P28067 (DMA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	261 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Immunity
Cellular component	Endosome Lysosome MHC II Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	antigen 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: Compara immunoglobulin mediated immune response Inferred from electronic annotation. Source: Compara inner ear development Inferred from electronic annotation. Source: Compara positive regulation of T cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of immune response Inferred from electronic annotation. Source: Compara positive thymic T cell selection Inferred from electronic annotation. Source: Compara protein complex assembly Inferred from electronic annotation. Source: Compara protein transport Inferred from electronic annotation. Source: Compara
Cellular_component	MHC class II protein complex Inferred from electronic annotation. Source: UniProtKB-KW integral to 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: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

26

Potential

Chain

27 – 261

235

HLA class II histocompatibility antigen, DM alpha chain

PRO_0000018958

Regions

Topological domain

27 – 233

207

Lumenal Potential

Transmembrane

234 – 254

21

Helical; Potential

Topological domain

255 – 261

7

Cytoplasmic Potential

Domain

121 – 215

95

Ig-like C1-type

Region

27 – 124

98

Alpha-1

Region

125 – 217

93

Alpha-2

Region

218 – 233

16

Connecting peptide Potential

Amino acid modifications

Glycosylation

41

1

N-linked (GlcNAc...) Potential

Disulfide bond

50 ↔ 105

Ref.6 Ref.7

Disulfide bond

147 ↔ 202

Ref.6 Ref.7

Natural variations

Natural variant

162

1

H → Q in allele DMA*01:03 and allele DMA*01:04.

VAR_016746

Natural variant

163

1

D → H in allele DMA*01:03 and allele DMA*01:04.

VAR_016747

Natural variant

166

1

V → I in allele DMA*01:02 and allele DMA*01:04.
Corresponds to variant rs1063478 [ dbSNP | Ensembl ].

VAR_016748

Natural variant

181

1

G → A in allele DMA*01:03.
Corresponds to variant rs6926628 [ dbSNP | Ensembl ].

VAR_016749

Natural variant

210

1

R → C in allele DMA*01:04.
Corresponds to variant rs17214044 [ dbSNP | Ensembl ].

VAR_016750

Natural variant

210

1

R → H in allele DMA*01:03.
Corresponds to variant rs41555121 [ dbSNP | Ensembl ].

VAR_016751

Natural variant

235

1

V → M.
Corresponds to variant rs9469319 [ dbSNP | Ensembl ].

VAR_056544

Secondary structure

1

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261

Helix Strand Turn

Details...

Beta strand

41 – 63

23

Beta strand

66 – 72

7

Turn

73 – 76

4

Beta strand

77 – 82

6

Helix

83 – 85

3

Helix

87 – 89

3

Helix

95 – 110

16

Turn

114 – 116

3

Turn

117 – 119

3

Beta strand

122 – 124

3

Beta strand

128 – 135

8

Beta strand

143 – 155

13

Beta strand

157 – 163

7

Beta strand

166 – 168

3

Beta strand

175 – 179

5

Turn

180 – 182

3

Beta strand

183 – 192

10

Beta strand

200 – 206

7

Turn

207 – 210

4

Beta strand

211 – 217

7

Sequences

	Sequence		Length	Mass (Da)
	P28067 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 1986C3C1989F02E9	FASTA	261	29,194
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00291924.

PIR

I38490.
S17886.

UniGene

Hs.728759.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HDM	X-ray	2.50	A	27-230	[»]
2BC4	X-ray	2.27	A/C	27-229	[»]
4FQX	X-ray	2.60	C	27-225	[»]
4GBX	X-ray	3.00	C	27-225	[»]

ProteinModelPortal

P28067.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6184N.

IntAct

P28067. 7 interactions.

STRING

9606.ENSP00000408311.

PTM databases

PhosphoSite

P28067.

Polymorphism databases

DMDM

133158.

Proteomic databases

PaxDb

P28067.

PRIDE

P28067.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000374843; ENSP00000363976; ENSG00000204257.
ENST00000383230; ENSP00000372717; ENSG00000243215.
ENST00000434337; ENSP00000407198; ENSG00000242361.
ENST00000441375; ENSP00000410591; ENSG00000239463.
ENST00000450601; ENSP00000392842; ENSG00000242685.
ENST00000452615; ENSP00000395349; ENSG00000243189.
ENST00000453490; ENSP00000404018; ENSG00000243719.

Organism-specific databases

GeneCards

GC06M032918.

H-InvDB

HIX0207683.

HGNC

HGNC:4934. HLA-DMA.

HPA

HPA012750.

MIM

142855. gene.

neXtProt

NX_P28067.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG43075.

HOGENOM

HOG000126882.

HOVERGEN

HBG001688.

InParanoid

P28067.

OrthoDB

EOG49ZXQ0.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P28067.

Bgee

P28067.

CleanEx

HS_HLA-DMA.

Genevestigator

P28067.

GermOnline

ENSG00000204257. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.
3.10.320.10. 1 hit.

InterPro

IPR007110. 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]

Pfam

PF07654. C1-set. 1 hit.
PF00993. MHC_II_alpha. 1 hit.
[Graphical view]

SMART

SM00407. IGc1. 1 hit.
SM00920. MHC_II_alpha. 1 hit.
[Graphical view]

SUPFAM

SSF54452. MHC_I/II-like_Ag-recog. 1 hit.

PROSITE

PS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P28067.

SOURCE

Search...

Entry information

Entry name

DMA_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 132 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.