OPTN_RAT
ID OPTN_RAT Reviewed; 585 AA.
AC Q8R5M4; Q5PQX8;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 3.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Optineurin;
DE AltName: Full=FIP-2-like protein;
GN Name=Optn;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Myokai F., Oyama M.;
RT "Identification of genes expressed in rat injured dental pulp.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188 AND SER-346, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Plays an important role in the maintenance of the Golgi
CC complex, in membrane trafficking, in exocytosis, through its
CC interaction with myosin VI and Rab8. Links myosin VI to the Golgi
CC complex and plays an important role in Golgi ribbon formation.
CC Negatively regulates the induction of IFNB in response to RNA virus
CC infection. Plays a neuroprotective role in the eye and optic nerve.
CC Probably part of the TNF-alpha signaling pathway that can shift the
CC equilibrium toward induction of cell death. May act by regulating
CC membrane trafficking and cellular morphogenesis via a complex that
CC contains Rab8 and hungtingtin (HD). Mediates the interaction of Rab8
CC with the probable GTPase-activating protein TBC1D17 during Rab8-
CC mediated endocytic trafficking, such as of transferrin receptor
CC (TFRC/TfR); regulates Rab8 recruitnment to tubules emanating from the
CC endocytic recycling compartment. Autophagy receptor that interacts
CC directly with both the cargo to become degraded and an autophagy
CC modifier of the MAP1 LC3 family; targets ubiquitin-coated bacteria
CC (xenophagy) and appears to function in the same pathway as SQSTM1 and
CC CALCOCO2/NDP52. {ECO:0000250, ECO:0000250|UniProtKB:Q96CV9}.
CC -!- SUBUNIT: Self-associates (By similarity). Interacts with HD, Rab8
CC (RAB8A and/or RAB8B) (active GTP-bound form), GTF3A, TRAF3, TBK1, MYO6
CC and TFRC. Binds to linear ubiquitin chains. Interacts with LC3 family
CC members MAP1LC3A, MAP1LC3B, GABARAP, GABARAPL1 and GABARAPL2; OPTN
CC phosphorylation increases the association (at least with MAP1LC3B).
CC Interacts with RAB12; the interaction may be indirect (By similarity).
CC Interacts with palmitoyltransferase ZDHHC17/HIP14; the interaction does
CC not lead to palmitoylation of OPTN (By similarity). Interacts with CYLD
CC (By similarity). {ECO:0000250|UniProtKB:Q96CV9}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000250}.
CC Golgi apparatus {ECO:0000250|UniProtKB:Q96CV9}. Golgi apparatus, trans-
CC Golgi network {ECO:0000250}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000250}. Cytoplasmic vesicle {ECO:0000250}. Recycling endosome
CC {ECO:0000250}. Note=Found in the perinuclear region and associates with
CC the Golgi apparatus. Colocalizes with MYO6 and RAB8 at the Golgi
CC complex and in vesicular structures close to the plasma membrane.
CC Localizes to LC3-positive cytoplasmic vesicles upon induction of
CC autophagy. {ECO:0000250, ECO:0000250|UniProtKB:Q96CV9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8R5M4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8R5M4-2; Sequence=VSP_013263, VSP_013264;
CC -!- DOMAIN: The LIR (LC3-interacting region) motif mediates the interaction
CC with ATG8 family proteins. {ECO:0000250}.
CC -!- DOMAIN: Ubiquitin-binding motif (UBAN) is essential for its inhibitory
CC function, subcellular localization and interaction with TBK1.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated by TBK1, leading to restrict bacterial
CC proliferation in case of infection. {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB84696.2; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB069907; BAB84696.2; ALT_FRAME; mRNA.
DR EMBL; BC086976; AAH86976.1; -; mRNA.
DR RefSeq; NP_659549.2; NM_145081.3.
DR AlphaFoldDB; Q8R5M4; -.
DR SMR; Q8R5M4; -.
DR BioGRID; 251574; 3.
DR iPTMnet; Q8R5M4; -.
DR PhosphoSitePlus; Q8R5M4; -.
DR PaxDb; Q8R5M4; -.
DR PRIDE; Q8R5M4; -.
DR GeneID; 246294; -.
DR KEGG; rno:246294; -.
DR CTD; 10133; -.
DR RGD; 628886; Optn.
DR eggNOG; ENOG502QTG2; Eukaryota.
DR InParanoid; Q8R5M4; -.
DR OrthoDB; 745047at2759; -.
DR PhylomeDB; Q8R5M4; -.
DR Reactome; R-RNO-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-RNO-8854214; TBC/RABGAPs.
DR PRO; PR:Q8R5M4; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:RGD.
DR GO; GO:0031267; F:small GTPase binding; ISO:RGD.
DR GO; GO:0001155; F:TFIIIA-class transcription factor binding; IPI:RGD.
DR GO; GO:0043130; F:ubiquitin binding; IDA:RGD.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:1905232; P:cellular response to L-glutamate; IEP:RGD.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0034620; P:cellular response to unfolded protein; ISS:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISO:RGD.
DR GO; GO:0007030; P:Golgi organization; IMP:UniProtKB.
DR GO; GO:0090161; P:Golgi ribbon formation; ISS:UniProtKB.
DR GO; GO:0043001; P:Golgi to plasma membrane protein transport; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0001920; P:negative regulation of receptor recycling; ISO:RGD.
DR GO; GO:0003407; P:neural retina development; IEP:RGD.
DR GO; GO:0061734; P:parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization; ISO:RGD.
DR GO; GO:0010508; P:positive regulation of autophagy; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0001819; P:positive regulation of cytokine production; IMP:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IMP:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:1904417; P:positive regulation of xenophagy; ISO:RGD.
DR GO; GO:0034067; P:protein localization to Golgi apparatus; ISO:RGD.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0042060; P:wound healing; IEP:RGD.
DR InterPro; IPR032419; CC2-LZ_dom.
DR InterPro; IPR021063; NEMO_N.
DR InterPro; IPR034735; NEMO_ZF.
DR InterPro; IPR032939; Optineurin.
DR PANTHER; PTHR31553:SF2; PTHR31553:SF2; 1.
DR Pfam; PF16516; CC2-LZ; 1.
DR Pfam; PF11577; NEMO; 1.
DR PROSITE; PS51801; ZF_CCHC_NOA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; Endosome; Golgi apparatus; Metal-binding;
KW Phosphoprotein; Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..585
FT /note="Optineurin"
FT /id="PRO_0000058072"
FT ZN_FING 555..585
FT /note="CCHC NOA-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 58..220
FT /note="Interaction with Rab8"
FT /evidence="ECO:0000250"
FT REGION 200..220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..299
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 415..585
FT /note="Interaction with HD"
FT /evidence="ECO:0000250"
FT REGION 416..525
FT /note="Interaction with MYO6"
FT /evidence="ECO:0000250"
FT COILED 38..181
FT /evidence="ECO:0000255"
FT COILED 244..512
FT /evidence="ECO:0000255"
FT MOTIF 187..192
FT /note="LIR"
FT MOTIF 478..483
FT /note="UBAN"
FT COMPBIAS 285..299
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 563
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 566
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 579
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 583
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96CV9"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96CV9"
FT VAR_SEQ 156..195
FT /note="IQVRRLQAEKADLLGIVSELQLKLNSGGSSEDSFVEIRMT -> NQ (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013263"
FT VAR_SEQ 515
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013264"
FT CONFLICT 78
FT /note="K -> R (in Ref. 1; BAB84696)"
FT /evidence="ECO:0000305"
FT CONFLICT 172..174
FT /note="VSE -> RLR (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 219
FT /note="S -> I (in Ref. 1; BAB84696)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="E -> G (in Ref. 1; BAB84696)"
FT /evidence="ECO:0000305"
FT CONFLICT 363
FT /note="R -> W (in Ref. 1; BAB84696)"
FT /evidence="ECO:0000305"
FT CONFLICT 545
FT /note="E -> K (in Ref. 1; BAB84696)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 585 AA; 67014 MW; 05D3390151DADEC7 CRC64;
MSHQPLSCLT EKGDSSCETP GNGPSNMVHP NLDTFTPEEL LQQMKELLVE NHQLKEAMKL
NNQAMKGRFE ELSAWTEKQK EERQLFEIQS KEAKERLKAL SHENERLKEE LGKLKEKSER
PFEDITGRCG FPRTDLEQEV EQLKRQVEQE VEHLKIQVRR LQAEKADLLG IVSELQLKLN
SGGSSEDSFV EIRMTEGEAE GAMKEMRNSA GPTRTDSISM GKCTEDARTC VEFEELTVSQ
LLLCLREGNQ KVERLEIALR EAKERISDFE KKANGHSAIE TQTEGSTQKE EEDKDPESVG
IEVETLNVQV ASLFKELQEA HTKLSEAELM KKRLQEKCQA LERKNSATPS ELNEKQELVY
SNRKLELQVE SMRSEIKMEQ AKTEEEKSRL ATLQATHDKL LQEHNKALRT IEELTKQQAE
KVDKVQLQEL SEKLELAEQA LASKQLQMDE MKQTIAKQEE DLETMAVLRA QMEVYCSDFH
AERAAREKIH EEKEQLALQL AILLKENNDF EDGGSRQSLM EMQCRHGART SDSDQQAYLF
QRGAEDMSWQ HGQQPRSIPI HSCPKCGEVL PDIDTLQIHV MDCII
