JIP3_HUMAN
ID JIP3_HUMAN Reviewed; 1336 AA.
AC Q9UPT6; A2A2B3; A7E2B3; Q96RY4; Q9H4I4; Q9H7P1; Q9NUG0;
DT 25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 3.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=C-Jun-amino-terminal kinase-interacting protein 3;
DE Short=JIP-3;
DE Short=JNK-interacting protein 3;
DE AltName: Full=JNK MAP kinase scaffold protein 3;
DE AltName: Full=Mitogen-activated protein kinase 8-interacting protein 3;
GN Name=MAPK8IP3; Synonyms=JIP3, KIAA1066;
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 {ECO:0000312|EMBL:AAK61290.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [2] {ECO:0000305}
RP SEQUENCE REVISION TO 324; 414 AND 753.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Spleen;
RX PubMed=11214971; DOI=10.1093/dnares/7.6.357;
RA Hattori A., Okumura K., Nagase T., Kikuno R., Hirosawa M., Ohara O.;
RT "Characterization of long cDNA clones from human adult spleen.";
RL DNA Res. 7:357-366(2000).
RN [4] {ECO:0000312|EMBL:AAK61290.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11157797; DOI=10.1093/hmg/10.4.339;
RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C.,
RA Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.;
RT "Sequence, structure and pathology of the fully annotated terminal 2 Mb of
RT the short arm of human chromosome 16.";
RL Hum. Mol. Genet. 10:339-352(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [7]
RP INTERACTION WITH MAP2K4/MEK4; MAP2K7/MKK7; MAPK10/JNK3 AND MAP3K5/ASK1, AND
RP FUNCTION.
RX PubMed=12189133; DOI=10.1074/jbc.m202004200;
RA Matsuura H., Nishitoh H., Takeda K., Matsuzawa A., Amagasa T., Ito M.,
RA Yoshioka K., Ichijo H.;
RT "Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK
RT signaling pathway. A new mode of regulation of the MAP kinase cascade.";
RL J. Biol. Chem. 277:40703-40709(2002).
RN [8]
RP INTERACTION WITH ROCK1, AND PHOSPHORYLATION AT SER-314; SER-364 AND
RP SER-365.
RX PubMed=19036714; DOI=10.1126/scisignal.1161938;
RA Ongusaha P.P., Qi H.H., Raj L., Kim Y.B., Aaronson S.A., Davis R.J.,
RA Shi Y., Liao J.K., Lee S.W.;
RT "Identification of ROCK1 as an upstream activator of the JIP-3 to JNK
RT signaling axis in response to UVB damage.";
RL Sci. Signal. 1:RA14-RA14(2008).
RN [9]
RP FUNCTION.
RX PubMed=21775604; DOI=10.1523/jneurosci.0436-11.2011;
RA Huang S.H., Duan S., Sun T., Wang J., Zhao L., Geng Z., Yan J., Sun H.J.,
RA Chen Z.Y.;
RT "JIP3 mediates TrkB axonal anterograde transport and enhances BDNF
RT signaling by directly bridging TrkB with kinesin-1.";
RL J. Neurosci. 31:10602-10614(2011).
RN [10]
RP INVOLVEMENT IN NEDBA, AND VARIANTS NEDBA 27-GLU--GLU-1336 DEL;
RP 37-TYR--GLU-1336 DEL; ARG-400; PRO-444; GLN-525; CYS-578; GLN-994 AND
RP CYS-1146.
RX PubMed=30612693; DOI=10.1016/j.ajhg.2018.12.008;
RA Platzer K., Sticht H., Edwards S.L., Allen W., Angione K.M., Bonati M.T.,
RA Brasington C., Cho M.T., Demmer L.A., Falik-Zaccai T., Gamble C.N.,
RA Hellenbroich Y., Iascone M., Kok F., Mahida S., Mandel H., Marquardt T.,
RA McWalter K., Panis B., Pepler A., Pinz H., Ramos L., Shinde D.N.,
RA Smith-Hicks C., Stegmann A.P.A., Stoebe P., Stumpel C.T.R.M., Wilson C.,
RA Lemke J.R., Di Donato N., Miller K.G., Jamra R.;
RT "De novo variants in MAPK8IP3 cause intellectual disability with variable
RT brain anomalies.";
RL Am. J. Hum. Genet. 104:203-212(2019).
RN [11]
RP INVOLVEMENT IN NEDBA, VARIANTS NEDBA CYS-578 AND CYS-1146, AND
RP CHARACTERIZATION OF VARIANTS NEDBA CYS-578 AND CYS-1146.
RX PubMed=30945334; DOI=10.1002/ana.25481;
RA Iwasawa S., Yanagi K., Kikuchi A., Kobayashi Y., Haginoya K., Matsumoto H.,
RA Kurosawa K., Ochiai M., Sakai Y., Fujita A., Miyake N., Niihori T.,
RA Shirota M., Funayama R., Nonoyama S., Ohga S., Kawame H., Nakayama K.,
RA Aoki Y., Matsumoto N., Kaname T., Matsubara Y., Shoji W., Kure S.;
RT "Recurrent de novo MAPK8IP3 variants cause neurological phenotypes.";
RL Ann. Neurol. 85:927-933(2019).
CC -!- FUNCTION: The JNK-interacting protein (JIP) group of scaffold proteins
CC selectively mediates JNK signaling by aggregating specific components
CC of the MAPK cascade to form a functional JNK signaling module
CC (PubMed:12189133). May function as a regulator of vesicle transport,
CC through interactions with the JNK-signaling components and motor
CC proteins (By similarity). Promotes neuronal axon elongation in a
CC kinesin- and JNK-dependent manner. Activates cofilin at axon tips via
CC local activation of JNK, thereby regulating filopodial dynamics and
CC enhancing axon elongation. Its binding to kinesin heavy chains (KHC),
CC promotes kinesin-1 motility along microtubules and is essential for
CC axon elongation and regeneration. Regulates cortical neuronal migration
CC by mediating NTRK2/TRKB anterograde axonal transport during brain
CC development (By similarity). Acts as an adapter that bridges the
CC interaction between NTRK2/TRKB and KLC1 and drives NTRK2/TRKB axonal
CC but not dendritic anterograde transport, which is essential for
CC subsequent BDNF-triggered signaling and filopodia formation
CC (PubMed:21775604). {ECO:0000250|UniProtKB:Q9ESN9,
CC ECO:0000269|PubMed:12189133, ECO:0000269|PubMed:21775604}.
CC -!- SUBUNIT: Forms homo- or heterooligomeric complexes. The central region
CC of MAPK8IP3 interacts with the C-terminal of MAPK8IP2 but not MAPK8IP1.
CC Binds specific components of the JNK signaling pathway namely
CC MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3 to the N-terminal region,
CC MAP2K4/MKK4 and MAP2K7/MKK7 to the central region and MAP3K11 to the C-
CC terminal region. Binds the TPR motif-containing C-terminal of kinesin
CC light chain, KLC1. Pre-assembled MAPK8IP1 scaffolding complexes are
CC then transported as a cargo of kinesin, to the required subcellular
CC location. Interacts with ROCK1 and this interaction is enhanced by
CC ultraviolet-B (UVB) radiation. Interacts with SH3RF2 (By similarity).
CC Interacts with NTRK2/TRKB and NTRK3/TRKC (By similarity).
CC {ECO:0000250|UniProtKB:E9PSK7, ECO:0000250|UniProtKB:Q9ESN9,
CC ECO:0000269|PubMed:12189133, ECO:0000269|PubMed:19036714}.
CC -!- INTERACTION:
CC Q9UPT6; Q07866-2: KLC1; NbExp=3; IntAct=EBI-717887, EBI-11979975;
CC Q9UPT6; Q5SW96: LDLRAP1; NbExp=6; IntAct=EBI-717887, EBI-747813;
CC Q9UPT6; O75771: RAD51D; NbExp=3; IntAct=EBI-717887, EBI-1055693;
CC Q9UPT6; Q9BR01: SULT4A1; NbExp=3; IntAct=EBI-717887, EBI-6690555;
CC Q9UPT6; Q86XF7: ZNF575; NbExp=3; IntAct=EBI-717887, EBI-14069183;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9ESN9}. Golgi
CC apparatus {ECO:0000250|UniProtKB:Q9ESN9}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:Q9ESN9}. Cell projection, growth cone
CC {ECO:0000250|UniProtKB:Q9ESN9}. Cell projection, axon
CC {ECO:0000250|UniProtKB:E9PSK7}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:E9PSK7}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:E9PSK7}. Note=Localized in the soma and growth
CC cones of differentiated neurites and the Golgi and vesicles of the
CC early secretory compartment of epithelial cells. KIF5A/B/C-mediated
CC transportation to axon tips is essential for its function in enhancing
CC neuronal axon elongation. {ECO:0000250|UniProtKB:E9PSK7,
CC ECO:0000250|UniProtKB:Q9ESN9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UPT6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UPT6-2; Sequence=VSP_024430, VSP_024431;
CC -!- PTM: Phosphorylation by ROCK1 is crucial for the recruitment of JNK.
CC {ECO:0000269|PubMed:19036714}.
CC -!- DISEASE: Neurodevelopmental disorder with or without variable brain
CC abnormalities (NEDBA) [MIM:618443]: A disorder characterized by global
CC developmental delay, impaired intellectual development, delayed
CC walking, poor or absent speech, and variable brain anomalies including
CC perisylvian polymicrogyria, cerebral or cerebellar atrophy, and
CC hypoplasia of the corpus callosum. {ECO:0000269|PubMed:30612693,
CC ECO:0000269|PubMed:30945334}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the JIP scaffold family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK61290.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAA83018.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB15727.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB72318.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AB028989; BAA83018.2; ALT_INIT; mRNA.
DR EMBL; AK024437; BAB15727.1; ALT_INIT; mRNA.
DR EMBL; AE006639; AAK61290.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL031718; CAB72318.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC012180; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL031710; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL031717; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC137123; AAI37124.1; -; mRNA.
DR EMBL; BC137124; AAI37125.1; -; mRNA.
DR EMBL; BC150266; AAI50267.1; -; mRNA.
DR CCDS; CCDS10442.2; -. [Q9UPT6-1]
DR RefSeq; NP_001035529.1; NM_001040439.1.
DR RefSeq; NP_001305781.1; NM_001318852.1.
DR RefSeq; NP_055948.2; NM_015133.4. [Q9UPT6-1]
DR PDB; 4PXJ; X-ray; 2.06 A; A/B/C=433-486.
DR PDBsum; 4PXJ; -.
DR AlphaFoldDB; Q9UPT6; -.
DR SASBDB; Q9UPT6; -.
DR SMR; Q9UPT6; -.
DR BioGRID; 116774; 56.
DR ELM; Q9UPT6; -.
DR IntAct; Q9UPT6; 23.
DR MINT; Q9UPT6; -.
DR STRING; 9606.ENSP00000250894; -.
DR GlyGen; Q9UPT6; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; Q9UPT6; -.
DR PhosphoSitePlus; Q9UPT6; -.
DR BioMuta; MAPK8IP3; -.
DR DMDM; 145559484; -.
DR EPD; Q9UPT6; -.
DR jPOST; Q9UPT6; -.
DR MassIVE; Q9UPT6; -.
DR MaxQB; Q9UPT6; -.
DR PaxDb; Q9UPT6; -.
DR PeptideAtlas; Q9UPT6; -.
DR PRIDE; Q9UPT6; -.
DR ProteomicsDB; 85440; -. [Q9UPT6-1]
DR ProteomicsDB; 85441; -. [Q9UPT6-2]
DR Antibodypedia; 3958; 166 antibodies from 34 providers.
DR DNASU; 23162; -.
DR Ensembl; ENST00000250894.8; ENSP00000250894.4; ENSG00000138834.15. [Q9UPT6-1]
DR GeneID; 23162; -.
DR KEGG; hsa:23162; -.
DR UCSC; uc002cmk.4; human. [Q9UPT6-1]
DR CTD; 23162; -.
DR DisGeNET; 23162; -.
DR GeneCards; MAPK8IP3; -.
DR HGNC; HGNC:6884; MAPK8IP3.
DR HPA; ENSG00000138834; Low tissue specificity.
DR MalaCards; MAPK8IP3; -.
DR MIM; 605431; gene.
DR MIM; 618443; phenotype.
DR neXtProt; NX_Q9UPT6; -.
DR OpenTargets; ENSG00000138834; -.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA30628; -.
DR VEuPathDB; HostDB:ENSG00000138834; -.
DR eggNOG; KOG2077; Eukaryota.
DR GeneTree; ENSGT00940000153496; -.
DR InParanoid; Q9UPT6; -.
DR OrthoDB; 324912at2759; -.
DR PhylomeDB; Q9UPT6; -.
DR TreeFam; TF313096; -.
DR PathwayCommons; Q9UPT6; -.
DR SignaLink; Q9UPT6; -.
DR SIGNOR; Q9UPT6; -.
DR BioGRID-ORCS; 23162; 9 hits in 1071 CRISPR screens.
DR ChiTaRS; MAPK8IP3; human.
DR GeneWiki; MAPK8IP3; -.
DR GenomeRNAi; 23162; -.
DR Pharos; Q9UPT6; Tbio.
DR PRO; PR:Q9UPT6; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9UPT6; protein.
DR Bgee; ENSG00000138834; Expressed in right hemisphere of cerebellum and 184 other tissues.
DR ExpressionAtlas; Q9UPT6; baseline and differential.
DR Genevisible; Q9UPT6; HS.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0044297; C:cell body; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0008432; F:JUN kinase binding; IBA:GO_Central.
DR GO; GO:0019894; F:kinesin binding; ISS:UniProtKB.
DR GO; GO:0005078; F:MAP-kinase scaffold activity; ISS:UniProtKB.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IBA:GO_Central.
DR GO; GO:0099641; P:anterograde axonal protein transport; ISS:UniProtKB.
DR GO; GO:0061564; P:axon development; ISS:UniProtKB.
DR GO; GO:0031103; P:axon regeneration; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:FlyBase.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:FlyBase.
DR GO; GO:0046328; P:regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:0016192; P:vesicle-mediated transport; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR039911; JIP3/JIP4.
DR InterPro; IPR032486; JIP_LZII.
DR InterPro; IPR019143; JNK/Rab-associated_protein-1_N.
DR InterPro; IPR034743; RH1.
DR InterPro; IPR034744; RH2.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR13886; PTHR13886; 1.
DR Pfam; PF16471; JIP_LZII; 1.
DR Pfam; PF09744; Jnk-SapK_ap_N; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS51776; RH1; 1.
DR PROSITE; PS51777; RH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell projection; Coiled coil;
KW Cytoplasm; Cytoplasmic vesicle; Disease variant; Golgi apparatus;
KW Intellectual disability; Phosphoprotein; Reference proteome.
FT CHAIN 1..1336
FT /note="C-Jun-amino-terminal kinase-interacting protein 3"
FT /id="PRO_0000220633"
FT DOMAIN 12..100
FT /note="RH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01112"
FT DOMAIN 520..594
FT /note="RH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01113"
FT REGION 50..80
FT /note="Kinesin-binding domain (KBD); essential for its
FT function in axon elongation"
FT /evidence="ECO:0000250|UniProtKB:Q9ESN9"
FT REGION 182..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 209..225
FT /note="JNK-binding domain (JBD); essential for its function
FT in axon elongation"
FT /evidence="ECO:0000250|UniProtKB:Q9ESN9"
FT REGION 243..318
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 423..458
FT /note="Leucine zipper-like domain (LZ); essential for its
FT function in axon elongation"
FT /evidence="ECO:0000250|UniProtKB:Q9ESN9"
FT REGION 458..514
FT /note="Interaction with NTRK2"
FT /evidence="ECO:0000250|UniProtKB:Q9ESN9"
FT REGION 719..766
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 879..969
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1296..1315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 58..177
FT /evidence="ECO:0000255"
FT COILED 440..554
FT /evidence="ECO:0000255"
FT COMPBIAS 243..289
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..318
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 736..766
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 882..897
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 939..955
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 265
FT /note="Phosphothreonine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:Q9ESN9"
FT MOD_RES 275
FT /note="Phosphothreonine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:Q9ESN9"
FT MOD_RES 286
FT /note="Phosphothreonine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:Q9ESN9"
FT MOD_RES 314
FT /note="Phosphoserine; by ROCK1"
FT /evidence="ECO:0000269|PubMed:19036714"
FT MOD_RES 364
FT /note="Phosphoserine; by ROCK1"
FT /evidence="ECO:0000269|PubMed:19036714"
FT MOD_RES 365
FT /note="Phosphoserine; by ROCK1"
FT /evidence="ECO:0000269|PubMed:19036714"
FT MOD_RES 602
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ESN9"
FT MOD_RES 676
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ESN9"
FT VAR_SEQ 249..250
FT /note="CP -> VL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11214971"
FT /id="VSP_024430"
FT VAR_SEQ 251..1336
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11214971"
FT /id="VSP_024431"
FT VARIANT 27..1336
FT /note="Missing (in NEDBA)"
FT /evidence="ECO:0000269|PubMed:30612693"
FT /id="VAR_082608"
FT VARIANT 37..1336
FT /note="Missing (in NEDBA)"
FT /evidence="ECO:0000269|PubMed:30612693"
FT /id="VAR_082609"
FT VARIANT 400
FT /note="G -> R (in NEDBA; unknown pathological significance;
FT dbSNP:rs1596711175)"
FT /evidence="ECO:0000269|PubMed:30612693"
FT /id="VAR_082610"
FT VARIANT 444
FT /note="L -> P (in NEDBA; dbSNP:rs1567198751)"
FT /evidence="ECO:0000269|PubMed:30612693"
FT /id="VAR_082611"
FT VARIANT 525
FT /note="R -> Q (in NEDBA; unknown pathological significance;
FT dbSNP:rs1596780112)"
FT /evidence="ECO:0000269|PubMed:30612693"
FT /id="VAR_082612"
FT VARIANT 578
FT /note="R -> C (in NEDBA; affects axon development when
FT expressed in a heterologous system; dbSNP:rs1567203083)"
FT /evidence="ECO:0000269|PubMed:30612693,
FT ECO:0000269|PubMed:30945334"
FT /id="VAR_082613"
FT VARIANT 753
FT /note="T -> A (in dbSNP:rs2294619)"
FT /id="VAR_049667"
FT VARIANT 994
FT /note="H -> Q (in NEDBA; unknown pathological significance;
FT dbSNP:rs1163583945)"
FT /evidence="ECO:0000269|PubMed:30612693"
FT /id="VAR_082614"
FT VARIANT 1146
FT /note="R -> C (in NEDBA; affects axon development when
FT expressed in a heterologous system; dbSNP:rs1567214097)"
FT /evidence="ECO:0000269|PubMed:30612693,
FT ECO:0000269|PubMed:30945334"
FT /id="VAR_082615"
FT HELIX 433..484
FT /evidence="ECO:0007829|PDB:4PXJ"
SQ SEQUENCE 1336 AA; 147457 MW; 84166F5725D74B25 CRC64;
MMEIQMDEGG GVVVYQDDYC SGSVMSERVS GLAGSIYREF ERLIHCYDEE VVKELMPLVV
NVLENLDSVL SENQEHEVEL ELLREDNEQL LTQYEREKAL RRQAEEKFIE FEDALEQEKK
ELQIQVEHYE FQTRQLELKA KNYADQISRL EERESEMKKE YNALHQRHTE MIQTYVEHIE
RSKMQQVGGN SQTESSLPGR RKERPTSLNV FPLADGTVRA QIGGKLVPAG DHWHLSDLGQ
LQSSSSYQCP QDEMSESGQS SAAATPSTTG TKSNTPTSSV PSAAVTPLNE SLQPLGDYGV
GSKNSKRARE KRDSRNMEVQ VTQEMRNVSI GMGSSDEWSD VQDIIDSTPE LDMCPETRLD
RTGSSPTQGI VNKAFGINTD SLYHELSTAG SEVIGDVDEG ADLLGEFSVR DDFFGMGKEV
GNLLLENSQL LETKNALNVV KNDLIAKVDQ LSGEQEVLRG ELEAAKQAKV KLENRIKELE
EELKRVKSEA IIARREPKEE AEDVSSYLCT ESDKIPMAQR RRFTRVEMAR VLMERNQYKE
RLMELQEAVR WTEMIRASRE HPSVQEKKKS TIWQFFSRLF SSSSSPPPAK RPYPSVNIHY
KSPTTAGFSQ RRNHAMCPIS AGSRPLEFFP DDDCTSSARR EQKREQYRQV REHVRNDDGR
LQACGWSLPA KYKQLSPNGG QEDTRMKNVP VPVYCRPLVE KDPTMKLWCA AGVNLSGWRP
NEDDAGNGVK PAPGRDPLTC DREGDGEPKS AHTSPEKKKA KELPEMDATS SRVWILTSTL
TTSKVVIIDA NQPGTVVDQF TVCNAHVLCI SSIPAASDSD YPPGEMFLDS DVNPEDPGAD
GVLAGITLVG CATRCNVPRS NCSSRGDTPV LDKGQGEVAT IANGKVNPSQ STEEATEATE
VPDPGPSEPE TATLRPGPLT EHVFTDPAPT PSSGPQPGSE NGPEPDSSST RPEPEPSGDP
TGAGSSAAPT MWLGAQNGWL YVHSAVANWK KCLHSIKLKD SVLSLVHVKG RVLVALADGT
LAIFHRGEDG QWDLSNYHLM DLGHPHHSIR CMAVVYDRVW CGYKNKVHVI QPKTMQIEKS
FDAHPRRESQ VRQLAWIGDG VWVSIRLDST LRLYHAHTHQ HLQDVDIEPY VSKMLGTGKL
GFSFVRITAL LVAGSRLWVG TGNGVVISIP LTETVVLHRG QLLGLRANKT SPTSGEGARP
GGIIHVYGDD SSDRAASSFI PYCSMAQAQL CFHGHRDAVK FFVSVPGNVL ATLNGSVLDS
PAEGPGPAAP ASEVEGQKLR NVLVLSGGEG YIDFRIGDGE DDETEEGAGD MSQVKPVLSK
AERSHIIVWQ VSYTPE
