P42081 (CD86_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
T-lymphocyte activation antigen CD86

Alternative name(s):
Activation B7-2 antigen
B70
BU63
CTLA-4 counter-receptor B7.2
FUN-1
CD_antigen=CD86

Gene names

Name:	CD86
Synonyms:	CD28LG2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	329 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 involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4. May play a critical role in the early events of T-cell activation and costimulation of naive T-cells, such as deciding between immunity and anergy that is made by T-cells within 24 hours after activation. Isoform 2 interferes with the formation of CD86 clusters, and thus acts as a negative regulator of T-cell activation.
Subunit structure	Homodimer. Interacts with MARCH8. Interacts with human herpesvirus 8 MIR2 protein Probable. Interacts with adenovirus subgroup B fiber proteins and acts as a receptor for these viruses. Ref.11 Ref.12 Ref.14
Subcellular location	Cell membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed by activated B-lymphocytes and monocytes.
Post-translational modification	Polyubiquitinated; which is promoted by MARCH8 and results in endocytosis and lysosomal degradation.
Sequence similarities	Contains 1 Ig-like C2-type (immunoglobulin-like) domain. Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Adaptive immunity Host-virus interaction Immunity
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell activation Inferred from electronic annotation. Source: Compara T cell activation Inferred by curator PubMed 9915850. Source: UniProtKB T cell costimulation Traceable author statement. Source: Reactome cell-cell signaling Inferred by curator PubMed 9915850. Source: UniProtKB defense response to virus Inferred from electronic annotation. Source: Compara epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome innate immune response Traceable author statement. Source: Reactome neurotrophin TRK receptor signaling pathway Traceable author statement. Source: Reactome phosphatidylinositol-mediated signaling Traceable author statement. Source: Reactome positive regulation of T-helper 2 cell differentiation Non-traceable author statement PubMed 9915850. Source: UniProtKB positive regulation of cell proliferation Traceable author statement PubMed 7513726. Source: ProtInc positive regulation of interleukin-2 biosynthetic process Non-traceable author statement PubMed 9915850. Source: UniProtKB positive regulation of interleukin-4 biosynthetic process Non-traceable author statement PubMed 9915850. Source: UniProtKB positive regulation of lymphotoxin A biosynthetic process Non-traceable author statement PubMed 9915850. Source: UniProtKB positive regulation of transcription, DNA-dependent Non-traceable author statement PubMed 9915850. Source: UniProtKB toll-like receptor signaling pathway Inferred from electronic annotation. Source: Compara virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to membrane Inferred by curator PubMed 9915850. Source: UniProtKB intracellular membrane-bounded organelle Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement. Source: Reactome
Molecular_function	coreceptor activity Non-traceable author statement PubMed 9915850. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CTLA4	P16410	2	EBI-1030956,EBI-1030991

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P42081-1)

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 2 (identifier: P42081-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: Missing.

Isoform 3 (identifier: P42081-2)

Also known as: CD86 deltaEC;

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: Missing.
     22-234: Missing.

Isoform 4 (identifier: P42081-4)

Also known as: CD86 deltaTM;

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: Missing.
     235-282: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Potential

Chain

24 – 329

306

T-lymphocyte activation antigen CD86

PRO_0000014550

Regions

Topological domain

24 – 247

224

Extracellular Potential

Transmembrane

248 – 268

21

Helical; Potential

Topological domain

269 – 329

61

Cytoplasmic Potential

Domain

33 – 131

99

Ig-like V-type

Domain

150 – 225

76

Ig-like C2-type

Amino acid modifications

Glycosylation

33

1

N-linked (GlcNAc...) Potential

Glycosylation

47

1

N-linked (GlcNAc...) Potential

Glycosylation

135

1

N-linked (GlcNAc...) Potential

Glycosylation

146

1

N-linked (GlcNAc...) Potential

Glycosylation

154

1

N-linked (GlcNAc...) Potential

Glycosylation

177

1

N-linked (GlcNAc...) Potential

Glycosylation

192

1

N-linked (GlcNAc...) Potential

Glycosylation

213

1

N-linked (GlcNAc...) Potential

Disulfide bond

40 ↔ 110

Ref.14

Disulfide bond

157 ↔ 218

Potential

Natural variations

Alternative sequence

1 – 6

6

Missing in isoform 2, isoform 3 and isoform 4.

VSP_023124

Alternative sequence

22 – 234

213

Missing in isoform 3.

VSP_009125

Alternative sequence

235 – 282

48

Missing in isoform 4.

VSP_040324

Natural variant

170

1

S → N.
Corresponds to variant rs9282642 [ dbSNP | Ensembl ].

VAR_021916

Natural variant

185

1

V → I. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.8
Corresponds to variant rs2681417 [ dbSNP | Ensembl ].

VAR_055003

Natural variant

310

1

A → T. Ref.7
Corresponds to variant rs1129055 [ dbSNP | Ensembl ].

VAR_014650

Natural variant

323

1

D → N.
Corresponds to variant rs9282648 [ dbSNP | Ensembl ].

VAR_021917

Experimental info

Sequence conflict

27

1

K → E in AAA86473. Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

329

Helix Strand Turn

Details...

Beta strand

26 – 31

6

Beta strand

36 – 39

4

Helix

50 – 52

3

Beta strand

53 – 59

7

Beta strand

64 – 69

6

Beta strand

76 – 78

3

Turn

80 – 84

5

Beta strand

85 – 89

5

Turn

90 – 93

4

Beta strand

94 – 97

4

Helix

102 – 104

3

Beta strand

106 – 115

10

Beta strand

117 – 133

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 11, 2011. Version 2. Checksum: C249DAEEB889D911	FASTA	329	37,682
	10 20 30 40 50 60 MDPQCTMGLS NILFVMAFLL SGAAPLKIQA YFNETADLPC QFANSQNQSL SELVVFWQDQ 70 80 90 100 110 120 ENLVLNEVYL GKEKFDSVHS KYMGRTSFDS DSWTLRLHNL QIKDKGLYQC IIHHKKPTGM 130 140 150 160 170 180 IRIHQMNSEL SVLANFSQPE IVPISNITEN VYINLTCSSI HGYPEPKKMS VLLRTKNSTI 190 200 210 220 230 240 EYDGVMQKSQ DNVTELYDVS ISLSVSFPDV TSNMTIFCIL ETDKTRLLSS PFSIELEDPQ 250 260 270 280 290 300 PPPDHIPWIT AVLPTVIICV MVFCLILWKW KKKKRPRNSY KCGTNTMERE ESEQTKKREK 310 320 IHIPERSDEA QRVFKSSKTS SCDKSDTCF
	Isoform 2 [UniParc]. Checksum: A492C705D89B65B7	FASTA	323	37,007
	10 20 30 40 50 60 MGLSNILFVM AFLLSGAAPL KIQAYFNETA DLPCQFANSQ NQSLSELVVF WQDQENLVLN 70 80 90 100 110 120 EVYLGKEKFD SVHSKYMGRT SFDSDSWTLR LHNLQIKDKG LYQCIIHHKK PTGMIRIHQM 130 140 150 160 170 180 NSELSVLANF SQPEIVPISN ITENVYINLT CSSIHGYPEP KKMSVLLRTK NSTIEYDGVM 190 200 210 220 230 240 QKSQDNVTEL YDVSISLSVS FPDVTSNMTI FCILETDKTR LLSSPFSIEL EDPQPPPDHI 250 260 270 280 290 300 PWITAVLPTV IICVMVFCLI LWKWKKKKRP RNSYKCGTNT MEREESEQTK KREKIHIPER 310 320 SDEAQRVFKS SKTSSCDKSD TCF
	Isoform 3 (CD86 deltaEC) [UniParc]. Checksum: 0AE70C853C85F666	FASTA	110	12,818
	10 20 30 40 50 60 MGLSNILFVM AFLLSELEDP QPPPDHIPWI TAVLPTVIIC VMVFCLILWK WKKKKRPRNS 70 80 90 100 110 YKCGTNTMER EESEQTKKRE KIHIPERSDE AQRVFKSSKT SSCDKSDTCF
	Isoform 4 (CD86 deltaTM) [UniParc]. Checksum: 137A523F73708BD5	FASTA	275	31,293
	10 20 30 40 50 60 MGLSNILFVM AFLLSGAAPL KIQAYFNETA DLPCQFANSQ NQSLSELVVF WQDQENLVLN 70 80 90 100 110 120 EVYLGKEKFD SVHSKYMGRT SFDSDSWTLR LHNLQIKDKG LYQCIIHHKK PTGMIRIHQM 130 140 150 160 170 180 NSELSVLANF SQPEIVPISN ITENVYINLT CSSIHGYPEP KKMSVLLRTK NSTIEYDGVM 190 200 210 220 230 240 QKSQDNVTEL YDVSISLSVS FPDVTSNMTI FCILETDKTR LLSSPFSIGT NTMEREESEQ 250 260 270 TKKREKIHIP ERSDEAQRVF KSSKTSSCDK SDTCF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"B70 antigen is a second ligand for CTLA-4 and CD28." Azuma M., Ito D., Yagita K., Okumura K., Phillips J.H., Lanier L.L., Somoza C. Nature 366:76-79(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ILE-185.
[2]	"Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation." Freeman G.J., Gribben J.G., Boussiotis V.A., Ng J.W., Restivo V.A. Jr., Lombard L.A., Gray G.S., Nadler L.M. Science 262:909-911(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ILE-185.
[3]	"Identification of an alternatively spliced variant of human CD86 mRNA." Magistrelli G., Caron G., Gauchat J.-F., Jeannin P., Bonnefoy J.-Y., Delneste Y. Biochem. Biophys. Res. Commun. 280:1211-1215(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), VARIANT ILE-185.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ILE-185.
[5]	Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., Nickerson D.A. Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ILE-185.
[6]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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 1), VARIANTS ILE-185 AND THR-310. Tissue: Brain.
[8]	"Genomic organization of the gene coding for the costimulatory human B-lymphocyte antigen B7-2 (CD86)." Jellis C.L., Wang S.S., Rennert P., Borriello F., Sharpe A.H., Green N.R., Gray G.S. Immunogenetics 42:85-89(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 7-329, VARIANT ILE-185. Tissue: Foreskin.
[9]	"CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL." Lanier L.L., O'Fallon S., Somoza C., Phillips J.H., Linsley P.S., Okumura K., Ito D., Azuma M. J. Immunol. 154:97-105(1995) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[10]	"The B7-2 (B70) costimulatory molecule expressed by monocytes and activated B lymphocytes is the CD86 differentiation antigen." Engel P., Gribben J.G., Freeman G.J., Zhou L.J., Nozawa Y., Abe M., Nadler L.M., Wakasa H., Tedder T.F. Blood 84:1402-1407(1994) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS CD86.
[11]	"c-MIR, a human E3 ubiquitin ligase, is a functional homolog of herpesvirus proteins MIR1 and MIR2 and has similar activity." Goto E., Ishido S., Sato Y., Ohgimoto S., Ohgimoto K., Nagano-Fujii M., Hotta H. J. Biol. Chem. 278:14657-14668(2003) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, INTERACTION WITH MARCH8.
[12]	"Members of adenovirus species B utilize CD80 and CD86 as cellular attachment receptors." Short J.J., Vasu C., Holterman M.J., Curiel D.T., Pereboev A. Virus Res. 122:144-153(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ADENOVIRUS SUBGROUP B FIBER PROTEINS.
[13]	"Structural basis for co-stimulation by the human CTLA-4/B7-2 complex." Schwartz J.C., Zhang X., Fedorov A.A., Nathenson S.G., Almo S.C. Nature 410:604-608(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 26-134 IN COMPLEX WITH CTLA4.
[14]	"Crystal structure of the receptor-binding domain of human B7-2: insights into organization and signaling." Zhang X., Schwartz J.C., Almo S.C., Nathenson S.G. Proc. Natl. Acad. Sci. U.S.A. 100:2586-2591(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 26-134, SUBUNIT, DISULFIDE BOND.
+	Additional computationally mapped references.

Web resources

Wikipedia

CD86 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U04343 mRNA. Translation: AAB03814.1.
L25259 mRNA. Translation: AAA58389.1.
CR541844 mRNA. Translation: CAG46642.1.
EF064748 Genomic DNA. Translation: ABK41931.1.
AC068630 Genomic DNA. No translation available.
BC040261 mRNA. Translation: AAH40261.1.
U17722 , U17717, U17718, U17719, U17721 Genomic DNA. Translation: AAA86473.1.

IPI

IPI00290621.
IPI00397658.
IPI00473032.
IPI00947322.

PIR

A48754.
JC7605.

RefSeq

NP_001193853.1. NM_001206924.1.
NP_001193854.1. NM_001206925.1.
NP_008820.3. NM_006889.4.
NP_787058.4. NM_175862.4.
NP_795711.1. NM_176892.1.

UniGene

Hs.171182.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1I85	X-ray	3.20	A/B	26-134	[»]
1NCN	X-ray	2.70	A/B	26-134	[»]

ProteinModelPortal

P42081.

SMR

P42081. Positions 26-227.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35606N.

IntAct

P42081. 3 interactions.

MINT

MINT-6631610.

STRING

9606.ENSP00000332049.

PTM databases

PhosphoSite

P42081.

Polymorphism databases

DMDM

1168851.

Proteomic databases

PaxDb

P42081.

PRIDE

P42081.

Protocols and materials databases

DNASU

942.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000330540; ENSP00000332049; ENSG00000114013.
ENST00000393627; ENSP00000377248; ENSG00000114013.

GeneID

942.

KEGG

hsa:942.

UCSC

uc003eet.3. human.
uc021xcz.1. human.

Organism-specific databases

CTD

942.

GeneCards

GC03P121774.

HGNC

HGNC:1705. CD86.

HPA

CAB004319.

MIM

601020. gene.

neXtProt

NX_P42081.

PharmGKB

PA26243.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG79621.

HOGENOM

HOG000276893.

HOVERGEN

HBG004093.

InParanoid

P42081.

KO

K05413.

OMA

LANFSQP.

PhylomeDB

P42081.

Enzyme and pathway databases

Pathway_Interaction_DB

il12_stat4pathway. IL12 signaling mediated by STAT4.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P42081.

Bgee

P42081.

CleanEx

HS_CD86.

Genevestigator

P42081.

GermOnline

ENSG00000114013. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
IPR003596. Ig_V-set_subgr.
[Graphical view]

Pfam

PF07686. V-set. 1 hit.
[Graphical view]

SMART

SM00406. IGv. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. False negative.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01281. Abatacept.

EvolutionaryTrace

P42081.

GenomeRNAi

942.

NextBio

3902.

SOURCE

Search...

Entry information

Entry name

CD86_HUMAN

Accession

Primary (citable) accession number: P42081
Secondary accession number(s): A0N0P0 , Q13655, Q6FHB1, Q6GTS4, Q7M4L5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	January 11, 2011
Last modified:	May 29, 2013
This is version 136 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.