Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0008133
UniProt IDP01903
Primary gene name(s)HLA-DRA
Synonym gene name(s)HLA-DRA1
Protein nameHLA class II histocompatibility antigen, DR alpha chain
Protein functionBinds peptides derived from antigens that access the endocytic route of antigen presenting cells, APC and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules, heterodimers of an alpha and a beta chain associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP, class-II-associated invariant chain peptide. The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells, DCs also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
Subcellular locationCell membrane;
Single-pass type I membrane protein. Endoplasmic reticulum membrane;
Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network membrane;
Single-pass type I membrane protein. Endosome membrane;
Single-pass type I membrane protein. Lysosome membrane;
Single-pass type I membrane protein. Late endosome membrane;
Single-pass type I membrane protein. Note=The MHC class II complex transits through a number of intracellular compartments in the endocytic pathway until it reaches the cell membrane for antigen presentation.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P01903
Gene Ontology
(Biological Process)
Complete annatation
antigen processing and presentation of exogenous peptide antigen via MHC class II [GO:0019886];
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II [GO:0002504];
cognition [GO:0050890];
immune response [GO:0006955];
interferon-gamma-mediated signaling pathway [GO:0060333];
peptide antigen assembly with MHC class II protein complex [GO:0002503];
polysaccharide assembly with MHC class II protein complex [GO:0002506];
T cell costimulation [GO:0031295];
T cell receptor signaling pathway [GO:0050852];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
MHC class II protein complex binding [GO:0023026];
MHC class II receptor activity [GO:0032395];
peptide antigen binding [GO:0042605]
Gene Ontology
(Cellular Component)
Complete annatation
cell surface [GO:0009986];
clathrin-coated endocytic vesicle membrane [GO:0030669];
endocytic vesicle membrane [GO:0030666];
ER to Golgi transport vesicle membrane [GO:0012507];
extracellular exosome [GO:0070062];
Golgi membrane [GO:0000139];
integral component of lumenal side of endoplasmic reticulum membrane [GO:0071556];
integral component of plasma membrane [GO:0005887];
late endosome membrane [GO:0031902];
lysosomal membrane [GO:0005765];
lysosome [GO:0005764];
MHC class II protein complex [GO:0042613];
plasma membrane [GO:0005886];
trans-Golgi network membrane [GO:0032588];
transport vesicle membrane [GO:0030658]
Protein-protein interaction109367
Phylogenetic treeP01903
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.711979317307540.03167084599716890.068108003420397
AZA vs. DISU-0.4291370814238560.09800375919154520.636496624753707
AZA vs. IL71.046754703502360.0003046141174319890.0340107303114991
AZA vs. SAHA1.155669721388980.001516601448526280.0274444780733315
DISU vs. CD3-1.152343899195030.001821279931656480.00691884417585429
DISU vs. IL71.465948943061286.53367895054879e-050.00374682735647962
DISU vs. SAHA1.586460193232550.0002527521167328130.00762738743470519
DMSO vs. AZA-0.1169804256470450.5059365396366771
DMSO vs. CD3-0.8384902805056750.00968410420005550.0242384166429367
DMSO vs. DISU0.3105453230501570.2527030384212730.771522445098983
DMSO vs. IL71.170381630847480.0001322683362353640.0145543442974315
DMSO vs. SAHA1.266072731418410.0008273443864280640.0158410242698584
HIV vs. Mock in Activation-0.2582884224071380.6792662120126160.999983755607037
HIV vs. Mock in Latency0.5277942967931210.453473387151760.999834320637052
IL7 vs. CD30.3419289830656930.2999479540357580.437906768172416
SAHA vs. CD30.4206557633742050.2560127825878740.366253335257192
SAHA vs. IL70.10820752591110.7970222716704230.9121290682859
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock 1.123 2.42E-09 2.03E-07
Infected vs. Bystander 1.363 5.58E-11 5.54E-09
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.854285 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
210982_s_at 2.06 No upregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1A6A X-ray 2.7Å A=30-205.
1AQD X-ray 2.4Å A/D/G/J=26-217.
1BX2 X-ray 2.6Å A/D=27-206.
1D5M X-ray 2.0Å A=26-206.
1D5X X-ray 2.4Å A=26-206.
1D5Z X-ray 2.0Å A=26-206.
1D6E X-ray 2.4Å A=26-206.
1DLH X-ray 2.8Å A/D=28-207.
1FV1 X-ray 1.9Å A/D=26-206.
1FYT X-ray 2.6Å A=26-206.
1H15 X-ray 3.1Å A/D=26-207.
1HQR X-ray 3.2Å A=26-206.
1HXY X-ray 2.6Å A=26-207.
1J8H X-ray 2.4Å A=26-206.
1JWM X-ray 2.7Å A=26-207.
1JWS X-ray 2.6Å A=26-207.
1JWU X-ray 2.3Å A=26-207.
1KG0 X-ray 2.6Å A=28-207.
1KLG X-ray 2.4Å A=29-205.
1KLU X-ray 1.9Å A=29-207.
1LO5 X-ray 3.2Å A=26-207.
1PYW X-ray 2.1Å A=26-207.
1R5I X-ray 2.6Å A/E=26-206.
1SEB X-ray 2.7Å A/E=26-206.
1SJE X-ray 2.4Å A=28-207.
1SJH X-ray 2.2Å A=28-207.
1T5W X-ray 2.4Å A/D=27-206.
1T5X X-ray 2.5Å A=27-207.
1YMM X-ray 3.5Å A=26-216.
1ZGL X-ray 2.8Å A/D/G/J=26-206.
2FSE X-ray 3.1Å A/C=29-205.
2G9H X-ray 2.0Å A=26-207.
2IAM X-ray 2.8Å A=26-207.
2IAN X-ray 2.8Å A/F/K/P=26-207.
2ICW X-ray 2.4Å A/D=28-206.
2IPK X-ray 2.3Å A=26-207.
2OJE X-ray 3.0Å A/E=27-206.
2Q6W X-ray 2.2Å A/D=26-207.
2SEB X-ray 2.5Å A=26-206.
2WBJ X-ray 3.0Å A/E=26-218.
2XN9 X-ray 2.3Å D=26-207.
3C5J X-ray 1.8Å A=26-206.
3L6F X-ray 2.1Å A=26-207.
3O6F X-ray 2.8Å A/E=26-207.
3PDO X-ray 1.9Å A=26-217.
3PGC X-ray 2.6Å A/D=26-217.
3PGD X-ray 2.7Å A/D=26-217.
3QXA X-ray 2.7Å A/D=26-207.
3QXD X-ray 2.3Å A/D=26-207.
3S4S X-ray 2.4Å A/D=26-207.
3S5L X-ray 2.1Å A/D=26-207.
3T0E X-ray 4.0Å A=26-207.
4AEN X-ray 2.2Å A=26-217.
4AH2 X-ray 2.3Å A=26-217.
4C56 X-ray 2.9Å D/J=26-207.
4E41 X-ray 2.6Å A/F=26-207.
4FQX X-ray 2.6Å A=26-216.
4GBX X-ray 3.0Å A=26-216.
4H1L X-ray 3.3Å A/D=28-205.
4H25 X-ray 2.2Å A/D=28-207.
4H26 X-ray 2.5Å A/D=28-206.
4I5B X-ray 2.1Å A/D=27-213.
4IS6 X-ray 2.5Å A=26-207.
4MCY X-ray 2.3Å A=26-206.
4MCZ X-ray 2.4Å A=26-206.
4MD0 X-ray 2.1Å A=26-206.
4MD4 X-ray 1.9Å A=26-206.
4MD5 X-ray 1.6Å A=26-206.
4MDI X-ray 2.0Å A=26-206.
4MDJ X-ray 1.7Å A=26-206.
4OV5 X-ray 2.2Å A/D/G/J/M/P=26-207.
4X5W X-ray 1.3Å A=26-217.
4X5X X-ray 3.2Å A/C=26-217.
4Y19 X-ray 2.5Å A=26-206.
4Y1A X-ray 4.0Å A=26-206.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Pr55(Gag) relocalizes 12202216
Envelope surface glycoprotein gp120 downregulates 23100517
Envelope surface glycoprotein gp120 interacts with 1869305
Pr55(Gag) relocalized by 16973583
Nef inhibits 11593029
Pr55(Gag) co-localizes with 12230470
capsid downregulates 1905983
Tat upregulates 11751963
Envelope surface glycoprotein gp120 inhibits 2543930
Pr55(Gag) downregulates 24505475
Pr55(Gag) upregulates 18945465
capsid co-localizes with 25240755
Envelope surface glycoprotein gp160; precursor interacts with 8450224
Envelope transmembrane glycoprotein gp41 incorporates 10729169
Nef binds 17411376
Envelope surface glycoprotein gp160; precursor associates with 3489470
Nef downregulates 12970439
Pr55(Gag) regulated by 22860026
Envelope surface glycoprotein gp120 upregulates 15784911
Tat downregulates 10661406
Vpu modulates 17959659
Envelope transmembrane glycoprotein gp41 upregulates 8084338

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04145 Phagosome - Homo sapiens (human)
hsa04514 Cell adhesion molecules (CAMs) - Homo sapiens (human)
hsa04612 Antigen processing and presentation - Homo sapiens (human)
hsa04640 Hematopoietic cell lineage - Homo sapiens (human)
hsa04658 Th1 and Th2 cell differentiation - Homo sapiens (human)
hsa04659 Th17 cell differentiation - Homo sapiens (human)
hsa04672 Intestinal immune network for IgA production - Homo sapiens (human)
hsa04940 Type I diabetes mellitus - Homo sapiens (human)
hsa05140 Leishmaniasis - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05150 Staphylococcus aureus infection - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05310 Asthma - Homo sapiens (human)
hsa05320 Autoimmune thyroid disease - Homo sapiens (human)
hsa05321 Inflammatory bowel disease (IBD) - Homo sapiens (human)
hsa05322 Systemic lupus erythematosus - Homo sapiens (human)
hsa05323 Rheumatoid arthritis - Homo sapiens (human)
hsa05330 Allograft rejection - Homo sapiens (human)
hsa05332 Graft-versus-host disease - Homo sapiens (human)
hsa05416 Viral myocarditis - Homo sapiens (human)