Primary Information
BoMiProt ID	Bomi8721
Protein Name	Reticulophagy regulator 1
Organism	Bos taurus
Uniprot ID	Q5E9K8
Milk Fraction	Whey
Ref Sequence ID	NP_001015672.1
Aminoacid Length	493
Molecular Weight	53680
FASTA Sequence	Download
Gene Name	RETREG1
Gene ID	540068
Protein Existence Status	reviewed
Secondary Information
Protein Function	It is an autophagy receptor anchoroed to ER.RETREG1 participates in the formation of the mitophagophore by interacting with OPA1 and is responsible for delivering ER into lysosomes through sequestration into autophagosomes.
Biochemical Properties	LC3 binding motif of RETREG1 is essential for autophagic degradation of AMFR.The reticulon homology domain provides capacity to bend the membrane and promotes ER scission.Structure analysis showed that the N-terminal half of FAM134B has 2 unusually long hydrophobic segments of about 35 amino acids each that are separated by a hydrophilic loop of about 60 amino acids.The C terminus of FAM134B contains a coiled-coil domain.
PTMs	Phosphorylation on Thr and Ser
Significance of PTMs	Mass spectrometry analysis resulted in the identification of serine 149, 151, and 153 (S149, S151, S153) as potential FAM134B phosphorylation sites and all of these three residues reside within RTND.Under ER-stress conditions, activated CAMK2B phosphorylates the reticulon-homology domain of FAM134B, which enhances FAM134B oligomerization and activity in membrane fragmentation to accommodate high demand for ERphagy.
Linking IDs	Bomi8721
Bibliography	1.Kurth, I., Pamminger, T., Hennings, J. C., Soehendra, D., Huebner, A. K., Rotthier, A., Baets, J., Senderek, J., Topaloglu, H., Farrell, S. A., Nurnberg, G., Nurnberg, P., De Jonghe, P., Gal, A., Kaether, C., Timmerman, V., Hubner, C. A. Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. Nature Genet. 41: 1179-1181, 2009. 2.Islam, F., Gopalan, V., & Lam, A. K. (2018). RETREG1 (FAM134B): A new player in human diseases: 15 years after the discovery in cancer. Journal of cellular physiology, 233(6), 4479–4489. https://doi.org/10.1002/jcp.26384 3.Jiang X, Wang X, Ding X, Du M, Li B, Weng X, Zhang J, Li L, Tian R, Zhu Q, Chen S, Wang L, Liu W, Fang L, Neculai D, Sun Q. FAM134B oligomerization drives endoplasmic reticulum membrane scission for ER-phagy. EMBO J. 2020 Mar 2;39(5):e102608. doi: 10.15252/embj.2019102608. Epub 2020 Jan 13. PMID: 31930741; PMCID: PMC7049798.
Protein Function	It is an autophagy receptor anchoroed to ER.RETREG1 participates in the formation of the mitophagophore by interacting with OPA1 and is responsible for delivering ER into lysosomes through sequestration into autophagosomes.
Biochemical Properties	LC3 binding motif of RETREG1 is essential for autophagic degradation of AMFR.The reticulon homology domain provides capacity to bend the membrane and promotes ER scission.Structure analysis showed that the N-terminal half of FAM134B has 2 unusually long hydrophobic segments of about 35 amino acids each that are separated by a hydrophilic loop of about 60 amino acids.The C terminus of FAM134B contains a coiled-coil domain.
PTMs	Phosphorylation on Thr and Ser
Site(s) of PTM(s) N-glycosylation, O-glycosylation, Phosphorylation	>sp|Q5E9K8|RETR1_BOVIN Reticulophagy regulator 1 OS=Bos taurus OX=9913 GN=RETREG1 PE=2 SV=2 MASPAPPEPAEQGSPALAAAPQAPPPPTRAPPEEPEGAAPPEEGAAAGAGRQVEEAAGGV AAVVTWLLGEPALWLGGRADELLSWKRPLHSLLAFVGANLVFWFLALTPWRVYHLISVMI LTRVIMQIIKDMILSRTRGAQLWRSLSESWEVINSKPDERPGFSHCLAESWMNFSIFLQE MSVFKQQSPGKFCLLVCSVCTFFTILGSYIPGVILSYLLLLCAFLCPLFKCNDIGQKIYS KIKSCLLKLDFGIREYINQKKRERSEADKEKSHKDDSELDFSALCPKISLTTAAKELSVS DTDVSEVSWTDNGTFNLSEGYTPQTDTSDDLDRPSEEVFSRDLSDFPSLENGT*353GTNDEDE LSLGLPTELKRKKEQLDGGPRRSTEKKSAAGLSLPLSSDQTLHLMSDLAGDVITAAVTAA VKDQLAGVRQALSQAAPSLGEDTDTEEGDDFELLDQSELDQIESELGLSQDQEAEAQQNK KSSGFLSNLLGGH
Predicted Disorder Regions	5 disordered segments; (1-54), (263-276), (313-363), (366-400), (415-493)
DisProt Annotation
TM Helix Prediction	2 TMHs;( 100-122) and ( 192-214)
Significance of PTMs	Mass spectrometry analysis resulted in the identification of serine 149, 151, and 153 (S149, S151, S153) as potential FAM134B phosphorylation sites and all of these three residues reside within RTND.Under ER-stress conditions, activated CAMK2B phosphorylates the reticulon-homology domain of FAM134B, which enhances FAM134B oligomerization and activity in membrane fragmentation to accommodate high demand for ERphagy.
Linking IDs
Bibliography	1.Kurth, I., Pamminger, T., Hennings, J. C., Soehendra, D., Huebner, A. K., Rotthier, A., Baets, J., Senderek, J., Topaloglu, H., Farrell, S. A., Nurnberg, G., Nurnberg, P., De Jonghe, P., Gal, A., Kaether, C., Timmerman, V., Hubner, C. A. Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. Nature Genet. 41: 1179-1181, 2009. 2.Islam, F., Gopalan, V., & Lam, A. K. (2018). RETREG1 (FAM134B): A new player in human diseases: 15 years after the discovery in cancer. Journal of cellular physiology, 233(6), 4479–4489. https://doi.org/10.1002/jcp.26384 3.Jiang X, Wang X, Ding X, Du M, Li B, Weng X, Zhang J, Li L, Tian R, Zhu Q, Chen S, Wang L, Liu W, Fang L, Neculai D, Sun Q. FAM134B oligomerization drives endoplasmic reticulum membrane scission for ER-phagy. EMBO J. 2020 Mar 2;39(5):e102608. doi: 10.15252/embj.2019102608. Epub 2020 Jan 13. PMID: 31930741; PMCID: PMC7049798.