OPTN_PIG
ID OPTN_PIG Reviewed; 574 AA.
AC Q7YS99;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Optineurin;
GN Name=OPTN;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15277488; DOI=10.1167/iovs.03-0572;
RA Obazawa M., Mashima Y., Sanuki N., Noda S., Kudoh J., Shimizu N.,
RA Oguchi Y., Tanaka Y., Iwata T.;
RT "Analysis of porcine optineurin and myocilin expression in trabecular
RT meshwork cells and astrocytes from optic nerve head.";
RL Invest. Ophthalmol. Vis. Sci. 45:2652-2659(2004).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=11834836; DOI=10.1126/science.1066901;
RA Rezaie T., Child A., Hitchings R., Brice G., Miller L., Coca-Prados M.,
RA Heon E., Krupin T., Ritch R., Kreutzer D., Crick R.P., Sarfarazi M.;
RT "Adult-onset primary open-angle glaucoma caused by mutations in
RT optineurin.";
RL Science 295:1077-1079(2002).
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 -!- TISSUE SPECIFICITY: Present in aqueous humor of the eye (at protein
CC level). Expressed in trabecular meshwork and astrocytes.
CC {ECO:0000269|PubMed:11834836, ECO:0000269|PubMed:15277488}.
CC -!- INDUCTION: Down-regulated upon treatment with dexamethasone. Not
CC regulated by hypoxic conditions. {ECO:0000269|PubMed:15277488}.
CC -!- DOMAIN: Ubiquitin-binding motif (UBAN) is essential for its inhibitory
CC function, subcellular localization and interaction with TBK1.
CC {ECO:0000250}.
CC -!- DOMAIN: The LIR (LC3-interacting region) motif mediates the interaction
CC with ATG8 family proteins. {ECO:0000250}.
CC -!- PTM: Phosphorylated by TBK1, leading to restrict bacterial
CC proliferation in case of infection. {ECO:0000250}.
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DR EMBL; AF513722; AAP47176.1; -; mRNA.
DR RefSeq; NP_999126.1; NM_213961.1.
DR RefSeq; XP_005656884.1; XM_005656827.2.
DR RefSeq; XP_013845202.1; XM_013989748.1.
DR AlphaFoldDB; Q7YS99; -.
DR SMR; Q7YS99; -.
DR STRING; 9823.ENSSSCP00000025164; -.
DR PaxDb; Q7YS99; -.
DR PeptideAtlas; Q7YS99; -.
DR PRIDE; Q7YS99; -.
DR Ensembl; ENSSSCT00005052360; ENSSSCP00005032364; ENSSSCG00005032795.
DR Ensembl; ENSSSCT00035059158; ENSSSCP00035023772; ENSSSCG00035044520.
DR Ensembl; ENSSSCT00045056961; ENSSSCP00045039796; ENSSSCG00045033326.
DR Ensembl; ENSSSCT00060016250; ENSSSCP00060006396; ENSSSCG00060012397.
DR Ensembl; ENSSSCT00065069382; ENSSSCP00065030224; ENSSSCG00065050651.
DR Ensembl; ENSSSCT00070054817; ENSSSCP00070046496; ENSSSCG00070027328.
DR GeneID; 397011; -.
DR KEGG; ssc:397011; -.
DR CTD; 10133; -.
DR eggNOG; ENOG502QTG2; Eukaryota.
DR HOGENOM; CLU_034097_1_0_1; -.
DR InParanoid; Q7YS99; -.
DR OMA; DMKQEMF; -.
DR OrthoDB; 745047at2759; -.
DR TreeFam; TF326608; -.
DR Reactome; R-SSC-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-SSC-8854214; TBC/RABGAPs.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 15.
DR Genevisible; Q7YS99; SS.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
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; IEA:Ensembl.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IEA:Ensembl.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0034620; P:cellular response to unfolded protein; ISS:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IEA:Ensembl.
DR GO; GO:0090161; P:Golgi ribbon formation; ISS:UniProtKB.
DR GO; GO:0043001; P:Golgi to plasma membrane protein transport; IEA:Ensembl.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0001920; P:negative regulation of receptor recycling; IEA:Ensembl.
DR GO; GO:0061734; P:parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization; IEA:Ensembl.
DR GO; GO:1904417; P:positive regulation of xenophagy; IEA:Ensembl.
DR GO; GO:0034067; P:protein localization to Golgi apparatus; IBA:GO_Central.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
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 Autophagy; Coiled coil; Cytoplasm; Cytoplasmic vesicle; Endosome;
KW Golgi apparatus; Metal-binding; Phosphoprotein; Reference proteome; Zinc;
KW Zinc-finger.
FT CHAIN 1..574
FT /note="Optineurin"
FT /id="PRO_0000058070"
FT ZN_FING 544..574
FT /note="CCHC NOA-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 58..209
FT /note="Interaction with Rab8"
FT /evidence="ECO:0000250"
FT REGION 262..292
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 405..574
FT /note="Interaction with HD"
FT /evidence="ECO:0000250"
FT REGION 406..515
FT /note="Interaction with MYO6"
FT /evidence="ECO:0000250"
FT COILED 38..170
FT /evidence="ECO:0000255"
FT COILED 233..496
FT /evidence="ECO:0000255"
FT MOTIF 176..181
FT /note="LIR"
FT MOTIF 468..473
FT /note="UBAN"
FT COMPBIAS 1..29
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 262..289
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 552
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 555
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 568
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 572
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT MOD_RES 177
FT /note="Phosphoserine; by TBK1"
FT /evidence="ECO:0000250|UniProtKB:Q96CV9"
FT MOD_RES 198
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96CV9"
FT MOD_RES 336
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96CV9"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96CV9"
SQ SEQUENCE 574 AA; 65703 MW; EA3A05311D305D70 CRC64;
MSHQPLSCLT EKGDSPTETT GNGPPTLAHP NLDTFTPHEL LQQMRELLIE NHQLKEAMKL
NNQAMKGRFE ELSAWTEKQK EERLFFETQS KEAKERLTAL SLENEKLKQE LGKLKGKTER
SFEDLTGDPR VPKAEAEQEV EQLKTQVARL QAEKADLLGI VSELQLKLNS GGPSEDSFVE
IRMAEGEADA AMKEIKTSPG PIRTDSIDTS KSAEGTRNYL EFEELTVSQL LLCLREGNQK
VERLEIALKE AKERILDFEK KAKDRSETET QTEEHKEQEK EEEKSPETVG SEVEMLNLQV
TTLFKELQEA HTKLSEAELM KKRLQEKCQA LERKNSATPS ELNEKQELLY NNKKLELQVE
SMRSEIKMEQ AKTEEEKSKL TTLQLTHNRL LQEYNNALKT IEELKRRESE KVDKVVLQEL
NGKLEMAEKA LASKQLQMDE MKQTIAKQEK DLETMAVLRA QMEVYCSDFH AERAAREKIH
EEKEQLALQL AVLLKDDNAF EEGASRQSLM EMQSRHGARA SDADQQAFLV QRGAEDRNWL
QQQQQNIPIH SCPKCGEVLP DIDTLLIHVT DCII
