Human Gene HLA-DPA1 (uc021zqp.1) Description and Page Index
Description: Homo sapiens major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1), transcript variant 2, mRNA. RefSeq Summary (NM_001242524): HLA-DPA1 belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta (DPB) chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: chr6_mann_hap4:4,489,886-4,506,101 Size: 16,216 Total Exon Count: 6 Strand: - Coding Region Position: chr6_mann_hap4:4,493,967-4,498,887 Size: 4,921 Coding Exon Count: 4
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Comments and Description Text from UniProtKB
ID:DPA1_HUMAN DESCRIPTION: RecName: Full=HLA class II histocompatibility antigen, DP alpha 1 chain; AltName: Full=DP(W3); AltName: Full=DP(W4); AltName: Full=HLA-SB alpha chain; AltName: Full=MHC class II DP3-alpha; AltName: Full=MHC class II DPA1; Flags: Precursor; 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. SUBCELLULAR LOCATION: Cell 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. 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. POLYMORPHISM: The following alleles of DPA1 are known: DPA1*01:03, DPA1*01:04, DPA1*01:05, DPA1*01:06, DPA1*01:07, DPA1*01:08, DPA1*01:09, DPA1*01:10, DPA1*02:01, DPA1*02:02, DPA1*02:03, DPA1*02:04, DPA1*03:01, DPA1*03:02, DPA1*03:03, DPA1*04:01 The sequence shown is that of DPA1*01:03. SIMILARITY: Belongs to the MHC class II family. SIMILARITY: Contains 1 Ig-like C1-type (immunoglobulin-like) domain. SEQUENCE CAUTION: Sequence=AAC64233.1; Type=Erroneous gene model prediction; Sequence=AAD42927.1; Type=Erroneous gene model prediction;
Genetic Association Studies of Complex Diseases and Disorders
Asthma Emiko Noguchi et al. PLoS genetics 2011, Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations., PLoS genetics.
cardiomyopathy Liu, W. et al. 2006, Association of HLA class II DRB1, DPA1 and DPB1 polymorphism with genetic susceptibility to idiopathic dilated cardiomyopathy in Chinese Han nationality, Autoimmunity 2006 39(6) 461-7.
cholestasis Zhang, L. et al. 2003, [Human leucocyte antigen-DPA1 polymorphism distribution in Chengdu Chinese families with intrahepatic cholestasis of pregnancy], Sichuan da xue xue bao Yi xue ban. 2003 Jul;34(3):530-2.
It is unlikely that an HLA-DPA1 allele is primarily associated with susceptibility or resistance to ICP.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P20036
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
X00457 - Human mRNA for SB classII histocompatibility antigen alpha-chain. AB209058 - Homo sapiens mRNA for HLA-DPA1 protein variant protein. BC009956 - Homo sapiens major histocompatibility complex, class II, DP alpha 1, mRNA (cDNA clone MGC:14114 IMAGE:4309471), complete cds. AK292709 - Homo sapiens cDNA FLJ75222 complete cds, highly similar to Homo sapiens major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1), mRNA. M27487 - Homo sapiens MHC class II DPw3-alpha-1 chain mRNA, complete cds. CU679537 - Synthetic construct Homo sapiens gateway clone IMAGE:100018648 5' read HLA-DPA1 mRNA. DQ893463 - Synthetic construct clone IMAGE:100006093; FLH193286.01X; RZPDo839E0878D major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) gene, encodes complete protein. DQ896324 - Synthetic construct Homo sapiens clone IMAGE:100010784; FLH193282.01L; RZPDo839E0868D major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) gene, encodes complete protein. AB590198 - Synthetic construct DNA, clone: pFN21AE1515, Homo sapiens HLA-DPA1 gene for major histocompatibility complex, class II, DP alpha 1, without stop codon, in Flexi system. CU680547 - Synthetic construct Homo sapiens gateway clone IMAGE:100023440 3' read HLA-DPB1 mRNA.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04514 - Cell adhesion molecules (CAMs) hsa04612 - Antigen processing and presentation hsa04672 - Intestinal immune network for IgA production hsa04940 - Type I diabetes mellitus hsa05140 - Leishmaniasis hsa05310 - Asthma hsa05320 - Autoimmune thyroid disease hsa05322 - Systemic lupus erythematosus hsa05330 - Allograft rejection hsa05332 - Graft-versus-host disease hsa05416 - Viral myocarditis