DRB4_HUMAN - dbPTM
DRB4_HUMAN - PTM Information in dbPTM
Basic Information of Protein
UniProt ID DRB4_HUMAN
UniProt AC P13762
Protein Name HLA class II histocompatibility antigen, DR beta 4 chain
Gene Name HLA-DRB4
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 membrane pro
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 MVCLKLPGGSCMAALTVTLTVLSSPLALAGDTQPRFLEQAKCECHFLNGTERVWNLIRYIYNQEEYARYNSDLGEYQAVTELGRPDAEYWNSQKDLLERRRAEVDTYCRYNYGVVESFTVQRRVQPKVTVYPSKTQPLQHHNLLVCSVNGFYPGSIEVRWFRNGQEEKAGVVSTGLIQNGDWTFQTLVMLETVPRSGEVYTCQVEHPSMMSPLTVQWSARSESAQSKMLSGVGGFVLGLLFLGTGLFIYFRNQKGHSGLQPTGLLS
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 Orthologous
Protein Cluster
10PhosphorylationCLKLPGGSCMAALTV
EEECCCCCCEEEEEE
13.46-
16PhosphorylationGSCMAALTVTLTVLS
CCCEEEEEEHHHHHH
13.50-
48N-linked_GlycosylationKCECHFLNGTERVWN
CCEEEECCCHHHHHH
55.16UniProtKB CARBOHYD
59PhosphorylationRVWNLIRYIYNQEEY
HHHHHHHHHHCHHHH
10.77-
61PhosphorylationWNLIRYIYNQEEYAR
HHHHHHHHCHHHHHH
11.23-
66PhosphorylationYIYNQEEYARYNSDL
HHHCHHHHHHHCCCC
8.81-
80PhosphorylationLGEYQAVTELGRPDA
CCHHHHHHHCCCCCH
28.6323532336
92PhosphorylationPDAEYWNSQKDLLER
CCHHHHHCHHHHHHH
25.1823532336
94UbiquitinationAEYWNSQKDLLERRR
HHHHHCHHHHHHHHH
50.60-
192PhosphorylationQTLVMLETVPRSGEV
EEEEEEEECCCCCEE
31.6724719451
254UbiquitinationFIYFRNQKGHSGLQP
EEEEECCCCCCCCCC
63.2419117940

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
-KUbiquitinationE3 ubiquitin ligaseMARCHF8Q5T0T0
PMID:19117940
-KUbiquitinationE3 ubiquitin ligaseMARCHF1Q8TCQ1
PMID:19117940
-KUbiquitinationE3 ubiquitin ligaseCDC20Q12834
PMID:22545099

Functions of PTM Sites
Modified Location Modified Residue Modification Function Reference
244Kubiquitylation

19117940
254Kubiquitylation

19117940

Disease-associated PTM Sites based on SAP

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

Modified Location Modification Variant Position
(Distance <= 10)
Residue Change SAP Related Disease Reference

Oops, there are no SNP-PTM records of DRB4_HUMAN !!

Protein-Protein Interaction
Interacting Protein Gene Name Interaction Type PPI Reference Domain-Domain Interactions
KPYM_HUMANPKMphysical
20458337
HS90A_HUMANHSP90AA1physical
20458337
HSP7C_HUMANHSPA8physical
20458337
ANX11_HUMANANXA11physical
20458337
HS90B_HUMANHSP90AB1physical
20458337
AT1B1_HUMANATP1B1physical
20458337
1433E_HUMANYWHAEphysical
20458337
CD20_HUMANMS4A1physical
20458337
MAGA6_HUMANMAGEA6physical
12631591

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.
Regulatory Network of DRB4_HUMAN

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Related Literatures of Post-Translational Modification
Ubiquitylation
ReferencePubMed
"The HLA-DRalpha chain is modified by polyubiquitination.";
Lapaque N., Jahnke M., Trowsdale J., Kelly A.P.;
J. Biol. Chem. 284:7007-7016(2009).
Cited for: UBIQUITINATION AT LYS-254 BY MARCH1 AND MARCH8, MUTAGENESIS OFLYS-254; LEU-264 AND LEU-265, AND SUBCELLULAR LOCATION.

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