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P28067 (DMA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
HLA class II histocompatibility antigen, DM alpha chain
Alternative name(s):
MHC class II antigen DMA
Really interesting new gene 6 protein
Gene names
Name:HLA-DMA
Synonyms:DMA, RING6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length261 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a critical role in catalyzing the release of class II-associated invariant chain peptide (CLIP) from newly synthesized MHC class II molecules and freeing the peptide binding site for acquisition of antigenic peptides. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Ref.5 Ref.6 Ref.7

Subunit structure

Heterodimer of an alpha chain (DMA) and a beta chain (DMB). Ref.6 Ref.7

Subcellular location

Late endosome membrane; Single-pass type I membrane protein. Lysosome membrane; Single-pass type I membrane protein. Note: Localizes to late endocytic compartment. Associates with lysosome membranes.

Polymorphism

The following alleles of DMA are known: DMA*01:01, DMA*01:02, DMA*01:03 (DMA3.2) and DMA*01:04 (DMA3.4). The sequence shown is that of DMA*01:01.

Sequence similarities

Belongs to the MHC class II family.

Contains 1 Ig-like C1-type (immunoglobulin-like) domain.

Ontologies

Keywords
   Biological processImmunity
   Cellular componentEndosome
Lysosome
Membrane
MHC II
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processantigen processing and presentation of exogenous peptide antigen via MHC class II

Traceable author statement. Source: Reactome

chaperone mediated protein folding requiring cofactor

Inferred from electronic annotation. Source: Ensembl

immunoglobulin mediated immune response

Inferred from electronic annotation. Source: Ensembl

inner ear development

Inferred from electronic annotation. Source: Ensembl

positive regulation of T cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of immune response

Inferred from electronic annotation. Source: Ensembl

positive thymic T cell selection

Inferred from electronic annotation. Source: Ensembl

protein complex assembly

Inferred from electronic annotation. Source: Ensembl

protein transport

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentMHC class II protein complex

Inferred from electronic annotation. Source: UniProtKB-KW

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

late endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

lysosomal membrane

Traceable author statement. Source: Reactome

multivesicular body

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 261235HLA class II histocompatibility antigen, DM alpha chain
PRO_0000018958

Regions

Topological domain27 – 233207Lumenal Potential
Transmembrane234 – 25421Helical; Potential
Topological domain255 – 2617Cytoplasmic Potential
Domain121 – 21595Ig-like C1-type
Region27 – 12498Alpha-1
Region125 – 21793Alpha-2
Region218 – 23316Connecting peptide Potential

Amino acid modifications

Glycosylation411N-linked (GlcNAc...) Potential
Disulfide bond50 ↔ 105 Ref.6 Ref.7
Disulfide bond147 ↔ 202 Ref.6 Ref.7

Natural variations

Natural variant1621H → Q in allele DMA*01:03 and allele DMA*01:04.
VAR_016746
Natural variant1631D → H in allele DMA*01:03 and allele DMA*01:04.
VAR_016747
Natural variant1661V → I in allele DMA*01:02 and allele DMA*01:04.
Corresponds to variant rs1063478 [ dbSNP | Ensembl ].
VAR_016748
Natural variant1811G → A in allele DMA*01:03.
Corresponds to variant rs6926628 [ dbSNP | Ensembl ].
VAR_016749
Natural variant2101R → C in allele DMA*01:04.
Corresponds to variant rs17214044 [ dbSNP | Ensembl ].
VAR_016750
Natural variant2101R → H in allele DMA*01:03.
Corresponds to variant rs41555121 [ dbSNP | Ensembl ].
VAR_016751
Natural variant2351V → M.
Corresponds to variant rs9469319 [ dbSNP | Ensembl ].
VAR_056544

Secondary structure

................................. 261
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P28067 [UniParc].

Last modified August 1, 1992. Version 1.
Checksum: 1986C3C1989F02E9

FASTA26129,194
        10         20         30         40         50         60 
MGHEQNQGAA LLQMLPLLWL LPHSWAVPEA PTPMWPDDLQ NHTFLHTVYC QDGSPSVGLS 

        70         80         90        100        110        120 
EAYDEDQLFF FDFSQNTRVP RLPEFADWAQ EQGDAPAILF DKEFCEWMIQ QIGPKLDGKI 

       130        140        150        160        170        180 
PVSRGFPIAE VFTLKPLEFG KPNTLVCFVS NLFPPMLTVN WHDHSVPVEG FGPTFVSAVD 

       190        200        210        220        230        240 
GLSFQAFSYL NFTPEPSDIF SCIVTHEIDR YTAIAYWVPR NALPSDLLEN VLCGVAFGLG 

       250        260 
VLGIIVGIVL IIYFRKPCSG D 

« Hide

References

« Hide 'large scale' references
[1]"A new human HLA class II-related locus, DM."
Kelly A.P., Monaco J.J., Cho S., Trowsdale J.
Nature 353:571-573(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DMA*01:01).
[2]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Limited polymorphism in HLA-DM does not involve the peptide binding groove."
Sanderson F., Powis S.H., Kelly A.P., Trowsdale J.
Immunogenetics 39:56-58(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 31-218 (ALLELE DMA*01:02).
[4]"Sequence analysis of two novel HLA-DMA alleles."
Carrington M., Harding A.
Immunogenetics 40:165-165(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 125-217 (ALLELES DMA*01:03 AND DMA*01:04).
[5]"Enhanced dissociation of HLA-DR-bound peptides in the presence of HLA-DM."
Weber D.A., Evavold B.D., Jensen P.E.
Science 274:618-620(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"The structure of HLA-DM, the peptide exchange catalyst that loads antigen onto class II MHC molecules during antigen presentation."
Mosyak L., Zaller D.M., Wiley D.C.
Immunity 9:377-383(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 27-230 IN COMPLEX WITH DMB, FUNCTION, SUBUNIT, DISULFIDE BONDS.
[7]"Small molecules that enhance the catalytic efficiency of HLA-DM."
Nicholson M.J., Moradi B., Seth N.P., Xing X., Cuny G.D., Stein R.L., Wucherpfennig K.W.
J. Immunol. 176:4208-4220(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 27-229 IN COMPLEX WITH DMB, FUNCTION, SUBUNIT, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X62744 mRNA. Translation: CAA44606.1.
AL935042 Genomic DNA. No translation available.
Z24753 Genomic DNA. No translation available.
U04878 Genomic DNA. Translation: AAA56994.1.
U04877 Genomic DNA. Translation: AAA56993.1.
PIRI38490.
S17886.
UniGeneHs.728759.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HDMX-ray2.50A27-230[»]
2BC4X-ray2.27A/C27-229[»]
4FQXX-ray2.60C27-225[»]
4GBXX-ray3.00C27-225[»]
ProteinModelPortalP28067.
SMRP28067. Positions 38-230.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-6184N.
IntActP28067. 7 interactions.
MINTMINT-1539780.
STRING9606.ENSP00000408311.

PTM databases

PhosphoSiteP28067.

Polymorphism databases

DMDM133158.

Proteomic databases

PaxDbP28067.
PRIDEP28067.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000374843; ENSP00000363976; ENSG00000204257.
ENST00000383230; ENSP00000372717; ENSG00000243215.
ENST00000434337; ENSP00000407198; ENSG00000242361.
ENST00000441375; ENSP00000410591; ENSG00000239463.
ENST00000450601; ENSP00000392842; ENSG00000242685.
ENST00000452615; ENSP00000395349; ENSG00000243189.
ENST00000453490; ENSP00000404018; ENSG00000243719.

Organism-specific databases

GeneCardsGC06M032924.
GC06Mi32899.
GC06Mj32838.
GC06Ml33070.
GC06Mm32949.
GC06Mn32845.
GC06Mo33006.
H-InvDBHIX0207683.
HGNCHGNC:4934. HLA-DMA.
HPAHPA012750.
MIM142855. gene.
neXtProtNX_P28067.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG43075.
HOGENOMHOG000126882.
HOVERGENHBG001688.
InParanoidP28067.
TreeFamTF333797.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP28067.
BgeeP28067.
CleanExHS_HLA-DMA.
GenevestigatorP28067.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
3.10.320.10. 1 hit.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
IPR011162. MHC_I/II-like_Ag-recog.
IPR014745. MHC_II_a/b_N.
IPR001003. MHC_II_a_N.
[Graphical view]
PfamPF07654. C1-set. 1 hit.
PF00993. MHC_II_alpha. 1 hit.
[Graphical view]
SMARTSM00407. IGc1. 1 hit.
SM00920. MHC_II_alpha. 1 hit.
[Graphical view]
SUPFAMSSF54452. SSF54452. 1 hit.
PROSITEPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP28067.
PROP28067.
SOURCESearch...

Entry information

Entry nameDMA_HUMAN
AccessionPrimary (citable) accession number: P28067
Secondary accession number(s): Q29639, Q29640
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: February 19, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM