dbPTM

E2AK1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	E2AK1_MOUSE
UniProt AC	Q9Z2R9
Protein Name	Eukaryotic translation initiation factor 2-alpha kinase 1
Gene Name	Eif2ak1
Organism	Mus musculus (Mouse).
Sequence Length	619
Subcellular Localization	Cytoplasm .
Protein Description	Inhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. Exerts its function through the phosphorylation of EIF2S1 at 'Ser-48' and 'Ser-51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions. In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties. Thus plays an essential protective role for RBC survival in anemias of iron deficiency. Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes. May also contain ER stress during acute heme-deficient conditions..
Protein Sequence	MLGGSSVDGERDTDDDAAGAVAAPPAIDFPAEVSDPKYDESDVPAELQVLKEPLQQPTFPFLVANQLLLVSLLEHLSHVHEPNPLHSKQVFKLLCQTFIKMGLLSSFTCSDEFSSLRLHHNRAITHLMRSAKERVRQDPCQDNSYMQKIRSREIAFEAQTSRYLNEFEELAILGKGGYGRVYKVRNKLDGQHYAIKKILIKSATKTDCMKVLREVKVLAGLQHPNIVGYHTAWIEHVHVVQPQDRVPIQLPSLEVLSEQEGDRDQGGVKDNESSSSIVFAELTPEKEKPFGESEVKNENNNLVSYTANLVVRNSSESESSIELQEDGLTDLSVRPVVRHQLPLGHSSELEGNFTSTDESSEGNLNLLGQTEVRYHLMLHIQMQLCELSLWDWITERNKRSREYVDEAACPYVMASVATKIFQELVEGVFYIHNMGIVHRDLKPRNIFLHGPDQQVKIGDFGLACADIIQNADWTNRNGKGTRTHTSRVGTCLYASPEQLEGSQYDAKSDMYSLGVILLELFQPFGTEMERATVLTGVRTGRIPESLSKRCPVQAKYIQLLTGRNVSQRPSALQLLQSELFQTTGNVNLTLQMKIIEQEKEIEELKKQLSLLSQDRGLKR

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
201	Ubiquitination	AIKKILIKSATKTDC EHHHHHHHHCCCCHH	30.50	-
205	Ubiquitination	ILIKSATKTDCMKVL HHHHHCCCCHHHHHH	41.92	-
283	Phosphorylation	SIVFAELTPEKEKPF EEEEEECCCCCCCCC	22.40	22817900
314	Phosphorylation	ANLVVRNSSESESSI EEEEEECCCCCCCCE	25.56	25293948
315	Phosphorylation	NLVVRNSSESESSIE EEEEECCCCCCCCEE	49.00	25293948
317	Phosphorylation	VVRNSSESESSIELQ EEECCCCCCCCEEEC	44.73	25293948
319	Phosphorylation	RNSSESESSIELQED ECCCCCCCCEEECCC	45.99	25293948
320	Phosphorylation	NSSESESSIELQEDG CCCCCCCCEEECCCC	18.94	25293948
442	Acetylation	GIVHRDLKPRNIFLH CEECCCCCCCCEEEE	46.34	7610251
483	Phosphorylation	RNGKGTRTHTSRVGT CCCCCCCCCCCCCEE	29.37	22817900
485	Phosphorylation	GKGTRTHTSRVGTCL CCCCCCCCCCCEEEE	20.02	22817900
490	Phosphorylation	THTSRVGTCLYASPE CCCCCCEEEEECCHH	9.11	22817900

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
483	T	Phosphorylation	Kinase	EIF2AK1	Q9Z2R9	GPS
485	T	Phosphorylation	Kinase	EIF2AK1	Q9Z2R9	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
485	T	Phosphorylation		12767237
Autophosphorylation at Thr-485 is required for kinase activation.

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 E2AK1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
Oops, there are no PPI records of E2AK1_MOUSE !!

Drug and Disease Associations

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

Regulatory Network of E2AK1_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Autophosphorylation of threonine 485 in the activation loop isessential for attaining eIF2alpha kinase activity of HRI."; Rafie-Kolpin M., Han A.P., Chen J.J.; Biochemistry 42:6536-6544(2003). Cited for: AUTOPHOSPHORYLATION AT THR-483; THR-485 AND THR-490, ENZYMEREGULATION, AND MUTAGENESIS OF LYS-196; THR-483; THR-485 AND THR-490.	12767237 [Abstract]

show