DRB5_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: DRB5_HUMAN
• UniProt AC: Q30154
• Protein Name: HLA class II histocompatibility antigen, DR beta 5 chain
• Gene Name: HLA-DRB5 {ECO:0000312|EMBL:CAI18079.1}
• 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: MVCLKLPGGSYMAKLTVTLMVLSSPLALAGDTRPRFLQQDKYECHFFNGTERVRFLHRDIYNQEEDLRFDSDVGEYRAVTELGRPDAEYWNSQKDFLEDRRAAVDTYCRHNYGVGESFTVQRRVEPKVTVYPARTQTLQHHNLLVCSVNGFYPGSIEVRWFRNSQEEKAGVVSTGLIQNGDWTFQTLVMLETVPRSGEVYTCQVEHPSVTSPLTVEWRAQSESAQSKMLSGVGGFVLGLLFLGAGLFIYFKNQKGHSGLHPTGLVS

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	CLKLPGGSYMAKLTV EEECCCCCEEEEEEE	20.04	24043423
11	Phosphorylation	LKLPGGSYMAKLTVT EECCCCCEEEEEEEE	12.36	24043423
48	N-linked_Glycosylation	KYECHFFNGTERVRF CEEEECCCCCCEEEE	56.38	19159218
107	Phosphorylation	RRAAVDTYCRHNYGV HHHHHHHHHHHCCCC	5.30	-
112	Phosphorylation	DTYCRHNYGVGESFT HHHHHHCCCCCCCEE	13.68	-
129	Phosphorylation	RRVEPKVTVYPARTQ ECCCCCEEEEECCCC	22.05	-
131	Phosphorylation	VEPKVTVYPARTQTL CCCCEEEEECCCCCC	5.04	-
192	Phosphorylation	QTLVMLETVPRSGEV EEEEEEEECCCCCEE	31.67	24719451
266	Phosphorylation	LHPTGLVS------- CCCCCCCC-------	39.28	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	MARCHF1	Q8TCQ1	PMID:18305173
-	K	Ubiquitination	E3 ubiquitin ligase	MARCHF8	Q5T0T0	PMID:18305173

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
254	K	ubiquitylation	Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to 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 DRB5_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
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
1A02_HUMAN	HLA-A	physical	26186194
1A03_HUMAN	HLA-A	physical	26186194
1A01_HUMAN	HLA-A	physical	26186194
1A26_HUMAN	HLA-A	physical	26186194
STAT1_HUMAN	STAT1	physical	26186194
CHK1_HUMAN	CHEK1	physical	26186194
CHK1_HUMAN	CHEK1	physical	28514442
GRP78_HUMAN	HSPA5	physical	28514442
UBR3_HUMAN	UBR3	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

"Glycoproteomics analysis of human liver tissue by combination ofmultiple enzyme digestion and hydrazide chemistry.";
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
J. Proteome Res. 8:651-661(2009).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-48, AND MASS SPECTROMETRY.
PubMed: 19159218