ID K0319_HUMAN Reviewed; 1072 AA. AC Q5VV43; A7MD37; B2RTU7; B4DHA7; B4DK75; B7ZML3; F5H123; Q9UJC8; Q9Y4G7; DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot. DT 07-DEC-2004, sequence version 1. DT 24-JAN-2024, entry version 168. DE RecName: Full=Dyslexia-associated protein KIAA0319; DE Flags: Precursor; GN Name=KIAA0319; 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 [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-142. RC TISSUE=Brain; RX PubMed=9205841; DOI=10.1093/dnares/4.2.141; RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. VII. The RT complete sequences of 100 new cDNA clones from brain which can code for RT large proteins in vitro."; RL DNA Res. 4:141-150(1997). RN [2] RP SEQUENCE REVISION. RA Ohara O., Nagase T., Kikuno R., Nomura N.; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANTS RP PRO-142 AND THR-311. RC TISSUE=Brain, and Thalamus; 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 GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS RP PRO-142 AND THR-311. RC TISSUE=Brain; 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 [6] RP TISSUE SPECIFICITY. RX PubMed=12834540; DOI=10.1186/1471-2164-4-25; RA Londin E.R., Meng H., Gruen J.R.; RT "A transcription map of the 6p22.3 reading disability locus identifying RT candidate genes."; RL BMC Genomics 4:25-25(2003). RN [7] RP POSSIBLE INVOLVEMENT IN DYX2, AND DEVELOPMENTAL STAGE. RX PubMed=16600991; DOI=10.1093/hmg/ddl089; RA Paracchini S., Thomas A., Castro S., Lai C., Paramasivam M., Wang Y., RA Keating B.J., Taylor J.M., Hacking D.F., Scerri T., Francks C., RA Richardson A.J., Wade-Martins R., Stein J.F., Knight J.C., Copp A.J., RA Loturco J., Monaco A.P.; RT "The chromosome 6p22 haplotype associated with dyslexia reduces the RT expression of KIAA0319, a novel gene involved in neuronal migration."; RL Hum. Mol. Genet. 15:1659-1666(2006). RN [8] RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY. RX PubMed=17846832; DOI=10.1007/s00335-007-9051-3; RA Velayos-Baeza A., Toma C., da Roza S., Paracchini S., Monaco A.P.; RT "Alternative splicing in the dyslexia-associated gene KIAA0319."; RL Mamm. Genome 18:627-634(2007). RN [9] RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND SUBUNIT. RX PubMed=18063668; DOI=10.1093/hmg/ddm358; RA Velayos-Baeza A., Toma C., Paracchini S., Monaco A.P.; RT "The dyslexia-associated gene KIAA0319 encodes highly N- and O-glycosylated RT plasma membrane and secreted isoforms."; RL Hum. Mol. Genet. 17:859-871(2008). RN [10] RP SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-995, ENDOCYTOSIS SIGNAL, AND RP INTERACTION WITH AP2M1. RX PubMed=19419997; DOI=10.1152/ajpcell.00630.2008; RA Levecque C., Velayos-Baeza A., Holloway Z.G., Monaco A.P.; RT "The dyslexia-associated protein KIAA0319 interacts with adaptor protein 2 RT and follows the classical clathrin-mediated endocytosis pathway."; RL Am. J. Physiol. 297:C160-C168(2009). RN [11] RP FUNCTION. RX PubMed=19679544; DOI=10.1093/cercor/bhp154; RA Peschansky V.J., Burbridge T.J., Volz A.J., Fiondella C., Wissner-Gross Z., RA Galaburda A.M., Lo Turco J.J., Rosen G.D.; RT "The effect of variation in expression of the candidate dyslexia RT susceptibility gene homolog Kiaa0319 on neuronal migration and dendritic RT morphology in the rat."; RL Cereb. Cortex 20:884-897(2010). RN [12] RP PROTEOLYTIC PROCESSING. RX PubMed=20943657; DOI=10.1074/jbc.m110.145961; RA Velayos-Baeza A., Levecque C., Kobayashi K., Holloway Z.G., Monaco A.P.; RT "The dyslexia-associated KIAA0319 protein undergoes proteolytic processing RT with {gamma}-secretase-independent intramembrane cleavage."; RL J. Biol. Chem. 285:40148-40162(2010). RN [13] RP STRUCTURE BY NMR OF 324-428. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the PKD domain (329-428) from human KIAA0319."; RL Submitted (JUL-2007) to the PDB data bank. RN [14] RP VARIANT THR-311, AND INVOLVEMENT IN DYX2. RX PubMed=15717286; DOI=10.1086/429131; RA Cope N., Harold D., Hill G., Moskvina V., Stevenson J., Holmans P., RA Owen M.J., O'Donovan M.C., Williams J.; RT "Strong evidence that KIAA0319 on chromosome 6p is a susceptibility gene RT for developmental dyslexia."; RL Am. J. Hum. Genet. 76:581-591(2005). CC -!- FUNCTION: Involved in neuronal migration during development of the CC cerebral neocortex. May function in a cell autonomous and a non-cell CC autonomous manner and play a role in appropriate adhesion between CC migrating neurons and radial glial fibers. May also regulate growth and CC differentiation of dendrites. {ECO:0000269|PubMed:19679544}. CC -!- SUBUNIT: Homodimer. Interacts with AP2M1; required for clathrin- CC mediated endocytosis. {ECO:0000269|PubMed:18063668, CC ECO:0000269|PubMed:19419997}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18063668, CC ECO:0000269|PubMed:19419997}; Single-pass type I membrane protein CC {ECO:0000269|PubMed:18063668}. Early endosome membrane CC {ECO:0000269|PubMed:19419997}; Single-pass type I membrane protein CC {ECO:0000269|PubMed:18063668}. Note=Low-abundance isoforms lacking the CC transmembrane domain have been described; these are secreted. CC {ECO:0000269|PubMed:18063668}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Comment=Additional isoforms seem to exist.; CC Name=1; Synonyms=A; CC IsoId=Q5VV43-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5VV43-2; Sequence=VSP_036235; CC Name=3; CC IsoId=Q5VV43-3; Sequence=VSP_036234; CC Name=4; CC IsoId=Q5VV43-4; Sequence=VSP_044971; CC -!- TISSUE SPECIFICITY: Detected in adult brain cortex and fetal frontal CC lobe (at protein level). Highly expressed in brain cortex, putamen, CC amygdala, hippocampus and cerebellum. {ECO:0000269|PubMed:12834540, CC ECO:0000269|PubMed:17846832}. CC -!- DEVELOPMENTAL STAGE: Expressed in the developing cerebral neocortex and CC glanglionic eminence in 57 days post-fertilization fetal brain. CC {ECO:0000269|PubMed:16600991}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:18063668}. CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:18063668}. CC -!- PTM: Shedding of the extracellular domain and intramembrane cleavage CC produce several proteolytic products. The intramembrane cleavage CC releases a soluble cytoplasmic polypeptide that translocates to the CC nucleolus. {ECO:0000269|PubMed:20943657}. CC -!- DISEASE: Dyslexia 2 (DYX2) [MIM:600202]: A relatively common, complex CC cognitive disorder characterized by an impairment of reading CC performance despite adequate motivational, educational and intellectual CC opportunities. It is a multifactorial trait, with evidence for familial CC clustering and heritability. {ECO:0000269|PubMed:15717286, CC ECO:0000269|PubMed:16600991}. Note=Disease susceptibility may be CC associated with variants affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=BAA20777.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The twisted way of things CC - Issue 125 of January 2011; CC URL="https://web.expasy.org/spotlight/back_issues/125"; 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; AB002317; BAA20777.2; ALT_INIT; mRNA. DR EMBL; AK295008; BAG58068.1; -; mRNA. DR EMBL; AK296310; BAG59008.1; -; mRNA. DR EMBL; AK296426; BAG59087.1; -; mRNA. DR EMBL; AL512385; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL031230; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC140821; AAI40822.1; -; mRNA. DR EMBL; BC144628; AAI44629.1; -; mRNA. DR EMBL; BC152460; AAI52461.1; -; mRNA. DR CCDS; CCDS34348.1; -. [Q5VV43-1] DR CCDS; CCDS54969.1; -. [Q5VV43-3] DR CCDS; CCDS54970.1; -. [Q5VV43-2] DR CCDS; CCDS54971.1; -. [Q5VV43-4] DR RefSeq; NP_001161846.1; NM_001168374.1. [Q5VV43-2] DR RefSeq; NP_001161847.1; NM_001168375.1. [Q5VV43-1] DR RefSeq; NP_001161848.1; NM_001168376.1. [Q5VV43-3] DR RefSeq; NP_001161849.1; NM_001168377.1. [Q5VV43-4] DR RefSeq; NP_055624.2; NM_014809.3. [Q5VV43-1] DR RefSeq; XP_011513327.1; XM_011515025.2. DR RefSeq; XP_011513328.1; XM_011515026.2. DR RefSeq; XP_016867030.1; XM_017011541.1. [Q5VV43-2] DR RefSeq; XP_016867034.1; XM_017011545.1. DR PDB; 2E7M; NMR; -; A=329-428. DR PDBsum; 2E7M; -. DR AlphaFoldDB; Q5VV43; -. DR SMR; Q5VV43; -. DR BioGRID; 115190; 4. DR IntAct; Q5VV43; 5. DR STRING; 9606.ENSP00000367459; -. DR GlyCosmos; Q5VV43; 10 sites, No reported glycans. DR GlyGen; Q5VV43; 10 sites. DR iPTMnet; Q5VV43; -. DR PhosphoSitePlus; Q5VV43; -. DR BioMuta; KIAA0319; -. DR DMDM; 74747200; -. DR jPOST; Q5VV43; -. DR MassIVE; Q5VV43; -. DR MaxQB; Q5VV43; -. DR PaxDb; 9606-ENSP00000367459; -. DR PeptideAtlas; Q5VV43; -. DR ProteomicsDB; 25518; -. DR ProteomicsDB; 65441; -. [Q5VV43-1] DR ProteomicsDB; 65442; -. [Q5VV43-2] DR ProteomicsDB; 65443; -. [Q5VV43-3] DR Antibodypedia; 2465; 135 antibodies from 27 providers. DR DNASU; 9856; -. DR Ensembl; ENST00000378214.8; ENSP00000367459.3; ENSG00000137261.15. [Q5VV43-1] DR Ensembl; ENST00000430948.6; ENSP00000401086.2; ENSG00000137261.15. [Q5VV43-3] DR Ensembl; ENST00000535378.5; ENSP00000442403.1; ENSG00000137261.15. [Q5VV43-2] DR Ensembl; ENST00000537886.5; ENSP00000439700.1; ENSG00000137261.15. [Q5VV43-4] DR GeneID; 9856; -. DR KEGG; hsa:9856; -. DR MANE-Select; ENST00000378214.8; ENSP00000367459.3; NM_014809.4; NP_055624.2. DR UCSC; uc003neh.2; human. [Q5VV43-1] DR AGR; HGNC:21580; -. DR CTD; 9856; -. DR DisGeNET; 9856; -. DR GeneCards; KIAA0319; -. DR HGNC; HGNC:21580; KIAA0319. DR HPA; ENSG00000137261; Tissue enhanced (brain, pituitary gland). DR MalaCards; KIAA0319; -. DR MIM; 600202; phenotype. DR MIM; 609269; gene. DR neXtProt; NX_Q5VV43; -. DR OpenTargets; ENSG00000137261; -. DR PharmGKB; PA134936721; -. DR VEuPathDB; HostDB:ENSG00000137261; -. DR eggNOG; ENOG502QR8M; Eukaryota. DR GeneTree; ENSGT00940000161462; -. DR HOGENOM; CLU_009448_0_1_1; -. DR InParanoid; Q5VV43; -. DR OMA; HPVDYQG; -. DR OrthoDB; 3021035at2759; -. DR PhylomeDB; Q5VV43; -. DR TreeFam; TF323356; -. DR PathwayCommons; Q5VV43; -. DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR SignaLink; Q5VV43; -. DR BioGRID-ORCS; 9856; 12 hits in 1140 CRISPR screens. DR ChiTaRS; KIAA0319; human. DR EvolutionaryTrace; Q5VV43; -. DR GeneWiki; KIAA0319; -. DR GenomeRNAi; 9856; -. DR Pharos; Q5VV43; Tbio. DR PRO; PR:Q5VV43; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q5VV43; Protein. DR Bgee; ENSG00000137261; Expressed in cortical plate and 114 other cell types or tissues. DR ExpressionAtlas; Q5VV43; baseline and differential. DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome. DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0033555; P:multicellular organismal response to stress; IEA:Ensembl. DR GO; GO:0030517; P:negative regulation of axon extension; IMP:MGI. DR GO; GO:0048692; P:negative regulation of axon extension involved in regeneration; IMP:MGI. DR GO; GO:2000171; P:negative regulation of dendrite development; IGI:UniProtKB. DR GO; GO:0001764; P:neuron migration; IGI:UniProtKB. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IMP:MGI. DR GO; GO:0010996; P:response to auditory stimulus; IEA:Ensembl. DR CDD; cd00146; PKD; 4. DR Gene3D; 2.60.40.10; Immunoglobulins; 5. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR029865; KIAA0319-like. DR InterPro; IPR013980; MANSC_dom. DR InterPro; IPR011106; MANSC_N. DR InterPro; IPR022409; PKD/Chitinase_dom. DR InterPro; IPR000601; PKD_dom. DR InterPro; IPR035986; PKD_dom_sf. DR PANTHER; PTHR46182:SF1; DYSLEXIA-ASSOCIATED PROTEIN KIAA0319; 1. DR PANTHER; PTHR46182; FI19480P1; 1. DR Pfam; PF18911; PKD_4; 1. DR SMART; SM00060; FN3; 4. DR SMART; SM00765; MANEC; 1. DR SMART; SM00089; PKD; 5. DR SUPFAM; SSF49299; PKD domain; 4. DR PROSITE; PS50986; MANSC; 1. DR PROSITE; PS50093; PKD; 1. DR Genevisible; Q5VV43; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Developmental protein; KW Endosome; Glycoprotein; Membrane; Neurogenesis; Reference proteome; Repeat; KW Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT CHAIN 21..1072 FT /note="Dyslexia-associated protein KIAA0319" FT /id="PRO_0000042946" FT TOPO_DOM 21..955 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 956..976 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 977..1072 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 21..99 FT /note="MANSC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00341" FT DOMAIN 341..427 FT /note="PKD 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00151" FT DOMAIN 435..524 FT /note="PKD 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00151" FT DOMAIN 530..620 FT /note="PKD 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00151" FT DOMAIN 621..714 FT /note="PKD 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00151" FT DOMAIN 720..811 FT /note="PKD 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00151" FT REGION 168..277 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 295..327 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1045..1072 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 995..998 FT /note="Endocytosis signal" FT COMPBIAS 247..269 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 196 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 219 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 262 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 394 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 421 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 498 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 513 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 536 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 551 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 733 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..45 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_036234" FT VAR_SEQ 1..19 FT /note="MAPPTGVLSSLLLLVTIAG -> MTRLGWPSPC (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_036235" FT VAR_SEQ 953..1013 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_044971" FT VARIANT 142 FT /note="T -> P (in dbSNP:rs4576240)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9205841" FT /id="VAR_023837" FT VARIANT 311 FT /note="A -> T (risk factor for DYX2; dbSNP:rs4504469)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15717286" FT /id="VAR_023838" FT VARIANT 567 FT /note="G -> S (in dbSNP:rs2744559)" FT /id="VAR_049505" FT VARIANT 773 FT /note="S -> G (in dbSNP:rs2744550)" FT /id="VAR_049506" FT VARIANT 774 FT /note="V -> A (in dbSNP:rs2817191)" FT /id="VAR_049507" FT VARIANT 919 FT /note="G -> A (in dbSNP:rs10946705)" FT /id="VAR_034032" FT VARIANT 1013 FT /note="Y -> C (in dbSNP:rs807534)" FT /id="VAR_049508" FT MUTAGEN 995 FT /note="Y->A: Loss of interaction with AP2M1 and impaired FT endocytosis." FT /evidence="ECO:0000269|PubMed:19419997" FT CONFLICT 97 FT /note="R -> S (in Ref. 3; BAG58068)" FT /evidence="ECO:0000305" FT CONFLICT 157 FT /note="S -> A (in Ref. 1; BAA20777 and 5; AAI52461)" FT /evidence="ECO:0000305" FT CONFLICT 256 FT /note="L -> H (in Ref. 3; BAG59087)" FT /evidence="ECO:0000305" FT CONFLICT 926 FT /note="L -> I (in Ref. 5; AAI44629)" FT /evidence="ECO:0000305" FT STRAND 336..338 FT /evidence="ECO:0007829|PDB:2E7M" FT STRAND 343..346 FT /evidence="ECO:0007829|PDB:2E7M" FT STRAND 352..355 FT /evidence="ECO:0007829|PDB:2E7M" FT STRAND 357..360 FT /evidence="ECO:0007829|PDB:2E7M" FT STRAND 374..376 FT /evidence="ECO:0007829|PDB:2E7M" FT STRAND 389..395 FT /evidence="ECO:0007829|PDB:2E7M" FT STRAND 400..405 FT /evidence="ECO:0007829|PDB:2E7M" FT STRAND 408..411 FT /evidence="ECO:0007829|PDB:2E7M" FT STRAND 414..417 FT /evidence="ECO:0007829|PDB:2E7M" FT STRAND 420..425 FT /evidence="ECO:0007829|PDB:2E7M" SQ SEQUENCE 1072 AA; 117763 MW; 94F33B03E7FE8C0F CRC64; MAPPTGVLSS LLLLVTIAGC ARKQCSEGRT YSNAVISPNL ETTRIMRVSH TFPVVDCTAA CCDLSSCDLA WWFEGRCYLV SCPHKENCEP KKMGPIRSYL TFVLRPVQRP AQLLDYGDMM LNRGSPSGIW GDSPEDIRKD LTFLGKDWGL EEMSEYSDDY RELEKDLLQP SGKQEPRGSA EYTDWGLLPG SEGAFNSSVG DSPAVPAETQ QDPELHYLNE SASTPAPKLP ERSVLLPLPT TPSSGEVLEK EKASQLQEQS SNSSGKEVLM PSHSLPPASL ELSSVTVEKS PVLTVTPGST EHSIPTPPTS AAPSESTPSE LPISPTTAPR TVKELTVSAG DNLIITLPDN EVELKAFVAP APPVETTYNY EWNLISHPTD YQGEIKQGHK QTLNLSQLSV GLYVFKVTVS SENAFGEGFV NVTVKPARRV NLPPVAVVSP QLQELTLPLT SALIDGSQST DDTEIVSYHW EEINGPFIEE KTSVDSPVLR LSNLDPGNYS FRLTVTDSDG ATNSTTAALI VNNAVDYPPV ANAGPNHTIT LPQNSITLNG NQSSDDHQIV LYEWSLGPGS EGKHVVMQGV QTPYLHLSAM QEGDYTFQLK VTDSSRQQST AVVTVIVQPE NNRPPVAVAG PDKELIFPVE SATLDGSSSS DDHGIVFYHW EHVRGPSAVE MENIDKAIAT VTGLQVGTYH FRLTVKDQQG LSSTSTLTVA VKKENNSPPR ARAGGRHVLV LPNNSITLDG SRSTDDQRIV SYLWIRDGQS PAAGDVIDGS DHSVALQLTN LVEGVYTFHL RVTDSQGASD TDTATVEVQP DPRKSGLVEL TLQVGVGQLT EQRKDTLVRQ LAVLLNVLDS DIKVQKIRAH SDLSTVIVFY VQSRPPFKVL KAAEVARNLH MRLSKEKADF LLFKVLRVDT AGCLLKCSGH GHCDPLTKRC ICSHLWMENL IQRYIWDGES NCEWSIFYVT VLAFTLIVLT GGFTWLCICC CKRQKRTKIR KKTKYTILDN MDEQERMELR PKYGIKHRST EHNSSLMVSE SEFDSDQDTI FSREKMERGN PKVSMNGSIR NGASFSYCSK DR //