ID U119A_HUMAN Reviewed; 240 AA. AC Q13432; A8K8G4; F1T095; O95126; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 182. DE RecName: Full=Protein unc-119 homolog A; DE AltName: Full=Retinal protein 4; DE Short=hRG4; GN Name=UNC119; Synonyms=RG4; 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 [MRNA] (ISOFORM A). RC TISSUE=Retina; RX PubMed=8576185; DOI=10.1074/jbc.271.3.1797; RA Higashide T., Murakami A., McLaren M.J., Inana G.; RT "Cloning of the cDNA for a novel photoreceptor protein."; RL J. Biol. Chem. 271:1797-1804(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), AND TISSUE SPECIFICITY. 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 [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A). RX PubMed=10329014; DOI=10.1006/geno.1999.5791; RA Higashide T., Inana G.; RT "Characterization of the gene for HRG4 (UNC119), a novel photoreceptor RT synaptic protein homologous to unc-119."; RL Genomics 57:446-450(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). RC TISSUE=Testis; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). RC TISSUE=Retinoblastoma; RX PubMed=21697133; DOI=10.1167/iovs.11-7479; RA Oshikawa M., Tsutsui C., Ikegami T., Fuchida Y., Matsubara M., Toyama S., RA Usami R., Ohtoko K., Kato S.; RT "Full-length transcriptome analysis of human retina-derived cell lines RT ARPE-19 and Y79 using the vector-capping method."; RL Invest. Ophthalmol. Vis. Sci. 52:6662-6670(2011). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). RC TISSUE=Lymph; 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 [9] RP INTERACTION WITH ARL1; ARL2 AND ARL3. RX PubMed=11303027; DOI=10.1074/jbc.m102359200; RA Van Valkenburgh H., Shern J.F., Sharer J.D., Zhu X., Kahn R.A.; RT "ADP-ribosylation factors (ARFs) and ARF-like 1 (ARL1) have both specific RT and shared effectors: characterizing ARL1-binding proteins."; RL J. Biol. Chem. 276:22826-22837(2001). RN [10] RP INTERACTION WITH LYN, AND FUNCTION IN LYN ACTIVATION. RX PubMed=12496276; DOI=10.1074/jbc.m208261200; RA Cen O., Gorska M.M., Stafford S.J., Sur S., Alam R.; RT "Identification of UNC119 as a novel activator of SRC-type tyrosine RT kinases."; RL J. Biol. Chem. 278:8837-8845(2003). RN [11] RP INTERACTION WITH LCK AND FYN, FUNCTION IN LCK AND FYN ACTIVATION, AND RP MUTAGENESIS OF 29-PRO--PRO-32. RX PubMed=14757743; DOI=10.1084/jem.20030589; RA Gorska M.M., Stafford S.J., Cen O., Sur S., Alam R.; RT "Unc119, a novel activator of Lck/Fyn, is essential for T cell RT activation."; RL J. Exp. Med. 199:369-379(2004). RN [12] RP IDENTIFICATION IN A COMPLEX WITH ARL3 AND RP2. RX PubMed=18588884; DOI=10.1016/j.febslet.2008.05.053; RA Veltel S., Kravchenko A., Ismail S., Wittinghofer A.; RT "Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3-effector- RT GAP complex."; RL FEBS Lett. 582:2501-2507(2008). RN [13] RP INTERACTION WITH CD44, IDENTIFICATION IN A COMPLEX WITH ABL1; ABL2 AND CRK, RP AND FUNCTION IN SHIGELLA FLEXNERI UPTAKE. RX PubMed=19381274; DOI=10.1371/journal.pone.0005211; RA Vepachedu R., Karim Z., Patel O., Goplen N., Alam R.; RT "Unc119 protects from Shigella infection by inhibiting the Abl family RT kinases."; RL PLoS ONE 4:E5211-E5211(2009). RN [14] RP FUNCTION, LIPID-BINDING, AND INTERACTION WITH NPHP3; CYS1 AND MACIR. RX PubMed=22085962; DOI=10.1101/gad.173443.111; RA Wright K.J., Baye L.M., Olivier-Mason A., Mukhopadhyay S., Sang L., RA Kwong M., Wang W., Pretorius P.R., Sheffield V.C., Sengupta P., RA Slusarski D.C., Jackson P.K.; RT "An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary RT cilium."; RL Genes Dev. 25:2347-2360(2011). RN [15] RP SUBCELLULAR LOCATION, INTERACTION WITH FYN AND RAB11A, AND FUNCTION IN RP ACTIVATION OF FYN. RX PubMed=23535298; DOI=10.4161/cc.24404; RA Lee Y., Chung S., Baek I.K., Lee T.H., Paik S.Y., Lee J.; RT "UNC119a bridges the transmission of Fyn signals to Rab11, leading to the RT completion of cytokinesis."; RL Cell Cycle 12:1303-1315(2013). RN [16] RP INTERACTION WITH ARL2. RX PubMed=30945270; DOI=10.1111/cge.13541; RA Cai X.B., Wu K.C., Zhang X., Lv J.N., Jin G.H., Xiang L., Chen J., RA Huang X.F., Pan D., Lu B., Lu F., Qu J., Jin Z.B.; RT "Whole-exome sequencing identified ARL2 as a novel candidate gene for MRCS RT (microcornea, rod-cone dystrophy, cataract, and posterior staphyloma) RT syndrome."; RL Clin. Genet. 96:61-71(2019). RN [17] RP PHOSPHORYLATION AT SER-37; SER-39 AND SER-41, MUTAGENESIS OF SER-37; SER-39 RP AND SER-41, AND INTERACTION WITH KLHL18. 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). RN [18] RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 56-240 IN COMPLEX WITH LAURYLATED RP GNAT1, FUNCTION, AND INTERACTION WITH GNAT1. 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 [19] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH ARL2 AND ARL3, AND RP INTERACTION WITH ARL2 AND ARL3. RX PubMed=22960633; DOI=10.1038/emboj.2012.257; RA Ismail S.A., Chen Y.X., Miertzschke M., Vetter I.R., Koerner C., RA Wittinghofer A.; RT "Structural basis for Arl3-specific release of myristoylated ciliary cargo RT from UNC119."; RL EMBO J. 31:4085-4094(2012). RN [20] RP VARIANT CORD24 57-LYS--PRO-240 DEL, CHARACTERIZATION OF VARIANT CORD24 RP 57-LYS--PRO-240 DEL, AND INVOLVEMENT IN CORD24. RX PubMed=11006213; RA Kobayashi A., Higashide T., Hamasaki D., Kubota S., Sakuma H., An W., RA Fujimaki T., McLaren M.J., Weleber R.G., Inana G.; RT "HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal RT degeneration in a transgenic model."; RL Invest. Ophthalmol. Vis. Sci. 41:3268-3277(2000). RN [21] RP VARIANT IMD13 VAL-22, AND CHARACTERIZATION OF VARIANT IMD13 VAL-22. RX PubMed=22184408; DOI=10.1182/blood-2011-04-350686; RA Gorska M.M., Alam R.; RT "A mutation in the human Uncoordinated 119 gene impairs TCR signaling and RT is associated with CD4 lymphopenia."; RL Blood 119:1399-1406(2012). RN [22] RP VARIANT CORD24 201-GLU--PRO-240 DEL. RX PubMed=35947183; DOI=10.1007/s00417-022-05786-4; RA Zenteno J.C., Arce-Gonzalez R., Matsui R., Lopez-Bolanos A., Montes L., RA Martinez-Aguilar A., Chacon-Camacho O.F.; RT "Clinical-genetic findings in a group of subjects with macular dystrophies RT due to mutations in rare inherited retinopathy genes."; RL Graefes Arch. Clin. Exp. Ophthalmol. 261:353-365(2023). 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. Probably plays a role in trafficking CC proteins in photoreceptor cells. Plays important roles in mediating Src CC family kinase signals for the completion of cytokinesis via RAB11A. CC {ECO:0000269|PubMed:12496276, ECO:0000269|PubMed:14757743, CC ECO:0000269|PubMed:19381274, ECO:0000269|PubMed:21642972, CC ECO:0000269|PubMed:22085962, ECO:0000269|PubMed:23535298, CC ECO:0000305|PubMed:22960633}. CC -!- SUBUNIT: Interacts with CABP4; in the absence of calcium (By CC similarity). Interacts with DNM1; leading to a decrease of DNM1 GTPase CC activity (By similarity). May interact with GTP-bound ARL1. Interacts CC with ARL2 and ARL3 (GTP-bound forms); this promotes the release of CC myyristoylated cargo proteins (PubMed:22960633, PubMed:30945270). Found CC in a complex with ARL3, RP2 and UNC119; RP2 induces hydrolysis of GTP CC ARL3 in the complex, leading to the release of UNC119. Interacts with CC NPHP3 (when myristoylated). Interacts with CYS1 (when myristoylated). CC Interacts with MACIR; interaction only takes place when UNC119 is not CC liganded with myristoylated proteins. Interacts with LCK; this CC interaction plays a crucial role in activation of LCK. Interacts with CC FYN. Interacts with RAB11A; in a cell cycle-dependent manner. Interacts CC with LYN (via SH2 and SH3 domains); leading to LYN activation. Found in CC a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CC CRK phosphorylation by ABL kinases. Interacts with CD44; leading to CC Shigella invasion. Interacts with KLHL18 (via kelch repeats) CC (PubMed:31696965). Interacts with PPP3CA, PPP3CB and PPP3CC (By CC similarity). {ECO:0000250|UniProtKB:Q9Z2R6, CC ECO:0000269|PubMed:11303027, ECO:0000269|PubMed:12496276, CC ECO:0000269|PubMed:14757743, ECO:0000269|PubMed:18588884, CC ECO:0000269|PubMed:19381274, ECO:0000269|PubMed:21642972, CC ECO:0000269|PubMed:22085962, ECO:0000269|PubMed:22960633, CC ECO:0000269|PubMed:23535298, ECO:0000269|PubMed:30945270, CC ECO:0000269|PubMed:31696965}. CC -!- INTERACTION: CC Q13432; A2BDD9: AMOT; NbExp=3; IntAct=EBI-711260, EBI-17286414; CC Q13432; Q4VCS5-2: AMOT; NbExp=3; IntAct=EBI-711260, EBI-3891843; CC Q13432; Q9NXU5: ARL15; NbExp=4; IntAct=EBI-711260, EBI-711759; CC Q13432; P36404: ARL2; NbExp=11; IntAct=EBI-711260, EBI-752365; CC Q13432; P36405: ARL3; NbExp=15; IntAct=EBI-711260, EBI-712710; CC Q13432; Q96GX8: C16orf74; NbExp=7; IntAct=EBI-711260, EBI-745814; CC Q13432; P13569: CFTR; NbExp=4; IntAct=EBI-711260, EBI-349854; CC Q13432; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-711260, EBI-11749135; CC Q13432; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-711260, EBI-1043191; CC Q13432; Q9BYQ0: KRTAP9-8; NbExp=3; IntAct=EBI-711260, EBI-11958364; CC Q13432; Q5T3J3: LRIF1; NbExp=3; IntAct=EBI-711260, EBI-473196; CC Q13432; Q7Z494: NPHP3; NbExp=3; IntAct=EBI-711260, EBI-2804263; CC Q13432; Q08209-2: PPP3CA; NbExp=5; IntAct=EBI-711260, EBI-11959013; CC Q13432; P48454: PPP3CC; NbExp=3; IntAct=EBI-711260, EBI-2827192; CC Q13432; Q6ZRY4: RBPMS2; NbExp=3; IntAct=EBI-711260, EBI-11987469; CC Q13432; Q9UKA8: RCAN3; NbExp=3; IntAct=EBI-711260, EBI-9091952; CC Q13432; Q86VY9: TMEM200A; NbExp=3; IntAct=EBI-711260, EBI-11732844; CC Q13432; Q96A56: TP53INP1; NbExp=3; IntAct=EBI-711260, EBI-9986117; CC Q13432; Q9D0J4: Arl2; Xeno; NbExp=2; IntAct=EBI-711260, EBI-1033319; CC Q13432; Q9WUL7: Arl3; Xeno; NbExp=3; IntAct=EBI-711260, EBI-6860857; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing CC center, centrosome {ECO:0000269|PubMed:23535298}. Cytoplasm, CC cytoskeleton, spindle pole {ECO:0000269|PubMed:23535298}. Cytoplasm, CC cytoskeleton, spindle {ECO:0000269|PubMed:23535298}. Note=Localizes to CC the centrosome in interphase cells and begins to translocate from the CC spindle pole to the spindle midzone after the onset of mitosis; it then CC localizes to the intercellular bridge in telophase cells and to the CC midbody in cytokinetic cells. {ECO:0000269|PubMed:23535298}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=A; CC IsoId=Q13432-1; Sequence=Displayed; CC Name=B; CC IsoId=Q13432-2; Sequence=VSP_004545; CC -!- TISSUE SPECIFICITY: Abundantly expressed in retina, in photoreceptor CC synapses and inner segments. Expressed in a much lesser extent in CC several other tissues. {ECO:0000269|PubMed:9761287}. CC -!- DOMAIN: Adopts an immunoglobulin-like beta-sandwich fold forming a CC hydrophobic cavity that captures N-terminally myristoylated target CC peptides (PubMed:21642972). Phe residues within the hydrophobic beta CC sandwich are required for myristate binding (PubMed:22085962). CC {ECO:0000269|PubMed:21642972, ECO:0000269|PubMed:22085962}. 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 -!- DISEASE: Immunodeficiency 13 (IMD13) [MIM:615518]: A rare and CC heterogeneous syndrome defined by a reproducible reduction in the CD4 CC T-lymphocyte count (less than 300 cells per microliter or less than 20% CC of total T-cells) in the absence of HIV infection or other known causes CC of immunodeficiency. IMD13 predisposes to infections and malignancy. CC {ECO:0000269|PubMed:22184408}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Cone-rod dystrophy 24 (CORD24) [MIM:620342]: An autosomal CC dominant form of cone-rod dystrophy, an inherited retinal dystrophy CC characterized by retinal pigment deposits visible on fundus CC examination, predominantly in the macular region, and initial loss of CC cone photoreceptors followed by rod degeneration. This leads to CC decreased visual acuity and sensitivity in the central visual field, CC followed by loss of peripheral vision. Severe loss of vision occurs CC earlier than in retinitis pigmentosa, due to cone photoreceptors CC degenerating at a higher rate than rod photoreceptors. CC {ECO:0000269|PubMed:11006213, ECO:0000269|PubMed:35947183}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the PDE6D/unc-119 family. {ECO:0000305}. CC -!- CAUTION: According to some authors, acts by extracting target proteins CC from membranes (PubMed:21642972). According to a another report, rather CC acts by targeting proteins to membranes (PubMed:22085962). CC {ECO:0000305|PubMed:21642972, ECO:0000305|PubMed:22085962}. 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; U40998; AAC50360.1; -; mRNA. DR EMBL; AF028788; AAD01875.1; -; mRNA. DR EMBL; AF028789; AAD01876.1; -; mRNA. DR EMBL; AF125998; AAD31422.1; -; Genomic_DNA. DR EMBL; AF125997; AAD31422.1; JOINED; Genomic_DNA. DR EMBL; AK292329; BAF85018.1; -; mRNA. DR EMBL; AB593014; BAJ83969.1; -; mRNA. DR EMBL; AC005726; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471159; EAW51095.1; -; Genomic_DNA. DR EMBL; BC027176; AAH27176.1; -; mRNA. DR CCDS; CCDS11233.1; -. [Q13432-1] DR CCDS; CCDS11234.1; -. [Q13432-2] DR RefSeq; NP_001317095.1; NM_001330166.1. DR RefSeq; NP_005139.1; NM_005148.3. [Q13432-1] DR RefSeq; NP_473376.1; NM_054035.2. [Q13432-2] DR PDB; 3GQQ; X-ray; 1.95 A; A/B/C/D/E/F=56-240. DR PDB; 3RBQ; X-ray; 2.00 A; A/B/C/D/E/F=56-240. DR PDB; 4GOJ; X-ray; 2.10 A; C/D=1-240. DR PDB; 4GOK; X-ray; 2.60 A; C/G=1-240. DR PDB; 5L7K; X-ray; 2.10 A; A/G=58-237. DR PDB; 6H6A; X-ray; 2.00 A; D/G/J=59-240. DR PDB; 7UMO; X-ray; 2.30 A; A/B/C/D/E/F=57-240. DR PDBsum; 3GQQ; -. DR PDBsum; 3RBQ; -. DR PDBsum; 4GOJ; -. DR PDBsum; 4GOK; -. DR PDBsum; 5L7K; -. DR PDBsum; 6H6A; -. DR PDBsum; 7UMO; -. DR AlphaFoldDB; Q13432; -. DR SMR; Q13432; -. DR BioGRID; 114548; 156. DR DIP; DIP-42697N; -. DR IntAct; Q13432; 126. DR MINT; Q13432; -. DR STRING; 9606.ENSP00000337040; -. DR GuidetoPHARMACOLOGY; 3011; -. DR iPTMnet; Q13432; -. DR MetOSite; Q13432; -. DR PhosphoSitePlus; Q13432; -. DR BioMuta; UNC119; -. DR DMDM; 2498854; -. DR EPD; Q13432; -. DR jPOST; Q13432; -. DR MassIVE; Q13432; -. DR MaxQB; Q13432; -. DR PaxDb; 9606-ENSP00000337040; -. DR PeptideAtlas; Q13432; -. DR ProteomicsDB; 59426; -. [Q13432-1] DR ProteomicsDB; 59427; -. [Q13432-2] DR Pumba; Q13432; -. DR Antibodypedia; 26315; 66 antibodies from 23 providers. DR DNASU; 9094; -. DR Ensembl; ENST00000301032.8; ENSP00000301032.4; ENSG00000109103.12. [Q13432-2] DR Ensembl; ENST00000335765.9; ENSP00000337040.3; ENSG00000109103.12. [Q13432-1] DR GeneID; 9094; -. DR KEGG; hsa:9094; -. DR MANE-Select; ENST00000335765.9; ENSP00000337040.3; NM_005148.4; NP_005139.1. DR UCSC; uc002hbk.3; human. [Q13432-1] DR AGR; HGNC:12565; -. DR CTD; 9094; -. DR DisGeNET; 9094; -. DR GeneCards; UNC119; -. DR HGNC; HGNC:12565; UNC119. DR HPA; ENSG00000109103; Tissue enriched (retina). DR MalaCards; UNC119; -. DR MIM; 604011; gene. DR MIM; 615518; phenotype. DR MIM; 620342; phenotype. DR neXtProt; NX_Q13432; -. DR OpenTargets; ENSG00000109103; -. DR Orphanet; 1872; Cone rod dystrophy. DR Orphanet; 228000; Idiopathic CD4 lymphocytopenia. DR PharmGKB; PA37202; -. DR VEuPathDB; HostDB:ENSG00000109103; -. DR eggNOG; KOG4037; Eukaryota. DR GeneTree; ENSGT00390000014595; -. DR InParanoid; Q13432; -. DR OMA; FYFVDNH; -. DR OrthoDB; 4200542at2759; -. DR PhylomeDB; Q13432; -. DR TreeFam; TF314474; -. DR PathwayCommons; Q13432; -. DR SignaLink; Q13432; -. DR BioGRID-ORCS; 9094; 57 hits in 1156 CRISPR screens. DR ChiTaRS; UNC119; human. DR EvolutionaryTrace; Q13432; -. DR GeneWiki; Protein_unc-119_homolog; -. DR GenomeRNAi; 9094; -. DR Pharos; Q13432; Tchem. DR PRO; PR:Q13432; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q13432; Protein. DR Bgee; ENSG00000109103; Expressed in granulocyte and 155 other cell types or tissues. DR ExpressionAtlas; Q13432; baseline and differential. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:ProtInc. DR GO; GO:0045171; C:intercellular bridge; IDA:UniProtKB. DR GO; GO:0051233; C:spindle midzone; IDA:UniProtKB. DR GO; GO:0000922; C:spindle pole; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0008289; F:lipid binding; IDA:UniProtKB. DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc. DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW. DR GO; GO:0042953; P:lipoprotein transport; IDA:UniProtKB. DR GO; GO:0000281; P:mitotic cytokinesis; IMP:UniProtKB. DR GO; GO:2001287; P:negative regulation of caveolin-mediated endocytosis; ISS:UniProtKB. DR GO; GO:1900186; P:negative regulation of clathrin-dependent endocytosis; ISS:UniProtKB. DR GO; GO:0007399; P:nervous system development; IBA:GO_Central. DR GO; GO:0007602; P:phototransduction; TAS:ProtInc. DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IMP:UniProtKB. DR GO; GO:0007601; P:visual perception; IBA:GO_Central. DR Gene3D; 2.70.50.40; GMP phosphodiesterase, delta subunit; 1. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR008015; PDED_dom. DR InterPro; IPR037036; PDED_dom_sf. DR PANTHER; PTHR12951:SF5; PROTEIN UNC-119 HOMOLOG A; 1. DR PANTHER; PTHR12951; RETINAL PROTEIN 4; 1. DR Pfam; PF05351; GMP_PDE_delta; 1. DR SUPFAM; SSF81296; E set domains; 1. DR Genevisible; Q13432; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cone-rod dystrophy; Cytoplasm; KW Cytoskeleton; Disease variant; Endocytosis; Lipid-binding; Phosphoprotein; KW Protein transport; Reference proteome; Sensory transduction; Transport; KW Vision. FT CHAIN 1..240 FT /note="Protein unc-119 homolog A" FT /id="PRO_0000221212" FT REGION 1..61 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1..59 FT /note="Required for midbody localization" FT REGION 121..240 FT /note="Required for centrosome localization" FT COMPBIAS 16..37 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 131 FT /ligand="tetradecanoate" FT /ligand_id="ChEBI:CHEBI:30807" FT MOD_RES 37 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:31696965" FT MOD_RES 39 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:31696965" FT MOD_RES 41 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:31696965" FT VAR_SEQ 204..240 FT /note="ISEMIRHPYETQSDSFYFVDDRLVMHNKADYSYSGTP -> SARAGSSGSGE FT VGASRD (in isoform B)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:21697133, ECO:0000303|PubMed:9761287" FT /id="VSP_004545" FT VARIANT 22 FT /note="G -> V (in IMD13; impairs interaction with LCK; FT impairs LCK activation; induces LCK mislocalization; FT dbSNP:rs199714731)" FT /evidence="ECO:0000269|PubMed:22184408" FT /id="VAR_071184" FT VARIANT 57..240 FT /note="Missing (in CORD24; when expressed in transgenic FT mice, it results in age-dependent fundus lesions, defects FT in photoreceptor synaptic transmission and retinal FT degeneration)" FT /evidence="ECO:0000269|PubMed:11006213" FT /id="VAR_088461" FT VARIANT 201..240 FT /note="Missing (in CORD24; uncertain significance)" FT /evidence="ECO:0000269|PubMed:35947183" FT /id="VAR_088462" FT MUTAGEN 29..32 FT /note="PQPP->AQPA: Impairs interaction with LCK." FT /evidence="ECO:0000269|PubMed:14757743" FT MUTAGEN 37 FT /note="S->A: Loss of phosphorylation; when associated with FT A-39 and A-41." FT /evidence="ECO:0000269|PubMed:31696965" FT MUTAGEN 39 FT /note="S->A: Loss of phosphorylation; when associated with FT A-37 and A-41." FT /evidence="ECO:0000269|PubMed:31696965" FT MUTAGEN 41 FT /note="S->A: Loss of phosphorylation; when associated with FT A-37 and A-39." FT /evidence="ECO:0000269|PubMed:31696965" FT HELIX 62..64 FT /evidence="ECO:0007829|PDB:3GQQ" FT TURN 65..67 FT /evidence="ECO:0007829|PDB:3GQQ" FT HELIX 79..81 FT /evidence="ECO:0007829|PDB:3GQQ" FT STRAND 87..95 FT /evidence="ECO:0007829|PDB:3GQQ" FT TURN 96..98 FT /evidence="ECO:0007829|PDB:3GQQ" FT STRAND 101..106 FT /evidence="ECO:0007829|PDB:3GQQ" FT TURN 123..127 FT /evidence="ECO:0007829|PDB:6H6A" FT STRAND 128..132 FT /evidence="ECO:0007829|PDB:3GQQ" FT HELIX 135..139 FT /evidence="ECO:0007829|PDB:3GQQ" FT STRAND 141..150 FT /evidence="ECO:0007829|PDB:3GQQ" FT STRAND 158..167 FT /evidence="ECO:0007829|PDB:3GQQ" FT STRAND 170..178 FT /evidence="ECO:0007829|PDB:3GQQ" FT STRAND 186..195 FT /evidence="ECO:0007829|PDB:3GQQ" FT HELIX 201..209 FT /evidence="ECO:0007829|PDB:3GQQ" FT STRAND 214..222 FT /evidence="ECO:0007829|PDB:3GQQ" FT STRAND 225..235 FT /evidence="ECO:0007829|PDB:3GQQ" SQ SEQUENCE 240 AA; 26962 MW; 22FD19C3518A4446 CRC64; MKVKKGGGGA GTATESAPGP SGQSVAPIPQ PPAESESGSE SEPDAGPGPR PGPLQRKQPI GPEDVLGLQR ITGDYLCSPE ENIYKIDFVR FKIRDMDSGT VLFEIKKPPV SERLPINRRD LDPNAGRFVR YQFTPAFLRL RQVGATVEFT VGDKPVNNFR MIERHYFRNQ LLKSFDFHFG FCIPSSKNTC EHIYDFPPLS EELISEMIRH PYETQSDSFY FVDDRLVMHN KADYSYSGTP //