ID HYCCI_HUMAN Reviewed; 521 AA. AC Q9BYI3; A0A024RA06; A4D145; B8ZZJ1; Q6N010; Q75MR4; Q7LDZ4; Q96MX1; Q96NQ6; DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2005, sequence version 2. DT 24-JAN-2024, entry version 151. DE RecName: Full=Hyccin {ECO:0000303|PubMed:16951682}; DE AltName: Full=Down-regulated by CTNNB1 protein A {ECO:0000303|PubMed:10910037}; GN Name=HYCC1 {ECO:0000312|HGNC:HGNC:24587}; GN Synonyms=DRCTNNB1A {ECO:0000303|PubMed:10910037}, FAM126A; 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 1), POSSIBLE FUNCTION, SUBCELLULAR RP LOCATION, TISSUE SPECIFICITY, AND INDUCTION. RC TISSUE=Fetal brain; RX PubMed=10910037; RA Kawasoe T., Furukawa Y., Daigo Y., Nishiwaki T., Ishiguro H., Fujita M., RA Satoh S., Miwa N., Nagasawa Y., Miyoshi Y., Ogawa M., Nakamura Y.; RT "Isolation and characterization of a novel human gene, DRCTNNB1A, the RT expression of which is down-regulated by beta-catenin."; RL Cancer Res. 60:3354-3358(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3). RA Yang X., Coulombe-Huntington J., Kang S., Sheynkman G.M., Hao T., RA Richardson A., Sun S., Yang F., Shen Y.A., Murray R., Spirohn K., RA Begg B.E., Duran-Frigola M., MacWilliams A., Pevzner S.J., Zhong Q., RA Trigg S.A., Tam S., Ghamsari L., Sahni N., Yi S., Rodriguez M.D., RA Balcha D., Tan G., Costanzo M., Andrews B., Boone C., Zhou X.J., RA Salehi-Ashtiani K., Charloteaux B., Chen A., Calderwood M.A., Aloy P., RA Roth F.P., Hill D.E., Iakoucheva L.M., Xia Y., Vidal M.; RT "Widespread expansion of protein interaction capabilities by alternative RT splicing."; RL Cell 0:0-0(2016). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Teratocarcinoma; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-453, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [10] RP INVOLVEMENT IN HLD5. RX PubMed=21911699; DOI=10.1001/archneurol.2011.201; RA Biancheri R., Zara F., Rossi A., Mathot M., Nassogne M.C., Yalcinkaya C., RA Erturk O., Tuysuz B., Di Rocco M., Gazzerro E., Bugiani M., RA van Spaendonk R., Sistermans E.A., Minetti C., van der Knaap M.S., RA Wolf N.I.; RT "Hypomyelination and congenital cataract: broadening the clinical RT phenotype."; RL Arch. Neurol. 68:1191-1194(2011). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-306; SER-415; SER-422; RP SER-433 AND SER-453, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 12-271 IN COMPLEX WITH TTC7B, RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TTC7B, IDENTIFICATION IN RP THE PI4K COMPLEX, AND CHARACTERIZATION OF VARIANTS HLD5 PRO-53 AND ARG-57. RX PubMed=26571211; DOI=10.1038/ncb3271; RA Baskin J.M., Wu X., Christiano R., Oh M.S., Schauder C.M., Gazzerro E., RA Messa M., Baldassari S., Assereto S., Biancheri R., Zara F., Minetti C., RA Raimondi A., Simons M., Walther T.C., Reinisch K.M., De Camilli P.; RT "The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis RT at the plasma membrane."; RL Nat. Cell Biol. 18:132-138(2016). RN [13] RP VARIANT HLD5 PRO-53, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=16951682; DOI=10.1038/ng1870; RA Zara F., Biancheri R., Bruno C., Bordo L., Assereto S., Gazzerro E., RA Sotgia F., Wang X.B., Gianotti S., Stringara S., Pedemonte M., Uziel G., RA Rossi A., Schenone A., Tortori-Donati P., van der Knaap M.S., Lisanti M.P., RA Minetti C.; RT "Deficiency of hyccin, a newly identified membrane protein, causes RT hypomyelination and congenital cataract."; RL Nat. Genet. 38:1111-1113(2006). RN [14] RP VARIANT HLD5 ARG-57. RX PubMed=23998934; DOI=10.1016/j.bbrc.2013.08.077; RA Traverso M., Assereto S., Gazzerro E., Savasta S., Abdalla E.M., Rossi A., RA Baldassari S., Fruscione F., Ruffinazzi G., Fassad M.R., El Beheiry A., RA Minetti C., Zara F., Biancheri R.; RT "Novel FAM126A mutations in hypomyelination and congenital cataract RT disease."; RL Biochem. Biophys. Res. Commun. 439:369-372(2013). RN [15] RP VARIANT GLN-217. RX PubMed=28887846; DOI=10.1002/humu.23335; RA Zhou X.L., He L.X., Yu L.J., Wang Y., Wang X.J., Wang E.D., Yang T.; RT "Mutations in KARS cause early-onset hearing loss and leukoencephalopathy: RT Potential pathogenic mechanism."; RL Hum. Mutat. 38:1740-1750(2017). CC -!- FUNCTION: Component of a complex required to localize CC phosphatidylinositol 4-kinase (PI4K) to the plasma membrane CC (PubMed:26571211). The complex acts as a regulator of CC phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis CC (PubMed:26571211). HYCC1 plays a key role in oligodendrocytes CC formation, a cell type with expanded plasma membrane that requires CC generation of PtdIns(4)P (PubMed:26571211). Its role in CC oligodendrocytes formation probably explains its importance in CC myelination of the central and peripheral nervous system CC (PubMed:26571211, PubMed:16951682). May also have a role in the beta- CC catenin/Lef signaling pathway (Probable). {ECO:0000269|PubMed:16951682, CC ECO:0000269|PubMed:26571211, ECO:0000305|PubMed:10910037}. CC -!- SUBUNIT: Component of a phosphatidylinositol 4-kinase (PI4K) complex, CC composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and CC HYCC (HYCC1 or HYCC2) (PubMed:26571211). Interacts with TTC7 (TTC7A or CC TTC7B), interaction is direct (PubMed:26571211). CC {ECO:0000269|PubMed:26571211}. CC -!- INTERACTION: CC Q9BYI3; O95273: CCNDBP1; NbExp=3; IntAct=EBI-11065686, EBI-748961; CC Q9BYI3; Q13643: FHL3; NbExp=3; IntAct=EBI-11065686, EBI-741101; CC Q9BYI3; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-11065686, EBI-16439278; CC Q9BYI3; P14373: TRIM27; NbExp=6; IntAct=EBI-11065686, EBI-719493; CC Q9BYI3; Q86TV6: TTC7B; NbExp=5; IntAct=EBI-11065686, EBI-12006098; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10910037, CC ECO:0000269|PubMed:26571211}. Cell membrane CC {ECO:0000269|PubMed:16951682, ECO:0000269|PubMed:26571211}. CC Note=Localizes to the cytosol and is recruited to the plasma membrane CC following interaction with other components of the phosphatidylinositol CC 4-kinase (PI4K) complex. {ECO:0000269|PubMed:26571211}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9BYI3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BYI3-2; Sequence=VSP_023126; CC Name=3; CC IsoId=Q9BYI3-3; Sequence=VSP_058128, VSP_058129; CC -!- TISSUE SPECIFICITY: Widely expressed. Highest levels in heart, brain, CC placenta, spleen and testis. {ECO:0000269|PubMed:10910037}. CC -!- INDUCTION: Down-regulated by beta-catenin. CC {ECO:0000269|PubMed:10910037}. CC -!- DISEASE: Leukodystrophy, hypomyelinating, 5 (HLD5) [MIM:610532]: A CC hypomyelinating leukodystrophy associated with congenital cataract. It CC is clinically characterized by congenital cataract, progressive CC neurologic impairment, and diffuse myelin deficiency. Affected CC individuals experience progressive pyramidal and cerebellar CC dysfunction, muscle weakness and wasting prevailingly in the lower CC limbs. Mental deficiency ranges from mild to moderate. HLD5 shows CC clinical variability, but features of hypomyelination combined with CC increased periventricular white matter water content are consistently CC observed. {ECO:0000269|PubMed:16951682, ECO:0000269|PubMed:21911699, CC ECO:0000269|PubMed:23998934, ECO:0000269|PubMed:26571211}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the Hyccin family. {ECO:0000305}. 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; AB030241; BAB39849.1; -; mRNA. DR EMBL; KU178808; ALQ34266.1; -; mRNA. DR EMBL; KU178809; ALQ34267.1; -; mRNA. DR EMBL; AK056319; BAB71148.1; -; mRNA. DR EMBL; AK054887; BAB70823.1; -; mRNA. DR EMBL; AC005682; AAS01991.1; -; Genomic_DNA. DR EMBL; AC006039; AAS07519.1; -; Genomic_DNA. DR EMBL; CH236948; EAL24262.1; -; Genomic_DNA. DR EMBL; CH471073; EAW93767.1; -; Genomic_DNA. DR EMBL; CH471073; EAW93768.1; -; Genomic_DNA. DR EMBL; BC018710; AAH18710.1; -; mRNA. DR EMBL; BX640757; CAE45864.1; -; mRNA. DR CCDS; CCDS5377.1; -. [Q9BYI3-1] DR CCDS; CCDS87486.1; -. [Q9BYI3-3] DR RefSeq; NP_115970.2; NM_032581.3. [Q9BYI3-1] DR RefSeq; XP_005249951.1; XM_005249894.3. DR RefSeq; XP_011513891.1; XM_011515589.2. [Q9BYI3-1] DR PDB; 5DSE; X-ray; 2.90 A; B/D=2-308. DR PDB; 6BQ1; EM; 3.60 A; C/G=2-289. DR PDBsum; 5DSE; -. DR PDBsum; 6BQ1; -. DR AlphaFoldDB; Q9BYI3; -. DR EMDB; EMD-7129; -. DR SMR; Q9BYI3; -. DR BioGRID; 124188; 42. DR CORUM; Q9BYI3; -. DR IntAct; Q9BYI3; 19. DR MINT; Q9BYI3; -. DR STRING; 9606.ENSP00000403396; -. DR GlyGen; Q9BYI3; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9BYI3; -. DR PhosphoSitePlus; Q9BYI3; -. DR BioMuta; FAM126A; -. DR DMDM; 77416421; -. DR EPD; Q9BYI3; -. DR jPOST; Q9BYI3; -. DR MassIVE; Q9BYI3; -. DR MaxQB; Q9BYI3; -. DR PaxDb; 9606-ENSP00000403396; -. DR PeptideAtlas; Q9BYI3; -. DR ProteomicsDB; 7387; -. DR ProteomicsDB; 79652; -. [Q9BYI3-1] DR ProteomicsDB; 79653; -. [Q9BYI3-2] DR Pumba; Q9BYI3; -. DR Antibodypedia; 53361; 82 antibodies from 19 providers. DR DNASU; 84668; -. DR Ensembl; ENST00000409923.5; ENSP00000386246.1; ENSG00000122591.13. [Q9BYI3-3] DR Ensembl; ENST00000432176.7; ENSP00000403396.2; ENSG00000122591.13. [Q9BYI3-1] DR GeneID; 84668; -. DR KEGG; hsa:84668; -. DR MANE-Select; ENST00000432176.7; ENSP00000403396.2; NM_032581.4; NP_115970.2. DR UCSC; uc003svm.5; human. [Q9BYI3-1] DR UCSC; uc064byk.1; human. DR AGR; HGNC:24587; -. DR CTD; 84668; -. DR DisGeNET; 84668; -. DR GeneCards; HYCC1; -. DR GeneReviews; HYCC1; -. DR HGNC; HGNC:24587; HYCC1. DR HPA; ENSG00000122591; Low tissue specificity. DR MalaCards; HYCC1; -. DR MIM; 610531; gene. DR MIM; 610532; phenotype. DR neXtProt; NX_Q9BYI3; -. DR OpenTargets; ENSG00000122591; -. DR Orphanet; 85163; Hypomyelination-congenital cataract syndrome. DR PharmGKB; PA162385852; -. DR VEuPathDB; HostDB:ENSG00000122591; -. DR eggNOG; KOG4688; Eukaryota. DR GeneTree; ENSGT00390000011295; -. DR HOGENOM; CLU_027457_3_0_1; -. DR InParanoid; Q9BYI3; -. DR OMA; RWKRHGD; -. DR OrthoDB; 3089164at2759; -. DR PhylomeDB; Q9BYI3; -. DR TreeFam; TF317153; -. DR PathwayCommons; Q9BYI3; -. DR SignaLink; Q9BYI3; -. DR BioGRID-ORCS; 84668; 13 hits in 1170 CRISPR screens. DR ChiTaRS; FAM126A; human. DR GenomeRNAi; 84668; -. DR Pharos; Q9BYI3; Tbio. DR PRO; PR:Q9BYI3; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q9BYI3; Protein. DR Bgee; ENSG00000122591; Expressed in calcaneal tendon and 188 other cell types or tissues. DR ExpressionAtlas; Q9BYI3; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0043005; C:neuron projection; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0042552; P:myelination; ISS:UniProtKB. DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IDA:UniProtKB. DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:UniProtKB. DR InterPro; IPR018619; Hyccin. DR PANTHER; PTHR31220:SF4; HYCCIN; 1. DR PANTHER; PTHR31220; HYCCIN RELATED; 1. DR Pfam; PF09790; Hyccin; 1. DR Genevisible; Q9BYI3; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cataract; Cell membrane; Cytoplasm; KW Disease variant; Leukodystrophy; Membrane; Phosphoprotein; KW Reference proteome. FT CHAIN 1..521 FT /note="Hyccin" FT /id="PRO_0000080005" FT REGION 355..413 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 501..521 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 355..383 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 386..410 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 306 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 321 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6P9N1" FT MOD_RES 415 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 422 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 433 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 453 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..341 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_023126" FT VAR_SEQ 331..419 FT /note="GNTELTGQEELMEISEVDEGFYSRAASSTSQSGLSNSSHNCSNKPSIGKNHR FT RSGGSKTGGKEKETTGESCKDHFARKQTQRAQSENLE -> EQPDNNNDATELGILVIP FT EISVTNVAGERTGNGEKGRTLGEIDAQHIQGVQETATDPRTESKGLPEIRRQKSVRKMM FT EDGINSPGRVQF (in isoform 3)" FT /id="VSP_058128" FT VAR_SEQ 420..521 FT /note="Missing (in isoform 3)" FT /id="VSP_058129" FT VARIANT 53 FT /note="L -> P (in HLD5; induces misfolding and degradation, FT leading to destabilization of the PI4K complex; FT dbSNP:rs72549407)" FT /evidence="ECO:0000269|PubMed:16951682, FT ECO:0000269|PubMed:26571211" FT /id="VAR_030647" FT VARIANT 57 FT /note="C -> R (in HLD5; induces misfolding and degradation, FT leading to destabilization of the PI4K complex)" FT /evidence="ECO:0000269|PubMed:23998934, FT ECO:0000269|PubMed:26571211" FT /id="VAR_075100" FT VARIANT 217 FT /note="R -> Q (in dbSNP:rs192409840)" FT /evidence="ECO:0000269|PubMed:28887846" FT /id="VAR_079751" FT CONFLICT 160 FT /note="V -> A (in Ref. 1; BAB39849)" FT /evidence="ECO:0000305" FT CONFLICT 194 FT /note="Y -> C (in Ref. 1; BAB39849)" FT /evidence="ECO:0000305" FT CONFLICT 474 FT /note="A -> V (in Ref. 4; CAE45864)" FT /evidence="ECO:0000305" FT HELIX 8..14 FT /evidence="ECO:0007829|PDB:5DSE" FT TURN 26..28 FT /evidence="ECO:0007829|PDB:5DSE" FT HELIX 37..46 FT /evidence="ECO:0007829|PDB:5DSE" FT HELIX 54..65 FT /evidence="ECO:0007829|PDB:5DSE" FT HELIX 69..76 FT /evidence="ECO:0007829|PDB:5DSE" FT HELIX 79..91 FT /evidence="ECO:0007829|PDB:5DSE" FT HELIX 100..112 FT /evidence="ECO:0007829|PDB:5DSE" FT STRAND 116..119 FT /evidence="ECO:0007829|PDB:5DSE" FT STRAND 123..126 FT /evidence="ECO:0007829|PDB:5DSE" FT HELIX 144..147 FT /evidence="ECO:0007829|PDB:5DSE" FT STRAND 159..163 FT /evidence="ECO:0007829|PDB:5DSE" FT HELIX 176..190 FT /evidence="ECO:0007829|PDB:5DSE" FT HELIX 197..212 FT /evidence="ECO:0007829|PDB:5DSE" FT HELIX 217..221 FT /evidence="ECO:0007829|PDB:5DSE" FT HELIX 234..248 FT /evidence="ECO:0007829|PDB:5DSE" FT TURN 249..251 FT /evidence="ECO:0007829|PDB:5DSE" FT HELIX 253..269 FT /evidence="ECO:0007829|PDB:5DSE" FT HELIX 273..285 FT /evidence="ECO:0007829|PDB:5DSE" SQ SEQUENCE 521 AA; 57625 MW; 722D7A9CFD5EC060 CRC64; MFTSEKGVVE EWLSEFKTLP ETSLPNYATN LKDKSSLVSS LYKVIQEPQS ELLEPVCHQL FEFYRSGEEQ LLQFTLQFLP ELIWCYLAVS ASRNVHSSGC IEALLLGVYN LEIVDKQGHT KVLSFTIPSL SKPSVYHEPS SIGSMALTES ALSQHGLSKV VYSGPHPQRE MLTAQNRFEV LTFLLLCYNA ALTYMPSVSL QSLCQICSRI CVCGYPRQHV RKYKGISSRI PVSSGFMVQM LTGIYFAFYN GEWDLAQKAL DDIIYRAQLE LYPEPLLVAN AIKASLPHGP MKSNKEGTRC IQVEITPTSS RISRNAVTSM SIRGHRWKRH GNTELTGQEE LMEISEVDEG FYSRAASSTS QSGLSNSSHN CSNKPSIGKN HRRSGGSKTG GKEKETTGES CKDHFARKQT QRAQSENLEL LSLKRLTLTT SQSLPKPSSH GLAKTAATVF SKSFEQVSGV TVPHNPSSAV GCGAGTDANR FSACSLQEEK LIYVSERTEL PMKHQSGQQR PPSISITLST D //