlyGen; P25942; 2 sites, 2 N-linked glycans (1 site). DR iPTMnet; P25942; -. DR PhosphoSitePlus; P25942; -. DR BioMuta; CD40; -. DR DMDM; 116000; -. DR CPTAC; CPTAC-5956; -. DR CPTAC; CPTAC-5957; -. DR EPD; P25942; -. DR jPOST; P25942; -. DR MassIVE; P25942; -. DR MaxQB; P25942; -. DR PaxDb; 9606-ENSP00000361359; -. DR PeptideAtlas; P25942; -. DR ProteomicsDB; 54302; -. [P25942-1] DR ProteomicsDB; 54303; -. [P25942-2] DR Pumba; P25942; -. DR ABCD; P25942; 40 sequenced antibodies. DR Antibodypedia; 3736; 3399 antibodies from 53 providers. DR CPTC; P25942; 4 antibodies. DR DNASU; 958; -. DR Ensembl; ENST00000372276.7; ENSP00000361350.3; ENSG00000101017.15. [P25942-2] DR Ensembl; ENST00000372285.8; ENSP00000361359.3; ENSG00000101017.15. [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 AGR; HGNC:11919; -. 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; KGRCCNR; -. DR OrthoDB; 4574260at2759; -. 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; 13 hits in 1160 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 168 other cell types or tissues. DR ExpressionAtlas; P25942; baseline and differential. 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:0043231; C:intracellular membrane-bounded organelle; IEA:Ensembl. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL. DR GO; GO:0043196; C:varicosity; IEA:Ensembl. DR GO; GO:0003823; F:antigen binding; IBA:GO_Central. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl. 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:0036018; P:cellular response to erythropoietin; IEA:Ensembl. DR GO; GO:0071347; P:cellular response to interleukin-1; IBA:GO_Central. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. 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; TAS:ProtInc. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IMP:BHF-UCL. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl. 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:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IEP:UniProtKB. 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: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:0065003; P:protein-containing complex assembly; TAS:ProtInc. DR GO; GO:0033590; P:response to cobalamin; IEA:Ensembl. DR GO; GO:1901652; P:response to peptide; IEA:Ensembl. DR GO; GO:0034341; P:response to type II interferon; IBA:GO_Central. DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; IBA:GO_Central. DR CDD; cd13407; TNFRSF5; 1. DR Gene3D; 2.10.50.10; Tumor Necrosis Factor Receptor, subunit A, domain 2; 4. DR IDEAL; IID00711; -. DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg. DR InterPro; IPR020435; TNFR_5. DR InterPro; IPR034021; TNFRSF5_N. DR PANTHER; PTHR46875; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 5; 1. DR PANTHER; PTHR46875:SF1; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 5; 1. DR Pfam; PF00020; TNFR_c6; 2. DR PRINTS; PR01922; TNFACTORR5. DR SMART; SM00208; TNFR; 4. DR SUPFAM; SSF57586; TNF receptor-like; 2. DR PROSITE; PS00652; TNFR_NGFR_1; 1. DR PROSITE; PS50050; TNFR_NGFR_2; 4. DR Genevisible; P25942; HS. 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 STRAND 30..33 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 36..39 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 45..49 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 53..55 FT /evidence="ECO:0007829|PDB:5DMJ" FT STRAND 58..61 FT /evidence="ECO:0007829|PDB:7P3I" 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:7P3I" FT STRAND 89..93 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 97..99 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 102..105 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 109..113 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 117..121 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 129..133 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 137..139 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 142..145 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 156..158 FT /evidence="ECO:0007829|PDB:7P3I" FT HELIX 168..170 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 173..176 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 180..182 FT /evidence="ECO:0007829|PDB:7P3I" FT STRAND 185..187 FT /evidence="ECO:0007829|PDB:7P3I" 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 //