B-cell maturation antigen

VALUE_ERROR (nil)

Identifiers
Aliases|
External IDs| GeneCards: [1]
Orthologs
Species| Human| Mouse
Entrez| |

n/a

n/a

Ensembl| |

n/a

n/a

UniProt| |

n/a

n/a

RefSeq (mRNA)| |

n/a

n/a

RefSeq (protein)| |

n/a

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Location (UCSC)| n/a| n/a
PubMed search| n/a| n/a
Wikidata
| View/Edit Human|

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BCMA TALL-1 binding domain

File:PDB 1oqd EBI.jpg

crystal structure of stall-1 and bcma

Identifiers
Symbol| BCMA-Tall_bind
Pfam| PF09257
InterPro| IPR015337
SCOP| 1oqd
SUPERFAMILY| 1oqd
| Available protein structures:

Pfam| structures
PDB| RCSB PDB; PDBe; PDBj
PDBsum| structure summary

B-cell maturation antigen (BCMA or BCM), also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17), is a protein that in humans is encoded by the TNFRSF17 gene.

TNFRSF17 is a cell surface receptor of the TNF receptor superfamily which recognizes B-cell activating factor (BAFF).[1][2][3]

## Contents

* 1 Function
* 2 Interactions
* 3 Clinical significance - Related Diseases
* 4 As a drug target
* 5 References
* 6 External links
* 7 Further reading

## Function

[edit | edit source]

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is preferentially expressed in mature B lymphocytes, and may be important for B cell development and autoimmune response. This receptor has been shown to specifically bind to the tumor necrosis factor (ligand) superfamily, member 13b (TNFSF13B/TALL-1/BAFF), and to lead to NF-kappaB and MAPK8/JNK activation. This receptor also binds to various TRAF family members, and thus may transduce signals for cell survival and proliferation.[3]

## Interactions

[edit | edit source]

TNFRSF17 has been shown to interact with the B-cell activating factor TNFSF13B.[4][5] A conserved domain at the N-terminus, BCMA TALL-1 binding domain, is required for binding to the TNFSF13B.[4]

## Clinical significance - Related Diseases

[edit | edit source]

TNFRSF17 is implicated in leukemia, lymphomas, and multiple myeloma [6] (see the "Mitelman Database" [7] and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,[8]).

## As a drug target

[edit | edit source]

In 2017, a phase 1 clinical trial employed a CAR-T therapy that targeted BCMA02 in multiple myeloma.[9] Side-effects seen include cytokine release syndrome and mild neurotoxicity.[10]

An antibody-drug conjugate GSK2857916 is in early clinical trials.[11][12] Side effects are expected to include corneal toxicity.[12]

## References

[edit | edit source]

1. ↑ Laâbi Y, Gras MP, Carbonnel F, Brouet JC, Berger R, Larsen CJ, Tsapis A (Nov 1992). "A new gene, BCM, on chromosome 16 is fused to the interleukin 2 gene by a t(4;16)(q26;p13) translocation in a malignant T cell lymphoma". The EMBO Journal. 11 (11): 3897–904. PMC 556899. PMID 1396583.
2. ↑ Laabi Y, Gras MP, Brouet JC, Berger R, Larsen CJ, Tsapis A (Apr 1994). "The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed". Nucleic Acids Research. 22 (7): 1147–54. doi:10.1093/nar/22.7.1147. PMC 523635. PMID 8165126.
3. ↑ 3.0 3.1 "Entrez Gene: TNFRSF17 tumor necrosis factor receptor superfamily, member 17".
4. ↑ 4.0 4.1 Liu Y, Hong X, Kappler J, Jiang L, Zhang R, Xu L, Pan CH, Martin WE, Murphy RC, Shu HB, Dai S, Zhang G (May 2003). "Ligand-receptor binding revealed by the TNF family member TALL-1". Nature. 423 (6935): 49–56. doi:10.1038/nature01543. PMID 12721620.
5. ↑ Shu HB, Johnson H (Aug 2000). "B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1". Proceedings of the National Academy of Sciences of the United States of America. 97 (16): 9156–61. doi:10.1073/pnas.160213497. PMC 16838. PMID 10908663.
6. ↑ "TNFRSF17 (tumor necrosis factor receptor superfamily, member 17)". atlasgeneticsoncology.org.
7. ↑ "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer".
8. ↑ "Atlas of Genetics and Cytogenetics in Oncology and Haematology". atlasgeneticsoncology.org.
9. ↑ "Study of bb2121 in Multiple Myeloma - Full Text View - ClinicalTrials.gov". Retrieved 2017-12-12.
10. ↑ CAR T-cell therapy bb2121 shows promising efficacy for multiple myeloma
11. ↑ Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of GSK2857916
12. ↑ 12.0 12.1 Early Promise for Experimental Antibody-Drug Conjugate in Multiple Myeloma

## External links

[edit | edit source]

* Human TNFRSF17 genome location and TNFRSF17 gene details page in the UCSC Genome Browser.

## Further reading

[edit | edit source]

* Treml LS, Crowley JE, Cancro MP (Oct 2006). "BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells". Seminars in Immunology. 18 (5): 297–304. doi:10.1016/j.smim.2006.07.001. PMID 16919470.
* Mackay F, Leung H (Oct 2006). "The role of the BAFF/APRIL system on T cell function". Seminars in Immunology. 18 (5): 284–9. doi:10.1016/j.smim.2006.04.005. PMID 16931039.
* Gras MP, Laâbi Y, Linares-Cruz G, Blondel MO, Rigaut JP, Brouet JC, Leca G, Haguenauer-Tsapis R, Tsapis A (Jul 1995). "BCMAp: an integral membrane protein in the Golgi apparatus of human mature B lymphocytes". International Immunology. 7 (7): 1093–106. doi:10.1093/intimm/7.7.1093. PMID 8527407.
* Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD (Sep 1999). "Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q". Genomics. 60 (3): 295–308. doi:10.1006/geno.1999.5927. PMID 10493829.
* Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, Xu W, Parrish-Novak J, Foster D, Lofton-Day C, Moore M, Littau A, Grossman A, Haugen H, Foley K, Blumberg H, Harrison K, Kindsvogel W, Clegg CH (Apr 2000). "TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease". Nature. 404 (6781): 995–9. doi:10.1038/35010115. PMID 10801128.
* Hatzoglou A, Roussel J, Bourgeade MF, Rogier E, Madry C, Inoue J, Devergne O, Tsapis A (Aug 2000). "TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase". Journal of Immunology. 165 (3): 1322–30. doi:10.4049/jimmunol.165.3.1322. PMID 10903733.
* Shu HB, Johnson H (Aug 2000). "B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1". Proceedings of the National Academy of Sciences of the United States of America. 97 (16): 9156–61. doi:10.1073/pnas.160213497. PMC 16838. PMID 10908663.
* Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu WR, Kornuc M, Xia XZ, Guo J, Stolina M, Boyle WJ, Sarosi I, Hsu H, Senaldi G, Theill LE (Sep 2000). "APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity". Nature Immunology. 1 (3): 252–6. doi:10.1038/79802. PMID 10973284.
* Kawasaki A, Tsuchiya N, Fukazawa T, Hashimoto H, Tokunaga K (Aug 2001). "Presence of four major haplotypes in human BCMA gene: lack of association with systemic lupus erythematosus and rheumatoid arthritis". Genes and Immunity. 2 (5): 276–9. doi:10.1038/sj.gene.6363770. PMID 11528522.
* Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, Gross JA, Greipp PR, Jelinek DF (Jan 2004). "Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival". Blood. 103 (2): 689–94. doi:10.1182/blood-2003-06-2043. PMID 14512299.
* Hymowitz SG, Patel DR, Wallweber HJ, Runyon S, Yan M, Yin J, Shriver SK, Gordon NC, Pan B, Skelton NJ, Kelley RF, Starovasnik MA (Feb 2005). "Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding". The Journal of Biological Chemistry. 280 (8): 7218–27. doi:10.1074/jbc.M411714200. PMID 15542592.
* Bellucci R, Alyea EP, Chiaretti S, Wu CJ, Zorn E, Weller E, Wu B, Canning C, Schlossman R, Munshi NC, Anderson KC, Ritz J (May 2005). "Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor". Blood. 105 (10): 3945–50. doi:10.1182/blood-2004-11-4463. PMC 1895080. PMID 15692072.
* Hendriks J, Planelles L, de Jong-Odding J, Hardenberg G, Pals ST, Hahne M, Spaargaren M, Medema JP (Jun 2005). "Heparan sulfate proteoglycan binding promotes APRIL-induced tumor cell proliferation". Cell Death and Differentiation. 12 (6): 637–48. doi:10.1038/sj.cdd.4401647. PMID 15846369.
* Chiu A, Xu W, He B, Dillon SR, Gross JA, Sievers E, Qiao X, Santini P, Hyjek E, Lee JW, Cesarman E, Chadburn A, Knowles DM, Cerutti A (Jan 2007). "Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL". Blood. 109 (2): 729–39. doi:10.1182/blood-2006-04-015958. PMC 1785096. PMID 16960154.
* Smirnova AS, Andrade-Oliveira V, Gerbase-DeLima M (Feb 2008). "Identification of new splice variants of the genes BAFF and BCMA". Molecular Immunology. 45 (4): 1179–1183. doi:10.1016/j.molimm.2007.07.028. PMID 17825416.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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* e

PDB gallery

* 1oqd: Crystal structure of sTALL-1 and BCMA

1oqd: Crystal structure of sTALL-1 and BCMA

* 1xu2: The crystal structure of APRIL bound to BCMA

1xu2: The crystal structure of APRIL bound to BCMA

* v
* t
* e

Proteins: clusters of differentiation (see also list of human clusters of differentiation)

1-50|

* CD1
* a-c
* 1A
* 1D
* 1E
* CD2
* CD3
* γ
* δ
* ε
* CD4
* CD5
* CD6
* CD7
* CD8
* a
* CD9
* CD10
* CD11
* a
* b
* c
* d
* CD13
* CD14
* CD15
* CD16
* A
* B
* CD18
* CD19
* CD20
* CD21
* CD22
* CD23
* CD24
* CD25
* CD26
* CD27
* CD28
* CD29
* CD30
* CD31
* CD32
* A
* B
* CD33
* CD34
* CD35
* CD36
* CD37
* CD38
* CD39
* CD40
* CD41
* CD42
* a
* b
* c
* d
* CD43
* CD44
* CD45
* CD46
* CD47
* CD48
* CD49
* a
* b
* c
* d
* e
* f
* CD50

51-100|

* CD51
* CD52
* CD53
* CD54
* CD55
* CD56
* CD57
* CD58
* CD59
* CD61
* CD62
* E
* L
* P
* CD63
* CD64
* A
* B
* C
* CD66
* a
* b
* c
* d
* e
* f
* CD68
* CD69
* CD70
* CD71
* CD72
* CD73
* CD74
* CD78
* CD79
* a
* b
* CD80
* CD81
* CD82
* CD83
* CD84
* CD85
* a
* d
* e
* h
* j
* k
* CD86
* CD87
* CD88
* CD89
* CD90
* CD91 \- CD92
* CD93
* CD94
* CD95
* CD96
* CD97
* CD98
* CD99
* CD100

101-150|

* CD101
* CD102
* CD103
* CD104
* CD105
* CD106
* CD107
* a
* b
* CD108
* CD109
* CD110
* CD111
* CD112
* CD113
* CD114
* CD115
* CD116
* CD117
* CD118
* CD119
* CD120
* a
* b
* CD121
* a
* b
* CD122
* CD123
* CD124
* CD125
* CD126
* CD127
* CD129
* CD130
* CD131
* CD132
* CD133
* CD134
* CD135
* CD136
* CD137
* CD138
* CD140b
* CD141
* CD142
* CD143
* CD144
* CD146
* CD147
* CD148
* CD150

151-200|

* CD151
* CD152
* CD153
* CD154
* CD155
* CD156
* a
* b
* c
* CD157
* CD158 (a
* d
* e
* i
* k)
* CD159
* a
* c
* CD160
* CD161
* CD162
* CD163
* CD164
* CD166
* CD167
* a
* b
* CD168
* CD169
* CD170
* CD171
* CD172
* a
* b
* g
* CD174
* CD177
* CD178
* CD179
* a
* b
* CD180
* CD181
* CD182
* CD183
* CD184
* CD185
* CD186
* CD191
* CD192
* CD193
* CD194
* CD195
* CD196
* CD197
* CDw198
* CDw199
* CD200

201-250|

* CD201
* CD202b
* CD204
* CD205
* CD206
* CD207
* CD208
* CD209
* CDw210
* a
* b
* CD212
* CD213a
* 1
* 2
* CD217
* CD218 (a
* b)
* CD220
* CD221
* CD222
* CD223
* CD224
* CD225
* CD226
* CD227
* CD228
* CD229
* CD230
* CD233
* CD234
* CD235
* a
* b
* CD236
* CD238
* CD239
* CD240CE
* CD240D
* CD241
* CD243
* CD244
* CD246
* CD247 \- CD248
* CD249

251-300|

* CD252
* CD253
* CD254
* CD256
* CD257
* CD258
* CD261
* CD262
* CD263
* CD264
* CD265
* CD266
* CD267
* CD268
* CD269
* CD271
* CD272
* CD273
* CD274
* CD275
* CD276
* CD278
* CD279
* CD280
* CD281
* CD282
* CD283
* CD284
* CD286
* CD288
* CD289
* CD290
* CD292
* CDw293
* CD294
* CD295
* CD297
* CD298
* CD299

301-350|

* CD300A
* CD301
* CD302
* CD303
* CD304
* CD305
* CD306
* CD307
* CD309
* CD312
* CD314
* CD315
* CD316
* CD317
* CD318
* CD320
* CD321
* CD322
* CD324
* CD325
* CD326
* CD328
* CD329
* CD331
* CD332
* CD333
* CD334
* CD335
* CD336
* CD337
* CD338
* CD339
* CD340
* CD344
* CD349
* CD350

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Cytokine receptors

Chemokine receptor
(GPCRs)|

| CC|

* CCR1 / CCRL1
* CCR2
* CCRL2
* CCR3
* CCR4
* CCR5
* CCR6
* CCR7
* CCR8
* CCR9
* CCR10

|

CXC|

* IL-8
* CXCR1
* CXCR2
* CXCR3
* CXCR4
* CXCR5
* CXCR6
* CXCR7

Other|

* CX3C
* CX3CR1
* XC
* XCR1
* CCBP2
* CMKLR1

TNF receptor|

| 1-10|

* TNFR1 (TNFRSF1A)
* TNFR2 (TNFRSF1B)
* LTBR (TNFRSF3)
* CD134 (TNFRSF4)
* CD40 (TNFRSF5)
* Fas receptor (TNFRSF6)
* DcR3 (TNFRSF6B)
* CD27 (TNFRSF7)
* CD30 (TNFRSF8)
* CD137 (TNFRSF9)

|

11-20|

* DR4 (TNFRSF10A)
* DR5 (TNFRSF10B)
* DcR1 (TNFRSF10C)
* DcR2 (TNFRSF10D)
* RANK (TNFRSF11A)
* Osteoprotegerin (TNFRSF11B)
* TweakR (TNFRSF12A)
* TACI (TNFRSF13B)
* BAFFR (TNFRSF13C)
* HVEM (TNFRSF14)
* NGFR (TNFRSF16)
* BCMA (TNFRSF17)
* GITR (TNFRSF18)
* TAJ/TROY (TNFRSF19)

21-27|

* DR6 (TNFRSF21)
* DR3 (TNFRSF25)
* EDA2R (TNFRSF27)

JAK-STAT|

| Type I|

| γ-chain|

* Interleukin receptors
* IL2R / IL2RA/IL2RB / IL15R
* IL4R / IL13R / IL13RA1 / IL13RA2
* IL7R / IL7RA
* IL9R
* IL21R

|

β-chain|

* Interleukin receptors
* IL3R / IL3RA
* IL5R / IL5RA
* GM-CSF

gp130|

* Interleukin receptors
* IL6RA
* 11/IL11RA
* 27/IL27RA
* OSMR
* LIFR
* CNTFR

IL12RB1|

* Interleukin receptors
* IL12R/IL12RB1/IL12RB2
* IL23R23

Other|

* other CSF receptors
* EPO
* G-CSF
* Thrombopoietin

* hormone receptor: GH
* prolactin

Type II|

* Interleukin receptors
* IL10R / IL10RA / IL10RB / IL22R / IL22RA1 / IL22RA2
* IL20R / IL20RA / IL20RB
* IL28R
* Interferon receptors
* -α/β / IFNAR1/IFNAR2
* -γ/IFNGR1 / IFNGR2

Ig superfamily|

* CSF1
* KIT
* IL1
* IL1R1
* IL1R2
* IL18R / IL18R1

IL 17 family|

* IL17
* IL17RA
* IL17RB
* IL17RC
* IL17RD
* IL17RE

S/T|

* TGF-beta
* TGFBR1
* TGFBR2

* v
* t
* e

Cytokine receptor modulators

Chemokine|

* See here instead.

CSF|

| Erythropoietin|

* Agonists: ARA-290
* Asialo erythropoietin
* Carbamylated erythropoietin
* CNTO-530
* Darbepoetin alfa
* Epoetin alfa
* Epoetin beta
* Epoetin delta
* Epoetin epsilon
* Epoetin gamma
* Epoetin kappa
* Epoetin omega
* Epoetin theta
* Epoetin zeta
* Erythropoietin (EPO)
* Erythropoietin-Fc
* Methoxy polyethylene glycol-epoetin beta (CERA/Mircera)
* Peginesatide
* Pegol sihematide (EPO-018B)

|

G-CSF (CSF3)|

* Agonists: Filgrastim
* Granulocyte colony-stimulating factor
* Lenograstim
* Leridistim
* Lipegfilgrastim
* Nartograstim
* Pegfilgrastim
* Pegnartograstim

GM-CSF (CSF2)|

* Agonists: Ecogramostim
* Granulocyte macrophage colony-stimulating factor
* Milodistim
* Molgramostim
* Regramostim
* Sargramostim

* Antibodies: Mavrilimumab
* MOR103
* Namilumab

M-CSF (CSF1)|

* Agonists: Cilmostim
* Interleukin-34
* Lanimostim
* Macrophage colony-stimulating factor
* Mirimostim

* Kinase inhibitors: Agerafenib

SCF (c-Kit)|

* See here instead.

Thrombopoietin|

* Agonists: Eltrombopag
* Pegacaristim
* Promegapoietin
* Romiplostim
* Thrombopoietin (THPO, MGDF)

Interferon|

| IFNAR (α/β, I)|

* Agonists: Albinterferon
* Interferon alpha (interferon alfa, IFN-α)
* Interferon alfa (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21)
* Interferon alfa 2a
* Interferon alfa 2b
* Interferon alfa n1
* Interferon alfacon-1
* Interferon alpha-n3
* Interferon beta (IFN-β) (IFNB1, IFNB3)
* Interferon beta 1a
* Interferon beta 1b
* Interferon kappa (IFN-ε/κ/τ/ζ, IFNK)
* Interferon omega (IFN-ω, IFNW1)
* Peginterferon alfa-2a
* Peginterferon alfa-2b

* Antibodies: Anifrolumab
* Faralimomab
* MEDI-545
* Rontalizumab
* Sifalimumab

* Decoy receptors: Bifarcept

|

IFNGR (γ, II)|

* Agonists: Interferon gamma (IFN-γ)
* Interferon gamma 1b

* Antibodies: Emapalumab
* Fontolizumab

IFNLR (λ, III)|

* See IL-28R (IFNLR) here instead.

Interleukin|

* See here instead.

TGFβ|

* See here instead.

TNF|

* See here instead.

Others|

| JAK
(inhibitors)|

| JAK1|

* Baricitinib
* Filgotinib
* Momelotinib
* Oclacitinib
* Ruxolitinib
* Tofacitinib (tasocitinib, CP-690550)
* Upadacitinib

|

JAK2|

* AG-490
* Atiprimod
* AZD-1480
* Baricitinib
* CHZ868
* Cucurbitacin I (elatericin B, JSI-124)
* CYT387
* Lestaurtinib
* NSC-7908
* NSC-33994
* Pacritinib
* Ruxolitinib
* SD-1008
* Tofacitinib (tasocitinib, CP-690550)

JAK3|

* AG-490
* Cercosporamide
* TCS-21311
* Tofacitinib (tasocitinib, CP-690550)
* WHI-P 154
* ZM-39923
* ZM-449829

Others|

* Additional cytokines: Cardiotrophin 1 (CT-1)
* FMS-like tyrosine kinase 3 ligand (FLT3L)
* Leukemia/leukocyte inhibitory factor (LIF)
* Oncostatin M (OSM)
* Thymic stromal lymphopoietin (TSLP)

* Additional cytokine receptor modulators: Emfilermin
* Lestaurtinib
* Midostaurin
* Quizartinib
* Sorafenib
* Sunitinib

See also
Receptor/signaling modulators
Signaling peptide/protein receptor modulators
Growth factor receptor modulators

This article incorporates text from the public domain Pfam and InterPro: IPR015337
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