P27512 (TNR5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor receptor superfamily member 5

Alternative name(s):
B-cell surface antigen CD40
Bp50
CD40L receptor
CD_antigen=CD40

Gene names

Name:	Cd40
Synonyms:	Tnfrsf5

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	289 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for TNFSF5/CD40LG.
Subunit structure	Monomer and homodimer. Interacts with TRAF1, TRAF2 and TRAF6 By similarity. Interacts with TRAF3 and TRAF5. Ref.9 Ref.10
Subcellular location	Isoform I: Cell membrane; Single-pass type I membrane protein. Isoform III: Cell membrane; Single-pass type I membrane protein. Isoform IV: Cell membrane; Single-pass type I membrane protein. Isoform V: Cell membrane; Single-pass type I membrane protein. Isoform II: Secreted.
Sequence similarities	Contains 4 TNFR-Cys repeats.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell activation Inferred from direct assay PubMed 14594818. Source: MGI cellular calcium ion homeostasis Inferred from mutant phenotype PubMed 21410936. Source: BHF-UCL cellular response to mechanical stimulus Inferred from electronic annotation. Source: Compara defense response to virus Inferred from direct assay PubMed 17277142. Source: MGI immune response-regulating cell surface receptor signaling pathway Inferred from direct assay PubMed 15240714. Source: MGI positive regulation of B cell proliferation Inferred from direct assay PubMed 10979977PubMed 11894097PubMed 14607964PubMed 8666928PubMed 8920854. Source: MGI positive regulation of Cdc42 GTPase activity Inferred from electronic annotation. Source: Compara positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from electronic annotation. Source: Compara positive regulation of MAP kinase activity Inferred from electronic annotation. Source: Compara positive regulation of NF-kappaB transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of Rac GTPase activity Inferred from electronic annotation. Source: Compara positive regulation of endothelial cell apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of interleukin-12 production Inferred from direct assay PubMed 15240714. Source: MGI positive regulation of isotype switching to IgG isotypes Inferred from direct assay PubMed 12882831. Source: MGI positive regulation of protein kinase C signaling cascade Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat1 protein Inferred from electronic annotation. Source: Compara regulation of immunoglobulin secretion Inferred from direct assay PubMed 12958312. Source: MGI
Cellular_component	CD40 receptor complex Inferred from direct assay PubMed 20614026. Source: BHF-UCL external side of plasma membrane Inferred from direct assay PubMed 10979977PubMed 14560001PubMed 15240714PubMed 17277142PubMed 18684012PubMed 8566034. Source: MGI extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell intracellular membrane-bounded organelle Inferred from direct assay PubMed 16708399. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Btk	P35991	3	EBI-525742,EBI-625119
Traf6	P70196	2	EBI-525742,EBI-448028

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform I (identifier: P27512-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform II (identifier: P27512-2)

The sequence of this isoform differs from the canonical sequence as follows:
     166-203: SCEDKNLEVL...ALLVIPVVMG → RFKVPDASPA...YQKGGQETKG
     204-289: Missing.

Isoform III (identifier: P27512-3)

The sequence of this isoform differs from the canonical sequence as follows:
     216-234: KKVVKKPKDNEILPPAARR → SECSGEEREGGFSPVEPAS
     235-289: Missing.

Isoform IV (identifier: P27512-4)

The sequence of this isoform differs from the canonical sequence as follows:
     216-222: KKVVKKP → SGQETKG
     223-289: Missing.

Isoform V (identifier: P27512-5)

The sequence of this isoform differs from the canonical sequence as follows:
     187-216: GLKSRMRALLVIPVVMGILITIFGVFLYIK → E

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 289	270	Tumor necrosis factor receptor superfamily member 5		PRO_0000034560
Regions
	Topological domain	20 – 193	174	Extracellular Potential
	Transmembrane	194 – 215	22	Helical; Potential
	Topological domain	216 – 289	74	Cytoplasmic Potential
	Repeat	25 – 60	36	TNFR-Cys 1
	Repeat	61 – 103	43	TNFR-Cys 2
	Repeat	104 – 144	41	TNFR-Cys 3
	Repeat	145 – 187	43	TNFR-Cys 4
Amino acid modifications
	Modified residue	273	1	Phosphoserine Ref.11
	Glycosylation	153	1	N-linked (GlcNAc...) Potential
	Disulfide bond	26 ↔ 37		By similarity
	Disulfide bond	38 ↔ 51		By similarity
	Disulfide bond	41 ↔ 59		By similarity
	Disulfide bond	62 ↔ 77		By similarity
	Disulfide bond	83 ↔ 103		By similarity
	Disulfide bond	105 ↔ 119		By similarity
	Disulfide bond	111 ↔ 116		By similarity
	Disulfide bond	125 ↔ 143		By similarity
Natural variations
	Alternative sequence	166 – 203	38	SCEDK…PVVMG → RFKVPDASPAGHSCRDGHPH HHFRGVSLYQKGGQETKG in isoform II.		VSP_006474
	Alternative sequence	187 – 216	30	GLKSR…FLYIK → E in isoform V.		VSP_006476
	Alternative sequence	204 – 289	86	Missing in isoform II.		VSP_006475
	Alternative sequence	216 – 234	19	KKVVK…PAARR → SECSGEEREGGFSPVEPAS in isoform III.		VSP_006477
	Alternative sequence	216 – 222	7	KKVVKKP → SGQETKG in isoform IV.		VSP_006479
	Alternative sequence	223 – 289	67	Missing in isoform IV.		VSP_006480
	Alternative sequence	235 – 289	55	Missing in isoform III.		VSP_006478
Experimental info
	Sequence conflict	21	1	G → W in BAE31440. Ref.5
	Sequence conflict	24	1	V → L in CAJ18551. Ref.6
	Sequence conflict	24	1	V → L in AAH29254. Ref.8
	Sequence conflict	92	1	K → N in BAE36843. Ref.5
	Sequence conflict	104	1	T → A in CAJ18551. Ref.6
	Sequence conflict	104	1	T → A in AAH29254. Ref.8
	Sequence conflict	194	1	A → T in BAE29991. Ref.5
	Sequence conflict	221	1	K → E in BAE31471. Ref.5
	Sequence conflict	227	1	I → M in AAB08705. Ref.1
	Sequence conflict	227	1	I → M in AAA37404. Ref.3
	Sequence conflict	227	1	I → M in CAC29430. Ref.4
	Sequence conflict	227	1	I → M in BAC40978. Ref.5
	Sequence conflict	227	1	I → M in BAE33789. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform I [UniParc]. Last modified February 26, 2008. Version 3. Checksum: C7970DAD2FEA534A	FASTA	289	32,093
	10 20 30 40 50 60 MVSLPRLCAL WGCLLTAVHL GQCVTCSDKQ YLHDGQCCDL CQPGSRLTSH CTALEKTQCH 70 80 90 100 110 120 PCDSGEFSAQ WNREIRCHQH RHCEPNQGLR VKKEGTAESD TVCTCKEGQH CTSKDCEACA 130 140 150 160 170 180 QHTPCIPGFG VMEMATETTD TVCHPCPVGF FSNQSSLFEK CYPWTSCEDK NLEVLQKGTS 190 200 210 220 230 240 QTNVICGLKS RMRALLVIPV VMGILITIFG VFLYIKKVVK KPKDNEILPP AARRQDPQEM 250 260 270 280 EDYPGHNTAA PVQETLHGCQ PVTQEDGKES RISVQERQVT DSIALRPLV
	Isoform II [UniParc]. Checksum: 0C4C94E7CC426202	FASTA	203	22,468
	10 20 30 40 50 60 MVSLPRLCAL WGCLLTAVHL GQCVTCSDKQ YLHDGQCCDL CQPGSRLTSH CTALEKTQCH 70 80 90 100 110 120 PCDSGEFSAQ WNREIRCHQH RHCEPNQGLR VKKEGTAESD TVCTCKEGQH CTSKDCEACA 130 140 150 160 170 180 QHTPCIPGFG VMEMATETTD TVCHPCPVGF FSNQSSLFEK CYPWTRFKVP DASPAGHSCR 190 200 DGHPHHHFRG VSLYQKGGQE TKG
	Isoform III [UniParc]. Checksum: 00DB1DD38347E325	FASTA	234	25,747
	10 20 30 40 50 60 MVSLPRLCAL WGCLLTAVHL GQCVTCSDKQ YLHDGQCCDL CQPGSRLTSH CTALEKTQCH 70 80 90 100 110 120 PCDSGEFSAQ WNREIRCHQH RHCEPNQGLR VKKEGTAESD TVCTCKEGQH CTSKDCEACA 130 140 150 160 170 180 QHTPCIPGFG VMEMATETTD TVCHPCPVGF FSNQSSLFEK CYPWTSCEDK NLEVLQKGTS 190 200 210 220 230 QTNVICGLKS RMRALLVIPV VMGILITIFG VFLYISECSG EEREGGFSPV EPAS
	Isoform IV [UniParc]. Checksum: EE21E6C76FB42DEF	FASTA	222	24,499
	10 20 30 40 50 60 MVSLPRLCAL WGCLLTAVHL GQCVTCSDKQ YLHDGQCCDL CQPGSRLTSH CTALEKTQCH 70 80 90 100 110 120 PCDSGEFSAQ WNREIRCHQH RHCEPNQGLR VKKEGTAESD TVCTCKEGQH CTSKDCEACA 130 140 150 160 170 180 QHTPCIPGFG VMEMATETTD TVCHPCPVGF FSNQSSLFEK CYPWTSCEDK NLEVLQKGTS 190 200 210 220 QTNVICGLKS RMRALLVIPV VMGILITIFG VFLYISGQET KG
	Isoform V [UniParc]. Checksum: 57A37C0E8CF2F142	FASTA	260	28,878
	10 20 30 40 50 60 MVSLPRLCAL WGCLLTAVHL GQCVTCSDKQ YLHDGQCCDL CQPGSRLTSH CTALEKTQCH 70 80 90 100 110 120 PCDSGEFSAQ WNREIRCHQH RHCEPNQGLR VKKEGTAESD TVCTCKEGQH CTSKDCEACA 130 140 150 160 170 180 QHTPCIPGFG VMEMATETTD TVCHPCPVGF FSNQSSLFEK CYPWTSCEDK NLEVLQKGTS 190 200 210 220 230 240 QTNVICEKVV KKPKDNEILP PAARRQDPQE MEDYPGHNTA APVQETLHGC QPVTQEDGKE 250 260 SRISVQERQV TDSIALRPLV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Differential increase of an alternatively polyadenylated mRNA species of murine CD40 upon B lymphocyte activation." Torres R.M., Clark E.A. J. Immunol. 148:620-626(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM I). Strain: BALB/c.
[2]	Torres R.M. Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Genomic structure and chromosomal mapping of the murine CD40 gene." Grimaldi J.C., Torres R., Kozak C.A., Chang R., Clark E.A., Howard M., Cockayne D.A. J. Immunol. 149:3921-3926(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM I). Strain: BALB/c. Tissue: Liver.
[4]	"Regulation of CD40 function by its isoforms generated through alternative splicing." Tone M., Tone Y., Fairchild P.J., Wykes M., Waldmann H. Proc. Natl. Acad. Sci. U.S.A. 98:1751-1756(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING (ISOFORMS II; III; IV AND V).
[5]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM I). Strain: C57BL/6J and NOD. Tissue: Bone marrow macrophage, Cerebellum, Colon and Spleen.
[6]	"Cloning of mouse full open reading frames in Gateway(R) system entry vector (pDONR201)." Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J., Wiemann S., Schick M., Korn B. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM I).
[7]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM I). Strain: Czech II. Tissue: Mammary tumor.
[9]	"Involvement of CRAF1, a relative of TRAF, in CD40 signaling." Cheng G., Cleary A.M., Ye Z.S., Hong D.I., Lederman S., Baltimore D. Science 267:1494-1498(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TRAF3.
[10]	"TRAF5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling." Ishida T., Tojo T., Aoki T., Kobayashi N., Ohishi T., Watanabe T., Yamamoto T., Inoue J. Proc. Natl. Acad. Sci. U.S.A. 93:9437-9442(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TRAF5.
[11]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-273, MASS SPECTROMETRY. Tissue: Macrophage.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M83312 mRNA. Translation: AAB08705.1. M94126 , M94129, M94128, M94127 Genomic DNA. Translation: AAA37404.1. AJ401387 mRNA. Translation: CAC29427.1. AJ401388 mRNA. Translation: CAC29428.1. AJ401389 mRNA. Translation: CAC29429.1. AJ401390 mRNA. Translation: CAC29430.1. AK089861 mRNA. Translation: BAC40978.1. AK150959 mRNA. Translation: BAE29991.1. AK152716 mRNA. Translation: BAE31440.1. AK152756 mRNA. Translation: BAE31471.1. AK152942 mRNA. Translation: BAE31613.1. AK156644 mRNA. Translation: BAE33789.1. AK161978 mRNA. Translation: BAE36663.1. AK162305 mRNA. Translation: BAE36843.1. CT010343 mRNA. Translation: CAJ18551.1. AL591495, AL591411 Genomic DNA. Translation: CAM26470.1. BC029254 mRNA. Translation: AAH29254.1.
IPI	IPI00117572. IPI00230174. IPI00230175. IPI00230176. IPI00845784.
PIR	A46476.
RefSeq	NP_035741.2. NM_011611.2. NP_733803.2. NM_170702.2. NP_733804.1. NM_170703.2. NP_733805.1. NM_170704.2.
UniGene	Mm.271833.
3D structure databases
ProteinModelPortal	P27512.
SMR	P27512. Positions 26-187.
ModBase	Search...
Protein-protein interaction databases
IntAct	P27512. 2 interactions.
MINT	MINT-1506277.
PTM databases
PhosphoSite	P27512.
Proteomic databases
PaxDb	P27512.
PRIDE	P27512.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000017799; ENSMUSP00000017799; ENSMUSG00000017652. ENSMUST00000073707; ENSMUSP00000073386; ENSMUSG00000017652. ENSMUST00000081310; ENSMUSP00000080059; ENSMUSG00000017652.
GeneID	21939.
KEGG	mmu:21939.
UCSC	uc008nwx.1. mouse. uc008nwy.1. mouse. uc008nwz.1. mouse.
Organism-specific databases
CTD	958.
MGI	MGI:88336. Cd40.
Phylogenomic databases
eggNOG	NOG28193.
GeneTree	ENSGT00700000104362.
HOVERGEN	HBG005117.
InParanoid	P27512.
KO	K03160.
OMA	EKCHPWT.
Gene expression databases
ArrayExpress	P27512.
Bgee	P27512.
CleanEx	MM_CD40.
Genevestigator	P27512.
GermOnline	ENSMUSG00000017652. Mus musculus.
Family and domain databases
InterPro	IPR001368. TNFR/NGFR_Cys_rich_reg. IPR020435. TNFR_5. [Graphical view]
Pfam	PF00020. TNFR_c6. 1 hit. [Graphical view]
PRINTS	PR01922. TNFACTORR5.
SMART	SM00208. TNFR. 4 hits. [Graphical view]
PROSITE	PS00652. TNFR_NGFR_1. 1 hit. PS50050. TNFR_NGFR_2. 4 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	301554.
SOURCE	Search...

Entry information

Entry name

TNR5_MOUSE

Accession

Primary (citable) accession number: P27512
Secondary accession number(s): Q3TS33 , Q3TSL2, Q3U799, Q3U7C9, Q3UBH3, Q542B1, Q8K2X6, Q99NE0, Q99NE1, Q99NE2, Q99NE3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	February 26, 2008
Last modified:	May 1, 2013
This is version 125 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program