ID   UNC5C_HUMAN             Reviewed;         931 AA.
AC   O95185; Q8IUT0;
DT   11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT   05-MAY-2009, sequence version 2.
DT   28-JUN-2023, entry version 181.
DE   RecName: Full=Netrin receptor UNC5C;
DE   AltName: Full=Protein unc-5 homolog 3;
DE   AltName: Full=Protein unc-5 homolog C;
DE   Flags: Precursor;
GN   Name=UNC5C; Synonyms=UNC5H3;
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), TISSUE SPECIFICITY, AND VARIANT
RP   THR-721.
RC   TISSUE=Brain;
RX   PubMed=9782087; DOI=10.1006/geno.1998.5425;
RA   Ackerman S.L., Knowles B.B.;
RT   "Cloning and mapping of the UNC5C gene to human chromosome 4q21-q23.";
RL   Genomics 52:205-208(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Lung;
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   [4]
RP   DOWN-REGULATION IN CANCER.
RX   PubMed=12655055; DOI=10.1073/pnas.0738063100;
RA   Thiebault K., Mazelin L., Pays L., Llambi F., Joly M.-O., Scoazec J.-Y.,
RA   Saurin J.-C., Romeo G., Mehlen P.;
RT   "The netrin-1 receptors UNC5H are putative tumor suppressors controlling
RT   cell death commitment.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:4173-4178(2003).
RN   [5]
RP   INTERACTION WITH DSCAM.
RX   PubMed=22685302; DOI=10.1074/jbc.m112.340174;
RA   Purohit A.A., Li W., Qu C., Dwyer T., Shao Q., Guan K.L., Liu G.;
RT   "Down syndrome cell adhesion molecule (DSCAM) associates with
RT   uncoordinated-5C (UNC5C) in netrin-1-mediated growth cone collapse.";
RL   J. Biol. Chem. 287:27126-27138(2012).
RN   [6]
RP   SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INVOLVEMENT IN AD, VARIANT AD
RP   MET-835, AND CHARACTERIZATION OF VARIANT AD MET-835.
RX   PubMed=25419706; DOI=10.1038/nm.3736;
RG   Alzheimer's Disease Genetics Consortium;
RA   Wetzel-Smith M.K., Hunkapiller J., Bhangale T.R., Srinivasan K.,
RA   Maloney J.A., Atwal J.K., Sa S.M., Yaylaoglu M.B., Foreman O., Ortmann W.,
RA   Rathore N., Hansen D.V., Tessier-Lavigne M., Mayeux R., Pericak-Vance M.,
RA   Haines J., Farrer L.A., Schellenberg G.D., Goate A., Behrens T.W.,
RA   Cruchaga C., Watts R.J., Graham R.R.;
RT   "A rare mutation in UNC5C predisposes to late-onset Alzheimer's disease and
RT   increases neuronal cell death.";
RL   Nat. Med. 20:1452-1457(2014).
RN   [7]
RP   INTERACTION WITH DAPK1, AND CHARACTERIZATION OF VARIANT AD MET-835.
RX   PubMed=27068745; DOI=10.1074/jbc.m115.698092;
RA   Hashimoto Y., Toyama Y., Kusakari S., Nawa M., Matsuoka M.;
RT   "An Alzheimer Disease-linked Rare Mutation Potentiates Netrin Receptor
RT   Uncoordinated-5C-induced Signaling That Merges with Amyloid beta Precursor
RT   Protein Signaling.";
RL   J. Biol. Chem. 291:12282-12293(2016).
RN   [8]
RP   FUNCTION, AND INTERACTION WITH TUBB3.
RX   PubMed=28483977; DOI=10.1523/jneurosci.2617-16.2017;
RA   Shao Q., Yang T., Huang H., Alarmanazi F., Liu G.;
RT   "Uncoupling of UNC5C with Polymerized TUBB3 in Microtubules Mediates
RT   Netrin-1 Repulsion.";
RL   J. Neurosci. 37:5620-5633(2017).
CC   -!- FUNCTION: Receptor for netrin required for axon guidance (By
CC       similarity). Mediates axon repulsion of neuronal growth cones in the
CC       developing nervous system upon ligand binding (By similarity).
CC       NTN1/Netrin-1 binding might cause dissociation of UNC5C from
CC       polymerized TUBB3 in microtubules and thereby lead to increased
CC       microtubule dynamics and axon repulsion (PubMed:28483977). Axon
CC       repulsion in growth cones may also be caused by its association with
CC       DCC that may trigger signaling for repulsion (By similarity). Might
CC       also collaborate with DSCAM in NTN1-mediated axon repulsion
CC       independently of DCC (By similarity). Also involved in corticospinal
CC       tract axon guidance independently of DCC (By similarity). Involved in
CC       dorsal root ganglion axon projection towards the spinal cord
CC       (PubMed:28483977). It also acts as a dependence receptor required for
CC       apoptosis induction when not associated with netrin ligand (By
CC       similarity). {ECO:0000250|UniProtKB:O08747,
CC       ECO:0000250|UniProtKB:Q761X5, ECO:0000269|PubMed:28483977}.
CC   -!- SUBUNIT: Interacts with DCC (via cytoplasmic domain) (By similarity).
CC       Interacts (tyrosine phosphorylated form) with PTPN11 (By similarity).
CC       Interacts (via extracellular domain) with FLRT3 (via extracellular
CC       domain) (By similarity). Interacts (via Ig-like C2-type domain) with
CC       DSCAM (via extracellular domain) (PubMed:22685302). Interacts (via
CC       death domain) with DAPK1 (PubMed:27068745). Interacts (via cytoplasmic
CC       domain) with TUBB3; this interaction is decreased by NTN1/Netrin-1
CC       (PubMed:28483977). {ECO:0000250|UniProtKB:O08747,
CC       ECO:0000269|PubMed:22685302, ECO:0000269|PubMed:27068745,
CC       ECO:0000269|PubMed:28483977}.
CC   -!- INTERACTION:
CC       O95185; Q13509: TUBB3; NbExp=2; IntAct=EBI-11343380, EBI-350989;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25419706};
CC       Single-pass type I membrane protein {ECO:0000255}. Cell surface
CC       {ECO:0000269|PubMed:25419706}. Synapse, synaptosome
CC       {ECO:0000250|UniProtKB:Q761X5}. Cell projection, axon
CC       {ECO:0000250|UniProtKB:O08747}. Cell projection, dendrite
CC       {ECO:0000250|UniProtKB:O08747}. Cell projection, growth cone
CC       {ECO:0000250|UniProtKB:O08747}. Cell projection, lamellipodium
CC       {ECO:0000250|UniProtKB:O08747}. Cell projection, filopodium
CC       {ECO:0000250|UniProtKB:O08747}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O95185-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O95185-2; Sequence=VSP_011700, VSP_011701;
CC   -!- TISSUE SPECIFICITY: Mainly expressed in brain (PubMed:9782087).
CC       Expressed in temporal lobe cortical neurons and in neurons of the
CC       hippocampal pyramidal layer (PubMed:25419706). Also expressed in kidney
CC       (PubMed:9782087). Not expressed in developing or adult lung
CC       (PubMed:9782087). {ECO:0000269|PubMed:25419706,
CC       ECO:0000269|PubMed:9782087}.
CC   -!- PTM: Proteolytically cleaved by caspases during apoptosis. The cleavage
CC       does not take place when the receptor is associated with netrin ligand.
CC       Its cleavage by caspases is required to induce apoptosis.
CC       {ECO:0000250|UniProtKB:Q761X5}.
CC   -!- PTM: Phosphorylated on different cytoplasmic tyrosine residues.
CC       Phosphorylation of Tyr-568 leads to an interaction with PTPN11
CC       phosphatase, suggesting that its activity is regulated by
CC       phosphorylation/dephosphorylation. Tyrosine phosphorylation is netrin-
CC       dependent. {ECO:0000250|UniProtKB:O08747}.
CC   -!- DISEASE: Alzheimer disease (AD) [MIM:104300]: Alzheimer disease is a
CC       neurodegenerative disorder characterized by progressive dementia, loss
CC       of cognitive abilities, and deposition of fibrillar amyloid proteins as
CC       intraneuronal neurofibrillary tangles, extracellular amyloid plaques
CC       and vascular amyloid deposits. The major constituents of these plaques
CC       are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42,
CC       that are produced by the proteolysis of the transmembrane APP protein.
CC       The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved
CC       products, such as C31, are also implicated in neuronal death.
CC       {ECO:0000269|PubMed:25419706, ECO:0000269|PubMed:27068745}.
CC       Note=Disease susceptibility may be associated with variants affecting
CC       the gene represented in this entry.
CC   -!- MISCELLANEOUS: Down-regulated in multiple cancers including colorectal,
CC       breast, ovary, uterus, stomach, lung, or kidney cancers.
CC       {ECO:0000269|PubMed:12655055}.
CC   -!- SIMILARITY: Belongs to the unc-5 family. {ECO:0000305}.
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DR   EMBL; AF055634; AAC67491.1; -; mRNA.
DR   EMBL; AC098584; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC105395; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC106881; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC041156; AAH41156.1; -; mRNA.
DR   CCDS; CCDS3643.1; -. [O95185-1]
DR   RefSeq; NP_003719.3; NM_003728.3. [O95185-1]
DR   AlphaFoldDB; O95185; -.
DR   SMR; O95185; -.
DR   BioGRID; 114186; 31.
DR   DIP; DIP-46276N; -.
DR   IntAct; O95185; 5.
DR   STRING; 9606.ENSP00000406022; -.
DR   GlyCosmos; O95185; 2 sites, No reported glycans.
DR   GlyGen; O95185; 3 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; O95185; -.
DR   PhosphoSitePlus; O95185; -.
DR   BioMuta; UNC5C; -.
DR   jPOST; O95185; -.
DR   MassIVE; O95185; -.
DR   PaxDb; O95185; -.
DR   PeptideAtlas; O95185; -.
DR   ProteomicsDB; 50694; -. [O95185-1]
DR   ProteomicsDB; 50695; -. [O95185-2]
DR   Antibodypedia; 2665; 298 antibodies from 34 providers.
DR   DNASU; 8633; -.
DR   Ensembl; ENST00000453304.6; ENSP00000406022.1; ENSG00000182168.15. [O95185-1]
DR   Ensembl; ENST00000506749.5; ENSP00000426153.1; ENSG00000182168.15. [O95185-2]
DR   GeneID; 8633; -.
DR   KEGG; hsa:8633; -.
DR   MANE-Select; ENST00000453304.6; ENSP00000406022.1; NM_003728.4; NP_003719.3.
DR   UCSC; uc003hto.4; human. [O95185-1]
DR   AGR; HGNC:12569; -.
DR   CTD; 8633; -.
DR   DisGeNET; 8633; -.
DR   GeneCards; UNC5C; -.
DR   HGNC; HGNC:12569; UNC5C.
DR   HPA; ENSG00000182168; Tissue enhanced (brain).
DR   MalaCards; UNC5C; -.
DR   MIM; 104300; phenotype.
DR   MIM; 603610; gene.
DR   neXtProt; NX_O95185; -.
DR   NIAGADS; ENSG00000182168; -.
DR   OpenTargets; ENSG00000182168; -.
DR   PharmGKB; PA37206; -.
DR   VEuPathDB; HostDB:ENSG00000182168; -.
DR   eggNOG; KOG1480; Eukaryota.
DR   GeneTree; ENSGT00950000182815; -.
DR   HOGENOM; CLU_014383_2_1_1; -.
DR   InParanoid; O95185; -.
DR   OMA; CECQAWS; -.
DR   OrthoDB; 2971005at2759; -.
DR   PhylomeDB; O95185; -.
DR   TreeFam; TF316767; -.
DR   PathwayCommons; O95185; -.
DR   Reactome; R-HSA-418886; Netrin mediated repulsion signals.
DR   SignaLink; O95185; -.
DR   SIGNOR; O95185; -.
DR   BioGRID-ORCS; 8633; 6 hits in 1142 CRISPR screens.
DR   ChiTaRS; UNC5C; human.
DR   GeneWiki; UNC5C; -.
DR   GenomeRNAi; 8633; -.
DR   Pharos; O95185; Tbio.
DR   PRO; PR:O95185; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; O95185; protein.
DR   Bgee; ENSG00000182168; Expressed in corpus callosum and 132 other tissues.
DR   ExpressionAtlas; O95185; baseline and differential.
DR   Genevisible; O95185; HS.
DR   GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR   GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR   GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR   GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR   GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR   GO; GO:0005042; F:netrin receptor activity; TAS:ProtInc.
DR   GO; GO:0005043; F:netrin receptor activity involved in chemorepulsion; ISS:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR   GO; GO:0015631; F:tubulin binding; IPI:UniProtKB.
DR   GO; GO:0033564; P:anterior/posterior axon guidance; IEA:Ensembl.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0007411; P:axon guidance; TAS:ProtInc.
DR   GO; GO:0007420; P:brain development; TAS:ProtInc.
DR   GO; GO:0061643; P:chemorepulsion of axon; ISS:UniProtKB.
DR   GO; GO:1990791; P:dorsal root ganglion development; IDA:UniProtKB.
DR   GO; GO:0035234; P:ectopic germ cell programmed cell death; IEA:Ensembl.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR   GO; GO:0051094; P:positive regulation of developmental process; IEA:Ensembl.
DR   GO; GO:2000243; P:positive regulation of reproductive process; IEA:Ensembl.
DR   GO; GO:2001222; P:regulation of neuron migration; IEA:Ensembl.
DR   CDD; cd08799; Death_UNC5C; 1.
DR   Gene3D; 2.60.220.30; -; 1.
DR   Gene3D; 1.10.533.10; Death Domain, Fas; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR   Gene3D; 2.20.100.10; Thrombospondin type-1 (TSP1) repeat; 2.
DR   InterPro; IPR011029; DEATH-like_dom_sf.
DR   InterPro; IPR000488; Death_domain.
DR   InterPro; IPR042154; Death_UNC5C.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR013098; Ig_I-set.
DR   InterPro; IPR003599; Ig_sub.
DR   InterPro; IPR003598; Ig_sub2.
DR   InterPro; IPR000884; TSP1_rpt.
DR   InterPro; IPR036383; TSP1_rpt_sf.
DR   InterPro; IPR037936; UNC5.
DR   InterPro; IPR033772; UPA.
DR   InterPro; IPR000906; ZU5_dom.
DR   PANTHER; PTHR12582; NETRIN RECEPTOR UNC5; 1.
DR   PANTHER; PTHR12582:SF7; NETRIN RECEPTOR UNC5C; 1.
DR   Pfam; PF00531; Death; 1.
DR   Pfam; PF07679; I-set; 1.
DR   Pfam; PF00090; TSP_1; 2.
DR   Pfam; PF17217; UPA; 1.
DR   Pfam; PF00791; ZU5; 1.
DR   PRINTS; PR01705; TSP1REPEAT.
DR   SMART; SM00005; DEATH; 1.
DR   SMART; SM00409; IG; 1.
DR   SMART; SM00408; IGc2; 1.
DR   SMART; SM00209; TSP1; 2.
DR   SMART; SM00218; ZU5; 1.
DR   SUPFAM; SSF47986; DEATH domain; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 2.
DR   SUPFAM; SSF82895; TSP-1 type 1 repeat; 2.
DR   PROSITE; PS50835; IG_LIKE; 1.
DR   PROSITE; PS50092; TSP1; 2.
DR   PROSITE; PS51145; ZU5; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Alzheimer disease; Amyloidosis; Apoptosis;
KW   Cell membrane; Cell projection; Developmental protein; Disulfide bond;
KW   Glycoprotein; Immunoglobulin domain; Membrane; Neurodegeneration;
KW   Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Synapse;
KW   Synaptosome; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..40
FT                   /evidence="ECO:0000255"
FT   CHAIN           41..931
FT                   /note="Netrin receptor UNC5C"
FT                   /id="PRO_0000036075"
FT   TOPO_DOM        41..380
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        381..401
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        402..931
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          62..159
FT                   /note="Ig-like"
FT   DOMAIN          161..256
FT                   /note="Ig-like C2-type"
FT   DOMAIN          260..314
FT                   /note="TSP type-1 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DOMAIN          316..368
FT                   /note="TSP type-1 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DOMAIN          530..673
FT                   /note="ZU5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT   DOMAIN          850..929
FT                   /note="Death"
FT   REGION          402..931
FT                   /note="Required for netrin-mediated axon repulsion of
FT                   neuronal growth cones"
FT                   /evidence="ECO:0000250|UniProtKB:O08747"
FT   REGION          694..712
FT                   /note="Interaction with DCC"
FT                   /evidence="ECO:0000250|UniProtKB:O08747"
FT   SITE            415..416
FT                   /note="Cleavage; by caspase-3"
FT                   /evidence="ECO:0000250|UniProtKB:Q761X5"
FT   MOD_RES         502
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O08747"
FT   MOD_RES         568
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:O08747"
FT   CARBOHYD        236
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        361
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        83..144
FT                   /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT   DISULFID        95..142
FT                   /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT   DISULFID        188..239
FT                   /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT   DISULFID        272..309
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DISULFID        276..313
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DISULFID        287..299
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DISULFID        328..362
FT                   /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT   DISULFID        332..367
FT                   /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT   DISULFID        340..352
FT                   /evidence="ECO:0000250|UniProtKB:Q6ZN44"
FT   VAR_SEQ         370
FT                   /note="T -> SFIYPISTEQRTQNEYGFSS (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_011700"
FT   VAR_SEQ         579..931
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_011701"
FT   VARIANT         37
FT                   /note="G -> V (in dbSNP:rs2306715)"
FT                   /id="VAR_019731"
FT   VARIANT         721
FT                   /note="M -> T (in dbSNP:rs2289043)"
FT                   /evidence="ECO:0000269|PubMed:9782087"
FT                   /id="VAR_019732"
FT   VARIANT         835
FT                   /note="T -> M (in AD; associated with susceptibility to
FT                   late-onset disease; increased susceptibility to neuronal
FT                   cell death; dbSNP:rs137875858)"
FT                   /evidence="ECO:0000269|PubMed:25419706,
FT                   ECO:0000269|PubMed:27068745"
FT                   /id="VAR_081368"
FT   VARIANT         841
FT                   /note="A -> T (in dbSNP:rs34585936)"
FT                   /id="VAR_055327"
FT   CONFLICT        219
FT                   /note="T -> I (in Ref. 3; AAH41156)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        489
FT                   /note="T -> S (in Ref. 1; AAC67491)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        651
FT                   /note="Q -> K (in Ref. 1; AAC67491)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   931 AA;  103146 MW;  98A95995129532A7 CRC64;
     MRKGLRATAA RCGLGLGYLL QMLVLPALAL LSASGTGSAA QDDDFFHELP ETFPSDPPEP
     LPHFLIEPEE AYIVKNKPVN LYCKASPATQ IYFKCNSEWV HQKDHIVDER VDETSGLIVR
     EVSIEISRQQ VEELFGPEDY WCQCVAWSSA GTTKSRKAYV RIAYLRKTFE QEPLGKEVSL
     EQEVLLQCRP PEGIPVAEVE WLKNEDIIDP VEDRNFYITI DHNLIIKQAR LSDTANYTCV
     AKNIVAKRKS TTATVIVYVN GGWSTWTEWS VCNSRCGRGY QKRTRTCTNP APLNGGAFCE
     GQSVQKIACT TLCPVDGRWT PWSKWSTCGT ECTHWRRREC TAPAPKNGGK DCDGLVLQSK
     NCTDGLCMQT APDSDDVALY VGIVIAVIVC LAISVVVALF VYRKNHRDFE SDIIDSSALN
     GGFQPVNIKA ARQDLLAVPP DLTSAAAMYR GPVYALHDVS DKIPMTNSPI LDPLPNLKIK
     VYNTSGAVTP QDDLSEFTSK LSPQMTQSLL ENEALSLKNQ SLARQTDPSC TAFGSFNSLG
     GHLIVPNSGV SLLIPAGAIP QGRVYEMYVT VHRKETMRPP MDDSQTLLTP VVSCGPPGAL
     LTRPVVLTMH HCADPNTEDW KILLKNQAAQ GQWEDVVVVG EENFTTPCYI QLDAEACHIL
     TENLSTYALV GHSTTKAAAK RLKLAIFGPL CCSSLEYSIR VYCLDDTQDA LKEILHLERQ
     MGGQLLEEPK ALHFKGSTHN LRLSIHDIAH SLWKSKLLAK YQEIPFYHVW SGSQRNLHCT
     FTLERFSLNT VELVCKLCVR QVEGEGQIFQ LNCTVSEEPT GIDLPLLDPA NTITTVTGPS
     AFSIPLPIRQ KLCSSLDAPQ TRGHDWRMLA HKLNLDRYLN YFATKSSPTG VILDLWEAQN
     FPDGNLSMLA AVLEEMGRHE TVVSLAAEGQ Y
//