DRA_HUMAN
ID DRA_HUMAN Reviewed; 254 AA.
AC P01903; A2BET4; Q30160; Q6IAZ1; Q861I2; Q9TP70;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2021, sequence version 2.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=HLA class II histocompatibility antigen, DR alpha chain;
DE AltName: Full=MHC class II antigen DRA;
DE Flags: Precursor;
GN Name=HLA-DRA; Synonyms=HLA-DRA1;
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 DRA*01:01).
RX PubMed=6811954; DOI=10.1038/299750a0;
RA Lee J.S., Trowsdale J., Travers P.J., Carey J., Grosveld F., Jenkins J.,
RA Bodmer W.F.;
RT "Sequence of an HLA-DR alpha-chain cDNA clone and intron-exon organization
RT of the corresponding gene.";
RL Nature 299:750-752(1982).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRA*01:01).
RX PubMed=6416803; DOI=10.1089/dna.1983.2.175;
RA Kajimura Y., Toyoda H., Sato M., Miyakoshi S., Kaplan S.A., Ike Y.,
RA Goyert S.M., Silver J., Hawke D., Shively J.E., Suggs S.V., Wallace R.B.,
RA Itakura K.;
RT "Cloning the heavy chain of human HLA-DR antigen using synthetic
RT oligodeoxyribonucleotides as hybridization probes.";
RL DNA 2:175-182(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRA*01:02).
RX PubMed=2212658;
RA Koppelman B., Cresswell P.;
RT "Rapid nonlysosomal degradation of assembled HLA class II glycoproteins
RT incorporating a mutant DR alpha-chain.";
RL J. Immunol. 145:2730-2736(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE DRA*01:02).
RX PubMed=6324094; DOI=10.1093/nar/11.24.8663;
RA Schamboeck A., Korman A.J., Kamb A., Strominger J.L.;
RT "Organization of the transcriptional unit of a human class II
RT histocompatibility antigen: HLA-DR heavy chain.";
RL Nucleic Acids Res. 11:8663-8675(1983).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE DRA*01:01).
RX PubMed=6304715; DOI=10.1073/pnas.80.12.3543;
RA Das H.K., Lawrance S.K., Weissman S.M.;
RT "Structure and nucleotide sequence of the heavy chain gene of HLA-DR.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:3543-3547(1983).
RN [6]
RP ERRATUM OF PUBMED:6304715, AND SEQUENCE REVISION.
RA Das H.K., Lawrance S.K., Weissman S.M.;
RL Proc. Natl. Acad. Sci. U.S.A. 80:7024-7024(1983).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE DRA*01:01).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELES DRA*01:01 AND
RP DRA*01:02).
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELE DRA*01:01).
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 32-202 AND 204-254, AND PROTEIN SEQUENCE OF
RP 26-60.
RX PubMed=6812963; DOI=10.1016/0092-8674(82)90021-6;
RA Larhammar D., Gustafsson K., Claesson L., Bill P., Wiman K., Schenning L.,
RA Sundelin J., Widmark E., Peterson P.A., Rask L.;
RT "Alpha chain of HLA-DR transplantation antigens is a member of the same
RT protein superfamily as the immunoglobulins.";
RL Cell 30:153-161(1982).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 29-254 (ALLELE DRA*01:02).
RX PubMed=6821129; DOI=10.1073/pnas.79.19.6013;
RA Korman A.J., Auffray C., Schamboeck A., Strominger J.L.;
RT "The amino acid sequence and gene organization of the heavy chain of the
RT HLA-DR antigen: homology to immunoglobulins.";
RL Proc. Natl. Acad. Sci. U.S.A. 79:6013-6017(1982).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 205-254 (ALLELE DRA*01:02).
RC TISSUE=Blood;
RX PubMed=12445311; DOI=10.1034/j.1399-0039.2002.600310.x;
RA Kralovicova J., Marsh S.G., Waller M.J., Hammarstrom L., Vorechovsky I.;
RT "The HLA-DRA*0102 allele: correct nucleotide sequence and associated HLA
RT haplotypes.";
RL Tissue Antigens 60:266-267(2002).
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELES DRA*01:01 AND DRA*01:02).
RC TISSUE=Blood, and Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [14]
RP PROTEIN SEQUENCE OF 26-204.
RX PubMed=6955253;
RA Yang C.-Y., Kratzin H., Gotz H., Thinnes F.P., Kruse T., Egert G.,
RA Pauly E., Kolbel S., Wernet P., Hilschmann N.;
RT "Primary structure of class II human histocompatibility antigens. 2nd
RT Communication. Amino acid sequence of the N-terminal 179 residues of the
RT alpha-chain of an HLA-Dw2/DR2 alloantigen.";
RL Hoppe-Seyler's Z. Physiol. Chem. 363:671-676(1982).
RN [15]
RP PROTEIN SEQUENCE OF 26-94.
RC TISSUE=B-cell;
RX PubMed=6600932; DOI=10.1021/bi00270a027;
RA Walker L.E., Hewick R., Hunkapiller M.W., Hood L.E., Dreyer W.J.,
RA Reisfeld R.A.;
RT "N-terminal amino acid sequences of the alpha and beta chains of HLA-DR1
RT and HLA-DR2 antigens.";
RL Biochemistry 22:185-188(1983).
RN [16]
RP FUNCTION, AND INTERACTION WITH STAPHYLOCOCCUS ENTEROTOXIN A/ (MICROBIAL
RP INFECTION).
RX PubMed=2658055; DOI=10.1126/science.2658055;
RA Mollick J.A., Cook R.G., Rich R.R.;
RT "Class II MHC molecules are specific receptors for staphylococcus
RT enterotoxin A.";
RL Science 244:817-820(1989).
RN [17]
RP INTERACTION WITH STAPHYLOCOCCUS AUREUS ENTEROTOXIN A/ENTA; B/ENTB; C1/ENTC1
RP AND D/ENTD (MICROBIAL INFECTION).
RX PubMed=2210803;
RA Dohlsten M., Lando P.A., Hedlund G., Trowsdale J., Kalland T.;
RT "Targeting of human cytotoxic T lymphocytes to MHC class II-expressing
RT cells by staphylococcal enterotoxins.";
RL Immunology 71:96-100(1990).
RN [18]
RP INTERACTION WITH CD74 HOMOTRIMER.
RX PubMed=7479981; DOI=10.1073/pnas.92.24.11289;
RA Park S.J., Sadegh-Nasseri S., Wiley D.C.;
RT "Invariant chain made in Escherichia coli has an exposed N-terminal segment
RT that blocks antigen binding to HLA-DR1 and a trimeric C-terminal segment
RT that binds empty HLA-DR1.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:11289-11293(1995).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CLIP AND HLA-DM
RP COMPLEX.
RX PubMed=9075930; DOI=10.1016/s1074-7613(00)80332-5;
RA Kropshofer H., Arndt S.O., Moldenhauer G., Haemmerling G.J., Vogt A.B.;
RT "HLA-DM acts as a molecular chaperone and rescues empty HLA-DR molecules at
RT lysosomal pH.";
RL Immunity 6:293-302(1997).
RN [20]
RP INTERACTION WITH HLA-DM COMPLEX AND CLIP, AND MUTAGENESIS OF GLU-65 AND
RP PHE-76.
RX PubMed=11070170; DOI=10.1016/s1074-7613(00)00051-0;
RA Doebele R.C., Busch R., Scott H.M., Pashine A., Mellins E.D.;
RT "Determination of the HLA-DM interaction site on HLA-DR molecules.";
RL Immunity 13:517-527(2000).
RN [21]
RP FUNCTION.
RX PubMed=15265931; DOI=10.4049/jimmunol.173.3.1966;
RA Shams H., Klucar P., Weis S.E., Lalvani A., Moonan P.K., Safi H., Wizel B.,
RA Ewer K., Nepom G.T., Lewinsohn D.M., Andersen P., Barnes P.F.;
RT "Characterization of a Mycobacterium tuberculosis peptide that is
RT recognized by human CD4+ and CD8+ T cells in the context of multiple HLA
RT alleles.";
RL J. Immunol. 173:1966-1977(2004).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15322540; DOI=10.1038/ni1108;
RA Roehn T.A., Boes M., Wolters D., Spindeldreher S., Mueller B., Langen H.,
RA Ploegh H., Vogt A.B., Kropshofer H.;
RT "Upregulation of the CLIP self peptide on mature dendritic cells
RT antagonizes T helper type 1 polarization.";
RL Nat. Immunol. 5:909-918(2004).
RN [23]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17182262; DOI=10.1016/j.immuni.2006.10.018;
RA Schmid D., Pypaert M., Muenz C.;
RT "Antigen-loading compartments for major histocompatibility complex class II
RT molecules continuously receive input from autophagosomes.";
RL Immunity 26:79-92(2007).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=18305173; DOI=10.1073/pnas.0708874105;
RA De Gassart A., Camosseto V., Thibodeau J., Ceppi M., Catalan N., Pierre P.,
RA Gatti E.;
RT "MHC class II stabilization at the surface of human dendritic cells is the
RT result of maturation-dependent MARCH I down-regulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:3491-3496(2008).
RN [25]
RP UBIQUITINATION AT LYS-244 BY MARCHF1 AND MARCHF8, MUTAGENESIS OF LYS-244,
RP AND SUBCELLULAR LOCATION.
RX PubMed=19117940; DOI=10.1074/jbc.m805736200;
RA Lapaque N., Jahnke M., Trowsdale J., Kelly A.P.;
RT "The HLA-DRalpha chain is modified by polyubiquitination.";
RL J. Biol. Chem. 284:7007-7016(2009).
RN [26]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-103 AND ASN-143.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [28]
RP FUNCTION.
RX PubMed=22327072; DOI=10.4049/jimmunol.1102190;
RA Kwok W.W., Tan V., Gillette L., Littell C.T., Soltis M.A., LaFond R.B.,
RA Yang J., James E.A., DeLong J.H.;
RT "Frequency of epitope-specific naive CD4(+) T cells correlates with
RT immunodominance in the human memory repertoire.";
RL J. Immunol. 188:2537-2544(2012).
RN [29]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23783831; DOI=10.1038/ncomms3039;
RA Adamopoulou E., Tenzer S., Hillen N., Klug P., Rota I.A., Tietz S.,
RA Gebhardt M., Stevanovic S., Schild H., Tolosa E., Melms A., Stoeckle C.;
RT "Exploring the MHC-peptide matrix of central tolerance in the human
RT thymus.";
RL Nat. Commun. 4:2039-2039(2013).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [31]
RP FUNCTION, AND INTERACTION WITH HLA-DM AND PEPTIDE.
RX PubMed=25413013; DOI=10.1038/ncomms6369;
RA Kim A., Hartman I.Z., Poore B., Boronina T., Cole R.N., Song N.,
RA Ciudad M.T., Caspi R.R., Jaraquemada D., Sadegh-Nasseri S.;
RT "Divergent paths for the selection of immunodominant epitopes from distinct
RT antigenic sources.";
RL Nat. Commun. 5:5369-5369(2014).
RN [32]
RP FUNCTION.
RX PubMed=27591323; DOI=10.4049/jimmunol.1600663;
RA Muehling L.M., Mai D.T., Kwok W.W., Heymann P.W., Pomes A., Woodfolk J.A.;
RT "Circulating Memory CD4+ T Cells Target Conserved Epitopes of Rhinovirus
RT Capsid Proteins and Respond Rapidly to Experimental Infection in Humans.";
RL J. Immunol. 197:3214-3224(2016).
RN [33]
RP INTERACTION WITH CD4, DOMAIN, AND MUTAGENESIS OF THR-115 AND LEU-117.
RX PubMed=27114505; DOI=10.1073/pnas.1513918113;
RA Joensson P., Southcombe J.H., Santos A.M., Huo J., Fernandes R.A.,
RA McColl J., Lever M., Evans E.J., Hudson A., Chang V.T., Hanke T.,
RA Godkin A., Dunne P.D., Horrocks M.H., Palayret M., Screaton G.R.,
RA Petersen J., Rossjohn J., Fugger L., Dushek O., Xu X.N., Davis S.J.,
RA Klenerman D.;
RT "Remarkably low affinity of CD4/peptide-major histocompatibility complex
RT class II protein interactions.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:5682-5687(2016).
RN [34]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=31495665; DOI=10.1016/j.immuni.2019.08.012;
RA Abelin J.G., Harjanto D., Malloy M., Suri P., Colson T., Goulding S.P.,
RA Creech A.L., Serrano L.R., Nasir G., Nasrullah Y., McGann C.D., Velez D.,
RA Ting Y.S., Poran A., Rothenberg D.A., Chhangawala S., Rubinsteyn A.,
RA Hammerbacher J., Gaynor R.B., Fritsch E.F., Greshock J., Oslund R.C.,
RA Barthelme D., Addona T.A., Arieta C.M., Rooney M.S.;
RT "Defining HLA-II Ligand Processing and Binding Rules with Mass Spectrometry
RT Enhances Cancer Epitope Prediction.";
RL Immunity 0:0-0(2019).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 28-207.
RX PubMed=8316295; DOI=10.1038/364033a0;
RA Brown J.H., Jardetzky T.S., Gorga J.C., Stern L.J., Urban R.G.,
RA Strominger J.L., Wiley D.C.;
RT "Three-dimensional structure of the human class II histocompatibility
RT antigen HLA-DR1.";
RL Nature 364:33-39(1993).
RN [36] {ECO:0007744|PDB:1DLH}
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 28-207 IN COMPLEX WITH
RP HLA-DRB1*01:01 AND IAV PEPTIDE, FUNCTION, AND DOMAIN.
RX PubMed=8145819; DOI=10.1038/368215a0;
RA Stern L.J., Brown J.H., Jardetzky T.J., Gorga J.C., Urban R.G.,
RA Strominger J.L., Wiley D.C.;
RT "Crystal structure of the human class II MHC protein HLA-DR1 complexed with
RT an influenza virus peptide.";
RL Nature 368:215-221(1994).
RN [37] {ECO:0007744|PDB:1SEB}
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 26-206 IN COMPLEX WITH
RP STAPHYLOCOCCUS ENTEROTOXIN B/ENTB (MICROBIAL INFECTION).
RX PubMed=8152483; DOI=10.1038/368711a0;
RA Jardetzky T.S., Brown J.H., Gorga J.C., Stern L.J., Urban R.G., Chi Y.I.,
RA Stauffacher C., Strominger J.L., Wiley D.C.;
RT "Three-dimensional structure of a human class II histocompatibility
RT molecule complexed with superantigen.";
RL Nature 368:711-718(1994).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 30-205 IN COMPLEX WITH
RP HLA-DRB1*03:01 AND CD74 PEPTIDE (CLIP), SUBUNIT, GLYCOSYLATION AT ASN-103
RP AND ASN-143, AND DISULFIDE BOND.
RX PubMed=7477400; DOI=10.1038/378457a0;
RA Ghosh P., Amaya M., Mellins E., Wiley D.C.;
RT "The structure of an intermediate in class II MHC maturation: CLIP bound to
RT HLA-DR3.";
RL Nature 378:457-462(1995).
RN [39] {ECO:0007744|PDB:2SEB}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 26-206 IN COMPLEX WITH
RP HLA-DRB1*04:01 AND COL2A1 PEPTIDE, SUBUNIT, AND DOMAIN.
RX PubMed=9354468; DOI=10.1016/s1074-7613(00)80369-6;
RA Dessen A., Lawrence C.M., Cupo S., Zaller D.M., Wiley D.C.;
RT "X-ray crystal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a
RT peptide from human collagen II.";
RL Immunity 7:473-481(1997).
RN [40] {ECO:0007744|PDB:1BX2}
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 27-206 IN COMPLEX WITH
RP HLA-DRB1*15:01 AND MBP PEPTIDE, SUBUNIT, AND DOMAIN.
RX PubMed=9782128; DOI=10.1084/jem.188.8.1511;
RA Smith K.J., Pyrdol J., Gauthier L., Wiley D.C., Wucherpfennig K.W.;
RT "Crystal structure of HLA-DR2 (DRA*0101, DRB1*1501) complexed with a
RT peptide from human myelin basic protein.";
RL J. Exp. Med. 188:1511-1520(1998).
RN [41] {ECO:0007744|PDB:1FV1}
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 26-206 IN COMPLEX WITH
RP HLA-DRB5*01:01 AND MBP PEPTIDE, AND SUBUNIT.
RX PubMed=11080454; DOI=10.1006/jmbi.2000.4198;
RA Li Y., Li H., Martin R., Mariuzza R.A.;
RT "Structural basis for the binding of an immunodominant peptide from myelin
RT basic protein in different registers by two HLA-DR2 proteins.";
RL J. Mol. Biol. 304:177-188(2000).
RN [42] {ECO:0007744|PDB:1HXY}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 26-207, AND INTERACTION WITH
RP STAPHYLOCOCCUS ENTEROTOXIN H/ENTH (MICROBIAL INFECTION).
RX PubMed=11432818; DOI=10.1093/emboj/20.13.3306;
RA Petersson K., Haakansson M., Nilsson H., Forsberg G., Svensson L.A.,
RA Liljas A., Walse B.;
RT "Crystal structure of a superantigen bound to MHC class II displays zinc
RT and peptide dependence.";
RL EMBO J. 20:3306-3312(2001).
RN [43] {ECO:0007744|PDB:1HQR}
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 26-206 IN COMPLEX WITH
RP HLA-DRB5*01:01; MBP PEPTIDE AND STREPTOCOCCUS PYOGENES SPEC PEPTIDE,
RP SUBUNIT, AND DISULFIDE BOND.
RX PubMed=11163233; DOI=10.1016/s1074-7613(01)00092-9;
RA Li Y., Li H., Dimasi N., McCormick J.K., Martin R., Schuck P.,
RA Schlievert P.M., Mariuzza R.A.;
RT "Crystal structure of a superantigen bound to the high-affinity, zinc-
RT dependent site on MHC class II.";
RL Immunity 14:93-104(2001).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 28-207 IN COMPLEX WITH
RP HLA-DRB1*01:01 EPSTEIN-BARR VIRUS BZLF2/GP42 (MICROBIAL INFECTION).
RX PubMed=11864610; DOI=10.1016/s1097-2765(02)00465-3;
RA Mullen M.M., Haan K.M., Longnecker R., Jardetzky T.S.;
RT "Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II
RT receptor HLA-DR1.";
RL Mol. Cell 9:375-385(2002).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 26-207 IN COMPLEX WITH
RP HLA-DRB5*01:01 AND EPSTEIN-BARR VIRUS BALF5 PEPTIDE, SUBUNIT, AND DISULFIDE
RP BOND.
RX PubMed=12244309; DOI=10.1038/ni835;
RA Lang H.L.E., Jacobsen H., Ikemizu S., Andersson C., Harlos K., Madsen L.,
RA Hjorth P., Sondergaard L., Svejgaard A., Wucherpfennig K., Stuart D.I.,
RA Bell J.I., Jones E.Y., Fugger L.;
RT "A functional and structural basis for TCR cross-reactivity in multiple
RT sclerosis.";
RL Nat. Immunol. 3:940-943(2002).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 26-206 IN COMPLEX WITH
RP HLA-DRB5*01:01; MBP PEPTIDE AND TRAC, SUBUNIT, AND DISULFIDE BOND.
RX PubMed=16079912; DOI=10.1038/sj.emboj.7600771;
RA Li Y., Huang Y., Lue J., Quandt J.A., Martin R., Mariuzza R.A.;
RT "Structure of a human autoimmune TCR bound to a myelin basic protein self-
RT peptide and a multiple sclerosis-associated MHC class II molecule.";
RL EMBO J. 24:2968-2979(2005).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 26-207 IN COMPLEX WITH
RP HLA-DRB3*01:01 AND ITGB3 PEPTIDE (ALLOANTIGEN HPA-1A), SUBUNIT, DOMAIN, AND
RP DISULFIDE BOND.
RX PubMed=17583734; DOI=10.1016/j.jmb.2007.05.025;
RA Parry C.S., Gorski J., Stern L.J.;
RT "Crystallographic structure of the human leukocyte antigen DRA, DRB3*0101:
RT models of a directional alloimmune response and autoimmunity.";
RL J. Mol. Biol. 371:435-446(2007).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 26-207 IN COMPLEX WITH
RP HLA-DRB1*01:01 AND NEOANTIGEN, INTERACTION WITH TCR, AND FUNCTION.
RX PubMed=17334368; DOI=10.1038/ni1447;
RA Deng L., Langley R.J., Brown P.H., Xu G., Teng L., Wang Q., Gonzales M.I.,
RA Callender G.G., Nishimura M.I., Topalian S.L., Mariuzza R.A.;
RT "Structural basis for the recognition of mutant self by a tumor-specific,
RT MHC class II-restricted T cell receptor.";
RL Nat. Immunol. 8:398-408(2007).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 26-206 IN COMPLEX WITH
RP HLA-DRB3*03:01 AND EEF1A2 PEPTIDE, AND SUBUNIT.
RX PubMed=18697946; DOI=10.1073/pnas.0805810105;
RA Dai S., Crawford F., Marrack P., Kappler J.W.;
RT "The structure of HLA-DR52c: comparison to other HLA-DRB3 alleles.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:11893-11897(2008).
RN [50]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 26-207, AND INTERACTION WITH
RP STAPHYLOCOCCUS ENTEROTOXIN H/ENTH (MICROBIAL INFECTION).
RX PubMed=21081917; DOI=10.1038/ncomms1117;
RA Saline M., Roedstroem K.E., Fischer G., Orekhov V.Y., Karlsson B.G.,
RA Lindkvist-Petersson K.;
RT "The structure of superantigen complexed with TCR and MHC reveals novel
RT insights into superantigenic T cell activation.";
RL Nat. Commun. 1:119-119(2010).
RN [51]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 26-217 IN COMPLEX WITH
RP HLA-DRB1*01:01 AND CLIP PEPTIDE, AND SUBUNIT.
RX PubMed=21115828; DOI=10.1073/pnas.1014708107;
RA Gunther S., Schlundt A., Sticht J., Roske Y., Heinemann U.,
RA Wiesmuller K.H., Jung G., Falk K., Rotzschke O., Freund C.;
RT "Bidirectional binding of invariant chain peptides to an MHC class II
RT molecule.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:22219-22224(2010).
RN [52]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 26-216 IN COMPLEX WITH
RP HLA-DRB1*15:01; HLA-DM HETERODIMER AND IAV HA PEPTIDE, AND MUTAGENESIS OF
RP GLU-65; TRP-68; GLY-74; PHE-76; SER-78; PHE-79; GLU-80; GLN-82; PRO-121 AND
RP ARG-125.
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).
RN [53]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 26-206 IN COMPLEX WITH HLA-DRB1
RP AND PEPTIDE, AND FUNCTION.
RX PubMed=24190431; DOI=10.1084/jem.20131241;
RA Scally S.W., Petersen J., Law S.C., Dudek N.L., Nel H.J., Loh K.L.,
RA Wijeyewickrema L.C., Eckle S.B., van Heemst J., Pike R.N., McCluskey J.,
RA Toes R.E., La Gruta N.L., Purcell A.W., Reid H.H., Thomas R., Rossjohn J.;
RT "A molecular basis for the association of the HLA-DRB1 locus,
RT citrullination, and rheumatoid arthritis.";
RL J. Exp. Med. 210:2569-2582(2013).
RN [54]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 26-206 IN COMPLEX WITH HLA-DRB
RP AND HIV-1 GAG-POL PEPTIDE, FUNCTION, INTERACTION WITH TCR, SUBCELLULAR
RP LOCATION, MUTAGENESIS OF GLU-80 AND ALA-93, AND DOMAIN.
RX PubMed=29884618; DOI=10.1126/sciimmunol.aat0687;
RA Galperin M., Farenc C., Mukhopadhyay M., Jayasinghe D., Decroos A.,
RA Benati D., Tan L.L., Ciacchi L., Reid H.H., Rossjohn J., Chakrabarti L.A.,
RA Gras S.;
RT "CD4+ T cell-mediated HLA class II cross-restriction in HIV controllers.";
RL Sci. Immunol. 3:0-0(2018).
RN [55]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 27-206 IN COMPLEX WITH
RP HLA-DRB1*01:01 AND TPBG 5T4 PEPTIDE, SUBUNIT, AND DISULFIDE BOND.
RX PubMed=31619516; DOI=10.1074/jbc.ra119.009437;
RA MacLachlan B.J., Dolton G., Papakyriakou A., Greenshields-Watson A.,
RA Mason G.H., Schauenburg A., Besneux M., Szomolay B., Elliott T.,
RA Sewell A.K., Gallimore A., Rizkallah P., Cole D.K., Godkin A.;
RT "Human leukocyte antigen (HLA) class II peptide flanking residues tune the
RT immunogenicity of a human tumor-derived epitope.";
RL J. Biol. Chem. 294:20246-20258(2019).
RN [56]
RP X-RAY CRYSTALLOGRAPHY (1.64 ANGSTROMS) OF 28-207 IN COMPLEX WITH
RP HLA-DRB1*01:01 AND IAV PEPTIDE, AND SUBUNIT.
RX PubMed=32668259; DOI=10.1016/j.celrep.2020.107885;
RA Greenshields-Watson A., Attaf M., MacLachlan B.J., Whalley T., Rius C.,
RA Wall A., Lloyd A., Hughes H., Strange K.E., Mason G.H., Schauenburg A.J.,
RA Hulin-Curtis S.L., Geary J., Chen Y., Lauder S.N., Smart K.,
RA Vijaykrishna D., Grau M.L., Shugay M., Andrews R., Dolton G.,
RA Rizkallah P.J., Gallimore A.M., Sewell A.K., Godkin A.J., Cole D.K.;
RT "CD4+ T Cells Recognize Conserved Influenza A Epitopes through Shared
RT Patterns of V-Gene Usage and Complementary Biochemical Features.";
RL Cell Rep. 32:107885-107885(2020).
CC -!- FUNCTION: An alpha chain of antigen-presenting major histocompatibility
CC complex class II (MHCII) molecule. In complex with the beta chain HLA-
CC DRB, displays antigenic peptides on professional antigen presenting
CC cells (APCs) for recognition by alpha-beta T cell receptor (TCR) on
CC HLA-DR-restricted CD4-positive T cells. This guides antigen-specific T-
CC helper effector functions, both antibody-mediated immune response and
CC macrophage activation, to ultimately eliminate the infectious agents
CC and transformed cells (PubMed:29884618, PubMed:17334368,
CC PubMed:8145819, PubMed:15322540, PubMed:22327072, PubMed:27591323,
CC PubMed:31495665, PubMed:15265931, PubMed:9075930, PubMed:24190431).
CC Typically presents extracellular peptide antigens of 10 to 30 amino
CC acids that arise from proteolysis of endocytosed antigens in lysosomes
CC (PubMed:8145819). In the tumor microenvironment, presents antigenic
CC peptides that are primarily generated in tumor-resident APCs likely via
CC phagocytosis of apoptotic tumor cells or macropinocytosis of secreted
CC tumor proteins (PubMed:31495665). Presents peptides derived from
CC intracellular proteins that are trapped in autolysosomes after
CC macroautophagy, a mechanism especially relevant for T cell selection in
CC the thymus and central immune tolerance (PubMed:17182262,
CC PubMed:23783831). The selection of the immunodominant epitopes follows
CC two processing modes: 'bind first, cut/trim later' for pathogen-derived
CC antigenic peptides and 'cut first, bind later' for autoantigens/self-
CC peptides (PubMed:25413013). The anchor residue at position 1 of the
CC peptide N-terminus, usually a large hydrophobic residue, is essential
CC for high affinity interaction with MHCII molecules (PubMed:8145819).
CC {ECO:0000269|PubMed:15265931, ECO:0000269|PubMed:15322540,
CC ECO:0000269|PubMed:17182262, ECO:0000269|PubMed:17334368,
CC ECO:0000269|PubMed:22327072, ECO:0000269|PubMed:23783831,
CC ECO:0000269|PubMed:24190431, ECO:0000269|PubMed:25413013,
CC ECO:0000269|PubMed:27591323, ECO:0000269|PubMed:29884618,
CC ECO:0000269|PubMed:31495665, ECO:0000269|PubMed:8145819,
CC ECO:0000269|PubMed:9075930}.
CC -!- SUBUNIT: Heterotrimer that consists of an alpha chain HLA-DRA, a beta
CC chain HLA-DRB and a peptide (peptide-MHCII) (PubMed:7477400,
CC PubMed:9354468, PubMed:9782128, PubMed:31619516, PubMed:32668259,
CC PubMed:11080454, PubMed:11163233, PubMed:12244309, PubMed:16079912,
CC PubMed:17583734, PubMed:18697946). Newly synthesized alpha and beta
CC chains forms a heterodimer (MHCII) that associates with the
CC CD74/invariant chain (Ii) in the endoplasmic reticulum (ER). Ii is a
CC trimer composed of three subunits and each subunit interacts with one
CC MHCII dimer, blocking the peptide-binding cleft (PubMed:7479981). As a
CC result, MHCII molecules cannot bind peptides present in the ER
CC (PubMed:7479981). The complex of MHCII and CD74/Ii is transported in
CC vesicles from ER to Golgi to lysosomes, where it encounters antigenic
CC peptides generated via proteolysis of endocytosed antigens. MHCII
CC dimers are dissociated from CD74/Ii by the combined action of
CC proteolysis and HLA-DM (PubMed:25413013, PubMed:23260142,
CC PubMed:21115828). Lysosomal enzymes such as cathepsin, degrade CD74/Ii
CC leaving a 24 amino acid remnant called class II-associated Ii or CLIP.
CC Interacts (via the peptide binding cleft) with CLIP; this interaction
CC inhibits antigen peptide binding before entry in the endosomal
CC compartment (PubMed:9075930, PubMed:7477400). The displacement of CLIP
CC and replacement by a high affinity peptide in lysosomes is performed by
CC HLA-DM heterodimer. HLA-DM catalyzes CLIP dissociation from MHCII,
CC stabilizes empty MHCII and mediates the selection of high affinity
CC peptides (PubMed:23260142, PubMed:11070170, PubMed:9075930). Interacts
CC with HLA-DM heterodimer; this interaction is direct (PubMed:25413013).
CC Interacts (via alpha-1 domain) with TCR (via CDRs) (PubMed:17334368,
CC PubMed:29884618). Interacts (via alpha-2 domain) with CD4 (via Ig-like
CC V-type domain); this interaction increases the affinity of TCR for
CC peptide-MHCII (PubMed:27114505). {ECO:0000269|PubMed:11070170,
CC ECO:0000269|PubMed:11080454, ECO:0000269|PubMed:11163233,
CC ECO:0000269|PubMed:12244309, ECO:0000269|PubMed:16079912,
CC ECO:0000269|PubMed:17334368, ECO:0000269|PubMed:17583734,
CC ECO:0000269|PubMed:18697946, ECO:0000269|PubMed:21115828,
CC ECO:0000269|PubMed:23260142, ECO:0000269|PubMed:25413013,
CC ECO:0000269|PubMed:27114505, ECO:0000269|PubMed:29884618,
CC ECO:0000269|PubMed:31619516, ECO:0000269|PubMed:32668259,
CC ECO:0000269|PubMed:7477400, ECO:0000269|PubMed:7479981,
CC ECO:0000269|PubMed:9075930, ECO:0000269|PubMed:9354468,
CC ECO:0000269|PubMed:9782128}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus
CC BZLF2/gp42. {ECO:0000269|PubMed:11864610}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Staphylococcus aureus
CC enterotoxin A/entA, enterotoxin B/entB, enterotoxin C1/entC1,
CC enterotoxin D/entD, and enterotoxin H/entH.
CC {ECO:0000269|PubMed:11432818, ECO:0000269|PubMed:21081917,
CC ECO:0000269|PubMed:2210803, ECO:0000269|PubMed:2658055,
CC ECO:0000269|PubMed:8152483}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15322540,
CC ECO:0000269|PubMed:18305173, ECO:0000269|PubMed:29884618}; Single-pass
CC type I membrane protein {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:18305173}; Single-pass type I membrane protein
CC {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:19117940};
CC Single-pass type I membrane protein {ECO:0000255}. Late endosome
CC membrane {ECO:0000269|PubMed:18305173, ECO:0000269|PubMed:19117940,
CC ECO:0000269|PubMed:9075930}; Single-pass type I membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:18305173,
CC ECO:0000269|PubMed:9075930}; Single-pass type I membrane protein
CC {ECO:0000255}. Autolysosome membrane {ECO:0000269|PubMed:17182262};
CC Single-pass type I membrane protein. Note=The MHCII complex transits
CC through a number of intracellular compartments in the endocytic pathway
CC until it reaches the cell membrane for antigen presentation
CC (PubMed:9075930, PubMed:18305173). Component of immunological synapses
CC at the interface between T cell and APC (PubMed:15322540,
CC PubMed:29884618). {ECO:0000269|PubMed:15322540,
CC ECO:0000269|PubMed:18305173, ECO:0000269|PubMed:29884618,
CC ECO:0000269|PubMed:9075930}.
CC -!- TISSUE SPECIFICITY: Expressed in professional APCs: macrophages,
CC dendritic cells and B cells (at protein level) (PubMed:31495665,
CC PubMed:15322540, PubMed:23783831). Expressed in thymic epithelial cells
CC (at protein level) (PubMed:23783831). {ECO:0000269|PubMed:15322540,
CC ECO:0000269|PubMed:23783831, ECO:0000269|PubMed:31495665}.
CC -!- INDUCTION: Up-regulated in dendritic cells upon maturation.
CC {ECO:0000269|PubMed:15322540}.
CC -!- DOMAIN: The alpha-1 domain is a structural part of the peptide-binding
CC cleft. It contains one alpha helix and 4 beta sheets, respectively
CC forming part of the wall and the floor of the peptide-binding cleft.
CC The other 4 beta sheets of the floor and the second alpha helix wall is
CC formed by the beta-1 domain of HLA-DRB. Forms hydrogen bonds with the
CC peptide main chain via conserved amino acids (PubMed:8145819,
CC PubMed:9354468, PubMed:9782128, PubMed:17583734, PubMed:29884618). The
CC peptide-bound alpha-1 domain forms hydrogen bonds with CDR2 and CDR3
CC alpha-domain of TCR (PubMed:29884618). {ECO:0000269|PubMed:17583734,
CC ECO:0000269|PubMed:29884618, ECO:0000269|PubMed:8145819,
CC ECO:0000269|PubMed:9354468, ECO:0000269|PubMed:9782128}.
CC -!- DOMAIN: The alpha-2 Ig-like domain mediates the interaction with CD4
CC coreceptor. {ECO:0000269|PubMed:27114505}.
CC -!- PTM: Ubiquitinated by MARCHF1 or MARCHF8 at Lys-244 leading to down-
CC regulation of MHCII. When associated with ubiquitination of the beta
CC chain at 'Lys-254', the down-regulation of MHCII may be highly
CC effective. {ECO:0000269|PubMed:19117940}.
CC -!- POLYMORPHISM: The following alleles of DRA are known: DRA*01:01 and
CC DRA*01:02. The sequence shown is that of DRA*01:02.
CC -!- SIMILARITY: Belongs to the MHC class II family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA25076.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; J00194; AAA36275.1; -; mRNA.
DR EMBL; K01171; AAA59785.1; -; mRNA.
DR EMBL; M60334; AAA59783.1; -; mRNA.
DR EMBL; X00274; CAA25076.1; ALT_INIT; Genomic_DNA.
DR EMBL; J00204; AAA36302.1; -; Genomic_DNA.
DR EMBL; J00203; AAA36302.1; JOINED; Genomic_DNA.
DR EMBL; CR457013; CAG33294.1; -; mRNA.
DR EMBL; AL662796; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL670296; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL935032; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX120007; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z84814; CAB06609.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03630.1; -; Genomic_DNA.
DR EMBL; V00523; CAA23782.1; -; mRNA.
DR EMBL; J00201; AAA36301.1; -; Genomic_DNA.
DR EMBL; AF481359; AAO23887.1; -; Genomic_DNA.
DR EMBL; BC032350; AAH32350.1; -; mRNA.
DR EMBL; BC071659; AAH71659.1; -; mRNA.
DR CCDS; CCDS4750.1; -.
DR PIR; A93952; HLHUDA.
DR RefSeq; NP_061984.2; NM_019111.4.
DR PDB; 1A6A; X-ray; 2.75 A; A=30-205.
DR PDB; 1AQD; X-ray; 2.45 A; A/D/G/J=26-217.
DR PDB; 1BX2; X-ray; 2.60 A; A/D=27-206.
DR PDB; 1D5M; X-ray; 2.00 A; A=26-206.
DR PDB; 1D5X; X-ray; 2.45 A; A=26-206.
DR PDB; 1D5Z; X-ray; 2.00 A; A=26-206.
DR PDB; 1D6E; X-ray; 2.45 A; A=26-206.
DR PDB; 1DLH; X-ray; 2.80 A; A/D=28-207.
DR PDB; 1FV1; X-ray; 1.90 A; A/D=26-206.
DR PDB; 1FYT; X-ray; 2.60 A; A=26-206.
DR PDB; 1H15; X-ray; 3.10 A; A/D=26-207.
DR PDB; 1HQR; X-ray; 3.20 A; A=26-206.
DR PDB; 1HXY; X-ray; 2.60 A; A=26-207.
DR PDB; 1J8H; X-ray; 2.40 A; A=26-206.
DR PDB; 1JWM; X-ray; 2.70 A; A=26-207.
DR PDB; 1JWS; X-ray; 2.60 A; A=26-207.
DR PDB; 1JWU; X-ray; 2.30 A; A=26-207.
DR PDB; 1KG0; X-ray; 2.65 A; A=28-207.
DR PDB; 1KLG; X-ray; 2.40 A; A=29-205.
DR PDB; 1KLU; X-ray; 1.93 A; A=29-207.
DR PDB; 1LO5; X-ray; 3.20 A; A=26-207.
DR PDB; 1PYW; X-ray; 2.10 A; A=26-207.
DR PDB; 1R5I; X-ray; 2.60 A; A/E=26-206.
DR PDB; 1SEB; X-ray; 2.70 A; A/E=26-206.
DR PDB; 1SJE; X-ray; 2.45 A; A=28-207.
DR PDB; 1SJH; X-ray; 2.25 A; A=28-207.
DR PDB; 1T5W; X-ray; 2.40 A; A/D=27-206.
DR PDB; 1T5X; X-ray; 2.50 A; A=27-207.
DR PDB; 1YMM; X-ray; 3.50 A; A=26-216.
DR PDB; 1ZGL; X-ray; 2.80 A; A/D/G/J=26-206.
DR PDB; 2FSE; X-ray; 3.10 A; A/C=29-205.
DR PDB; 2G9H; X-ray; 2.00 A; A=26-207.
DR PDB; 2IAM; X-ray; 2.80 A; A=26-207.
DR PDB; 2IAN; X-ray; 2.80 A; A/F/K/P=26-207.
DR PDB; 2ICW; X-ray; 2.41 A; A/D=28-206.
DR PDB; 2IPK; X-ray; 2.30 A; A=26-207.
DR PDB; 2OJE; X-ray; 3.00 A; A/E=27-206.
DR PDB; 2Q6W; X-ray; 2.25 A; A/D=26-207.
DR PDB; 2SEB; X-ray; 2.50 A; A=26-206.
DR PDB; 2WBJ; X-ray; 3.00 A; A/E=26-218.
DR PDB; 2XN9; X-ray; 2.30 A; D=26-207.
DR PDB; 3C5J; X-ray; 1.80 A; A=26-206.
DR PDB; 3L6F; X-ray; 2.10 A; A=26-207.
DR PDB; 3O6F; X-ray; 2.80 A; A/E=26-207.
DR PDB; 3PDO; X-ray; 1.95 A; A=26-217.
DR PDB; 3PGC; X-ray; 2.66 A; A/D=26-217.
DR PDB; 3PGD; X-ray; 2.72 A; A/D=26-217.
DR PDB; 3QXA; X-ray; 2.71 A; A/D=26-207.
DR PDB; 3QXD; X-ray; 2.30 A; A/D=26-207.
DR PDB; 3S4S; X-ray; 2.40 A; A/D=26-207.
DR PDB; 3S5L; X-ray; 2.10 A; A/D=26-207.
DR PDB; 3T0E; X-ray; 4.00 A; A=26-207.
DR PDB; 4AEN; X-ray; 2.20 A; A=26-217.
DR PDB; 4AH2; X-ray; 2.36 A; A=26-217.
DR PDB; 4C56; X-ray; 2.90 A; D/J=26-207.
DR PDB; 4E41; X-ray; 2.60 A; A/F=26-207.
DR PDB; 4FQX; X-ray; 2.60 A; A=26-216.
DR PDB; 4GBX; X-ray; 3.00 A; A=26-216.
DR PDB; 4H1L; X-ray; 3.30 A; A/D=28-205.
DR PDB; 4H25; X-ray; 2.20 A; A/D=28-207.
DR PDB; 4H26; X-ray; 2.50 A; A/D=28-206.
DR PDB; 4I5B; X-ray; 2.12 A; A/D=27-213.
DR PDB; 4IS6; X-ray; 2.50 A; A=26-207.
DR PDB; 4MCY; X-ray; 2.30 A; A=26-206.
DR PDB; 4MCZ; X-ray; 2.41 A; A=26-206.
DR PDB; 4MD0; X-ray; 2.19 A; A=26-206.
DR PDB; 4MD4; X-ray; 1.95 A; A=26-206.
DR PDB; 4MD5; X-ray; 1.65 A; A=26-206.
DR PDB; 4MDI; X-ray; 2.00 A; A=26-206.
DR PDB; 4MDJ; X-ray; 1.70 A; A=26-206.
DR PDB; 4OV5; X-ray; 2.20 A; A/D/G/J/M/P=26-207.
DR PDB; 4X5W; X-ray; 1.34 A; A=26-217.
DR PDB; 4X5X; X-ray; 3.20 A; A/C=26-217.
DR PDB; 4Y19; X-ray; 2.50 A; A=26-206.
DR PDB; 4Y1A; X-ray; 4.00 A; A=26-206.
DR PDB; 5JLZ; X-ray; 1.99 A; A/C=26-206.
DR PDB; 5LAX; X-ray; 2.60 A; A/C=26-206.
DR PDB; 5NI9; X-ray; 1.33 A; A=26-206.
DR PDB; 5NIG; X-ray; 1.35 A; A=26-206.
DR PDB; 5V4M; X-ray; 2.10 A; A/D/G/J=26-206.
DR PDB; 5V4N; X-ray; 3.40 A; A/D=26-206.
DR PDB; 6ATF; X-ray; 1.90 A; A/D=26-206.
DR PDB; 6ATI; X-ray; 1.98 A; A/D=26-206.
DR PDB; 6ATZ; X-ray; 2.70 A; A/C=29-205.
DR PDB; 6BIJ; X-ray; 2.10 A; A=29-205.
DR PDB; 6BIL; X-ray; 2.40 A; A=26-206.
DR PDB; 6BIN; X-ray; 2.50 A; A=30-206.
DR PDB; 6BIR; X-ray; 2.30 A; A=26-206.
DR PDB; 6BIV; X-ray; 2.90 A; B=26-206.
DR PDB; 6BIX; X-ray; 2.20 A; A=26-206.
DR PDB; 6BIY; X-ray; 2.05 A; A=26-206.
DR PDB; 6BIZ; X-ray; 2.10 A; A=26-206.
DR PDB; 6CPL; X-ray; 2.45 A; A=26-254.
DR PDB; 6CPN; X-ray; 2.00 A; A=26-206.
DR PDB; 6CPO; X-ray; 2.40 A; A/D=26-207.
DR PDB; 6CQJ; X-ray; 2.75 A; A/D/G=26-207.
DR PDB; 6CQL; X-ray; 2.40 A; A=26-206.
DR PDB; 6CQN; X-ray; 2.50 A; A=26-206.
DR PDB; 6CQQ; X-ray; 2.80 A; A/F=26-207.
DR PDB; 6CQR; X-ray; 3.04 A; A/F=26-207.
DR PDB; 6NIX; X-ray; 2.10 A; A=30-206.
DR PDB; 6QZA; X-ray; 3.09 A; AAA/DDD=26-207.
DR PDB; 6QZC; X-ray; 1.64 A; AAA=28-207.
DR PDB; 6QZD; X-ray; 2.66 A; AAA/DDD=28-207.
DR PDB; 6R0E; X-ray; 1.91 A; AAA=26-207.
DR PDB; 6V0Y; X-ray; 2.70 A; A=26-206.
DR PDB; 6V13; X-ray; 2.75 A; A=30-206.
DR PDB; 6V15; X-ray; 2.80 A; A=30-206.
DR PDB; 6V18; X-ray; 2.35 A; A=26-206.
DR PDB; 6V19; X-ray; 2.60 A; A=26-206.
DR PDB; 6V1A; X-ray; 2.29 A; A=26-206.
DR PDB; 7N19; X-ray; 2.38 A; A/D/G/J=26-206.
DR PDBsum; 1A6A; -.
DR PDBsum; 1AQD; -.
DR PDBsum; 1BX2; -.
DR PDBsum; 1D5M; -.
DR PDBsum; 1D5X; -.
DR PDBsum; 1D5Z; -.
DR PDBsum; 1D6E; -.
DR PDBsum; 1DLH; -.
DR PDBsum; 1FV1; -.
DR PDBsum; 1FYT; -.
DR PDBsum; 1H15; -.
DR PDBsum; 1HQR; -.
DR PDBsum; 1HXY; -.
DR PDBsum; 1J8H; -.
DR PDBsum; 1JWM; -.
DR PDBsum; 1JWS; -.
DR PDBsum; 1JWU; -.
DR PDBsum; 1KG0; -.
DR PDBsum; 1KLG; -.
DR PDBsum; 1KLU; -.
DR PDBsum; 1LO5; -.
DR PDBsum; 1PYW; -.
DR PDBsum; 1R5I; -.
DR PDBsum; 1SEB; -.
DR PDBsum; 1SJE; -.
DR PDBsum; 1SJH; -.
DR PDBsum; 1T5W; -.
DR PDBsum; 1T5X; -.
DR PDBsum; 1YMM; -.
DR PDBsum; 1ZGL; -.
DR PDBsum; 2FSE; -.
DR PDBsum; 2G9H; -.
DR PDBsum; 2IAM; -.
DR PDBsum; 2IAN; -.
DR PDBsum; 2ICW; -.
DR PDBsum; 2IPK; -.
DR PDBsum; 2OJE; -.
DR PDBsum; 2Q6W; -.
DR PDBsum; 2SEB; -.
DR PDBsum; 2WBJ; -.
DR PDBsum; 2XN9; -.
DR PDBsum; 3C5J; -.
DR PDBsum; 3L6F; -.
DR PDBsum; 3O6F; -.
DR PDBsum; 3PDO; -.
DR PDBsum; 3PGC; -.
DR PDBsum; 3PGD; -.
DR PDBsum; 3QXA; -.
DR PDBsum; 3QXD; -.
DR PDBsum; 3S4S; -.
DR PDBsum; 3S5L; -.
DR PDBsum; 3T0E; -.
DR PDBsum; 4AEN; -.
DR PDBsum; 4AH2; -.
DR PDBsum; 4C56; -.
DR PDBsum; 4E41; -.
DR PDBsum; 4FQX; -.
DR PDBsum; 4GBX; -.
DR PDBsum; 4H1L; -.
DR PDBsum; 4H25; -.
DR PDBsum; 4H26; -.
DR PDBsum; 4I5B; -.
DR PDBsum; 4IS6; -.
DR PDBsum; 4MCY; -.
DR PDBsum; 4MCZ; -.
DR PDBsum; 4MD0; -.
DR PDBsum; 4MD4; -.
DR PDBsum; 4MD5; -.
DR PDBsum; 4MDI; -.
DR PDBsum; 4MDJ; -.
DR PDBsum; 4OV5; -.
DR PDBsum; 4X5W; -.
DR PDBsum; 4X5X; -.
DR PDBsum; 4Y19; -.
DR PDBsum; 4Y1A; -.
DR PDBsum; 5JLZ; -.
DR PDBsum; 5LAX; -.
DR PDBsum; 5NI9; -.
DR PDBsum; 5NIG; -.
DR PDBsum; 5V4M; -.
DR PDBsum; 5V4N; -.
DR PDBsum; 6ATF; -.
DR PDBsum; 6ATI; -.
DR PDBsum; 6ATZ; -.
DR PDBsum; 6BIJ; -.
DR PDBsum; 6BIL; -.
DR PDBsum; 6BIN; -.
DR PDBsum; 6BIR; -.
DR PDBsum; 6BIV; -.
DR PDBsum; 6BIX; -.
DR PDBsum; 6BIY; -.
DR PDBsum; 6BIZ; -.
DR PDBsum; 6CPL; -.
DR PDBsum; 6CPN; -.
DR PDBsum; 6CPO; -.
DR PDBsum; 6CQJ; -.
DR PDBsum; 6CQL; -.
DR PDBsum; 6CQN; -.
DR PDBsum; 6CQQ; -.
DR PDBsum; 6CQR; -.
DR PDBsum; 6NIX; -.
DR PDBsum; 6QZA; -.
DR PDBsum; 6QZC; -.
DR PDBsum; 6QZD; -.
DR PDBsum; 6R0E; -.
DR PDBsum; 6V0Y; -.
DR PDBsum; 6V13; -.
DR PDBsum; 6V15; -.
DR PDBsum; 6V18; -.
DR PDBsum; 6V19; -.
DR PDBsum; 6V1A; -.
DR PDBsum; 7N19; -.
DR AlphaFoldDB; P01903; -.
DR SMR; P01903; -.
DR BioGRID; 109367; 217.
DR DIP; DIP-6063N; -.
DR IntAct; P01903; 35.
DR MINT; P01903; -.
DR STRING; 9606.ENSP00000378786; -.
DR DrugBank; DB05121; 1D09C3.
DR DrugBank; DB11294; Coccidioides immitis spherule.
DR Allergome; 8362; Hom s HLA-DR-alpha.
DR GlyConnect; 1368; 16 N-Linked glycans (2 sites).
DR GlyGen; P01903; 4 sites, 14 N-linked glycans (2 sites).
DR iPTMnet; P01903; -.
DR PhosphoSitePlus; P01903; -.
DR SwissPalm; P01903; -.
DR BioMuta; HLA-DRA; -.
DR DMDM; 122206; -.
DR EPD; P01903; -.
DR jPOST; P01903; -.
DR MassIVE; P01903; -.
DR MaxQB; P01903; -.
DR PaxDb; P01903; -.
DR PeptideAtlas; P01903; -.
DR PRIDE; P01903; -.
DR ProteomicsDB; 51508; -.
DR ABCD; P01903; 22 sequenced antibodies.
DR Antibodypedia; 28584; 1821 antibodies from 46 providers.
DR CPTC; P01903; 1 antibody.
DR DNASU; 3122; -.
DR Ensembl; ENST00000383127.6; ENSP00000372608.2; ENSG00000227993.9.
DR Ensembl; ENST00000383259.6; ENSP00000372746.2; ENSG00000206308.11.
DR Ensembl; ENST00000395388.7; ENSP00000378786.2; ENSG00000204287.14.
DR Ensembl; ENST00000411524.6; ENSP00000405295.2; ENSG00000234794.9.
DR Ensembl; ENST00000414698.6; ENSP00000402951.2; ENSG00000230726.9.
DR Ensembl; ENST00000416883.6; ENSP00000410443.2; ENSG00000228987.9.
DR Ensembl; ENST00000442960.6; ENSP00000404533.2; ENSG00000226260.9.
DR Ensembl; ENST00000613328.1; ENSP00000479287.1; ENSG00000277263.1.
DR GeneID; 3122; -.
DR KEGG; hsa:3122; -.
DR MANE-Select; ENST00000395388.7; ENSP00000378786.2; NM_019111.5; NP_061984.2.
DR UCSC; uc003obh.5; human.
DR CTD; 3122; -.
DR DisGeNET; 3122; -.
DR GeneCards; HLA-DRA; -.
DR HGNC; HGNC:4947; HLA-DRA.
DR HPA; ENSG00000204287; Tissue enhanced (lung, lymphoid tissue).
DR MalaCards; HLA-DRA; -.
DR MIM; 142860; gene.
DR MIM; 610424; phenotype.
DR neXtProt; NX_P01903; -.
DR NIAGADS; ENSG00000204287; -.
DR OpenTargets; ENSG00000204287; -.
DR Orphanet; 505; Graham Little-Piccardi-Lassueur syndrome.
DR PharmGKB; PA35071; -.
DR VEuPathDB; HostDB:ENSG00000204287; -.
DR eggNOG; ENOG502RXYJ; Eukaryota.
DR GeneTree; ENSGT00940000160997; -.
DR HOGENOM; CLU_069380_0_0_1; -.
DR InParanoid; P01903; -.
DR OMA; QAEFYMT; -.
DR OrthoDB; 1132781at2759; -.
DR PhylomeDB; P01903; -.
DR TreeFam; TF333797; -.
DR PathwayCommons; P01903; -.
DR Reactome; R-HSA-202424; Downstream TCR signaling.
DR Reactome; R-HSA-202427; Phosphorylation of CD3 and TCR zeta chains.
DR Reactome; R-HSA-202430; Translocation of ZAP-70 to Immunological synapse.
DR Reactome; R-HSA-202433; Generation of second messenger molecules.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-389948; PD-1 signaling.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR SignaLink; P01903; -.
DR SIGNOR; P01903; -.
DR BioGRID-ORCS; 3122; 10 hits in 1065 CRISPR screens.
DR ChiTaRS; HLA-DRA; human.
DR EvolutionaryTrace; P01903; -.
DR GeneWiki; HLA-DRA; -.
DR GenomeRNAi; 3122; -.
DR Pharos; P01903; Tbio.
DR PRO; PR:P01903; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P01903; protein.
DR Bgee; ENSG00000204287; Expressed in monocyte and 98 other tissues.
DR ExpressionAtlas; P01903; baseline and differential.
DR Genevisible; P01903; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0001772; C:immunological synapse; IDA:UniProtKB.
DR GO; GO:0071556; C:integral component of lumenal side of endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; NAS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:MGI.
DR GO; GO:0042613; C:MHC class II protein complex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
DR GO; GO:0030658; C:transport vesicle membrane; TAS:Reactome.
DR GO; GO:0023026; F:MHC class II protein complex binding; HDA:UniProtKB.
DR GO; GO:0032395; F:MHC class II receptor activity; NAS:UniProtKB.
DR GO; GO:0042605; F:peptide antigen binding; IDA:UniProtKB.
DR GO; GO:0030247; F:polysaccharide binding; IDA:UniProtKB.
DR GO; GO:0042608; F:T cell receptor binding; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0002491; P:antigen processing and presentation of endogenous peptide antigen via MHC class II; IDA:UniProtKB.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; IDA:UniProtKB.
DR GO; GO:0002504; P:antigen processing and presentation of peptide or polysaccharide antigen via MHC class II; IDA:UniProtKB.
DR GO; GO:0050890; P:cognition; IMP:UniProtKB.
DR GO; GO:0006955; P:immune response; NAS:UniProtKB.
DR GO; GO:0002469; P:myeloid dendritic cell antigen processing and presentation; IDA:UniProtKB.
DR GO; GO:0002503; P:peptide antigen assembly with MHC class II protein complex; IDA:UniProtKB.
DR GO; GO:2000516; P:positive regulation of CD4-positive, alpha-beta T cell activation; IDA:UniProtKB.
DR GO; GO:0032831; P:positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation; IDA:UniProtKB.
DR GO; GO:0043382; P:positive regulation of memory T cell differentiation; IDA:UniProtKB.
DR GO; GO:0050870; P:positive regulation of T cell activation; IBA:GO_Central.
DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IDA:UniProtKB.
DR GO; GO:0045622; P:regulation of T-helper cell differentiation; IDA:UniProtKB.
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; Cell membrane; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; Endosome;
KW Glycoprotein; Host-virus interaction; Immunity; Isopeptide bond; Lysosome;
KW Membrane; MHC II; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:6600932,
FT ECO:0000269|PubMed:6812963, ECO:0000269|PubMed:6955253"
FT CHAIN 26..254
FT /note="HLA class II histocompatibility antigen, DR alpha
FT chain"
FT /id="PRO_0000018947"
FT TOPO_DOM 26..216
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 217..239
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 240..254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 112..204
FT /note="Ig-like C1-type"
FT REGION 26..109
FT /note="Alpha-1"
FT REGION 110..203
FT /note="Alpha-2"
FT REGION 204..216
FT /note="Connecting peptide"
FT SITE 34
FT /note="Self- and pathogen-derived peptide antigen"
FT /evidence="ECO:0000269|PubMed:17583734,
FT ECO:0000269|PubMed:21115828, ECO:0000269|PubMed:23260142,
FT ECO:0000269|PubMed:8145819, ECO:0007744|PDB:4GBX"
FT SITE 74
FT /note="Self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:31619516"
FT SITE 76
FT /note="Self- and pathogen-derived peptide antigen"
FT /evidence="ECO:0000269|PubMed:21115828,
FT ECO:0000269|PubMed:8145819"
FT SITE 77
FT /note="Self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:31619516"
FT SITE 78
FT /note="Self- and pathogen-derived peptide antigen"
FT /evidence="ECO:0000269|PubMed:17583734,
FT ECO:0000269|PubMed:21115828, ECO:0000269|PubMed:31619516,
FT ECO:0000269|PubMed:8145819"
FT SITE 80
FT /note="Pathogen-derived peptide antigen"
FT /evidence="ECO:0000269|PubMed:23260142,
FT ECO:0007744|PDB:4GBX"
FT SITE 87
FT /note="Self- and pathogen-derived peptide antigen"
FT /evidence="ECO:0000269|PubMed:17583734,
FT ECO:0000269|PubMed:21115828, ECO:0000269|PubMed:23260142,
FT ECO:0000269|PubMed:31619516, ECO:0000269|PubMed:8145819,
FT ECO:0007744|PDB:4GBX"
FT SITE 94
FT /note="Pathogen-derived peptide antigen"
FT /evidence="ECO:0000269|PubMed:17583734,
FT ECO:0000269|PubMed:21115828, ECO:0000269|PubMed:23260142,
FT ECO:0000269|PubMed:8145819, ECO:0007744|PDB:4FQX,
FT ECO:0007744|PDB:4GBX"
FT SITE 101
FT /note="Self- and pathogen-derived peptide antigen"
FT /evidence="ECO:0000269|PubMed:17583734,
FT ECO:0000269|PubMed:23260142, ECO:0000269|PubMed:31619516,
FT ECO:0000269|PubMed:8145819, ECO:0007744|PDB:4FQX,
FT ECO:0007744|PDB:4GBX"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:7477400"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:7477400"
FT DISULFID 132..188
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:11163233, ECO:0000269|PubMed:12244309,
FT ECO:0000269|PubMed:16079912, ECO:0000269|PubMed:17583734,
FT ECO:0000269|PubMed:31619516, ECO:0000269|PubMed:7477400"
FT CROSSLNK 244
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:19117940"
FT VARIANT 16
FT /note="V -> L (in dbSNP:rs16822586)"
FT /id="VAR_035241"
FT VARIANT 242
FT /note="L -> V (in allele DRA*01:01; dbSNP:rs7192)"
FT /id="VAR_004399"
FT MUTAGEN 65
FT /note="E->K: Impairs the interaction with HLA-DM complex,
FT CLIP dissociation and peptide exchange."
FT /evidence="ECO:0000269|PubMed:11070170,
FT ECO:0000269|PubMed:23260142"
FT MUTAGEN 68
FT /note="W->F: Decreases the interaction with HLA-DM complex
FT and peptide exchange."
FT /evidence="ECO:0000269|PubMed:23260142"
FT MUTAGEN 74
FT /note="G->S: Increases the interaction with HLA-DM complex
FT and peptide exchange."
FT /evidence="ECO:0000269|PubMed:23260142"
FT MUTAGEN 76
FT /note="F->A,S,V,L: Impairs the interaction with HLA-DM
FT complex, CLIP dissociation and peptide exchange."
FT /evidence="ECO:0000269|PubMed:11070170,
FT ECO:0000269|PubMed:23260142"
FT MUTAGEN 76
FT /note="F->W: Increases the interaction with HLA-DM complex
FT and peptide exchange."
FT /evidence="ECO:0000269|PubMed:23260142"
FT MUTAGEN 78
FT /note="S->D,H: Decreases the interaction with HLA-DM
FT complex and peptide exchange."
FT /evidence="ECO:0000269|PubMed:23260142"
FT MUTAGEN 79
FT /note="F->A,C: Increases the interaction with HLA-DM
FT complex and peptide exchange."
FT /evidence="ECO:0000269|PubMed:23260142"
FT MUTAGEN 80
FT /note="E->A: Increases the interaction with HLA-DM complex
FT and peptide exchange. Decreases the affinity of the
FT interaction with TCR by more than five-fold."
FT /evidence="ECO:0000269|PubMed:23260142,
FT ECO:0000269|PubMed:29884618"
FT MUTAGEN 82
FT /note="Q->A: Decreases the interaction with HLA-DM complex
FT and peptide exchange."
FT /evidence="ECO:0000269|PubMed:23260142"
FT MUTAGEN 93
FT /note="A->L: Decreases the affinity of the interaction with
FT TCR by more than five-fold."
FT /evidence="ECO:0000269|PubMed:29884618"
FT MUTAGEN 115
FT /note="T->R: Decreases the interaction with CD4."
FT /evidence="ECO:0000269|PubMed:27114505"
FT MUTAGEN 117
FT /note="L->R: Decreases the interaction with CD4."
FT /evidence="ECO:0000269|PubMed:27114505"
FT MUTAGEN 121
FT /note="P->S: Decreases the interaction with HLA-DM complex
FT and peptide exchange."
FT /evidence="ECO:0000269|PubMed:23260142"
FT MUTAGEN 125
FT /note="R->A: Impairs the interaction with HLA-DM complex
FT and peptide exchange."
FT /evidence="ECO:0000269|PubMed:23260142"
FT MUTAGEN 244
FT /note="K->R: Almost no change in down-regulation of MHCII.
FT No ubiquitination and complete loss of down-regulation of
FT MHCII; when associated with 'R-254' of HLA-DRB."
FT /evidence="ECO:0000269|PubMed:19117940"
FT CONFLICT 28..29
FT /note="EE -> AD (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 33
FT /note="I -> T (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 34..35
FT /note="QA -> YP (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 48
FT /note="M -> Q (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 54
FT /note="D -> T (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 59
FT /note="V -> Y (in Ref. 15; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 64
FT /note="K -> L (in Ref. 15; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 67
FT /note="V -> A (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 69
FT /note="R -> L (in Ref. 15; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="R -> P (in Ref. 15; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 78
FT /note="S -> D (in Ref. 15; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 149
FT /note="N -> E (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 29..40
FT /evidence="ECO:0007829|PDB:5NI9"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:5NI9"
FT STRAND 44..51
FT /evidence="ECO:0007829|PDB:5NI9"
FT STRAND 54..60
FT /evidence="ECO:0007829|PDB:5NI9"
FT TURN 61..64
FT /evidence="ECO:0007829|PDB:5NI9"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:5NI9"
FT HELIX 71..74
FT /evidence="ECO:0007829|PDB:5NI9"
FT HELIX 82..101
FT /evidence="ECO:0007829|PDB:5NI9"
FT TURN 102..104
FT /evidence="ECO:0007829|PDB:3C5J"
FT STRAND 113..120
FT /evidence="ECO:0007829|PDB:5NI9"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:3S4S"
FT STRAND 128..140
FT /evidence="ECO:0007829|PDB:5NI9"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:5NI9"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:4X5W"
FT STRAND 155..159
FT /evidence="ECO:0007829|PDB:2FSE"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:6CPN"
FT STRAND 170..178
FT /evidence="ECO:0007829|PDB:5NI9"
FT STRAND 186..191
FT /evidence="ECO:0007829|PDB:5NI9"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:3C5J"
FT STRAND 199..203
FT /evidence="ECO:0007829|PDB:5NI9"
SQ SEQUENCE 254 AA; 28621 MW; 3CD1CDBA89D92350 CRC64;
MAISGVPVLG FFIIAVLMSA QESWAIKEEH VIIQAEFYLN PDQSGEFMFD FDGDEIFHVD
MAKKETVWRL EEFGRFASFE AQGALANIAV DKANLEIMTK RSNYTPITNV PPEVTVLTNS
PVELREPNVL ICFIDKFTPP VVNVTWLRNG KPVTTGVSET VFLPREDHLF RKFHYLPFLP
STEDVYDCRV EHWGLDEPLL KHWEFDAPSP LPETTENVVC ALGLTVGLVG IIIGTIFIIK
GLRKSNAAER RGPL
