ID DMA_HUMAN Reviewed; 261 AA.
AC P28067; Q29639; Q29640;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 24-JAN-2024, entry version 198.
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].
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 (2.5 ANGSTROMS) OF 27-230 IN COMPLEX WITH DMB,
RP FUNCTION, SUBUNIT, AND DISULFIDE 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 (2.27 ANGSTROMS) OF 27-229 IN COMPLEX WITH DMB,
RP FUNCTION, SUBUNIT, AND DISULFIDE 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 (2.60 ANGSTROMS) OF 27-225 IN COMPLEX WITH MHCII,
RP SUBUNIT, DISULFIDE BOND, GLYCOSYLATION AT ASN-41, FUNCTION, AND MUTAGENESIS
RP OF ARG-124; PHE-126; 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.
CC -!- SIMILARITY: Belongs to the MHC class II family. {ECO:0000305}.
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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 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 PDBsum; 1HDM; -.
DR PDBsum; 2BC4; -.
DR PDBsum; 4FQX; -.
DR PDBsum; 4GBX; -.
DR AlphaFoldDB; P28067; -.
DR SMR; P28067; -.
DR DIP; DIP-6184N; -.
DR IntAct; P28067; 10.
DR MINT; P28067; -.
DR STRING; 9606.ENSP00000363976; -.
DR GlyCosmos; P28067; 1 site, No reported glycans.
DR GlyGen; P28067; 1 site.
DR iPTMnet; P28067; -.
DR PhosphoSitePlus; P28067; -.
DR BioMuta; HLA-DMA; -.
DR DMDM; 133158; -.
DR EPD; P28067; -.
DR jPOST; P28067; -.
DR MassIVE; P28067; -.
DR MaxQB; P28067; -.
DR PaxDb; 9606-ENSP00000363976; -.
DR PeptideAtlas; P28067; -.
DR ProteomicsDB; 54442; -.
DR Antibodypedia; 2402; 395 antibodies from 33 providers.
DR Ensembl; ENST00000374843.9; ENSP00000363976.4; ENSG00000204257.15.
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 MANE-Select; ENST00000374843.9; ENSP00000363976.4; NM_006120.4; NP_006111.2.
DR AGR; HGNC:4934; -.
DR GeneCards; HLA-DMA; -.
DR HGNC; HGNC:4934; HLA-DMA.
DR HPA; ENSG00000204257; Tissue enhanced (lymphoid).
DR MIM; 142855; gene.
DR neXtProt; NX_P28067; -.
DR VEuPathDB; HostDB:ENSG00000204257; -.
DR eggNOG; ENOG502S6RX; Eukaryota.
DR HOGENOM; CLU_069380_1_0_1; -.
DR InParanoid; P28067; -.
DR PhylomeDB; P28067; -.
DR TreeFam; TF333797; -.
DR PathwayCommons; P28067; -.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR SignaLink; P28067; -.
DR SIGNOR; P28067; -.
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 Genevisible; P28067; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
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:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; IBA:GO_Central.
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 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; 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; Reference proteome; Signal;
KW 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="H -> Q (in allele DMA*01:03 and allele DMA*01:04)"
FT /id="VAR_016746"
FT VARIANT 163
FT /note="D -> H (in allele DMA*01:03 and allele DMA*01:04)"
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"
SQ SEQUENCE 261 AA; 29194 MW; 1986C3C1989F02E9 CRC64;
MGHEQNQGAA LLQMLPLLWL LPHSWAVPEA PTPMWPDDLQ NHTFLHTVYC QDGSPSVGLS
EAYDEDQLFF FDFSQNTRVP RLPEFADWAQ EQGDAPAILF DKEFCEWMIQ QIGPKLDGKI
PVSRGFPIAE VFTLKPLEFG KPNTLVCFVS NLFPPMLTVN WHDHSVPVEG FGPTFVSAVD
GLSFQAFSYL NFTPEPSDIF SCIVTHEIDR YTAIAYWVPR NALPSDLLEN VLCGVAFGLG
VLGIIVGIVL IIYFRKPCSG D
//
