ID DMA_HUMAN Reviewed; 261 AA. AC P28067; Q29639; Q29640; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 27-NOV-2024, sequence version 2. DT 04-NOV-2026, entry version 209. DE RecName: Full=HLA class II histocompatibility antigen, DM alpha chain; DE AltName: Full=MHC class II antigen DMA; DE AltName: Full=Really interesting new gene 6 protein; DE Flags: Precursor; GN Name=HLA-DMA; Synonyms=DMA, RING6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DMA*01:01). RX PubMed=1922365; DOI=10.1038/353571a0; RA Kelly A.P., Monaco J.J., Cho S., Trowsdale J.; RT "A new human HLA class II-related locus, DM."; RL Nature 353:571-573(1991). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELE DMA*01:01). RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 31-218 (ALLELE DMA*01:02). RX PubMed=8225438; DOI=10.1007/bf00171797; RA Sanderson F., Powis S.H., Kelly A.P., Trowsdale J.; RT "Limited polymorphism in HLA-DM does not involve the peptide binding RT groove."; RL Immunogenetics 39:56-58(1994). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 125-217 (ALLELES DMA*01:03 AND RP DMA*01:04). RX PubMed=8026867; DOI=10.1007/bf00188184; RA Carrington M., Harding A.; RT "Sequence analysis of two novel HLA-DMA alleles."; RL Immunogenetics 40:165-165(1994). RN [5] RP FUNCTION. RX PubMed=8849454; DOI=10.1126/science.274.5287.618; RA Weber D.A., Evavold B.D., Jensen P.E.; RT "Enhanced dissociation of HLA-DR-bound peptides in the presence of HLA- RT DM."; RL Science 274:618-620(1996). RN [6] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH DMB, FUNCTION, SUBUNIT, AND DISULFIDE RP BONDS. RX PubMed=9768757; DOI=10.1016/s1074-7613(00)80620-2; RA Mosyak L., Zaller D.M., Wiley D.C.; RT "The structure of HLA-DM, the peptide exchange catalyst that loads antigen RT onto class II MHC molecules during antigen presentation."; RL Immunity 9:377-383(1998). RN [7] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH DMB, FUNCTION, SUBUNIT, AND DISULFIDE RP BONDS. RX PubMed=16547258; DOI=10.4049/jimmunol.176.7.4208; RA Nicholson M.J., Moradi B., Seth N.P., Xing X., Cuny G.D., Stein R.L., RA Wucherpfennig K.W.; RT "Small molecules that enhance the catalytic efficiency of HLA-DM."; RL J. Immunol. 176:4208-4220(2006). RN [8] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH MHCII, SUBUNIT, DISULFIDE BOND, RP GLYCOSYLATION AT ASN-41, FUNCTION, AND MUTAGENESIS OF ARG-124; PHE-126; RP ASN-151; ILE-199 AND ARG-220. RX PubMed=23260142; DOI=10.1016/j.cell.2012.11.025; RA Pos W., Sethi D.K., Call M.J., Schulze M.S., Anders A.K., Pyrdol J., RA Wucherpfennig K.W.; RT "Crystal structure of the HLA-DM-HLA-DR1 complex defines mechanisms for RT rapid peptide selection."; RL Cell 151:1557-1568(2012). CC -!- FUNCTION: Plays a critical role in catalyzing the release of class II- CC associated invariant chain peptide (CLIP) from newly synthesized MHC CC class II molecules and freeing the peptide binding site for acquisition CC of antigenic peptides. In B-cells, the interaction between HLA-DM and CC MHC class II molecules is regulated by HLA-DO. CC {ECO:0000269|PubMed:16547258, ECO:0000269|PubMed:23260142, CC ECO:0000269|PubMed:8849454, ECO:0000269|PubMed:9768757}. CC -!- SUBUNIT: Heterodimer of an alpha chain (DMA) and a beta chain (DMB) CC (PubMed:16547258, PubMed:9768757). Interacts with MHCII; this CC interaction mediates rapid selection of high-affinity peptides in a pH- CC dependent manner, with an optimum at pH 5.5 (PubMed:23260142). CC {ECO:0000269|PubMed:16547258, ECO:0000269|PubMed:23260142, CC ECO:0000269|PubMed:9768757}. CC -!- INTERACTION: CC P28067; P28068: HLA-DMB; NbExp=22; IntAct=EBI-3865396, EBI-2877138; CC -!- SUBCELLULAR LOCATION: Late endosome membrane; Single-pass type I CC membrane protein. Lysosome membrane; Single-pass type I membrane CC protein. Note=Localizes to late endocytic compartment. Associates with CC lysosome membranes. CC -!- POLYMORPHISM: The following alleles of DMA are known: DMA*01:01, CC DMA*01:02, DMA*01:03 (DMA3.2) and DMA*01:04 (DMA3.4). The sequence CC shown is that of DMA*01:01. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the MHC class II family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X62744; CAA44606.1; -; mRNA. DR EMBL; AL935042; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z24753; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U04878; AAA56994.1; -; Genomic_DNA. DR EMBL; U04877; AAA56993.1; -; Genomic_DNA. DR CCDS; CCDS4761.1; -. DR PIR; I38490; I38490. DR PIR; S17886; S17886. DR RefSeq; NP_006111.2; NM_006120.4. DR PDB; 1HDM; X-ray; 2.50 A; A=27-230. DR PDB; 2BC4; X-ray; 2.27 A; A/C=27-229. DR PDB; 4FQX; X-ray; 2.60 A; C=27-225. DR PDB; 4GBX; X-ray; 3.00 A; C=27-225. DR AlphaFoldDB; P28067; -. DR SMR; P28067; -. DR DIP; DIP-6184N; -. DR FunCoup; P28067; 91. DR IntAct; P28067; 10. DR NDEx; IQUERY-CP-HLA-DMA; 7 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000363976; -. DR GlyCosmos; P28067; 2 sites, No reported glycans. DR GlyGen; P28067; 2 sites. DR iPTMnet; P28067; -. DR PhosphoSitePlus; P28067; -. DR BioMuta; HLA-DMA; -. DR DMDM; 133158; -. DR jPOST; P28067; -. DR MassIVE; P28067; -. DR PaxDb; 9606-ENSP00000363976; -. DR PeptideAtlas; P28067; -. DR ProteomicsDB; 54442; -. DR Antibodypedia; 2402; 395 antibodies from 34 providers. DR Ensembl; ENST00000374843.9; ENSP00000363976.4; ENSG00000204257.16. DR Ensembl; ENST00000383230.8; ENSP00000372717.4; ENSG00000243215.7. DR Ensembl; ENST00000434337.6; ENSP00000407198.2; ENSG00000242361.7. DR Ensembl; ENST00000441375.6; ENSP00000410591.2; ENSG00000239463.7. DR Ensembl; ENST00000450601.6; ENSP00000392842.2; ENSG00000242685.7. DR Ensembl; ENST00000452615.6; ENSP00000395349.2; ENSG00000243189.7. DR Ensembl; ENST00000453490.6; ENSP00000404018.2; ENSG00000243719.7. DR GeneID; 3108; -. DR KEGG; hsa:3108; -. DR MANE-Select; ENST00000374843.9; ENSP00000363976.4; NM_006120.4; NP_006111.2. DR AGR; HGNC:4934; -. DR CTD; 3108; -. DR DisGeNET; 3108; -. DR GeneCards; HLA-DMA; -. DR HGNC; HGNC:4934; HLA-DMA. DR HPA; ENSG00000204257; Tissue enhanced (lymphoid). DR MIM; 142855; gene. DR OpenTargets; ENSG00000204257; -. DR VEuPathDB; HostDB:ENSG00000204257; -. DR eggNOG; ENOG502S6RX; Eukaryota. DR GeneTree; ENSGT00940000161157; -. DR HOGENOM; CLU_069380_1_0_1; -. DR InParanoid; P28067; -. DR OMA; ACVVTRQ; -. DR OrthoDB; 8935021at2759; -. DR PAN-GO; P28067; 9 GO annotations based on evolutionary models. DR PhylomeDB; P28067; -. DR PathwayCommons; P28067; -. DR Reactome; R-HSA-2132295; MHC class II antigen presentation. DR Reactome; R-HSA-9979719; Processing of antigen in germinal center B cells. DR SignaLink; P28067; -. DR SIGNOR; P28067; -. DR Agora; ENSG00000204257; -. DR ChiTaRS; HLA-DMA; human. DR EvolutionaryTrace; P28067; -. DR Pharos; P28067; Tbio. DR PRO; PR:P28067; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; P28067; protein. DR Bgee; ENSG00000204257; Expressed in granulocyte and 99 other cell types or tissues. DR ExpressionAtlas; P28067; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0042613; C:MHC class II protein complex; IDA:UniProtKB. DR GO; GO:0023026; F:MHC class II protein complex binding; IDA:UniProtKB. DR GO; GO:0042605; F:peptide antigen binding; IBA:GO_Central. DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; IBA:GO_Central. DR GO; GO:0006955; P:immune response; IEA:InterPro. DR GO; GO:0002503; P:peptide antigen assembly with MHC class II protein complex; IDA:UniProtKB. DR GO; GO:0050778; P:positive regulation of immune response; IBA:GO_Central. DR GO; GO:0050870; P:positive regulation of T cell activation; IBA:GO_Central. DR CDD; cd21009; IgC1_MHC_II_alpha_HLA-DM; 1. DR FunFam; 2.60.40.10:FF:000790; HLA class II histocompatibility antigen, DM alpha chain; 1. DR FunFam; 3.10.320.10:FF:000003; HLA class II histocompatibility antigen, DM alpha chain; 1. DR Gene3D; 3.10.320.10; Class II Histocompatibility Antigen, M Beta Chain, Chain B, domain 1; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003006; Ig/MHC_CS. DR InterPro; IPR003597; Ig_C1-set. DR InterPro; IPR050160; MHC/Immunoglobulin. DR InterPro; IPR011162; MHC_I/II-like_Ag-recog. DR InterPro; IPR014745; MHC_II_a/b_N. DR InterPro; IPR001003; MHC_II_a_N. DR PANTHER; PTHR19944:SF50; HLA CLASS II HISTOCOMPATIBILITY ANTIGEN, DM ALPHA CHAIN; 1. DR PANTHER; PTHR19944; MHC CLASS II-RELATED; 1. DR Pfam; PF07654; C1-set; 1. DR Pfam; PF00993; MHC_II_alpha; 1. DR SMART; SM00407; IGc1; 1. DR SMART; SM00920; MHC_II_alpha; 1. DR SUPFAM; SSF48726; Immunoglobulin; 1. DR SUPFAM; SSF54452; MHC antigen-recognition domain; 1. DR PROSITE; PS50835; IG_LIKE; 1. DR PROSITE; PS00290; IG_MHC; 1. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Disulfide bond; Endosome; Glycoprotein; KW Immunity; Lysosome; Membrane; MHC II; Proteomics identification; KW Reference proteome; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..26 FT /evidence="ECO:0000255" FT CHAIN 27..261 FT /note="HLA class II histocompatibility antigen, DM alpha FT chain" FT /id="PRO_0000018958" FT TOPO_DOM 27..233 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 234..254 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 255..261 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 121..215 FT /note="Ig-like C1-type" FT REGION 27..124 FT /note="Alpha-1" FT REGION 125..217 FT /note="Alpha-2" FT REGION 218..233 FT /note="Connecting peptide" FT /evidence="ECO:0000255" FT CARBOHYD 41 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:23260142, FT ECO:0007744|PDB:4GBX" FT DISULFID 50..105 FT /evidence="ECO:0000269|PubMed:23260142, FT ECO:0007744|PDB:4GBX" FT DISULFID 147..202 FT /evidence="ECO:0000269|PubMed:23260142, FT ECO:0007744|PDB:4GBX" FT VARIANT 162 FT /note="Q -> H" FT /id="VAR_016746" FT VARIANT 163 FT /note="H -> D" FT /id="VAR_016747" FT VARIANT 166 FT /note="V -> I (in allele DMA*01:02 and allele DMA*01:04; FT dbSNP:rs1063478)" FT /id="VAR_016748" FT VARIANT 181 FT /note="G -> A (in allele DMA*01:03; dbSNP:rs6926628)" FT /id="VAR_016749" FT VARIANT 210 FT /note="R -> C (in allele DMA*01:04; dbSNP:rs17214044)" FT /id="VAR_016750" FT VARIANT 210 FT /note="R -> H (in allele DMA*01:03; dbSNP:rs41555121)" FT /id="VAR_016751" FT VARIANT 235 FT /note="V -> M (in dbSNP:rs9469319)" FT /id="VAR_056544" FT MUTAGEN 124 FT /note="R->A: Decreases the interaction with MHCII and FT peptide exchange; when associated with A-220." FT /evidence="ECO:0000269|PubMed:23260142" FT MUTAGEN 126 FT /note="F->A: Decreases the interaction with MHCII and FT peptide exchange." FT /evidence="ECO:0000269|PubMed:23260142" FT MUTAGEN 151 FT /note="N->A,R: Abrogates the interaction with MHCII and FT peptide exchange." FT /evidence="ECO:0000269|PubMed:23260142" FT MUTAGEN 199 FT /note="I->N: Decreases the interaction with MHCII and FT peptide exchange." FT /evidence="ECO:0000269|PubMed:23260142" FT MUTAGEN 220 FT /note="R->A: Decreases the interaction with MHCII and FT peptide exchange; when associated with A-124." FT /evidence="ECO:0000269|PubMed:23260142" FT STRAND 41..63 FT /evidence="ECO:0007829|PDB:2BC4" FT STRAND 66..72 FT /evidence="ECO:0007829|PDB:2BC4" FT TURN 73..76 FT /evidence="ECO:0007829|PDB:2BC4" FT STRAND 77..82 FT /evidence="ECO:0007829|PDB:2BC4" FT HELIX 83..85 FT /evidence="ECO:0007829|PDB:2BC4" FT HELIX 87..89 FT /evidence="ECO:0007829|PDB:2BC4" FT HELIX 95..110 FT /evidence="ECO:0007829|PDB:2BC4" FT TURN 114..116 FT /evidence="ECO:0007829|PDB:2BC4" FT TURN 117..119 FT /evidence="ECO:0007829|PDB:1HDM" FT STRAND 122..124 FT /evidence="ECO:0007829|PDB:4FQX" FT STRAND 128..135 FT /evidence="ECO:0007829|PDB:2BC4" FT STRAND 143..155 FT /evidence="ECO:0007829|PDB:2BC4" FT STRAND 157..163 FT /evidence="ECO:0007829|PDB:2BC4" FT STRAND 166..168 FT /evidence="ECO:0007829|PDB:2BC4" FT STRAND 175..179 FT /evidence="ECO:0007829|PDB:2BC4" FT TURN 180..182 FT /evidence="ECO:0007829|PDB:2BC4" FT STRAND 183..192 FT /evidence="ECO:0007829|PDB:2BC4" FT STRAND 200..206 FT /evidence="ECO:0007829|PDB:2BC4" FT TURN 207..210 FT /evidence="ECO:0007829|PDB:2BC4" FT STRAND 211..217 FT /evidence="ECO:0007829|PDB:2BC4" FT HELIX 222..225 FT /evidence="ECO:0007829|PDB:2BC4" SQ SEQUENCE 261 AA; 29207 MW; BAAB2528874DFFC6 CRC64; MGHEQNQGAA LLQMLPLLWL LPHSWAVPEA PTPMWPDDLQ NHTFLHTVYC QDGSPSVGLS EAYDEDQLFF FDFSQNTRVP RLPEFADWAQ EQGDAPAILF DKEFCEWMIQ QIGPKLDGKI PVSRGFPIAE VFTLKPLEFG KPNTLVCFVS NLFPPMLTVN WQHHSVPVEG FGPTFVSAVD GLSFQAFSYL NFTPEPSDIF SCIVTHEIDR YTAIAYWVPR NALPSDLLEN VLCGVAFGLG VLGIIVGIVL IIYFRKPCSG D //