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DMA_HUMAN
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   03-AUG-2022, entry version 190.
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   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; P28067; -.
DR   PeptideAtlas; P28067; -.
DR   PRIDE; P28067; -.
DR   ProteomicsDB; 54442; -.
DR   Antibodypedia; 2402; 386 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   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 98 other tissues.
DR   ExpressionAtlas; P28067; baseline and differential.
DR   Genevisible; P28067; HS.
DR   GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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: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:0050870; P:positive regulation of T cell activation; IBA:GO_Central.
DR   Gene3D; 2.60.40.10; -; 1.
DR   Gene3D; 3.10.320.10; -; 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   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; SSF48726; 1.
DR   SUPFAM; SSF54452; SSF54452; 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
 
 
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