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Protein

CD276 antigen

Gene

CD276

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

May participate in the regulation of T-cell-mediated immune response. May play a protective role in tumor cells by inhibiting natural-killer mediated cell lysis as well as a role of marker for detection of neuroblastoma cells. May be involved in the development of acute and chronic transplant rejection and in the regulation of lymphocytic activity at mucosal surfaces. Could also play a key role in providing the placenta and fetus with a suitable immunological environment throughout pregnancy. Both isoform 1 and isoform 2 appear to be redundant in their ability to modulate CD4 T-cell responses. Isoform 2 is shown to enhance the induction of cytotoxic T-cells and selectively stimulates interferon gamma production in the presence of T-cell receptor signaling.6 Publications

Miscellaneous

B7-H3 locus underwent genomic duplication leading to tandemly repeated immunoglobulin-like V and C domains (VC domains). The dominantly expressed human B7-H3 isoform contains tandemly duplicated VC domains. In contrast, mouse B7-H3 transcript contains only one single VC domain form due to an exon structure corresponding to V domain-(pseudoexon C)-(pseudoexon V)-C domain. This duplication appearing in primates is suggested to be very recent supporting a model of multiple independent emergence of tandem VC repeats within human and monkey species.

GO - Molecular functioni

  • signaling receptor binding Source: HGNC

GO - Biological processi

  • cell proliferation Source: UniProtKB
  • immune response Source: UniProtKB
  • positive regulation of interferon-gamma biosynthetic process Source: HGNC
  • positive regulation of T cell proliferation Source: HGNC
  • regulation of immune response Source: HGNC
  • T cell activation Source: UniProtKB

Names & Taxonomyi

Protein namesi
Recommended name:
CD276 antigen
Alternative name(s):
4Ig-B7-H3
B7 homolog 3
Short name:
B7-H3
Costimulatory molecule
CD_antigen: CD276
Gene namesi
Name:CD276
Synonyms:B7H3
ORF Names:PSEC0249, UNQ309/PRO352
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000103855.17
HGNCiHGNC:19137 CD276
MIMi605715 gene
neXtProtiNX_Q5ZPR3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini29 – 466ExtracellularSequence analysisAdd BLAST438
Transmembranei467 – 487HelicalSequence analysisAdd BLAST21
Topological domaini488 – 534CytoplasmicSequence analysisAdd BLAST47

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi80381
OpenTargetsiENSG00000103855
PharmGKBiPA142672148

Chemistry databases

ChEMBLiCHEMBL3712879
GuidetoPHARMACOLOGYi2938

Polymorphism and mutation databases

BioMutaiCD276
DMDMi74757248

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 281 PublicationAdd BLAST28
ChainiPRO_000004580129 – 534CD276 antigenAdd BLAST506

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi50 ↔ 122PROSITE-ProRule annotation
Glycosylationi104N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi165 ↔ 220PROSITE-ProRule annotation
Glycosylationi189N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi215N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi268 ↔ 340PROSITE-ProRule annotation
Glycosylationi322N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi383 ↔ 438PROSITE-ProRule annotation
Glycosylationi407N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi433N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei525PhosphoserineCombined sources1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ5ZPR3
MaxQBiQ5ZPR3
PaxDbiQ5ZPR3
PeptideAtlasiQ5ZPR3
PRIDEiQ5ZPR3
ProteomicsDBi65865
65866 [Q5ZPR3-2]
65867 [Q5ZPR3-3]
65868 [Q5ZPR3-4]

PTM databases

iPTMnetiQ5ZPR3
PhosphoSitePlusiQ5ZPR3
SwissPalmiQ5ZPR3

Expressioni

Tissue specificityi

Ubiquitous but not detectable in peripheral blood lymphocytes or granulocytes. Weakly expressed in resting monocytes. Expressed in dendritic cells derived from monocytes. Expressed in epithelial cells of sinonasal tissue. Expressed in extravillous trophoblast cells and Hofbauer cells of the first trimester placenta and term placenta.5 Publications

Inductioni

By bacterial lipopolysaccharides (LPS) in monocytes and by ionomycin in T and B-lymphocytes. Up-regulated in cells mediating rejection of human transplants.2 Publications

Gene expression databases

BgeeiENSG00000103855
CleanExiHS_CD276
ExpressionAtlasiQ5ZPR3 baseline and differential
GenevisibleiQ5ZPR3 HS

Organism-specific databases

HPAiCAB017826
HPA009285
HPA017139

Interactioni

Subunit structurei

Interacts with TREML2 and this interaction enhances T-cell activation.1 Publication

GO - Molecular functioni

  • signaling receptor binding Source: HGNC

Protein-protein interaction databases

BioGridi123260, 12 interactors
IntActiQ5ZPR3, 1 interactor
STRINGi9606.ENSP00000320084

Structurei

3D structure databases

ProteinModelPortaliQ5ZPR3
SMRiQ5ZPR3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini29 – 139Ig-like V-type 1Add BLAST111
Domaini145 – 238Ig-like C2-type 1Add BLAST94
Domaini243 – 357Ig-like V-type 2Add BLAST115
Domaini363 – 456Ig-like C2-type 2Add BLAST94

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IR2H Eukaryota
ENOG410ZB69 LUCA
GeneTreeiENSGT00700000104325
HOVERGENiHBG079786
InParanoidiQ5ZPR3
KOiK06746
OMAiFESPSHY
OrthoDBiEOG091G0IEZ
PhylomeDBiQ5ZPR3
TreeFamiTF331083

Family and domain databases

Gene3Di2.60.40.10, 4 hits
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003597 Ig_C1-set
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR013106 Ig_V-set
PfamiView protein in Pfam
PF07686 V-set, 2 hits
SMARTiView protein in SMART
SM00409 IG, 4 hits
SM00407 IGc1, 2 hits
SM00408 IGc2, 4 hits
SM00406 IGv, 2 hits
SUPFAMiSSF48726 SSF48726, 4 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 4 hits

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5ZPR3-1) [UniParc]FASTAAdd to basket
Also known as: 4Ig-B7-H3

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.

« Hide

        10         20         30         40         50
MLRRRGSPGM GVHVGAALGA LWFCLTGALE VQVPEDPVVA LVGTDATLCC
60 70 80 90 100
SFSPEPGFSL AQLNLIWQLT DTKQLVHSFA EGQDQGSAYA NRTALFPDLL
110 120 130 140 150
AQGNASLRLQ RVRVADEGSF TCFVSIRDFG SAAVSLQVAA PYSKPSMTLE
160 170 180 190 200
PNKDLRPGDT VTITCSSYQG YPEAEVFWQD GQGVPLTGNV TTSQMANEQG
210 220 230 240 250
LFDVHSILRV VLGANGTYSC LVRNPVLQQD AHSSVTITPQ RSPTGAVEVQ
260 270 280 290 300
VPEDPVVALV GTDATLRCSF SPEPGFSLAQ LNLIWQLTDT KQLVHSFTEG
310 320 330 340 350
RDQGSAYANR TALFPDLLAQ GNASLRLQRV RVADEGSFTC FVSIRDFGSA
360 370 380 390 400
AVSLQVAAPY SKPSMTLEPN KDLRPGDTVT ITCSSYRGYP EAEVFWQDGQ
410 420 430 440 450
GVPLTGNVTT SQMANEQGLF DVHSVLRVVL GANGTYSCLV RNPVLQQDAH
460 470 480 490 500
GSVTITGQPM TFPPEALWVT VGLSVCLIAL LVALAFVCWR KIKQSCEEEN
510 520 530
AGAEDQDGEG EGSKTALQPL KHSDSKEDDG QEIA
Note: Contains tandemly repeated immunoglobulin-like V and C domains.
Length:534
Mass (Da):57,235
Last modified:November 23, 2004 - v1
Checksum:i2181A064404C7939
GO
Isoform 2 (identifier: Q5ZPR3-2) [UniParc]FASTAAdd to basket
Also known as: B7-H3

The sequence of this isoform differs from the canonical sequence as follows:
     159-376: Missing.

Note: Minor transcript. Contains one single set of immunoglobulin-like V and C domains.
Show »
Length:316
Mass (Da):33,791
Checksum:iFF97007F191CCFA1
GO
Isoform 3 (identifier: Q5ZPR3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     465-493: EALWVTVGLSVCLIALLVALAFVCWRKIK → GPASSAVPLSPAHPPHGSMCWSHWFSRGL
     494-534: Missing.

Note: Contains tandemly repeated immunoglobulin-like V and C domains.
Show »
Length:493
Mass (Da):52,761
Checksum:iCD7C5591CC4822D2
GO
Isoform 4 (identifier: Q5ZPR3-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     528-534: DDGQEIA → GKDTWA

Note: Contains tandemly repeated immunoglobulin-like V and C domains.
Show »
Length:533
Mass (Da):57,165
Checksum:iBC38033295EBE978
GO

Sequence cautioni

The sequence BAC11344 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti387R → Q in AAQ88709 (PubMed:12975309).Curated1
Sequence conflicti473L → P in BAC11243 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04985797P → L. Corresponds to variant dbSNP:rs7173448Ensembl.1
Natural variantiVAR_049858111R → S. Corresponds to variant dbSNP:rs7173476Ensembl.1
Natural variantiVAR_049859137Q → L. Corresponds to variant dbSNP:rs11574477Ensembl.1
Natural variantiVAR_049860160T → M2 PublicationsCorresponds to variant dbSNP:rs11574479Ensembl.1
Natural variantiVAR_049861267R → H. Corresponds to variant dbSNP:rs11574483Ensembl.1
Natural variantiVAR_049862279A → T. Corresponds to variant dbSNP:rs10083681Ensembl.1
Natural variantiVAR_049863315P → L. Corresponds to variant dbSNP:rs148625372Ensembl.1
Natural variantiVAR_049864329R → S. Corresponds to variant dbSNP:rs7173476Ensembl.1
Natural variantiVAR_049865378T → M. Corresponds to variant dbSNP:rs11574479Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_017088159 – 376Missing in isoform 2. 2 PublicationsAdd BLAST218
Alternative sequenceiVSP_017089465 – 493EALWV…WRKIK → GPASSAVPLSPAHPPHGSMC WSHWFSRGL in isoform 3. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_017090494 – 534Missing in isoform 3. 1 PublicationAdd BLAST41
Alternative sequenceiVSP_017091528 – 534DDGQEIA → GKDTWA in isoform 4. 1 Publication7

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF302102 mRNA Translation: AAK15438.1
AJ583695 mRNA Translation: CAE47548.1
AY358343 mRNA Translation: AAQ88709.1
AK074849 mRNA Translation: BAC11243.1
AK074997 mRNA Translation: BAC11344.1 Different initiation.
AK075549 mRNA Translation: BAC11692.1
BC062581 mRNA Translation: AAH62581.1
CCDSiCCDS10251.1 [Q5ZPR3-2]
CCDS32288.1 [Q5ZPR3-1]
RefSeqiNP_001019907.1, NM_001024736.1 [Q5ZPR3-1]
NP_001316557.1, NM_001329628.1 [Q5ZPR3-2]
NP_001316558.1, NM_001329629.1
NP_079516.1, NM_025240.2 [Q5ZPR3-2]
XP_005254757.1, XM_005254700.4
XP_011520397.1, XM_011522095.2 [Q5ZPR3-1]
XP_011520398.1, XM_011522096.2 [Q5ZPR3-1]
XP_016878127.1, XM_017022638.1 [Q5ZPR3-1]
UniGeneiHs.744915

Genome annotation databases

EnsembliENST00000318424; ENSP00000320058; ENSG00000103855 [Q5ZPR3-2]
ENST00000318443; ENSP00000320084; ENSG00000103855 [Q5ZPR3-1]
ENST00000561213; ENSP00000452736; ENSG00000103855 [Q5ZPR3-4]
ENST00000564751; ENSP00000454940; ENSG00000103855 [Q5ZPR3-2]
GeneIDi80381
KEGGihsa:80381
UCSCiuc002avu.2 human [Q5ZPR3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCD276_HUMAN
AccessioniPrimary (citable) accession number: Q5ZPR3
Secondary accession number(s): Q6P5Y4
, Q6UXI2, Q8NBI8, Q8NC34, Q8NCB6, Q9BXR1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2006
Last sequence update: November 23, 2004
Last modified: July 18, 2018
This is version 132 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

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