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ZWILC_CAEEL
ID   ZWILC_CAEEL             Reviewed;         630 AA.
AC   Q95XP9; A0A061AD83; A0A061AEC9; H2KZV1;
DT   15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   03-AUG-2022, entry version 116.
DE   RecName: Full=Protein zwilch homolog;
GN   Name=zwl-1; ORFNames=Y39G10AR.2;
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2;
RX   PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG   The C. elegans sequencing consortium;
RT   "Genome sequence of the nematode C. elegans: a platform for investigating
RT   biology.";
RL   Science 282:2012-2018(1998).
RN   [2]
RP   FUNCTION, IDENTIFICATION IN RZZ COMPLEX, INTERACTION WITH SPDL-1,
RP   SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX   PubMed=18765790; DOI=10.1101/gad.1687508;
RA   Gassmann R., Essex A., Hu J.-S., Maddox P.S., Motegi F., Sugimoto A.,
RA   O'Rourke S.M., Bowerman B., McLeod I., Yates J.R. III, Oegema K.,
RA   Cheeseman I.M., Desai A.;
RT   "A new mechanism controlling kinetochore-microtubule interactions revealed
RT   by comparison of two dynein-targeting components: SPDL-1 and the
RT   Rod/Zwilch/Zw10 complex.";
RL   Genes Dev. 22:2385-2399(2008).
RN   [3]
RP   FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX   PubMed=19109417; DOI=10.1091/mbc.e08-10-1047;
RA   Essex A., Dammermann A., Lewellyn L., Oegema K., Desai A.;
RT   "Systematic analysis in Caenorhabditis elegans reveals that the spindle
RT   checkpoint is composed of two largely independent branches.";
RL   Mol. Biol. Cell 20:1252-1267(2009).
RN   [4]
RP   SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX   PubMed=20729837; DOI=10.1038/ncb2093;
RA   Dumont J., Oegema K., Desai A.;
RT   "A kinetochore-independent mechanism drives anaphase chromosome separation
RT   during acentrosomal meiosis.";
RL   Nat. Cell Biol. 12:894-901(2010).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH NDC-80.
RX   PubMed=24231804; DOI=10.1126/science.1246232;
RA   Cheerambathur D.K., Gassmann R., Cook B., Oegema K., Desai A.;
RT   "Crosstalk between microtubule attachment complexes ensures accurate
RT   chromosome segregation.";
RL   Science 342:1239-1242(2013).
CC   -!- FUNCTION: Essential component of the mitotic checkpoint, which prevents
CC       cells from prematurely exiting mitosis (PubMed:18765790). Required for
CC       chromosome segregation, the assembly of the dynein-dynactin and mdf-1-
CC       mdf-2 complexes onto kinetochores and spindle pole separation
CC       (PubMed:18765790). Its function related to the spindle assembly
CC       machinery and kinetochore-microtubule attachments likely depends on its
CC       association in the mitotic RZZ complex (PubMed:18765790). The RZZ
CC       complex recruits the spindly-like protein spdl-1 to kinetochores
CC       (PubMed:18765790). To prevent irregular chromosome segregation, the
CC       complex also inhibits the attachment of the kinetochore-associated
CC       NDC80 complex to microtubules (PubMed:24231804). The recruitment of
CC       spdl-1 to kinetochores relieves this inhibition (PubMed:24231804).
CC       Required for embryonic development (PubMed:18765790, PubMed:19109417).
CC       {ECO:0000269|PubMed:18765790, ECO:0000269|PubMed:19109417,
CC       ECO:0000269|PubMed:24231804}.
CC   -!- SUBUNIT: Component of the RZZ complex composed of rod-1, czw-1 and zwl-
CC       1 (PubMed:18765790). Interacts with the spindly-like protein spdl-1
CC       (PubMed:18765790). Interacts with NDC80 complex component ndc-80
CC       (PubMed:24231804). {ECO:0000269|PubMed:18765790,
CC       ECO:0000269|PubMed:24231804}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex
CC       {ECO:0000269|PubMed:20729837}. Chromosome, centromere, kinetochore
CC       {ECO:0000269|PubMed:18765790, ECO:0000269|PubMed:19109417,
CC       ECO:0000269|PubMed:20729837}. Cytoplasm, cytoskeleton, spindle
CC       {ECO:0000305}. Note=Localizes to the kinetochore during nuclear
CC       envelope breakdown and remains there until the metaphase-anaphase
CC       transition (PubMed:18765790). Localizes to kinetochores, spindle-
CC       associated rod-shaped structures and near the cell cortex in a knl-1-
CC       dependent manner in anaphase (PubMed:18765790, PubMed:20729837).
CC       {ECO:0000269|PubMed:18765790, ECO:0000269|PubMed:20729837,
CC       ECO:0000305|PubMed:18765790}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=a {ECO:0000312|WormBase:Y39G10AR.2a};
CC         IsoId=Q95XP9-1; Sequence=Displayed;
CC       Name=b {ECO:0000312|WormBase:Y39G10AR.2b};
CC         IsoId=Q95XP9-2; Sequence=VSP_057650;
CC       Name=c {ECO:0000312|WormBase:Y39G10AR.2c};
CC         IsoId=Q95XP9-3; Sequence=VSP_057649;
CC       Name=d {ECO:0000312|WormBase:Y39G10AR.2d};
CC         IsoId=Q95XP9-4; Sequence=VSP_057649, VSP_057650;
CC   -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in embryonic
CC       lethality (PubMed:18765790, PubMed:19109417). RNAi-mediated knockdown
CC       results in defective chromosome segregation, premature spindle pole
CC       separation and incorrectly attached kinetochores (PubMed:18765790). In
CC       addition, knl-1 localization to the spindle-associated rod-shaped
CC       structures but not to kinetochores is lost during anaphase of meiosis I
CC       (PubMed:20729837). RNAi-mediated knockdown also results in abolished
CC       targeting of the spindly-like protein spdl-1 to the kinetochore
CC       (PubMed:18765790). {ECO:0000269|PubMed:18765790,
CC       ECO:0000269|PubMed:19109417, ECO:0000269|PubMed:20729837}.
CC   -!- SIMILARITY: Belongs to the ZWILCH family. {ECO:0000305}.
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DR   EMBL; FO081209; CCD69901.1; -; Genomic_DNA.
DR   EMBL; FO081209; CCE67248.1; -; Genomic_DNA.
DR   EMBL; FO081209; CDR32818.1; -; Genomic_DNA.
DR   EMBL; FO081209; CDR32819.1; -; Genomic_DNA.
DR   RefSeq; NP_001249150.1; NM_001262221.1. [Q95XP9-1]
DR   RefSeq; NP_001249151.1; NM_001262222.1. [Q95XP9-2]
DR   RefSeq; NP_001293318.1; NM_001306389.1. [Q95XP9-3]
DR   RefSeq; NP_001293319.1; NM_001306390.1. [Q95XP9-4]
DR   AlphaFoldDB; Q95XP9; -.
DR   BioGRID; 37283; 10.
DR   ComplexPortal; CPX-810; Rzz complex.
DR   STRING; 6239.Y39G10AR.2a; -.
DR   EPD; Q95XP9; -.
DR   PaxDb; Q95XP9; -.
DR   PeptideAtlas; Q95XP9; -.
DR   EnsemblMetazoa; Y39G10AR.2a.1; Y39G10AR.2a.1; WBGene00021460. [Q95XP9-1]
DR   EnsemblMetazoa; Y39G10AR.2b.1; Y39G10AR.2b.1; WBGene00021460. [Q95XP9-2]
DR   EnsemblMetazoa; Y39G10AR.2c.1; Y39G10AR.2c.1; WBGene00021460. [Q95XP9-3]
DR   EnsemblMetazoa; Y39G10AR.2d.1; Y39G10AR.2d.1; WBGene00021460. [Q95XP9-4]
DR   GeneID; 171798; -.
DR   KEGG; cel:CELE_Y39G10AR.2; -.
DR   UCSC; Y39G10AR.2; c. elegans. [Q95XP9-1]
DR   CTD; 171798; -.
DR   WormBase; Y39G10AR.2a; CE26992; WBGene00021460; zwl-1. [Q95XP9-1]
DR   WormBase; Y39G10AR.2b; CE46826; WBGene00021460; zwl-1. [Q95XP9-2]
DR   WormBase; Y39G10AR.2c; CE49916; WBGene00021460; zwl-1. [Q95XP9-3]
DR   WormBase; Y39G10AR.2d; CE49848; WBGene00021460; zwl-1. [Q95XP9-4]
DR   eggNOG; KOG4803; Eukaryota.
DR   GeneTree; ENSGT00390000013696; -.
DR   InParanoid; Q95XP9; -.
DR   OMA; MMEIGVE; -.
DR   OrthoDB; 669333at2759; -.
DR   PhylomeDB; Q95XP9; -.
DR   PRO; PR:Q95XP9; -.
DR   Proteomes; UP000001940; Chromosome I.
DR   Bgee; WBGene00021460; Expressed in adult organism and 4 other tissues.
DR   GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR   GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR   GO; GO:1990423; C:RZZ complex; IDA:UniProtKB.
DR   GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; ISS:UniProtKB.
DR   GO; GO:0010696; P:positive regulation of mitotic spindle pole body separation; IMP:UniProtKB.
DR   GO; GO:1905342; P:positive regulation of protein localization to kinetochore; IMP:UniProtKB.
DR   GO; GO:0034501; P:protein localization to kinetochore; IDA:ComplexPortal.
DR   GO; GO:1903394; P:protein localization to kinetochore involved in kinetochore assembly; IMP:UniProtKB.
DR   GO; GO:0051988; P:regulation of attachment of spindle microtubules to kinetochore; IC:ComplexPortal.
DR   InterPro; IPR018630; Zwilch.
DR   PANTHER; PTHR15995; PTHR15995; 1.
DR   Pfam; PF09817; Zwilch; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell cycle; Cell division; Centromere; Chromosome;
KW   Cytoplasm; Cytoskeleton; Developmental protein; Kinetochore; Meiosis;
KW   Mitosis; Reference proteome.
FT   CHAIN           1..630
FT                   /note="Protein zwilch homolog"
FT                   /id="PRO_0000314807"
FT   VAR_SEQ         1..321
FT                   /note="Missing (in isoform c and isoform d)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_057649"
FT   VAR_SEQ         354..356
FT                   /note="NFR -> K (in isoform b and isoform d)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_057650"
SQ   SEQUENCE   630 AA;  71096 MW;  A5E4373C5E262928 CRC64;
     MPLTIEQLKQ YNEKMAAKGE EDDAPAPVLL LDKYRVRVLP LTSIPFVMNH SSVSQLSLSS
     EDVLVVDFPS KGTGSGAGKA EKKMIFKKKI EPMEDSFEDK ENVNEGGPLM TSFLTLEKLR
     KGMVGDVEII GYECETSFFD ANPIPLSDGV SLQRYIRLNC SEHFSPSIST LPVWISTTSS
     KFPSICWLAA GRTNRNVQFA AATRVLGHFN NENSERVVKQ LNQACGTSQL NKYRAVYEEI
     RKIATENRPA PGEVTIDVRW STKSTLVLLE HPDNAADCTI KIDLGWGDKR FFVDDEIFEQ
     LFFVLNLADV LANPDNEVIF PMAPPANFDD LVQEMDALVE ASSREDNVFV SNENFRGGDI
     TDKVWNIVRK CNDVKQVTLL FRNFLQALAY GKIKSHAQER NKSHLASLIR ISKSSEFKIP
     VLERLSTIDM MMEIGVESLR RRVIDIFSSQ LLYPSDELEF ILQTCENDLP AGNGAMNSAA
     ISLLPITMAL ATANRIYELL NEKDHVILPD LTRRILQKYT ASMIEKSRRG ETETEYTFET
     TLPLLRMYKE GFMSKRPCIW TCENSNTVGA NVQARVLTSL ELQPSLEHIN RLVNDSRPVW
     TATEEKPAMI KDLNADYTVV HTIFSYLPKM
 
 
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