U119A_MOUSE
ID U119A_MOUSE Reviewed; 240 AA.
AC Q9Z2R6;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Protein unc-119 homolog A;
DE AltName: Full=Retinal protein 4;
DE Short=mRG4;
GN Name=Unc119; Synonyms=Unc119h;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=9761287;
RA Swanson D.A., Chang J.T., Campochiaro P.A., Zack D.J., Valle D.;
RT "Mammalian orthologs of C. elegans unc-119 highly expressed in
RT photoreceptors.";
RL Invest. Ophthalmol. Vis. Sci. 39:2085-2094(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17174953; DOI=10.1016/j.exer.2006.10.016;
RA Ishiba Y., Higashide T., Mori N., Kobayashi A., Kubota S., McLaren M.J.,
RA Satoh H., Wong F., Inana G.;
RT "Targeted inactivation of synaptic HRG4 (UNC119) causes dysfunction in the
RT distal photoreceptor and slow retinal degeneration, revealing a new
RT function.";
RL Exp. Eye Res. 84:473-485(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP INTERACTION WITH CABP4, AND TISSUE SPECIFICITY.
RX PubMed=18296658; DOI=10.1167/iovs.07-1166;
RA Haeseleer F.;
RT "Interaction and colocalization of CaBP4 and Unc119 (MRG4) in
RT photoreceptors.";
RL Invest. Ophthalmol. Vis. Sci. 49:2366-2375(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; SER-39 AND SER-41, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION IN ENDOCYTOSIS, AND INTERACTION WITH DNM1.
RX PubMed=19781630; DOI=10.1016/j.cellsig.2009.09.022;
RA Karim Z., Vepachedu R., Gorska M., Alam R.;
RT "UNC119 inhibits dynamin and dynamin-dependent endocytic processes.";
RL Cell. Signal. 22:128-137(2010).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21642972; DOI=10.1038/nn.2835;
RA Zhang H., Constantine R., Vorobiev S., Chen Y., Seetharaman J., Huang Y.J.,
RA Xiao R., Montelione G.T., Gerstner C.D., Davis M.W., Inana G., Whitby F.G.,
RA Jorgensen E.M., Hill C.P., Tong L., Baehr W.;
RT "UNC119 is required for G protein trafficking in sensory neurons.";
RL Nat. Neurosci. 14:874-880(2011).
RN [9]
RP PHOSPHORYLATION AT SER-37; SER-39 AND SER-41, MUTAGENESIS OF SER-37; SER-39
RP AND SER-41, AND INTERACTION WITH KLHL18; PPP3CA; PPP3CB AND PPP3CC.
RX PubMed=31696965; DOI=10.15252/embj.2018101409;
RA Chaya T., Tsutsumi R., Varner L.R., Maeda Y., Yoshida S., Furukawa T.;
RT "Cul3-Klhl18 ubiquitin ligase modulates rod transducin translocation during
RT light-dark adaptation.";
RL EMBO J. 2019:E101409-E101409(2019).
CC -!- FUNCTION: Involved in synaptic functions in photoreceptor cells, the
CC signal transduction in immune cells as a Src family kinase activator,
CC endosome recycling, the uptake of bacteria and endocytosis, protein
CC trafficking in sensory neurons and as lipid-binding chaperone with
CC specificity for a diverse subset of myristoylated proteins.
CC Specifically binds the myristoyl moiety of a subset of N-terminally
CC myristoylated proteins and is required for their localization. Binds
CC myristoylated GNAT1 and is required for G-protein localization and
CC trafficking in sensory neurons (PubMed:21642972). Probably plays a role
CC in trafficking proteins in photoreceptor cells (PubMed:17174953). Plays
CC important roles in mediating Src family kinase signals for the
CC completion of cytokinesis via RAB11A. {ECO:0000250|UniProtKB:Q13432,
CC ECO:0000269|PubMed:17174953, ECO:0000269|PubMed:19781630,
CC ECO:0000269|PubMed:21642972}.
CC -!- SUBUNIT: May interact with GTP-bound ARL1. Interacts with ARL2 and ARL3
CC (GTP-bound forms); this promotes the release of myristoylated cargo
CC proteins (By similarity). Found in a complex with ARL3, RP2 and UNC119;
CC RP2 induces hydrolysis of GTP ARL3 in the complex, leading to the
CC release of UNC119. Interacts with NPHP3 (when myristoylated). Interacts
CC with CYS1 (when myristoylated). Interacts with MACIR; interaction only
CC takes place when UNC119 is not liganded with myristoylated proteins (By
CC similarity). Interacts with CABP4; in the absence of calcium. Interacts
CC with DNM1; leading to a decrease of DNM1 GTPase activity. Interacts
CC with LCK; this interaction plays a crucial role in activation of LCK
CC (By similarity). Interacts with FYN (By similarity). Interacts with
CC RAB11A; in a cell cycle-dependent manner (By similarity). Interacts
CC with LYN (via SH2 and SH3 domains); leading to LYN activation (By
CC similarity). Found in a complex with ABL1, ABL2, CRK and UNC119;
CC leading to the inhibition of CRK phosphorylation by ABL kinases.
CC Interacts with CD44 (By similarity). Interacts with KLHL18 (via kelch
CC repeats). Interacts with PPP3CA, PPP3CB and PPP3CC (PubMed:31696965).
CC {ECO:0000250|UniProtKB:Q13432, ECO:0000269|PubMed:31696965}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000250|UniProtKB:Q13432}. Cytoplasm,
CC cytoskeleton, spindle {ECO:0000250|UniProtKB:Q13432}. Cytoplasm,
CC cytoskeleton, spindle pole {ECO:0000250|UniProtKB:Q13432}.
CC Note=ocalizes to the centrosome in interphase cells and begins to
CC translocate from the spindle pole to the spindle midzone after the
CC onset of mitosis; it then localizes to the intercellular bridge in
CC telophase cells and to the midbody in cytokinetic cells.
CC {ECO:0000250|UniProtKB:Q13432}.
CC -!- TISSUE SPECIFICITY: Localized in photoreceptor synapses in the outer
CC plexiform layer of the retina. {ECO:0000269|PubMed:18296658}.
CC -!- DOMAIN: Adopts an immunoglobulin-like beta-sandwich fold forming a
CC hydrophobic cavity that captures N-terminally myristoylated target
CC peptides. Phe residues within the hydrophobic beta sandwich are
CC required for myristate binding (By similarity).
CC {ECO:0000250|UniProtKB:Q13432}.
CC -!- PTM: Phosphorylation suppresses its interaction with KLHL18 and down-
CC regulates its KLHL18-mediated degradation (PubMed:31696965).
CC Phosphorylated more under light conditions than dark conditions
CC (PubMed:31696965). Dephosphorylated by calcineurin (PubMed:31696965).
CC {ECO:0000269|PubMed:31696965}.
CC -!- DISRUPTION PHENOTYPE: Mice develop a slowly progressive retinal
CC degeneration, characterized by mottling in the fundus, mild thinning of
CC the photoreceptor layer, and increase in apoptosis as early as 6
CC months, dramatic acceleration at approximately 17 months, and virtual
CC obliteration of the photoreceptors by 20 months. Phenotypes are due to
CC defects in protein trafficking, such as Gnat1 mislocalization.
CC {ECO:0000269|PubMed:17174953, ECO:0000269|PubMed:21642972}.
CC -!- SIMILARITY: Belongs to the PDE6D/unc-119 family. {ECO:0000305}.
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DR EMBL; AF030169; AAD01893.1; -; mRNA.
DR EMBL; BC001990; AAH01990.1; -; mRNA.
DR CCDS; CCDS25101.1; -.
DR RefSeq; NP_035806.1; NM_011676.3.
DR AlphaFoldDB; Q9Z2R6; -.
DR BioGRID; 204443; 5.
DR CORUM; Q9Z2R6; -.
DR STRING; 10090.ENSMUSP00000002127; -.
DR iPTMnet; Q9Z2R6; -.
DR PhosphoSitePlus; Q9Z2R6; -.
DR EPD; Q9Z2R6; -.
DR jPOST; Q9Z2R6; -.
DR MaxQB; Q9Z2R6; -.
DR PaxDb; Q9Z2R6; -.
DR PRIDE; Q9Z2R6; -.
DR ProteomicsDB; 298161; -.
DR Antibodypedia; 26315; 58 antibodies from 22 providers.
DR DNASU; 22248; -.
DR Ensembl; ENSMUST00000002127; ENSMUSP00000002127; ENSMUSG00000002058.
DR GeneID; 22248; -.
DR KEGG; mmu:22248; -.
DR UCSC; uc007kjb.1; mouse.
DR CTD; 9094; -.
DR MGI; MGI:1328357; Unc119.
DR VEuPathDB; HostDB:ENSMUSG00000002058; -.
DR eggNOG; KOG4037; Eukaryota.
DR GeneTree; ENSGT00390000014595; -.
DR InParanoid; Q9Z2R6; -.
DR PhylomeDB; Q9Z2R6; -.
DR TreeFam; TF314474; -.
DR BioGRID-ORCS; 22248; 5 hits in 74 CRISPR screens.
DR PRO; PR:Q9Z2R6; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9Z2R6; protein.
DR Bgee; ENSMUSG00000002058; Expressed in retinal neural layer and 249 other tissues.
DR ExpressionAtlas; Q9Z2R6; baseline and differential.
DR Genevisible; Q9Z2R6; MM.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0045171; C:intercellular bridge; ISS:UniProtKB.
DR GO; GO:0051233; C:spindle midzone; ISS:UniProtKB.
DR GO; GO:0000922; C:spindle pole; ISS:UniProtKB.
DR GO; GO:0008289; F:lipid binding; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0042953; P:lipoprotein transport; IMP:UniProtKB.
DR GO; GO:0000281; P:mitotic cytokinesis; ISS:UniProtKB.
DR GO; GO:2001287; P:negative regulation of caveolin-mediated endocytosis; IMP:UniProtKB.
DR GO; GO:1900186; P:negative regulation of clathrin-dependent endocytosis; IMP:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; IBA:GO_Central.
DR Gene3D; 2.70.50.40; -; 1.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR008015; PDED_dom.
DR InterPro; IPR037036; PDED_dom_sf.
DR InterPro; IPR032977; UNC119_homologue_A.
DR PANTHER; PTHR12951:SF5; PTHR12951:SF5; 1.
DR Pfam; PF05351; GMP_PDE_delta; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
PE 1: Evidence at protein level;
KW Cone-rod dystrophy; Cytoplasm; Cytoskeleton; Endocytosis; Lipid-binding;
KW Phosphoprotein; Protein transport; Reference proteome;
KW Sensory transduction; Transport; Vision.
FT CHAIN 1..240
FT /note="Protein unc-119 homolog A"
FT /id="PRO_0000221213"
FT REGION 1..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 131
FT /ligand="tetradecanoate"
FT /ligand_id="ChEBI:CHEBI:30807"
FT /evidence="ECO:0000250"
FT MOD_RES 37
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:31696965,
FT ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:21183079"
FT MOD_RES 39
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:31696965,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 41
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:31696965,
FT ECO:0007744|PubMed:21183079"
FT MUTAGEN 37
FT /note="S->A: Up-regulation of KLH18-mediated degradation;
FT when associated with A-39 and A-41."
FT /evidence="ECO:0000269|PubMed:31696965"
FT MUTAGEN 39
FT /note="S->A: Up-regulation of KLH18-mediated degradation;
FT when associated with A-37 and A-41."
FT /evidence="ECO:0000269|PubMed:31696965"
FT MUTAGEN 41
FT /note="S->A: Up-regulation of KLH18-mediated degradation;
FT when associated with A-37 and A-39."
FT /evidence="ECO:0000269|PubMed:31696965"
SQ SEQUENCE 240 AA; 27010 MW; 9EDF51191F0F5203 CRC64;
MKVKKGGGGT GSGAEPVPGA SNRSAEPTRE PGAEAESGSE SEPEPGPGPR LGPLQGKQPI
GPEDVLGLQR ITGDYLCSPE ENIYKIDFVR FKIRDMDSGT VLFEIKKPPV SERLPINRRD
LDPNAGRFVR YQFTPAFLRL RQVGATVEFT VGDKPVNNFR MIERHYFRNQ LLKSFDFHFG
FCIPSSKNTC EHIYDFPPLS EELISEMIRH PYETQSDSFY FVDDRLVMHN KADYSYSGTP
