DRB3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: DRB3_HUMAN
• UniProt AC: P79483
• Protein Name: HLA class II histocompatibility antigen, DR beta 3 chain
• Gene Name: HLA-DRB3
• Organism: Homo sapiens (Human).
• Sequence Length: 266
• Subcellular Localization: Cell membrane ; Single-pass type I membrane protein . Endoplasmic reticulum membrane ; Single-pass type I membrane protein . Golgi apparatus, trans-Golgi network membrane ; Single-pass type I membrane protein . Endosome membrane ; Single-pass type I membr
• Protein Description: Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading..
• Protein Sequence: MVCLKLPGGSSLAALTVTLMVLSSRLAFAGDTRPRFLELRKSECHFFNGTERVRYLDRYFHNQEEFLRFDSDVGEYRAVTELGRPVAESWNSQKDLLEQKRGRVDNYCRHNYGVGESFTVQRRVHPQVTVYPAKTQPLQHHNLLVCSVSGFYPGSIEVRWFRNGQEEKAGVVSTGLIQNGDWTFQTLVMLETVPRSGEVYTCQVEHPSVTSALTVEWRARSESAQSKMLSGVGGFVLGLLFLGAGLFIYFRNQKGHSGLQPTGFLS

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
10	Phosphorylation	CLKLPGGSSLAALTV EEECCCCHHHHHHHH	28.26	24043423
11	Phosphorylation	LKLPGGSSLAALTVT EECCCCHHHHHHHHH	25.88	24043423
16	Phosphorylation	GSSLAALTVTLMVLS CHHHHHHHHHHHHHH	13.50	24043423
18	Phosphorylation	SLAALTVTLMVLSSR HHHHHHHHHHHHHHH	12.14	24043423
23	Phosphorylation	TVTLMVLSSRLAFAG HHHHHHHHHHHHHCC	11.29	24043423
24	Phosphorylation	VTLMVLSSRLAFAGD HHHHHHHHHHHHCCC	27.44	24719451
32	Phosphorylation	RLAFAGDTRPRFLEL HHHHCCCCCHHHHHH	41.47	24043423
48	N-linked_Glycosylation	KSECHFFNGTERVRY HCCCCCCCCCHHHHH	56.38	18697946
100	Ubiquitination	QKDLLEQKRGRVDNY HHHHHHHHHCCHHCH	47.66	-
192	Phosphorylation	QTLVMLETVPRSGEV EEEEEEEECCCCCEE	31.67	24719451
257	Phosphorylation	FRNQKGHSGLQPTGF EECCCCCCCCCCCCC	50.28	27080861
262	Phosphorylation	GHSGLQPTGFLS--- CCCCCCCCCCCC---	27.83	27080861
266	Phosphorylation	LQPTGFLS------- CCCCCCCC-------	35.59	30108239

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
-	K	Ubiquitination	E3 ubiquitin ligase	MARCHF8	Q5T0T0	PMID:18305173
-	K	Ubiquitination	E3 ubiquitin ligase	MARCHF1	Q8TCQ1	PMID:18305173

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
254	K	ubiquitylation	Ubiquitinated by MARCHF1 and MARCHF8 at Lys-254 leading to sorting into the endosome system and down-regulation of MHC class II.	18305173

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of DRB3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
COLI_HUMAN	POMC	physical	7477400
KPYM_HUMAN	PKM	physical	20458337
HS90A_HUMAN	HSP90AA1	physical	20458337
HSP7C_HUMAN	HSPA8	physical	20458337
ANX11_HUMAN	ANXA11	physical	20458337
HS90B_HUMAN	HSP90AB1	physical	20458337
AT1B1_HUMAN	ATP1B1	physical	20458337
1433E_HUMAN	YWHAE	physical	20458337
CD20_HUMAN	MS4A1	physical	20458337
M3K13_HUMAN	MAP3K13	physical	21988832
2B1F_HUMAN	HLA-DRB1	physical	26186194
2B13_HUMAN	HLA-DRB1	physical	26186194
2B1G_HUMAN	HLA-DRB1	physical	26186194
SELN_HUMAN	SEPN1	physical	26186194
SEM4F_HUMAN	SEMA4F	physical	26186194
2B1F_HUMAN	HLA-DRB1	physical	28514442
2B13_HUMAN	HLA-DRB1	physical	28514442
2B1G_HUMAN	HLA-DRB1	physical	28514442
SELN_HUMAN	SEPN1	physical	28514442

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• D02967: Apolizumab (USAN/INN)
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

N-linked Glycosylation

"The structure of HLA-DR52c: comparison to other HLA-DRB3 alleles.";
Dai S., Crawford F., Marrack P., Kappler J.W.;
Proc. Natl. Acad. Sci. U.S.A. 105:11893-11897(2008).
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 30-219 OF HLA-DRA/HLA-DRB3HETERODIMER IN COMPLEX WITH EEF1A2 PEPTIDE, GLYCOSYLATION AT ASN-48,AND DISULFIDE BOND.
PubMed: 18697946