RETR1_HUMAN
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 03-AUG-2022, entry version 147.
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 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-anchored autophagy receptor that
CC mediates ER delivery into lysosomes through sequestration into
CC autophagosomes (PubMed:26040720). Promotes membrane remodeling and ER
CC scission via its membrane bending capacity and targets the fragments
CC into autophagosomes via interaction with ATG8 family proteins
CC (PubMed:26040720). Required for long-term survival of nociceptive and
CC autonomic ganglion neurons (PubMed:19838196, PubMed:26040720).
CC {ECO:0000269|PubMed:19838196, ECO:0000269|PubMed:26040720}.
CC -!- SUBUNIT: Interacts with ATG8 family modifier proteins MAP1LC3A,
CC MAP1LC3B, GABARAP, GABARAPL1 and GABARAPL2.
CC {ECO:0000269|PubMed:26040720}.
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 -!- 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:26040720}.
CC -!- DOMAIN: The reticulon homology domain provides capacity to bend the
CC membrane and promotes ER scission (PubMed:26040720). This domain does
CC not show relevant similarities with reticulon domains, preventing any
CC domain predictions within the protein sequence.
CC {ECO:0000269|PubMed:26040720, ECO:0000305}.
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};
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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; 59.
DR DIP; DIP-61577N; -.
DR IntAct; Q9H6L5; 21.
DR MINT; Q9H6L5; -.
DR STRING; 9606.ENSP00000304642; -.
DR TCDB; 9.B.362.1.1; the fam134 reticulon protein (fam134) family.
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; Q9H6L5; -.
DR PeptideAtlas; Q9H6L5; -.
DR PRIDE; Q9H6L5; -.
DR ProteomicsDB; 81002; -. [Q9H6L5-1]
DR ProteomicsDB; 81003; -. [Q9H6L5-2]
DR Antibodypedia; 5201; 142 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 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; WPLISSQ; -.
DR OrthoDB; 901531at2759; -.
DR PhylomeDB; Q9H6L5; -.
DR TreeFam; TF329111; -.
DR PathwayCommons; Q9H6L5; -.
DR SignaLink; Q9H6L5; -.
DR BioGRID-ORCS; 54463; 6 hits in 1067 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 199 other tissues.
DR ExpressionAtlas; Q9H6L5; baseline and differential.
DR Genevisible; Q9H6L5; HS.
DR GO; GO:0005801; C:cis-Golgi network; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0030176; C:integral component of 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: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:GO_Central.
DR GO; GO:0019233; P:sensory perception of pain; IMP:UniProtKB.
DR GO; GO:0050872; P:white fat cell differentiation; IEA:Ensembl.
DR InterPro; IPR033358; RETREG1.
DR InterPro; IPR043384; RETREG1/3.
DR PANTHER; PTHR28659; PTHR28659; 1.
DR PANTHER; PTHR28659:SF3; PTHR28659:SF3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Autophagy; Endoplasmic reticulum;
KW Golgi apparatus; Membrane; Neurodegeneration; Neuropathy;
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 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 pathological significance; 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 453..458
FT /note="DDFELL->AAAAAA: Abolishes interaction with ATG8
FT family proteins."
FT /evidence="ECO:0000269|PubMed:26040720"
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
