ZWILC_HUMAN
ID ZWILC_HUMAN Reviewed; 591 AA.
AC Q9H900; B3KVB8; Q6N049; Q8N404; Q96SY7; Q9NWG7;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Protein zwilch homolog;
DE Short=hZwilch;
GN Name=ZWILCH;
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] (ISOFORMS 1 AND 2).
RC TISSUE=Teratocarcinoma, and 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Prostate;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
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 [5]
RP INTERACTION WITH KNTC1 AND ZW10.
RX PubMed=12686595; DOI=10.1091/mbc.e02-09-0624;
RA Williams B.C., Li Z., Liu S., Williams E.V., Leung G., Yen T.J.,
RA Goldberg M.L.;
RT "Zwilch, a new component of the ZW10/ROD complex required for kinetochore
RT functions.";
RL Mol. Biol. Cell 14:1379-1391(2003).
RN [6]
RP ASSOCIATION WITH COLORECTAL CANCER.
RX PubMed=15126332; DOI=10.1158/0008-5472.can-04-0587;
RA Wang Z., Cummins J.M., Shen D., Cahill D.P., Jallepalli P.V., Wang T.-L.,
RA Parsons D.W., Traverso G., Awad M., Silliman N., Ptak J., Szabo S.,
RA Willson J.K.V., Markowitz S.D., Goldberg M.L., Karess R., Kinzler K.W.,
RA Vogelstein B., Velculescu V.E., Lengauer C.;
RT "Three classes of genes mutated in colorectal cancers with chromosomal
RT instability.";
RL Cancer Res. 64:2998-3001(2004).
RN [7]
RP FUNCTION, AND IDENTIFICATION IN THE RZZ COMPLEX.
RX PubMed=15824131; DOI=10.1083/jcb.200411118;
RA Kops G.J.P.L., Kim Y., Weaver B.A.A., Mao Y., McLeod I., Yates J.R. III,
RA Tagaya M., Cleveland D.W.;
RT "ZW10 links mitotic checkpoint signaling to the structural kinetochore.";
RL J. Cell Biol. 169:49-60(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS), INTERACTION WITH KNTC1,
RP IDENTIFICATION IN THE RRZ COMPLEX, SUBCELLULAR LOCATION, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RX PubMed=20462495; DOI=10.1016/j.str.2010.02.014;
RA Civril F., Wehenkel A., Giorgi F.M., Santaguida S., Di Fonzo A.,
RA Grigorean G., Ciccarelli F.D., Musacchio A.;
RT "Structural analysis of the RZZ complex reveals common ancestry with
RT multisubunit vesicle tethering machinery.";
RL Structure 18:616-626(2010).
CC -!- FUNCTION: Essential component of the mitotic checkpoint, which prevents
CC cells from prematurely exiting mitosis. Required for the assembly of
CC the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Its
CC function related to the spindle assembly machinery is proposed to
CC depend on its association in the mitotic RZZ complex (PubMed:15824131).
CC {ECO:0000269|PubMed:15824131}.
CC -!- SUBUNIT: Component of the RZZ complex composed of KNTC1/ROD, ZW10 and
CC ZWILCH; in the complex interacts directly with KNTC1/ROD.
CC {ECO:0000269|PubMed:12686595, ECO:0000269|PubMed:15824131,
CC ECO:0000269|PubMed:20462495}.
CC -!- INTERACTION:
CC Q9H900; P50748: KNTC1; NbExp=2; IntAct=EBI-1001239, EBI-1001245;
CC -!- SUBCELLULAR LOCATION: Chromosome, centromere, kinetochore
CC {ECO:0000269|PubMed:20462495}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H900-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H900-2; Sequence=VSP_030365;
CC -!- MISCELLANEOUS: ZWILCH gene is deleted in a patient suffering from
CC colorectal cancer with chromosomal instability.
CC -!- SIMILARITY: Belongs to the ZWILCH family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AK000898; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AK000898; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB55133.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK000898; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK023175; BAB14446.1; -; mRNA.
DR EMBL; AK027468; BAB55133.1; ALT_INIT; mRNA.
DR EMBL; AK122787; BAG53730.1; -; mRNA.
DR EMBL; BX640701; CAE45821.1; -; mRNA.
DR EMBL; CH471082; EAW77779.1; -; Genomic_DNA.
DR EMBL; BC036900; AAH36900.1; -; mRNA.
DR EMBL; BC090041; AAH90041.1; -; mRNA.
DR CCDS; CCDS10219.1; -. [Q9H900-1]
DR CCDS; CCDS73746.1; -. [Q9H900-2]
DR RefSeq; NP_001274750.1; NM_001287821.1. [Q9H900-2]
DR RefSeq; NP_001274751.1; NM_001287822.1. [Q9H900-2]
DR RefSeq; NP_001274752.1; NM_001287823.1. [Q9H900-2]
DR RefSeq; NP_060445.3; NM_017975.4. [Q9H900-1]
DR PDB; 3IF8; X-ray; 2.55 A; A=1-334, B=335-591.
DR PDB; 7QPG; EM; 3.90 A; B/C=1-591.
DR PDBsum; 3IF8; -.
DR PDBsum; 7QPG; -.
DR AlphaFoldDB; Q9H900; -.
DR SMR; Q9H900; -.
DR BioGRID; 120376; 26.
DR ComplexPortal; CPX-6017; RZZ complex.
DR CORUM; Q9H900; -.
DR DIP; DIP-36478N; -.
DR IntAct; Q9H900; 7.
DR STRING; 9606.ENSP00000311429; -.
DR GlyGen; Q9H900; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H900; -.
DR PhosphoSitePlus; Q9H900; -.
DR BioMuta; ZWILCH; -.
DR DMDM; 166228729; -.
DR EPD; Q9H900; -.
DR jPOST; Q9H900; -.
DR MassIVE; Q9H900; -.
DR MaxQB; Q9H900; -.
DR PaxDb; Q9H900; -.
DR PeptideAtlas; Q9H900; -.
DR PRIDE; Q9H900; -.
DR ProteomicsDB; 81259; -. [Q9H900-1]
DR ProteomicsDB; 81260; -. [Q9H900-2]
DR Antibodypedia; 26194; 141 antibodies from 23 providers.
DR DNASU; 55055; -.
DR Ensembl; ENST00000307897.10; ENSP00000311429.5; ENSG00000174442.12. [Q9H900-1]
DR Ensembl; ENST00000446801.6; ENSP00000402217.2; ENSG00000174442.12. [Q9H900-2]
DR Ensembl; ENST00000535141.6; ENSP00000437749.2; ENSG00000174442.12. [Q9H900-2]
DR Ensembl; ENST00000565627.5; ENSP00000454737.1; ENSG00000174442.12. [Q9H900-2]
DR Ensembl; ENST00000613446.4; ENSP00000477955.1; ENSG00000174442.12. [Q9H900-2]
DR GeneID; 55055; -.
DR KEGG; hsa:55055; -.
DR MANE-Select; ENST00000307897.10; ENSP00000311429.5; NM_017975.5; NP_060445.3.
DR UCSC; uc002aqa.5; human. [Q9H900-1]
DR CTD; 55055; -.
DR DisGeNET; 55055; -.
DR GeneCards; ZWILCH; -.
DR HGNC; HGNC:25468; ZWILCH.
DR HPA; ENSG00000174442; Tissue enhanced (testis).
DR MIM; 609984; gene.
DR neXtProt; NX_Q9H900; -.
DR OpenTargets; ENSG00000174442; -.
DR PharmGKB; PA142670465; -.
DR VEuPathDB; HostDB:ENSG00000174442; -.
DR eggNOG; KOG4803; Eukaryota.
DR GeneTree; ENSGT00390000013696; -.
DR HOGENOM; CLU_466141_0_0_1; -.
DR InParanoid; Q9H900; -.
DR OMA; CAAEEFY; -.
DR OrthoDB; 1212968at2759; -.
DR PhylomeDB; Q9H900; -.
DR TreeFam; TF324453; -.
DR PathwayCommons; Q9H900; -.
DR Reactome; R-HSA-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR Reactome; R-HSA-68877; Mitotic Prometaphase.
DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR SignaLink; Q9H900; -.
DR SIGNOR; Q9H900; -.
DR BioGRID-ORCS; 55055; 61 hits in 1091 CRISPR screens.
DR ChiTaRS; ZWILCH; human.
DR EvolutionaryTrace; Q9H900; -.
DR GenomeRNAi; 55055; -.
DR Pharos; Q9H900; Tbio.
DR PRO; PR:Q9H900; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9H900; protein.
DR Bgee; ENSG00000174442; Expressed in sperm and 160 other tissues.
DR ExpressionAtlas; Q9H900; baseline and differential.
DR Genevisible; Q9H900; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0005828; C:kinetochore microtubule; IC:ComplexPortal.
DR GO; GO:1990423; C:RZZ complex; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0034501; P:protein localization to kinetochore; IMP:UniProtKB.
DR InterPro; IPR018630; Zwilch.
DR PANTHER; PTHR15995; PTHR15995; 1.
DR Pfam; PF09817; Zwilch; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Cell division; Centromere;
KW Chromosome; Kinetochore; Mitosis; Phosphoprotein; Reference proteome.
FT CHAIN 1..591
FT /note="Protein zwilch homolog"
FT /id="PRO_0000314800"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT VAR_SEQ 1..114
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005"
FT /id="VSP_030365"
FT VARIANT 344
FT /note="S -> G (in dbSNP:rs11071896)"
FT /id="VAR_038055"
FT CONFLICT 239
FT /note="Q -> R (in Ref. 2; CAE45821)"
FT /evidence="ECO:0000305"
FT CONFLICT 537
FT /note="S -> R (in Ref. 1; BAB14446)"
FT /evidence="ECO:0000305"
FT CONFLICT 555
FT /note="D -> G (in Ref. 1; AK000898)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="N -> S (in Ref. 1; AK000898)"
FT /evidence="ECO:0000305"
FT HELIX 2..5
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 8..23
FT /evidence="ECO:0007829|PDB:3IF8"
FT STRAND 32..43
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:3IF8"
FT STRAND 61..66
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 103..117
FT /evidence="ECO:0007829|PDB:3IF8"
FT STRAND 136..140
FT /evidence="ECO:0007829|PDB:3IF8"
FT STRAND 148..158
FT /evidence="ECO:0007829|PDB:3IF8"
FT STRAND 161..176
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 182..193
FT /evidence="ECO:0007829|PDB:3IF8"
FT STRAND 199..209
FT /evidence="ECO:0007829|PDB:3IF8"
FT STRAND 224..232
FT /evidence="ECO:0007829|PDB:3IF8"
FT STRAND 245..252
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 267..281
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 295..307
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 348..357
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 363..378
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 393..402
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 415..438
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 444..451
FT /evidence="ECO:0007829|PDB:3IF8"
FT STRAND 453..455
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 457..477
FT /evidence="ECO:0007829|PDB:3IF8"
FT TURN 478..480
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 485..501
FT /evidence="ECO:0007829|PDB:3IF8"
FT STRAND 510..513
FT /evidence="ECO:0007829|PDB:3IF8"
FT HELIX 517..522
FT /evidence="ECO:0007829|PDB:3IF8"
FT TURN 523..525
FT /evidence="ECO:0007829|PDB:3IF8"
FT STRAND 529..536
FT /evidence="ECO:0007829|PDB:3IF8"
FT STRAND 542..551
FT /evidence="ECO:0007829|PDB:3IF8"
FT STRAND 578..589
FT /evidence="ECO:0007829|PDB:3IF8"
SQ SEQUENCE 591 AA; 67214 MW; 522ECA229D2C0AE9 CRC64;
MWERLNCAAE DFYSRLLQKF NEEKKGIRKD PFLYEADVQV QLISKGQPNP LKNILNENDI
VFIVEKVPLE KEETSHIEEL QSEETAISDF STGENVGPLA LPVGKARQLI GLYTMAHNPN
MTHLKINLPV TALPPLWVRC DSSDPEGTCW LGAELITTNN SITGIVLYVV SCKADKNYSV
NLENLKNLHK KRHHLSTVTS KGFAQYELFK SSALDDTITA SQTAIALDIS WSPVDEILQI
PPLSSTATLN IKVESGEPRG PLNHLYRELK FLLVLADGLR TGVTEWLEPL EAKSAVELVQ
EFLNDLNKLD GFGDSTKKDT EVETLKHDTA AVDRSVKRLF KVRSDLDFAE QLWCKMSSSV
ISYQDLVKCF TLIIQSLQRG DIQPWLHSGS NSLLSKLIHQ SYHGTMDTVS LSGTIPVQML
LEIGLDKLKK DYISFFIGQE LASLNHLEYF IAPSVDIQEQ VYRVQKLHHI LEILVSCMPF
IKSQHELLFS LTQICIKYYK QNPLDEQHIF QLPVRPTAVK NLYQSEKPQK WRVEIYSGQK
KIKTVWQLSD SSPIDHLNFH KPDFSELTLN GSLEERIFFT NMVTCSQVHF K
