ID NFH_HUMAN Reviewed; 1026 AA. AC P12036; B4DYY4; Q96HF8; Q9UJS7; Q9UQ14; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 24-MAR-2009, sequence version 4. DT 27-MAR-2024, entry version 214. DE RecName: Full=Neurofilament heavy polypeptide; DE Short=NF-H; DE AltName: Full=200 kDa neurofilament protein; DE AltName: Full=Neurofilament triplet H protein; GN Name=NEFH; Synonyms=KIAA0845, NFH; 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 [GENOMIC DNA], AND VARIANT ALA-811. RX PubMed=3138108; DOI=10.1002/j.1460-2075.1988.tb03032.x; RA Lees J.F., Shneidman P.S., Skuntz S.F., Carden M.J., Lazzarini R.A.; RT "The structure and organization of the human heavy neurofilament subunit RT (NF-H) and the gene encoding it."; RL EMBO J. 7:1947-1955(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Zhu Y., Han Y.; RT "Molecular Cloning of human hSTE cDNA."; RL Beijing Yi Ke Da Xue Xue Bao 31:531-531(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10048485; DOI=10.1093/dnares/5.6.355; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 5:355-364(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 606-1026 (ISOFORM 2). RC TISSUE=Eye; 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 [7] RP PHOSPHORYLATION BY PKN1. RX PubMed=8621664; DOI=10.1074/jbc.271.16.9816; RA Mukai H., Toshimori M., Shibata H., Kitagawa M., Shimakawa M., Miyahara M., RA Sunakawa H., Ono Y.; RT "PKN associates and phosphorylates the head-rod domain of neurofilament RT protein."; RL J. Biol. Chem. 271:9816-9822(1996). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-540; SER-574; SER-628; RP SER-674 AND SER-688, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [9] RP SUBCELLULAR LOCATION, AND INVOLVEMENT IN CMT2CC. RX PubMed=27040688; DOI=10.1016/j.ajhg.2016.02.022; RA Rebelo A.P., Abrams A.J., Cottenie E., Horga A., Gonzalez M., Bis D.M., RA Sanchez-Mejias A., Pinto M., Buglo E., Markel K., Prince J., Laura M., RA Houlden H., Blake J., Woodward C., Sweeney M.G., Holton J.L., Hanna M., RA Dallman J.E., Auer-Grumbach M., Reilly M.M., Zuchner S.; RT "Cryptic amyloidogenic elements in the 3' UTRs of neurofilament genes RT trigger axonal neuropathy."; RL Am. J. Hum. Genet. 98:597-614(2016). RN [10] RP VARIANT ALS LYS-796 DEL. RX PubMed=7849698; DOI=10.1093/hmg/3.10.1757; RA Figlewicz D.A., Krizus A., Martinoli M.G., Meininger V., Dib M., RA Rouleau G.A., Julien J.-P.; RT "Variants of the heavy neurofilament subunit are associated with the RT development of amyotrophic lateral sclerosis."; RL Hum. Mol. Genet. 3:1757-1761(1994). CC -!- FUNCTION: Neurofilaments usually contain three intermediate filament CC proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of CC neuronal caliber. NEFH has an important function in mature axons that CC is not subserved by the two smaller NF proteins. May additionally CC cooperate with the neuronal intermediate filament proteins PRPH and INA CC to form neuronal filamentous networks (By similarity). CC {ECO:0000250|UniProtKB:P19246}. CC -!- SUBUNIT: Forms heterodimers with NEFL; which can further hetero- CC oligomerize (in vitro) (By similarity). Forms heterodimers with INA (in CC vitro) (By similarity). {ECO:0000250|UniProtKB:P16884}. CC -!- INTERACTION: CC P12036; P05067: APP; NbExp=3; IntAct=EBI-2880271, EBI-77613; CC P12036; P10809: HSPD1; NbExp=3; IntAct=EBI-2880271, EBI-352528; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:27040688}. Cell projection, axon CC {ECO:0000250|UniProtKB:P19246}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P12036-1; Sequence=Displayed; CC Name=2; CC IsoId=P12036-2; Sequence=VSP_036706; CC -!- PTM: There are a number of repeats of the tripeptide K-S-P, NFH is CC phosphorylated on a number of the serines in this motif. It is thought CC that phosphorylation of NFH results in the formation of interfilament CC cross bridges that are important in the maintenance of axonal caliber. CC {ECO:0000269|PubMed:8621664}. CC -!- PTM: Phosphorylation seems to play a major role in the functioning of CC the larger neurofilament polypeptides (NF-M and NF-H), the levels of CC phosphorylation being altered developmentally and coincidentally with a CC change in the neurofilament function. {ECO:0000269|PubMed:8621664}. CC -!- PTM: Phosphorylated in the head and rod regions by the PKC kinase PKN1, CC leading to the inhibition of polymerization. CC {ECO:0000269|PubMed:8621664}. CC -!- POLYMORPHISM: The number of repeats is shown to vary between 29 and 30. CC -!- DISEASE: Amyotrophic lateral sclerosis (ALS) [MIM:105400]: A CC neurodegenerative disorder affecting upper motor neurons in the brain CC and lower motor neurons in the brain stem and spinal cord, resulting in CC fatal paralysis. Sensory abnormalities are absent. The pathologic CC hallmarks of the disease include pallor of the corticospinal tract due CC to loss of motor neurons, presence of ubiquitin-positive inclusions CC within surviving motor neurons, and deposition of pathologic CC aggregates. The etiology of amyotrophic lateral sclerosis is likely to CC be multifactorial, involving both genetic and environmental factors. CC The disease is inherited in 5-10% of the cases. CC {ECO:0000269|PubMed:7849698}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- DISEASE: Charcot-Marie-Tooth disease, axonal, 2CC (CMT2CC) CC [MIM:616924]: An axonal form of Charcot-Marie-Tooth disease, a disorder CC of the peripheral nervous system, characterized by progressive weakness CC and atrophy, initially of the peroneal muscles and later of the distal CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two CC main groups on the basis of electrophysiologic properties and CC histopathology: primary peripheral demyelinating neuropathies CC (designated CMT1 when they are dominantly inherited) and primary CC peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group CC are characterized by signs of axonal degeneration in the absence of CC obvious myelin alterations, normal or slightly reduced nerve conduction CC velocities, and progressive distal muscle weakness and atrophy. CC {ECO:0000269|PubMed:27040688}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the intermediate filament family. CC {ECO:0000255|PROSITE-ProRule:PRU01188}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA74868.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAG63896.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Alsod; Note=ALS genetic mutations db; CC URL="https://alsod.ac.uk/"; 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; X15306; CAA33366.1; -; Genomic_DNA. DR EMBL; X15307; CAA33366.1; JOINED; Genomic_DNA. DR EMBL; X15308; CAA33366.1; JOINED; Genomic_DNA. DR EMBL; X15309; CAA33366.1; JOINED; Genomic_DNA. DR EMBL; AF203032; AAF13722.1; -; mRNA. DR EMBL; AB020652; BAA74868.2; ALT_INIT; mRNA. DR EMBL; AK302660; BAG63896.1; ALT_INIT; mRNA. DR EMBL; AC000035; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC008648; AAH08648.1; -; mRNA. DR EMBL; BC073969; AAH73969.1; -; mRNA. DR PIR; S00979; QFHUH. DR RefSeq; NP_066554.2; NM_021076.3. DR AlphaFoldDB; P12036; -. DR SMR; P12036; -. DR BioGRID; 110819; 56. DR IntAct; P12036; 32. DR MINT; P12036; -. DR STRING; 9606.ENSP00000311997; -. DR CarbonylDB; P12036; -. DR GlyCosmos; P12036; 4 sites, 1 glycan. DR GlyGen; P12036; 11 sites, 1 O-linked glycan (11 sites). DR iPTMnet; P12036; -. DR PhosphoSitePlus; P12036; -. DR SwissPalm; P12036; -. DR BioMuta; NEFH; -. DR DMDM; 226726294; -. DR EPD; P12036; -. DR jPOST; P12036; -. DR MassIVE; P12036; -. DR MaxQB; P12036; -. DR PaxDb; 9606-ENSP00000311997; -. DR PeptideAtlas; P12036; -. DR ProteomicsDB; 52821; -. [P12036-1] DR ProteomicsDB; 52822; -. [P12036-2] DR Pumba; P12036; -. DR Antibodypedia; 3579; 1896 antibodies from 47 providers. DR DNASU; 4744; -. DR Ensembl; ENST00000310624.7; ENSP00000311997.6; ENSG00000100285.10. DR GeneID; 4744; -. DR KEGG; hsa:4744; -. DR MANE-Select; ENST00000310624.7; ENSP00000311997.6; NM_021076.4; NP_066554.2. DR UCSC; uc003afo.4; human. [P12036-1] DR AGR; HGNC:7737; -. DR CTD; 4744; -. DR DisGeNET; 4744; -. DR GeneCards; NEFH; -. DR GeneReviews; NEFH; -. DR HGNC; HGNC:7737; NEFH. DR HPA; ENSG00000100285; Group enriched (brain, prostate). DR MalaCards; NEFH; -. DR MIM; 105400; phenotype. DR MIM; 162230; gene. DR MIM; 616924; phenotype. DR neXtProt; NX_P12036; -. DR Orphanet; 803; Amyotrophic lateral sclerosis. DR PharmGKB; PA31540; -. DR VEuPathDB; HostDB:ENSG00000100285; -. DR eggNOG; ENOG502QYDU; Eukaryota. DR HOGENOM; CLU_012560_7_2_1; -. DR InParanoid; P12036; -. DR OrthoDB; 4640531at2759; -. DR PhylomeDB; P12036; -. DR TreeFam; TF330122; -. DR PathwayCommons; P12036; -. DR SignaLink; P12036; -. DR SIGNOR; P12036; -. DR BioGRID-ORCS; 4744; 13 hits in 1154 CRISPR screens. DR ChiTaRS; NEFH; human. DR GenomeRNAi; 4744; -. DR Pharos; P12036; Tbio. DR PRO; PR:P12036; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P12036; Protein. DR Bgee; ENSG00000100285; Expressed in dorsal root ganglion and 163 other cell types or tissues. DR GO; GO:0030424; C:axon; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005856; C:cytoskeleton; IDA:ARUK-UCL. DR GO; GO:0097418; C:neurofibrillary tangle; IDA:BHF-UCL. DR GO; GO:0005883; C:neurofilament; IBA:GO_Central. DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl. DR GO; GO:0099160; C:postsynaptic intermediate filament cytoskeleton; IEA:Ensembl. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl. DR GO; GO:0070840; F:dynein complex binding; TAS:BHF-UCL. DR GO; GO:0019894; F:kinesin binding; TAS:BHF-UCL. DR GO; GO:0008017; F:microtubule binding; TAS:BHF-UCL. DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISS:BHF-UCL. DR GO; GO:0005200; F:structural constituent of cytoskeleton; IMP:BHF-UCL. DR GO; GO:0099184; F:structural constituent of postsynaptic intermediate filament cytoskeleton; IBA:GO_Central. DR GO; GO:0061564; P:axon development; IMP:BHF-UCL. DR GO; GO:0007409; P:axonogenesis; TAS:BHF-UCL. DR GO; GO:0030031; P:cell projection assembly; TAS:BHF-UCL. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl. DR GO; GO:0045110; P:intermediate filament bundle assembly; IBA:GO_Central. DR GO; GO:0000226; P:microtubule cytoskeleton organization; IEA:Ensembl. DR GO; GO:0033693; P:neurofilament bundle assembly; IMP:BHF-UCL. DR GO; GO:0060052; P:neurofilament cytoskeleton organization; IEA:Ensembl. DR GO; GO:0048936; P:peripheral nervous system neuron axonogenesis; IEA:Ensembl. DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; IEA:Ensembl. DR GO; GO:1902513; P:regulation of organelle transport along microtubule; IMP:BHF-UCL. DR Gene3D; 1.20.5.170; -; 1. DR Gene3D; 1.20.5.500; Single helix bin; 1. DR Gene3D; 1.20.5.1160; Vasodilator-stimulated phosphoprotein; 1. DR InterPro; IPR010790; DUF1388. DR InterPro; IPR018039; IF_conserved. DR InterPro; IPR039008; IF_rod_dom. DR InterPro; IPR033183; NF-H. DR PANTHER; PTHR23214:SF1; NEUROFILAMENT HEAVY POLYPEPTIDE; 1. DR PANTHER; PTHR23214; NEUROFILAMENT TRIPLET H PROTEIN; 1. DR Pfam; PF07142; DUF1388; 1. DR Pfam; PF00038; Filament; 1. DR SMART; SM01391; Filament; 1. DR SUPFAM; SSF64593; Intermediate filament protein, coiled coil region; 2. DR PROSITE; PS00226; IF_ROD_1; 1. DR PROSITE; PS51842; IF_ROD_2; 1. DR UCD-2DPAGE; P12036; -. DR Genevisible; P12036; HS. PE 1: Evidence at protein level; KW Alternative splicing; Amyotrophic lateral sclerosis; Cell projection; KW Charcot-Marie-Tooth disease; Coiled coil; Cytoplasm; Cytoskeleton; KW Disease variant; Intermediate filament; Neurodegeneration; Neuropathy; KW Phosphoprotein; Reference proteome; Repeat. FT CHAIN 1..1026 FT /note="Neurofilament heavy polypeptide" FT /id="PRO_0000063800" FT DOMAIN 97..413 FT /note="IF rod" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188" FT REPEAT 525..530 FT /note="1" FT REPEAT 531..536 FT /note="2" FT REPEAT 539..544 FT /note="3" FT REPEAT 545..550 FT /note="4" FT REPEAT 559..564 FT /note="5" FT REPEAT 573..578 FT /note="6" FT REPEAT 579..584 FT /note="7" FT REPEAT 593..598 FT /note="8" FT REPEAT 599..604 FT /note="9" FT REPEAT 613..618 FT /note="10" FT REPEAT 627..632 FT /note="11" FT REPEAT 633..638 FT /note="12" FT REPEAT 647..652 FT /note="13" FT REPEAT 653..658 FT /note="14" FT REPEAT 667..672 FT /note="15" FT REPEAT 673..678 FT /note="16" FT REPEAT 681..686 FT /note="17" FT REPEAT 687..692 FT /note="18" FT REPEAT 695..700 FT /note="19" FT REPEAT 701..706 FT /note="20" FT REPEAT 709..714 FT /note="21" FT REPEAT 715..720 FT /note="22" FT REPEAT 723..728 FT /note="23" FT REPEAT 729..734 FT /note="24" FT REPEAT 743..748 FT /note="25" FT REPEAT 751..756 FT /note="26" FT REPEAT 768..773 FT /note="27" FT REPEAT 792..797 FT /note="28" FT REPEAT 800..805 FT /note="29" FT REPEAT 827..832 FT /note="30" FT REGION 1..100 FT /note="Head" FT REGION 58..83 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 101..132 FT /note="Coil 1A" FT REGION 133..145 FT /note="Linker 1" FT REGION 146..244 FT /note="Coil 1B" FT REGION 245..266 FT /note="Linker 12" FT REGION 267..288 FT /note="Coil 2A" FT REGION 289..292 FT /note="Linker 2" FT REGION 293..413 FT /note="Coil 2B" FT REGION 414..1026 FT /note="Tail" FT REGION 456..1026 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 525..832 FT /note="30 X 6 AA repeats of K-S-P-[AEPV]-[EAK]-[AEVK]" FT COMPBIAS 58..81 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 462..498 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 499..1026 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 76 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 124 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 347 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P16884" FT MOD_RES 421 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 511 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P16884" FT MOD_RES 526 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P16884" FT MOD_RES 532 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 540 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 546 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 552 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 560 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 566 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 574 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 580 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 586 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 594 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 600 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 606 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 614 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 620 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 628 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 634 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 640 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 648 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 654 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 660 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 668 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P16884" FT MOD_RES 674 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 682 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 688 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 696 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 702 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 710 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 724 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 730 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 744 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P16884" FT MOD_RES 758 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P16884" FT MOD_RES 769 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 774 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P16884" FT MOD_RES 793 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 801 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 828 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19246" FT MOD_RES 894 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P16884" FT VAR_SEQ 750..812 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_036706" FT VARIANT 575 FT /note="P -> S (in dbSNP:rs6006164)" FT /id="VAR_054787" FT VARIANT 615 FT /note="P -> L (in dbSNP:rs5763269)" FT /id="VAR_056025" FT VARIANT 796 FT /note="Missing (in ALS)" FT /evidence="ECO:0000269|PubMed:7849698" FT /id="VAR_023063" FT VARIANT 811 FT /note="E -> A (in dbSNP:rs165602)" FT /evidence="ECO:0000269|PubMed:3138108" FT /id="VAR_026163" FT CONFLICT 647..652 FT /note="Missing (in Ref. 1; CAA33366 and 5; AC000035)" FT /evidence="ECO:0000305" SQ SEQUENCE 1026 AA; 112479 MW; 0879B6A08D208C17 CRC64; MMSFGGADAL LGAPFAPLHG GGSLHYALAR KGGAGGTRSA AGSSSGFHSW TRTSVSSVSA SPSRFRGAGA ASSTDSLDTL SNGPEGCMVA VATSRSEKEQ LQALNDRFAG YIDKVRQLEA HNRSLEGEAA ALRQQQAGRS AMGELYEREV REMRGAVLRL GAARGQLRLE QEHLLEDIAH VRQRLDDEAR QREEAEAAAR ALARFAQEAE AARVDLQKKA QALQEECGYL RRHHQEEVGE LLGQIQGSGA AQAQMQAETR DALKCDVTSA LREIRAQLEG HAVQSTLQSE EWFRVRLDRL SEAAKVNTDA MRSAQEEITE YRRQLQARTT ELEALKSTKD SLERQRSELE DRHQADIASY QEAIQQLDAE LRNTKWEMAA QLREYQDLLN VKMALDIEIA AYRKLLEGEE CRIGFGPIPF SLPEGLPKIP SVSTHIKVKS EEKIKVVEKS EKETVIVEEQ TEETQVTEEV TEEEEKEAKE EEGKEEEGGE EEEAEGGEEE TKSPPAEEAA SPEKEAKSPV KEEAKSPAEA KSPEKEEAKS PAEVKSPEKA KSPAKEEAKS PPEAKSPEKE EAKSPAEVKS PEKAKSPAKE EAKSPAEAKS PEKAKSPVKE EAKSPAEAKS PVKEEAKSPA EVKSPEKAKS PTKEEAKSPE KAKSPEKAKS PEKEEAKSPE KAKSPVKAEA KSPEKAKSPV KAEAKSPEKA KSPVKEEAKS PEKAKSPVKE EAKSPEKAKS PVKEEAKTPE KAKSPVKEEA KSPEKAKSPE KAKTLDVKSP EAKTPAKEEA RSPADKFPEK AKSPVKEEVK SPEKAKSPLK EDAKAPEKEI PKKEEVKSPV KEEEKPQEVK VKEPPKKAEE EKAPATPKTE EKKDSKKEEA PKKEAPKPKV EEKKEPAVEK PKESKVEAKK EEAEDKKKVP TPEKEAPAKV EVKEDAKPKE KTEVAKKEPD DAKAKEPSKP AEKKEAAPEK KDTKEEKAKK PEEKPKTEAK AKEDDKTLSK EPSKPKAEKA EKSSSTDQKD SKPPEKATED KAAKGK //