P28068 (DMB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
HLA class II histocompatibility antigen, DM beta chain

Alternative name(s):
MHC class II antigen DMB
Really interesting new gene 7 protein

Gene names

Name:	HLA-DMB
Synonyms:	DMB, RING7

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	263 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.12 Ref.15 Ref.16
Subunit structure	Heterodimer of an alpha chain (DMA) and a beta chain (DMB). Ref.15 Ref.16
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. Ref.13
Domain	The YXXZ (Tyr-Xaa-Xaa-Zaa, where Zaa is a hydrophobic residue) motif mediates the targeting to the lysosomal compartments.
Polymorphism	The following alleles of DMB are known: DMB*01:01, DMB*01:02, DMB*01:03, DMB*01:04 (DMB3.4), DMB*01:05, DMB*01:06, and DMB*01:07. The sequence shown is that of DMB*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 Membrane MHC II
Coding sequence diversity	Polymorphism
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MHC class II protein complex assembly Inferred from mutant phenotype PubMed 8139689. Source: UniProt antigen processing and presentation of exogenous peptide antigen via MHC class II Inferred from mutant phenotype PubMed 8139689. Source: UniProt immune response Inferred from electronic annotation. Source: InterPro peptide antigen assembly with MHC class II protein complex Inferred from direct assay PubMed 22733780PubMed 7606781. Source: UniProt positive regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell Inferred from mutant phenotype PubMed 8139689. Source: UniProt positive regulation of T cell proliferation Inferred from mutant phenotype PubMed 8139689. Source: UniProt
Cellular_component	MHC class II protein complex Inferred from direct assay PubMed 22247549PubMed 22733780PubMed 7606781. Source: UniProt 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
Molecular_function	MHC class II protein complex binding Inferred from direct assay PubMed 22733780. Source: UniProt
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 263

245

HLA class II histocompatibility antigen, DM beta chain

PRO_0000018960

Regions

Topological domain

19 – 218

200

Lumenal Potential

Transmembrane

219 – 239

21

Helical; Potential

Topological domain

240 – 263

24

Cytoplasmic Potential

Domain

114 – 208

95

Ig-like C1-type

Region

19 – 112

94

Beta-1

Region

113 – 207

95

Beta-2

Region

208 – 218

11

Connecting peptide Potential

Motif

248 – 251

4

YXXZ motif

Amino acid modifications

Glycosylation

110

1

N-linked (GlcNAc...) Ref.14

Disulfide bond

29 ↔ 97

Ref.15 Ref.16

Disulfide bond

135 ↔ 192

Ref.15 Ref.16

Natural variations

Natural variant

28

1

T → A in allele DMB*01:07.
Corresponds to variant rs17583782 [ dbSNP | Ensembl ].

VAR_050360

Natural variant

45

1

S → F in allele DMB*01:06.
Corresponds to variant rs41560814 [ dbSNP | Ensembl ].

VAR_016752

Natural variant

49

1

D → V in allele DMB*01:07.
Corresponds to variant rs17617333 [ dbSNP | Ensembl ].

VAR_050361

Natural variant

71

1

S → N in allele DMB*01:07.
Corresponds to variant rs17617321 [ dbSNP | Ensembl ].

VAR_050362

Natural variant

162

1

A → E in allele DMB*01:02 and allele DMB*01:06.

VAR_016753

Natural variant

162

1

A → V in allele DMB*01:04 and allele DMB*01:05.

VAR_016754

Natural variant

197

1

I → T in allele DMB*01:03, allele DMB*01:04 and allele DMB*01:06. Ref.5
Corresponds to variant rs1042337 [ dbSNP | Ensembl ].

VAR_016755

Experimental info

Mutagenesis

248

1

Y → A: Abolishes targeting to endosomes and results in relocalization to the cell membrane. Ref.13

Mutagenesis

251

1

L → A: Abolishes targeting to endosomes and results in relocalization to the cell membrane. Ref.13

Secondary structure

1

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263

Helix Strand Turn

Details...

Beta strand

22 – 32

11

Beta strand

33 – 35

3

Beta strand

37 – 46

10

Beta strand

49 – 55

7

Turn

56 – 59

4

Beta strand

60 – 63

4

Beta strand

67 – 69

3

Helix

70 – 81

12

Helix

84 – 91

8

Helix

93 – 109

17

Beta strand

116 – 121

6

Beta strand

128 – 143

16

Beta strand

146 – 151

6

Beta strand

154 – 156

3

Beta strand

170 – 172

3

Beta strand

174 – 182

9

Beta strand

190 – 195

6

Beta strand

199 – 201

3

Beta strand

203 – 207

5

Sequences

	Sequence		Length	Mass (Da)
	P28068 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 9B50F6CC22B3A4BA	FASTA	263	28,943
	10 20 30 40 50 60 MITFLPLLLG LSLGCTGAGG FVAHVESTCL LDDAGTPKDF TYCISFNKDL LTCWDPEENK 70 80 90 100 110 120 MAPCEFGVLN SLANVLSQHL NQKDTLMQRL RNGLQNCATH TQPFWGSLTN RTRPPSVQVA 130 140 150 160 170 180 KTTPFNTREP VMLACYVWGF YPAEVTITWR KNGKLVMPHS SAHKTAQPNG DWTYQTLSHL 190 200 210 220 230 240 ALTPSYGDTY TCVVEHIGAP EPILRDWTPG LSPMQTLKVS VSAVTLGLGL IIFSLGVISW 250 260 RRAGHSSYTP LPGSNYSEGW HIS

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 DMB*01:01).
[2]	"Genomic organization of HLA-DMA and HLA-DMB. Comparison of the gene organization of all six class II families in the human major histocompatibility complex." Radley E., Alderton R.P., Kelly A., Trowsdale J., Beck S. J. Biol. Chem. 269:18834-18838(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE DMB*01:01).
[3]	"Evolutionary dynamics of non-coding sequences within the class II region of the human MHC." Beck S., Abdulla S., Alderton R.P., Glynne R.J., Gut I.G., Hosking L.K., Jackson A., Kelly A., Newell W.R., Sanseau P., Radley E., Thorpe K.L., Trowsdale J. J. Mol. Biol. 255:1-13(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE DMB*01:01).
[4]	"Identification of a novel HLA-DMB allele (DMB*0107) in the Korean population." Gu H., Moon S.-M., Kim J.-J., Ryu H.-J., Kwack K., Kimm K., Lee J.-K., Oh B. Tissue Antigens 65:393-394(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DMB*01:07).
[5]	"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], VARIANT THR-197.
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE DMB*01:01). Tissue: Lymph.
[8]	"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 114-207 (ALLELES DMB*01:02 AND DMB*01:03).
[9]	"Characterization of HLA-DMB polymorphism." Carrington M., Yeager M., Mann D. Immunogenetics 38:446-449(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 121-200 (ALLELE DMB*01:04).
[10]	"Three HLA-DMB variants in Korean patients with autoimmune diseases." Kim T.-G., Carrington M., Choi H.B., Kim H.Y., Han H. Hum. Immunol. 46:58-60(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 113-207 (ALLELE DMB*01:05). Tissue: Blood.
[11]	"The nucleotide sequence of a new DMB allele, DMB*0106." McTernan C.L., Mijovic C.H., Cockram C.S., Barnett A.H. Tissue Antigens 55:470-472(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 19-112 AND 152-207 (ALLELE DMB*01:06).
[12]	"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.
[13]	"Targeting signal and subcellular compartments involved in the intracellular trafficking of HLA-DMB." Copier J., Kleijmeer M.J., Ponnambalam S., Oorschot V., Potter P., Trowsdale J., Kelly A. J. Immunol. 157:1017-1027(1996) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-248 AND LEU-251.
[14]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-110. Tissue: Plasma.
[15]	"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 19-218 IN COMPLEX WITH DMA, FUNCTION, SUBUNIT, DISULFIDE BONDS.
[16]	"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 19-218 IN COMPLEX WITH DMA, FUNCTION, SUBUNIT, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z23139 mRNA. Translation: CAA80670.1.
U15085 mRNA. Translation: AAB60387.1.
X76776 Genomic DNA. Translation: CAA54171.1.
X87344 Genomic DNA. Translation: CAA60782.1.
AY645722 mRNA. Translation: AAV97947.1.
AL662845 Genomic DNA. Translation: CAI17490.1.
AL645941 Genomic DNA. Translation: CAI18108.1.
AL935042 Genomic DNA. Translation: CAI18685.1.
BX088556 Genomic DNA. Translation: CAM26271.1.
BX927138 Genomic DNA. Translation: CAQ08457.1.
CR936913 Genomic DNA. Translation: CAQ08780.1.
CR759798 Genomic DNA. Translation: CAQ09462.1.
CR752645 Genomic DNA. Translation: CAQ09834.1.
CH471081 Genomic DNA. Translation: EAX03657.1.
BC027175 mRNA. Translation: AAH27175.1.
Z24750 Genomic DNA. No translation available.
Z24751 Genomic DNA. No translation available.
U00700 Genomic DNA. Translation: AAA03296.1.
U16762 Genomic DNA. Translation: AAC50514.1.
AF134890 Genomic DNA. Translation: AAD30279.1.
AF072680 Genomic DNA. Translation: AAC26112.1.

CCDS

CCDS4760.1.

PIR

I37533.

RefSeq

NP_002109.2. NM_002118.4.

UniGene

Hs.351279.

3D structure databases

PDBe
RCSB-PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HDM	X-ray	2.50	B	19-218	[»]
2BC4	X-ray	2.27	B/D	19-256	[»]
4FQX	X-ray	2.60	D	19-211	[»]
4GBX	X-ray	3.00	D	19-211	[»]
4I0P	X-ray	3.20	B/F	21-211	[»]

ProteinModelPortal

P28068.

SMR

P28068. Positions 21-217.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

109354. 6 interactions.

DIP

DIP-6185N.

IntAct

P28068. 7 interactions.

MINT

MINT-1539801.

STRING

9606.ENSP00000393646.

PTM databases

PhosphoSite

P28068.

Polymorphism databases

DMDM

133160.

Proteomic databases

PaxDb

P28068.

PRIDE

P28068.

Protocols and materials databases

DNASU

3109.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000383231; ENSP00000372718; ENSG00000241674.
ENST00000395312; ENSP00000378723; ENSG00000242092.
ENST00000412948; ENSP00000413471; ENSG00000241296.
ENST00000418107; ENSP00000398890; ENSG00000242574.
ENST00000424822; ENSP00000414817; ENSG00000234154.
ENST00000428420; ENSP00000393646; ENSG00000239329.
ENST00000440078; ENSP00000411321; ENSG00000226264.
ENST00000450897; ENSP00000408453; ENSG00000242386.

GeneID

3109.

KEGG

hsa:3109.

Organism-specific databases

CTD

3109.

GeneCards

GC06M032903.
GC06Mi32885.
GC06Mj32824.
GC06Mk32880.
GC06Ml33056.
GC06Mm32935.
GC06Mn32831.
GC06Mo32992.

H-InvDB

HIX0166396.
HIX0207613.
HIX0207705.
HIX0207762.

HGNC

HGNC:4935. HLA-DMB.

HPA

HPA012298.

MIM

142856. gene.

neXtProt

NX_P28068.

PharmGKB

PA35059.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG40558.

HOVERGEN

HBG007327.

InParanoid

P28068.

KO

K06752.

OMA

DCATHTQ.

PhylomeDB

P28068.

TreeFam

TF335727.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P28068.

Bgee

P28068.

CleanEx

HS_HLA-DMB.

Genevestigator

P28068.

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.
IPR000353. MHC_II_b_N.
[Graphical view]

Pfam

PF07654. C1-set. 1 hit.
PF00969. MHC_II_beta. 1 hit.
[Graphical view]

SMART

SM00407. IGc1. 1 hit.
SM00921. MHC_II_beta. 1 hit.
[Graphical view]

SUPFAM

SSF54452. SSF54452. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

EvolutionaryTrace

P28068.

GeneWiki

HLA-DMB.

GenomeRNAi

3109.

NextBio

12337.

PRO

P28068.

SOURCE

Search...

Entry information

Entry name

DMB_HUMAN

Accession

Primary (citable) accession number: P28068
Secondary accession number(s): O77936 , Q13012, Q29751, Q58ZE2, Q5SNZ8, Q5STC4, Q9XRX2

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	July 9, 2014
This is version 144 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.