ID RETR1_HUMAN Reviewed; 497 AA. AC Q9H6L5; Q69YN8; Q9H6K6; Q9H764; Q9NXM8; DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 27-MAR-2024, entry version 156. DE RecName: Full=Reticulophagy regulator 1 {ECO:0000312|HGNC:HGNC:25964}; DE AltName: Full=Reticulophagy receptor 1 {ECO:0000305}; GN Name=RETREG1 {ECO:0000312|HGNC:HGNC:25964}; GN Synonyms=FAM134B, JK1 {ECO:0000303|PubMed:17487424}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Colon; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Colon, and Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 80-497. RC TISSUE=Melanoma; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP TISSUE SPECIFICITY. RX PubMed=17487424; RA Tang W.K., Chui C.H., Fatima S., Kok S.H., Pak K.C., Ou T.M., Hui K.S., RA Wong M.M., Wong J., Law S., Tsao S.W., Lam K.Y., Beh P.S., Srivastava G., RA Chan A.S., Ho K.P., Tang J.C.; RT "Oncogenic properties of a novel gene JK-1 located in chromosome 5p and its RT overexpression in human esophageal squamous cell carcinoma."; RL Int. J. Mol. Med. 19:915-923(2007). RN [5] RP FUNCTION, AND INVOLVEMENT IN HSAN2B. RX PubMed=19838196; DOI=10.1038/ng.464; RA Kurth I., Pamminger T., Hennings J.C., Soehendra D., Huebner A.K., RA Rotthier A., Baets J., Senderek J., Topaloglu H., Farrell S.A., RA Nuernberg G., Nurnberg P., De Jonghe P., Gal A., Kaether C., Timmerman V., RA Huebner C.A.; RT "Mutations in FAM134B, encoding a newly identified Golgi protein, cause RT severe sensory and autonomic neuropathy."; RL Nat. Genet. 41:1179-1181(2009). RN [6] RP FUNCTION, INTERACTION WITH MAP1LC3A; MAP1LC3B; GABARAP; GABARAPL1 AND RP GABARAPL2, SUBCELLULAR LOCATION, TOPOLOGY, DOMAIN, AND MUTAGENESIS OF RP 453-ASP--LEU-458. RX PubMed=26040720; DOI=10.1038/nature14498; RA Khaminets A., Heinrich T., Mari M., Grumati P., Huebner A.K., Akutsu M., RA Liebmann L., Stolz A., Nietzsche S., Koch N., Mauthe M., Katona I., RA Qualmann B., Weis J., Reggiori F., Kurth I., Huebner C.A., Dikic I.; RT "Regulation of endoplasmic reticulum turnover by selective autophagy."; RL Nature 522:354-358(2015). RN [7] RP FUNCTION, SUBUNIT, DOMAIN, PHOSPHORYLATION AT SER-149; SER-151 AND SER-153, RP MUTAGENESIS OF SER-149; SER-151 AND SER-153, AND CHARACTERIZATION OF RP VARIANT ARG-216. RX PubMed=31930741; DOI=10.15252/embj.2019102608; RA Jiang X., Wang X., Ding X., Du M., Li B., Weng X., Zhang J., Li L., RA Tian R., Zhu Q., Chen S., Wang L., Liu W., Fang L., Neculai D., Sun Q.; RT "FAM134B oligomerization drives endoplasmic reticulum membrane scission for RT ER-phagy."; RL EMBO J. 39:e102608-e102608(2020). RN [8] RP FUNCTION, INTERACTION WITH MAP1LC3A; MAP1LC3B; MAP1LC3C; GABARAP; GABARAPL1 RP AND GABARAPL2, AND MUTAGENESIS OF 455-PHE--LEU-458. RX PubMed=34338405; DOI=10.15252/embr.202052289; RA Reggio A., Buonomo V., Berkane R., Bhaskara R.M., Tellechea M., Peluso I., RA Polishchuk E., Di Lorenzo G., Cirillo C., Esposito M., Hussain A., RA Huebner A.K., Huebner C.A., Settembre C., Hummer G., Grumati P., Stolz A.; RT "Role of FAM134 paralogues in endoplasmic reticulum remodeling, ER-phagy, RT and Collagen quality control."; RL EMBO Rep. 22:e52289-e52289(2021). RN [9] RP FUNCTION (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION (MICROBIAL RP INFECTION). RX PubMed=35239449; DOI=10.1080/15548627.2022.2039992; RA Zhang X., Yang Z., Pan T., Long X., Sun Q., Wang P.H., Li X., Kuang E.; RT "SARS-CoV-2 ORF3a induces RETREG1/FAM134B-dependent reticulophagy and RT triggers sequential ER stress and inflammatory responses during SARS-CoV-2 RT infection."; RL Autophagy 0:0-0(2022). RN [10] {ECO:0007744|PDB:7BRQ} RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 450-468 IN CHIMERIC CONSTRUCT RP WITH GABARAP. RX PubMed=32620754; DOI=10.1038/s41467-020-17163-y; RA Mochida K., Yamasaki A., Matoba K., Kirisako H., Noda N.N., Nakatogawa H.; RT "Super-assembly of ER-phagy receptor Atg40 induces local ER remodeling at RT contacts with forming autophagosomal membranes."; RL Nat. Commun. 11:3306-3306(2020). RN [11] {ECO:0007744|PDB:7FB5} RP X-RAY CRYSTALLOGRAPHY (2.84 ANGSTROMS) OF 451-476 IN COMPLEX WITH MOUSE RP GABARAP, INTERACTION WITH GABARAP; GABARAPL1; MAP1LC3A AND MAP1LC3B, RP DOMAIN, AND MUTAGENESIS OF GLU-456; GLU-462; LEU-463 AND ILE-466. RX PubMed=34854256; DOI=10.1002/2211-5463.13340; RA Zhao J., Li Z., Li J.; RT "The crystal structure of the FAM134B-GABARAP complex provides mechanistic RT insights into the selective binding of FAM134 to the GABARAP subfamily."; RL FEBS Open Bio 12:320-331(2022). RN [12] RP VARIANT ARG-216. RX PubMed=22302274; DOI=10.1007/s00415-011-6397-y; RA Davidson G.L., Murphy S.M., Polke J.M., Laura M., Salih M.A., Muntoni F., RA Blake J., Brandner S., Davies N., Horvath R., Price S., Donaghy M., RA Roberts M., Foulds N., Ramdharry G., Soler D., Lunn M.P., Manji H., RA Davis M.B., Houlden H., Reilly M.M.; RT "Frequency of mutations in the genes associated with hereditary sensory and RT autonomic neuropathy in a UK cohort."; RL J. Neurol. 259:1673-1685(2012). CC -!- FUNCTION: Endoplasmic reticulum (ER)-anchored autophagy regulator which CC mediates ER delivery into lysosomes through sequestration into CC autophagosomes (PubMed:26040720, PubMed:31930741, PubMed:34338405). CC Promotes membrane remodeling and ER scission via its membrane bending CC capacity and targets the fragments into autophagosomes via interaction CC with ATG8 family proteins (PubMed:26040720, PubMed:31930741, CC PubMed:34338405). Active under basal conditions (PubMed:34338405). CC Required for collagen quality control in a LIR motif-dependent manner CC (By similarity). Required for long-term survival of nociceptive and CC autonomic ganglion neurons (PubMed:19838196, PubMed:26040720). CC {ECO:0000250|UniProtKB:Q8VE91, ECO:0000269|PubMed:19838196, CC ECO:0000269|PubMed:26040720, ECO:0000269|PubMed:34338405}. CC -!- FUNCTION: (Microbial infection) During SARS-CoV-2 infection, RETREG1- CC mediated reticulophagy is promoted by SARS-CoV-2 ORF3A protein CC (PubMed:35239449). This induces endoplasmic reticulum stress and CC inflammatory responses and facilitates viral infection CC (PubMed:35239449). {ECO:0000269|PubMed:35239449}. CC -!- SUBUNIT: Homooligomer; oligomerization is enhanced following CC endoplasmic reticulum stress and is mediated by the reticulon homology CC domain (PubMed:31930741). Interacts with ATG8 family modifier proteins CC MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAP, GABARAPL1 and GABARAPL2 CC (PubMed:26040720, PubMed:34338405, PubMed:34854256). Shows higher CC affinity for GABARAPL1 than for MAP1LC3A or MAP1LC3B (PubMed:34854256). CC {ECO:0000269|PubMed:26040720, ECO:0000269|PubMed:31930741, CC ECO:0000269|PubMed:34338405, ECO:0000269|PubMed:34854256}. CC -!- INTERACTION: CC Q9H6L5-1; P60520: GABARAPL2; NbExp=2; IntAct=EBI-16159046, EBI-720116; CC Q9H6L5-1; Q9H492-1: MAP1LC3A; NbExp=2; IntAct=EBI-16159046, EBI-16082793; CC Q9H6L5-2; O95817: BAG3; NbExp=3; IntAct=EBI-13382642, EBI-747185; CC Q9H6L5-2; P60520: GABARAPL2; NbExp=3; IntAct=EBI-13382642, EBI-720116; CC -!- SUBCELLULAR LOCATION: Golgi apparatus, cis-Golgi network membrane CC {ECO:0000250|UniProtKB:Q8VE91}; Multi-pass membrane protein CC {ECO:0000255}. Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:26040720}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:35239449}; Multi-pass membrane protein CC {ECO:0000255}. Note=(Microbial infection) Following SARS-CoV-2 CC infection, colocalizes with SARS-CoV-2 ORF3A protein at the endoplasmic CC reticulum. {ECO:0000269|PubMed:35239449}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9H6L5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H6L5-2; Sequence=VSP_025685, VSP_025686; CC -!- TISSUE SPECIFICITY: Overexpressed in esophageal squamous cell carcinoma CC (PubMed:17487424). {ECO:0000269|PubMed:17487424}. CC -!- DOMAIN: The LIR motif interacts with ATG8 family proteins and is CC necessary to target the ER fragments to autophagosomes for subsequent CC lysosomal degradation. {ECO:0000269|PubMed:19838196, CC ECO:0000269|PubMed:26040720}. CC -!- DOMAIN: The reticulon homology domain provides capacity to bend the CC membrane and promotes ER scission (PubMed:26040720, PubMed:31930741). CC It is required for homooligomerization (PubMed:31930741). This domain CC does not show relevant similarities with reticulon domains, preventing CC any domain predictions within the protein sequence. CC {ECO:0000269|PubMed:26040720, ECO:0000269|PubMed:31930741, CC ECO:0000305}. CC -!- PTM: Phosphorylation at Ser-151 by CAMK2B enhances oligomerization and CC membrane scission and reticulophagy activity. CC {ECO:0000269|PubMed:31930741}. CC -!- DISEASE: Neuropathy, hereditary sensory and autonomic, 2B (HSAN2B) CC [MIM:613115]: A form of hereditary sensory and autonomic neuropathy, a CC genetically and clinically heterogeneous group of disorders CC characterized by degeneration of dorsal root and autonomic ganglion CC cells, and by sensory and/or autonomic abnormalities. HSAN2B is an CC autosomal recessive disorder characterized by impairment of pain, CC temperature and touch sensation. Onset occurs in the first or second CC decade, with impaired nociception and progressive mutilating ulceration CC of the hands and feet with osteomyelitis and acroosteolysis. CC Amputations of the hands and feet are common. Autonomic dysfunction CC includes hyperhidrosis, urinary incontinence, and slow pupillary light CC response. {ECO:0000269|PubMed:19838196}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the RETREG family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH30517.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA90982.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB15252.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK000159; BAA90982.1; ALT_INIT; mRNA. DR EMBL; AK024920; BAB15034.1; -; mRNA. DR EMBL; AK025808; BAB15241.1; -; mRNA. DR EMBL; AK025832; BAB15252.1; ALT_INIT; mRNA. DR EMBL; BC030517; AAH30517.1; ALT_INIT; mRNA. DR EMBL; BC053326; AAH53326.1; -; mRNA. DR EMBL; BC073132; AAH73132.1; -; mRNA. DR EMBL; AL832438; CAH10610.1; -; mRNA. DR CCDS; CCDS43304.1; -. [Q9H6L5-1] DR CCDS; CCDS43305.1; -. [Q9H6L5-2] DR RefSeq; NP_001030022.1; NM_001034850.2. [Q9H6L5-1] DR RefSeq; NP_061873.2; NM_019000.4. [Q9H6L5-2] DR PDB; 7BRQ; X-ray; 1.40 A; A=450-468. DR PDB; 7FB5; X-ray; 2.84 A; B=451-476. DR PDBsum; 7BRQ; -. DR PDBsum; 7FB5; -. DR AlphaFoldDB; Q9H6L5; -. DR SMR; Q9H6L5; -. DR BioGRID; 119969; 66. DR DIP; DIP-61577N; -. DR IntAct; Q9H6L5; 22. DR MINT; Q9H6L5; -. DR STRING; 9606.ENSP00000304642; -. DR TCDB; 9.B.362.1.1; the fam134 reticulon protein (fam134) family. DR GlyGen; Q9H6L5; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9H6L5; -. DR PhosphoSitePlus; Q9H6L5; -. DR BioMuta; RETREG1; -. DR DMDM; 74733613; -. DR EPD; Q9H6L5; -. DR jPOST; Q9H6L5; -. DR MassIVE; Q9H6L5; -. DR MaxQB; Q9H6L5; -. DR PaxDb; 9606-ENSP00000304642; -. DR PeptideAtlas; Q9H6L5; -. DR ProteomicsDB; 81002; -. [Q9H6L5-1] DR ProteomicsDB; 81003; -. [Q9H6L5-2] DR Pumba; Q9H6L5; -. DR Antibodypedia; 5201; 180 antibodies from 22 providers. DR DNASU; 54463; -. DR Ensembl; ENST00000306320.10; ENSP00000304642.9; ENSG00000154153.15. [Q9H6L5-1] DR Ensembl; ENST00000399793.6; ENSP00000382691.2; ENSG00000154153.15. [Q9H6L5-2] DR GeneID; 54463; -. DR KEGG; hsa:54463; -. DR MANE-Select; ENST00000306320.10; ENSP00000304642.9; NM_001034850.3; NP_001030022.1. DR UCSC; uc003jfr.4; human. [Q9H6L5-1] DR AGR; HGNC:25964; -. DR CTD; 54463; -. DR DisGeNET; 54463; -. DR GeneCards; RETREG1; -. DR GeneReviews; RETREG1; -. DR HGNC; HGNC:25964; RETREG1. DR HPA; ENSG00000154153; Tissue enhanced (heart muscle, skeletal muscle). DR MalaCards; RETREG1; -. DR MIM; 613114; gene. DR MIM; 613115; phenotype. DR neXtProt; NX_Q9H6L5; -. DR OpenTargets; ENSG00000154153; -. DR Orphanet; 970; Hereditary sensory and autonomic neuropathy type 2. DR PharmGKB; PA162386188; -. DR VEuPathDB; HostDB:ENSG00000154153; -. DR eggNOG; ENOG502QPW8; Eukaryota. DR GeneTree; ENSGT00940000160746; -. DR HOGENOM; CLU_036265_0_0_1; -. DR InParanoid; Q9H6L5; -. DR OMA; IKGAQLW; -. DR OrthoDB; 5400903at2759; -. DR PhylomeDB; Q9H6L5; -. DR TreeFam; TF329111; -. DR PathwayCommons; Q9H6L5; -. DR SignaLink; Q9H6L5; -. DR SIGNOR; Q9H6L5; -. DR BioGRID-ORCS; 54463; 9 hits in 1146 CRISPR screens. DR ChiTaRS; FAM134B; human. DR GenomeRNAi; 54463; -. DR Pharos; Q9H6L5; Tbio. DR PRO; PR:Q9H6L5; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q9H6L5; Protein. DR Bgee; ENSG00000154153; Expressed in skeletal muscle tissue of rectus abdominis and 201 other cell types or tissues. DR ExpressionAtlas; Q9H6L5; baseline and differential. DR GO; GO:0005801; C:cis-Golgi network; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:GO_Central. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0140506; F:endoplasmic reticulum-autophagosome adaptor activity; IEA:Ensembl. DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB. DR GO; GO:0030574; P:collagen catabolic process; IEA:Ensembl. DR GO; GO:0007029; P:endoplasmic reticulum organization; IEA:Ensembl. DR GO; GO:0000423; P:mitophagy; IEA:Ensembl. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:GO_Central. DR GO; GO:0061709; P:reticulophagy; IMP:UniProtKB. DR GO; GO:0019233; P:sensory perception of pain; IMP:UniProtKB. DR GO; GO:0050872; P:white fat cell differentiation; IEA:Ensembl. DR CDD; cd22560; RETR1_RHD; 1. DR InterPro; IPR043384; RETREG1/3. DR PANTHER; PTHR28659:SF3; RETICULOPHAGY REGULATOR 1; 1. DR PANTHER; PTHR28659; RETICULOPHAGY REGULATOR 3; 1. DR Genevisible; Q9H6L5; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Autophagy; Endoplasmic reticulum; KW Golgi apparatus; Membrane; Neurodegeneration; Neuropathy; Phosphoprotein; KW Reference proteome; Transmembrane; Transmembrane helix. FT CHAIN 1..497 FT /note="Reticulophagy regulator 1" FT /id="PRO_0000288466" FT TOPO_DOM 1..59 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:26040720" FT TRANSMEM 60..80 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 81..95 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 96..116 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 117..118 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 119..139 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 140..208 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 209..229 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 230..497 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:26040720" FT REGION 1..51 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 84..233 FT /note="Reticulon homology domain" FT /evidence="ECO:0000305|PubMed:26040720" FT REGION 319..365 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 377..396 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 436..455 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 468..497 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 453..458 FT /note="LIR motif" FT /evidence="ECO:0000305|PubMed:26040720" FT COMPBIAS 20..34 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 468..490 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 149 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:31930741" FT MOD_RES 151 FT /note="Phosphoserine; by CAMK2B" FT /evidence="ECO:0000269|PubMed:31930741" FT MOD_RES 153 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:31930741" FT VAR_SEQ 1..141 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_025685" FT VAR_SEQ 142..152 FT /note="RGAQLWRSLSE -> MPEGEDFGPGK (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_025686" FT VARIANT 216 FT /note="G -> R (found in a patient with HSAN2B; uncertain FT significance; dramatically enhances homooligomerization FT which results in aberrant endoplasmic reticulum scission FT and excessive reticulophagy; induces sensory neuron death FT in vitro; dbSNP:rs1579584286)" FT /evidence="ECO:0000269|PubMed:22302274" FT /id="VAR_068477" FT VARIANT 379 FT /note="Q -> E (in dbSNP:rs34432513)" FT /id="VAR_032422" FT MUTAGEN 149 FT /note="S->A: Reduces self-association." FT /evidence="ECO:0000269|PubMed:31930741" FT MUTAGEN 149 FT /note="S->D: Phosphomimetic mutant which enhances FT self-association. Enhanced membrane scission activity; when FT associated with D-151 and D-153." FT /evidence="ECO:0000269|PubMed:31930741" FT MUTAGEN 151 FT /note="S->A: Abolishes phosphorylation and reduces FT self-association." FT /evidence="ECO:0000269|PubMed:31930741" FT MUTAGEN 151 FT /note="S->D: Phosphomimetic mutant which enhances FT self-association. Enhanced membrane scission activity; when FT associated with D-149 and D-153." FT /evidence="ECO:0000269|PubMed:31930741" FT MUTAGEN 153 FT /note="S->A: Reduces self-association." FT /evidence="ECO:0000269|PubMed:31930741" FT MUTAGEN 153 FT /note="S->D: Phosphomimetic mutant which enhances FT self-association. Enhanced membrane scission activity; when FT associated with D-149 and D-151." FT /evidence="ECO:0000269|PubMed:31930741" FT MUTAGEN 453..458 FT /note="DDFELL->AAAAAA: Abolishes interaction with ATG8 FT family proteins." FT /evidence="ECO:0000269|PubMed:26040720" FT MUTAGEN 455..458 FT /note="FELL->AELA: Abolishes interaction with ATG8 family FT proteins and reduces endoplasmic reticulum branching." FT /evidence="ECO:0000269|PubMed:34338405" FT MUTAGEN 456 FT /note="E->R: Severely impaired binding to GABARAP." FT /evidence="ECO:0000269|PubMed:34854256" FT MUTAGEN 462 FT /note="E->R: Severely impaired binding to GABARAP." FT /evidence="ECO:0000269|PubMed:34854256" FT MUTAGEN 463 FT /note="L->Q: Mildly weakened binding to GABARAP." FT /evidence="ECO:0000269|PubMed:34854256" FT MUTAGEN 466 FT /note="I->Q: Mildly weakened binding to GABARAP." FT /evidence="ECO:0000269|PubMed:34854256" FT CONFLICT 382 FT /note="S -> G (in Ref. 1; BAB15252)" FT /evidence="ECO:0000305" FT HELIX 461..465 FT /evidence="ECO:0007829|PDB:7BRQ" SQ SEQUENCE 497 AA; 54681 MW; 4EEB84B941DBFCE5 CRC64; MASPAPPEHA EEGCPAPAAE EQAPPSPPPP QASPAERQQQ EEEAQEAGAA EGAGLQVEEA AGRAAAAVTW LLGEPVLWLG CRADELLSWK RPLRSLLGFV AANLLFWFLA LTPWRVYHLI SVMILGRVIM QIIKDMVLSR TRGAQLWRSL SESWEVINSK PDERPRLSHC IAESWMNFSI FLQEMSLFKQ QSPGKFCLLV CSVCTFFTIL GSYIPGVILS YLLLLCAFLC PLFKCNDIGQ KIYSKIKSVL LKLDFGIGEY INQKKRERSE ADKEKSHKDD SELDFSALCP KISLTVAAKE LSVSDTDVSE VSWTDNGTFN LSEGYTPQTD TSDDLDRPSE EVFSRDLSDF PSLENGMGTN DEDELSLGLP TELKRKKEQL DSGHRPSKET QSAAGLTLPL NSDQTFHLMS NLAGDVITAA VTAAIKDQLE GVQQALSQAA PIPEEDTDTE EGDDFELLDQ SELDQIESEL GLTQDQEAEA QQNKKSSGFL SNLLGGH //