Details of Host Protein

KEGG: hsa03013 Pathway Download ×

Host Protein General Information (ID: PT1168)
Protein Name	Transmembrane protein 33 (TMEM33)	Gene Name	TMEM33
Host Species	Homo sapiens	Uniprot Entry Name	TMM33_HUMAN
Protein Families	PER33/POM33 family
Subcellular Location	Endoplasmic reticulum membrane
External Link
	NCBI Gene ID	55161
	Uniprot ID	P57088
	Ensembl ID	ENSG00000109133
	HGNC ID	HGNC:25541
Function in Host	Acts as a regulator of the tubular endoplasmic reticulum (ER) network by modulating intracellular calcium homeostasis. Mechanistically, stimulates PKD2 calcium-dependent activity. Suppresses the RTN3/4-induced formation of the ER tubules. Positively regulates PERK-mediated and IRE1-mediatedunfolded protein response signaling. Plays anessential role in VEGF-mediated release of Ca (2+) from ER stores duringangiogenesis. Plays also a role in the modulation ofinnate immune signaling through the cGAS-STING pathway by interactingwith RNF26. Participates in lipid metabolism byacting as a downstream effector of the pyruvate kinase/PKM. Forms acomplex with RNF5 to facilitate polyubiquitination and subsequentdegradation of SCAP on the ER membrane. [1-4] Click to Show/Hide
Related KEGG Pathway
Related KEGG Pathway	Nucleocytoplasmic transport	hsa03013		Pathway Map
3D Structure	AlphaFold ID: P57088 2D PNG Download mmCIF File Download PDB File Download

Function of This Protein During Virus Infection
Virus Name	SARS-COV-2	Protein Function	Pro-viral	[5]
Infected Tissue	Lung	Infection Time	7-9 Days
Infected Cell	Calu-3 Cells (Human epithelial cell line)	Cellosaurus ID	CVCL_0609
Method Description	To detect the role of host protein TMEM33 in viral infection, TMEM33 protein knockout Calu-3 Cells were infected with SARS-COV-2 for 7 - 9 Days , and the effects on infection was detected through CRISPR-based genome-wide gene-knockout screen.
Results	It is reported that knockout of TMEM33 leads to the decreased SARS-CoV-2 RNA levels compared with control group.

Full List of Virus RNA Interacting with This Protien
*RNA Region: 3'-UTR (hCoV-19/IPBCAMS-YL01/2020 )*
RNA Region Details	RNA Info Click to show the detail information of this RNA binding region	[6]
Strains Name	hCoV-19/IPBCAMS-YL01/2020
Strains Family	Beta (B.1.351)
RNA Binding Region	3'-UTR
Virus Name	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Interaction Type	Unlikely to be direct binder
Infection Cells	Huh7.5.1 cells (Hepatocyte derived cellular carcinoma cell) (CVCL_E049 )
Cell Originated Tissue	Liver
Infection Time	30 h
Interaction Score	MIST = 0.617987238
Method Description	comprehensive identification of RNA-binding proteins by massspectrometry (ChIRP-MS)

Differential Gene Expression During SARS-COV-2 Infection

GEO Accession: GSE152641

Sample Type: Blood

Samples Details: Healthy Control: 24; COVID-19: 62

Platform: GPL24676 Illumina NovaSeq 6000

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GEO Accession: GSE162835

Sample Type: Nasopharyngeal Swabs

Samples Details: COVID-19 (Mild Symptoms): 37; COVID-19 (Moderate Symptoms): 10; COVID-19 (Severe Symptoms): 3

Platform: GPL24676 Illumina NovaSeq 6000

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GEO Accession: GSE175779

Sample Type: Human Bronchial Epithelial Cells

Samples Details: Healthy Control: 4 (0, 24, 48, 72 and 96 h); COVID-19: 4 (24, 48, 72 and 96 h)

Platform: GPL18573 Illumina NextSeq 500

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Protein Sequence Information
MADTTPNGPQGAGAVQFMMTNKLDTAMWLSRLFTVYCSALFVLPLLGLHEAASFYQRALLANALTSALRLHQRLPHFQLSRAFLAQALLEDSCHYLLYSLIFVNSYPVTMSIFPVLLFSLLHAATYTKKVLDARGSNSLPLLRSVLDKLSANQQNILKFIACNEIFLMPATVFMLFSGQGSLLQPFIYYRFLTLRYSSRRNPYCRTLFNELRIVVEHIIMKPACPLFVRRLCLQSIAFISRLAPTVP Click to Show/Hide

References
1	Interaction mapping of endoplasmic reticulum ubiquitin ligases identifies modulators of innate immune signalling. Elife. 2020 Jul 2;9:e57306.
2	tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis. Nat Commun. 2019 Feb 13;10(1):732.
3	TMEM33: a new stress-inducible endoplasmic reticulum transmembrane protein and modulator of the unfolded protein response signaling. Breast Cancer Res Treat. 2015 Sep;153(2):285-97.
4	Identification and characterization of TMEM33 as a reticulon-binding protein. Kobe J Med Sci. 2014 Nov 6;60(3):E57-65.
5	Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2. Nat Commun. 2022 Apr 25;13(1):2237.
6	Comparison of viral RNA-host protein interactomes across pathogenic RNA viruses informs rapid antiviral drug discovery for SARS-CoV-2. Cell Res. 2022 Jan;32(1):9-23.