DRA_HUMAN » HLA class II histocompatibility antigen, DR alpha chain

DRA_HUMAN » HLA class II histocompatibility antigen, DR alpha chain
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
DRA_HUMAN » HLA class II histocompatibility antigen, DR alpha chain » MHC class II antigen DRA;
Hydrophobic Thickness 35.2 ± 3.0 Å
Tilt Angle 30 ± 0°
ΔGtransfer -24.1 kcal/mol
ΔGfold -15.0 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome
Topology Out
TM Segments 215-242 (212-245)
Pathways

Allograft rejection (KEGG)

Antigen processing and presentation (KEGG)

Asthma (KEGG)

Autoimmune thyroid disease (KEGG)

Cell adhesion molecules (KEGG)

Epstein-Barr virus infection (KEGG)

Graft-versus-host disease (KEGG)

Hematopoietic cell lineage (KEGG)

Herpes simplex infection (KEGG)

HTLV-I infection (KEGG)

Immune System (Reactome)

Influenza A (KEGG)

Intestinal immune network for IgA production (KEGG)

Leishmaniasis (KEGG)

Phagosome (KEGG)

Rheumatoid arthritis (KEGG)

Staphylococcus aureus infection (KEGG)

Systemic lupus erythematosus (KEGG)

Toxoplasmosis (KEGG)

Tuberculosis (KEGG)

Type I diabetes mellitus (KEGG)

Viral myocarditis (KEGG)

PDB 2fse (A/C=29-205), 4ov5 (A/D...=26-207), 1zgl (A/D/G/J=26-206), 1aqd (A/D/G/J=26-217), 1fv1 (A/D=26-206), 3s4s (A/D=26-207), 2q6w (A/D=26-207), 3qxa (A/D=26-207), 3qxd (A/D=26-207), 3s5l (A/D=26-207), 1h15 (A/D=26-207), 3pgc (A/D=26-217), 3pgd (A/D=26-217), 1bx2 (A/D=27-206), 1t5w (A/D=27-206), 4i5b (A/D=27-213), 4h1l (A/D=28-205), 4h26 (A/D=28-206), 2icw (A/D=28-206), 4h25 (A/D=28-207), 1dlh (A/D=28-207), 1r5i (A/E=26-206), 1seb (A/E=26-206), 3o6f (A/E=26-207), 2wbj (A/E=26-218), 2oje (A/E=27-206), 2ian (A/F/K/P=26-207), 4e41 (A/F=26-207), 3c5j (A=26-206), 2seb (A=26-206), 4mdj (A=26-206), 4mdi (A=26-206), 1d5z (A=26-206), 4md5 (A=26-206), 4mcy (A=26-206), 4mcz (A=26-206), 4md0 (A=26-206), 4md4 (A=26-206), 1d6e (A=26-206), 1fyt (A=26-206), 1hqr (A=26-206), 1d5m (A=26-206), 1j8h (A=26-206), 1d5x (A=26-206), 2iam (A=26-207), 1hxy (A=26-207), 1jwm (A=26-207), 4is6 (A=26-207), 1jws (A=26-207), 1jwu (A=26-207), 3t0e (A=26-207), 1pyw (A=26-207), 2ipk (A=26-207), 2g9h (A=26-207), 3l6f (A=26-207), 1lo5 (A=26-207), 4fqx (A=26-216), 4gbx (A=26-216), 1ymm (A=26-216), 4aen (A=26-217), 4ah2 (A=26-217), 3pdo (A=26-217), 1t5x (A=27-207), 1sje (A=28-207), 1sjh (A=28-207), 1kg0 (A=28-207), 1klg (A=29-205), 1klu (A=29-207), 1a6a (A=30-205), 4c56 (D/J=26-207), 2xn9 (D=26-207)
OPM none
Complexes

DRA:2B11:CD4:HEMA_HUMAN

2B14:TRBC2:DRA:TCA:CD4_HUMAN

MBP:DRB5:DRA:TCA:TRBC1_HUMAN

DRA:2B11:TCA:TRBC1:HEMA_HUMAN

DRA:2B11:TCA:TRBC1:TPIS_HUMAN

HEMA:ETXH:DRA:2B11:TCA:TRBC1_HUMAN

2B14:DRA:TCA:TRBC1:HEMA_HUMAN

MBP:2B1F:DRA:TCA:TRBC1_HUMAN

TRBC2:DRA:2B11:TCA:ETXB:HEMA_HUMAN

2B14:TRBC2:DRA:TCA_HUMAN

DRA:2B11:ETXB_HUMAN

HG2A:DRA:2B11_HUMAN

2B13:HG2A:DRA_HUMAN

ENTC3:DRA:2B11_HUMAN

ENTC3:DRA:2B11:TPIS_HUMAN

ENTC3:GAG:DRA:2B11_HUMAN

MIG1:ENTC3:DRA:2B11_HUMAN

A8CDU0:HEMA:ENTC3:DRA:2B11_HUMAN

CO2A1:DRA:2B11_HUMAN

DRA:2B11:1A02_HUMAN

HEMA:DRA:2B11_HUMAN

DRA:2B11:MAR1_HUMAN

GP42:DRA:2B11_HUMAN

MIG1:DRA:2B11_HUMAN

Q91LS8:Q48898:DRA:2B11_HUMAN

ETXA:DRA:2B11_HUMAN

HEMA:ETXH:DRA:2B11_HUMAN

HEMA:Q48898:DRA:2B11_HUMAN

HEMA:Q52T95:DRA:2B11_HUMAN

DPOL:DRB5:DRA_HUMAN

MBP:DRB5:DRA_HUMAN

EF1A2:Q96EB3:DRB3:DRA_HUMAN

L7MTK9:L7MTL0:DRB3:DRA_HUMAN

DRB3:ITB3:DRA_HUMAN

SPEC:MBP:DRB5:DRA_HUMAN

2B14:DRA:ETXB_HUMAN

CO2A1:2B14:DRA:ETXB_HUMAN

PMEL:2B14:DRA_HUMAN

PGCA:2B14:DRA_HUMAN

VIME:2B14:DRA_HUMAN

MBP:2B1F:DRA_HUMAN

2B1F:DRA_HUMAN

DMA:DMB:DRA:2B11_HUMAN

Interactions

1A02, Complex: DRA:2B11:1A02, PDBID: 1AQD

2B11, Complex: HEMA:DRA:2B11, PDBID: 1DLH, PubMed

2B13, Complex: HG2A:DRA:2B13.2B1F.2B1G, PubMed

2B14, Complex: 2B14:DRA:ETXB, PDBID: 1D5M

2B1F, Complex: MBP:2B1F:DRA, PDBID: 1BX2, PubMed

AT1B1, Complex: DRA:AT1B1, PubMed

CD1D, Complex: DRA:HG2A:CD1D:2B13.2B1F.2B1G, PubMed

CD38, Complex: 2B13.2B1F.2B1G:DRA:CD38, PubMed

DMA, Complex: DRA:DMA, PubMed

DMB, Complex: DRA:DMB, PubMed

DRB3, Complex: DRB3:ITB3:DRA, PDBID: 2q6w, PubMed

DRB5, Complex: MBP:DRB5:DRA, PDBID: 1fv1, PubMed

HG2A, Complex: 2B13:HG2A:DRA, PDBID: 1a6a, PubMed

TCA, Complex: DRA:2B11:TCA:TRBC1:HEMA, PDBID: 1FYT

Domains

AA: 29-108, PDBID: 1A6A, Subunit A, Seq Identity:100%, Class II histocompatibility antigen, alpha domain

AA: 112-195, PDBID: 1A6A, Subunit A, Seq Identity:100%, Immunoglobulin C1-set domain

AA: 201-253, PDBID: 1A6A, Subunit A, Seq Identity:100%, C1-set C-terminal domain

UniProt annotation for DRA_HUMAN » HLA class II histocompatibility antigen, DR alpha chain
FUNCTION: Binds 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.

SUBUNIT: Heterodimer of an alpha and a beta subunit; also referred as MHC class II molecule. In the endoplasmic reticulum (ER) it forms a heterononamer; 3 MHC class II molecules bind to a CD74 homotrimer (also known as invariant chain or HLA class II histocompatibility antigen gamma chain). In the endosomal/lysosomal system; CD74 undergoes sequential degradation by various proteases; leaving a small fragment termed CLIP on each MHC class II molecule. MHC class II molecule interacts with HLA_DM, and HLA_DO in B-cells, in order to release CLIP and facilitate the binding of antigenic peptides.

UniProt features for DRA_HUMAN » HLA class II histocompatibility antigen, DR alpha chain
SIGNAL 1 25
CHAIN 26 254 HLA class II histocompatibility antigen, DR alpha chain.
DOMAIN 112 204 Ig-like C1-type.
REGION 26 109 Alpha-1.
REGION 110 203 Alpha-2.
REGION 204 216 Connecting peptide.
DISULFID 132 188
CROSSLNK 244 244 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin).
Amino Acid Sequence for DRA_HUMAN » HLA class II histocompatibility antigen, DR alpha chain
MAISGVPVLG FFIIAVLMSA QESWAIKEEH VIIQAEFYLN PDQSGEFMFD FDGDEIFHVD MAKKETVWRL EEFGRFASFE AQGALANIAV DKANLEIMTK RSNYTPITNV PPEVTVLTNS PVELREPNVL ICFIDKFTPP VVNVTWLRNG KPVTTGVSET VFLPREDHLF RKFHYLPFLP STEDVYDCRV EHWGLDEPLL KHWEFDAPSP LPETTENVVC ALGLTVGLVG IIIGTIFIIK GVRKSNAAER RGPL