CD276

CD276
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4I0K
Identifiers
Aliases	CD276, 4Ig-B7-H3, B7-H3, B7H3, B7RP-2, CD276 molecule
External IDs	OMIM: 605715 MGI: 2183926 HomoloGene: 11892 GeneCards: CD276
Gene location (Human)
Chr.	Chromosome 15 (human)
End	73,714,514 bp
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)
End	58,462,720 bp
RNA expression pattern
	Top expressed in
	synovial membrane; ; gallbladder; ; left ventricle;
	More reference expression data
	n/a
Gene ontology
Molecular function	GO:0001948 protein binding; signaling receptor binding;
Cellular component	membrane; integral component of membrane; external side of plasma membrane;
Biological process	cell population proliferation; T cell activation; immune response; positive regulation of T cell proliferation; regulation of immune response; T cell receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	80381
	102657
	ENSG00000103855
	ENSMUSG00000035914
	Q5ZPR3
	Q8VE98
	NM_001024736; NM_025240; NM_001329628; NM_001329629
	NM_133983
	NP_001019907; NP_001316557; NP_001316558; NP_079516
	NP_598744
	Wikidata
View/Edit Human	View/Edit Mouse

Cluster of Differentiation 276 (CD276) or B7 Homolog 3 (B7-H3) is a human protein encoded by the CD276 gene.^[5]

Structure[]

B7-H3 is a 316 amino acid-long type I transmembrane protein, existing in two isoforms determined by its extracellular domain. In mice, the extracellular domain consists of a single pair of immunoglobulin variable (IgV)-like and immunoglobulin constant (IgC)-like domains, whereas in humans it consists of one pair (2Ig-B7-H3) or two identical pairs (4Ig-B7-H3) due to . B7-H3 mRNA is expressed in most normal tissues. In contrast, B7-H3 protein has a very limited expression on normal tissues because of its post-transcriptional regulation by microRNAs. However, B7-H3 protein is expressed at high frequency on many different cancer types (60% of all cancers). ^[6]

Function[]

In non-malignant tissues, B7-H3 has a predominantly inhibitory role in adaptive immunity, suppressing T cell activation and proliferation.

In malignant tissues, B7-H3 is an immune checkpoint molecule that inhibits tumor antigen-specific immune responses. B7-H3 also possesses non-immunological pro-tumorigenic functions such as promoting migration, invasion, angiogenesis, chemoresistance, epithelial-to-mesenchymal transition, and affecting tumor cell metabolism.^[6]

As a possible drug target[]

Due to its selective expression on solid tumors, B7-H3 has been the target of several anticancer agents such as enoblituzumab (MGA271),^[7] , MGD009, MGC018, DS-7300a, and CAR T cells.^[6]

References[]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000103855 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000035914 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: CD276 CD276 molecule".
^ ^a ^b ^c Kontos F, Michelakos T, Kurokawa T, Sadagopan A, Schwab JH, Ferrone CR, Ferrone S (October 2020). "B7-H3: an attractive target for antibody-based immunotherapy". Clinical Cancer Research. 27 (5): 1227–1235. doi:10.1158/1078-0432.CCR-20-2584. PMC 7925343. PMID 33051306.
^ "Servier Pays MacroGenics $20M for Option to Anticancer Antibody - GEN". GEN. December 2011.

Further reading[]

Kontos F, Michelakos T, Kurokawa T, Sadagopan A, Schwab JH, Ferrone CR, Ferrone S (October 2020). "B7-H3: an attractive target for antibody-based immunotherapy". Clinical Cancer Research. 27 (5): 1227–1235. doi:10.1158/1078-0432.CCR-20-2584. PMC 7925343. PMID 33051306.
Chapoval AI, Ni J, Lau JS, Wilcox RA, Flies DB, Liu D, Dong H, Sica GL, Zhu G, Tamada K, Chen L (March 2001). "B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production". Nature Immunology. 2 (3): 269–74. doi:10.1038/85339. PMID 11224528. S2CID 43480199.
Sun M, Richards S, Prasad DV, Mai XM, Rudensky A, Dong C (June 2002). "Characterization of mouse and human B7-H3 genes". Journal of Immunology. 168 (12): 6294–7. doi:10.4049/jimmunol.168.12.6294. PMID 12055244.
Ling V, Wu PW, Spaulding V, Kieleczawa J, Luxenberg D, Carreno BM, Collins M (September 2003). "Duplication of primate and rodent B7-H3 immunoglobulin V- and C-like domains: divergent history of functional redundancy and exon loss". Genomics. 82 (3): 365–77. doi:10.1016/S0888-7543(03)00126-5. PMID 12906861.
Steinberger P, Majdic O, Derdak SV, Pfistershammer K, Kirchberger S, Klauser C, Zlabinger G, Pickl WF, Stöckl J, Knapp W (February 2004). "Molecular characterization of human 4Ig-B7-H3, a member of the B7 family with four Ig-like domains". Journal of Immunology. 172 (4): 2352–9. doi:10.4049/jimmunol.172.4.2352. PMID 14764704.
Zhang GB, Chen YJ, Shi Q, Ma HB, Ge Y, Wang Q, Jiang Z, Xu Y, Zhang XG (June 2004). "Human recombinant B7-H3 expressed in E. coli enhances T lymphocyte proliferation and IL-10 secretion in vitro". Acta Biochimica et Biophysica Sinica. 36 (6): 430–6. doi:10.1093/abbs/36.6.430. PMID 15188059.
Castriconi R, Dondero A, Augugliaro R, Cantoni C, Carnemolla B, Sementa AR, Negri F, Conte R, Corrias MV, Moretta L, Moretta A, Bottino C (August 2004). "Identification of 4Ig-B7-H3 as a neuroblastoma-associated molecule that exerts a protective role from an NK cell-mediated lysis". Proceedings of the National Academy of Sciences of the United States of America. 101 (34): 12640–5. Bibcode:2004PNAS..10112640C. doi:10.1073/pnas.0405025101. PMC 515110. PMID 15314238.
Wang L, Fraser CC, Kikly K, Wells AD, Han R, Coyle AJ, Chen L, Hancock WW (February 2005). "B7-H3 promotes acute and chronic allograft rejection". European Journal of Immunology. 35 (2): 428–38. doi:10.1002/eji.200425518. PMID 15682454. S2CID 607942.
Kim J, Myers AC, Chen L, Pardoll DM, Truong-Tran QA, Lane AP, McDyer JF, Fortuno L, Schleimer RP (September 2005). "Constitutive and inducible expression of b7 family of ligands by human airway epithelial cells". American Journal of Respiratory Cell and Molecular Biology. 33 (3): 280–9. doi:10.1165/rcmb.2004-0129OC. PMC 2715317. PMID 15961727.
Petroff MG, Kharatyan E, Torry DS, Holets L (August 2005). "The immunomodulatory proteins B7-DC, B7-H2, and B7-H3 are differentially expressed across gestation in the human placenta". The American Journal of Pathology. 167 (2): 465–73. doi:10.1016/S0002-9440(10)62990-2. PMC 1603571. PMID 16049332.
Zhang G, Dong Q, Xu Y, Yu G, Zhang X (August 2005). "B7-H3: another molecule marker for Mo-DCs?". Cellular & Molecular Immunology. 2 (4): 307–11. PMID 16274630.
Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Research. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
Sakthivel P, Wang X, Gharizadeh B, Giscombe R, Pirskanen R, Nyren P, Lefvert AK (December 2006). "Single-nucleotide polymorphisms in the B7H3 gene are not associated with human autoimmune myasthenia gravis". Journal of Genetics. 85 (3): 217–20. doi:10.1007/BF02935335. PMID 17406098. S2CID 20818492.

External links[]

CD276+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
Human CD276 genome location and CD276 gene details page in the UCSC Genome Browser.
Overview of all the structural information available in the PDB for UniProt: Q8VE98 (CD276 antigen) at the PDBe-KB.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000103855 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000035914 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: CD276 CD276 molecule".

[ccr-review-6] Kontos F, Michelakos T, Kurokawa T, Sadagopan A, Schwab JH, Ferrone CR, Ferrone S (October 2020). "B7-H3: an attractive target for antibody-based immunotherapy". Clinical Cancer Research. 27 (5): 1227–1235. doi:10.1158/1078-0432.CCR-20-2584. PMC 7925343. PMID 33051306.

[7] "Servier Pays MacroGenics $20M for Option to Anticancer Antibody - GEN". GEN. December 2011.

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v t Proteins: clusters of differentiation (see also list of human clusters of differentiation)
1–50	CD1 a-c 1A 1B 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