DQA1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: DQA1_HUMAN
• UniProt AC: P01909
• Protein Name: HLA class II histocompatibility antigen, DQ alpha 1 chain
• Gene Name: HLA-DQA1
• Organism: Homo sapiens (Human).
• Sequence Length: 254
• 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: MILNKALMLGALALTTVMSPCGGEDIVADHVASYGVNLYQSYGPSGQYTHEFDGDEQFYVDLGRKETVWCLPVLRQFRFDPQFALTNIAVLKHNLNSLIKRSNSTAATNEVPEVTVFSKSPVTLGQPNILICLVDNIFPPVVNITWLSNGHSVTEGVSETSFLSKSDHSFFKISYLTLLPSAEESYDCKVEHWGLDKPLLKHWEPEIPAPMSELTETVVCALGLSVGLVGIVVGTVFIIRGLRSVGASRHQGPL

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
65	Ubiquitination	FYVDLGRKETVWCLP EEEECCCCEEEEHHH	56.81	21906983
65	Ubiquitination	FYVDLGRKETVWCLP EEEECCCCEEEEHHH	56.81	21906983
76	Ubiquitination	WCLPVLRQFRFDPQF EHHHHHHHHCCCCHH	29.70	21906983
93	Ubiquitination	TNIAVLKHNLNSLIK HHHHHHHHHHHHHHH	39.59	21906983
93	Ubiquitination	TNIAVLKHNLNSLIK HHHHHHHHHHHHHHH	39.59	21906983
97	Phosphorylation	VLKHNLNSLIKRSNS HHHHHHHHHHHHCCC	34.34	24719451
103	N-linked_Glycosylation	NSLIKRSNSTAATNE HHHHHHCCCCCCCCC	47.62	UniProtKB CARBOHYD
104	Phosphorylation	SLIKRSNSTAATNEV HHHHHCCCCCCCCCC	22.22	22468782
118	Phosphorylation	VPEVTVFSKSPVTLG CCEEEEEECCCCCCC	28.08	22468782
143	N-linked_Glycosylation	NIFPPVVNITWLSNG CCCCCEEEEEEECCC	26.63	UniProtKB CARBOHYD
212	Phosphorylation	PEIPAPMSELTETVV CCCCCCHHHHHHHHH	28.53	22210691
215	Phosphorylation	PAPMSELTETVVCAL CCCHHHHHHHHHHHH	26.09	22210691

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	MARCHF9	Q86YJ5	PMID:19457934

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of DQA1_HUMAN !!

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of DQA1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
APLP1_HUMAN	APLP1	physical	16169070
SH3G2_HUMAN	SH3GL2	physical	16169070
LRIF1_HUMAN	LRIF1	physical	16169070
TLE1_HUMAN	TLE1	physical	16169070
U119A_HUMAN	UNC119	physical	16169070
NEMO_HUMAN	IKBKG	physical	21988832
AT2B2_HUMAN	ATP2B2	physical	26186194
TM214_HUMAN	TMEM214	physical	26186194
VPP2_HUMAN	ATP6V0A2	physical	26186194
VPP1_HUMAN	ATP6V0A1	physical	26186194
MYO19_HUMAN	MYO19	physical	26186194
ZNT9_HUMAN	SLC30A9	physical	26186194
TM246_HUMAN	TMEM246	physical	26186194
1A02_HUMAN	HLA-A	physical	26186194
1A03_HUMAN	HLA-A	physical	26186194
1A01_HUMAN	HLA-A	physical	26186194
1A26_HUMAN	HLA-A	physical	26186194
CUX1_HUMAN	CUX1	physical	26186194
CASP_HUMAN	CUX1	physical	26186194
EFNB1_HUMAN	EFNB1	physical	26186194
MACOI_HUMAN	TMEM57	physical	26186194
TM219_HUMAN	TMEM219	physical	26186194
DD19B_HUMAN	DDX19B	physical	26186194
S27A6_HUMAN	SLC27A6	physical	26186194
GALT_HUMAN	GALT	physical	26186194
KCNJ8_HUMAN	KCNJ8	physical	26186194
S38A9_HUMAN	SLC38A9	physical	26186194
COT2_HUMAN	NR2F2	physical	26186194
ST7_HUMAN	ST7	physical	26186194
NSMA_HUMAN	SMPD2	physical	26186194
MFSD8_HUMAN	MFSD8	physical	26186194
GALT_HUMAN	GALT	physical	28514442
TM219_HUMAN	TMEM219	physical	28514442
S38A9_HUMAN	SLC38A9	physical	28514442
MFSD8_HUMAN	MFSD8	physical	28514442
EFNB1_HUMAN	EFNB1	physical	28514442
CUX1_HUMAN	CUX1	physical	28514442
CASP_HUMAN	CUX1	physical	28514442
MYO19_HUMAN	MYO19	physical	28514442
KCNJ8_HUMAN	KCNJ8	physical	28514442
TM214_HUMAN	TMEM214	physical	28514442
S22AI_HUMAN	SLC22A18	physical	28514442
ZNT9_HUMAN	SLC30A9	physical	28514442
ST7_HUMAN	ST7	physical	28514442

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.