MCIN_HUMAN
ID MCIN_HUMAN Reviewed; 385 AA.
AC D6RGH6; C9JGY3; D6R920; F8KGQ8;
DT 27-JUL-2011, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Multicilin {ECO:0000305};
DE AltName: Full=Multiciliate differentiation and DNA synthesis-associated cell cycle protein;
DE Short=McIdas protein;
DE AltName: Full=Protein Idas;
GN Name=MCIDAS {ECO:0000312|HGNC:HGNC:40050}; Synonyms=IDAS, MCI, MCIN;
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], FUNCTION, SUBCELLULAR LOCATION, INTERACTION
RP WITH GMNN, HOMODIMERIZATION, SUBUNIT, AND DEVELOPMENTAL STAGE.
RX PubMed=21543332; DOI=10.1074/jbc.m110.207688;
RA Pefani D.E., Dimaki M., Spella M., Karantzelis N., Mitsiki E., Kyrousi C.,
RA Symeonidou I.E., Perrakis A., Taraviras S., Lygerou Z.;
RT "Idas, a novel phylogenetically conserved geminin-related protein, binds to
RT geminin and is required for cell cycle progression.";
RL J. Biol. Chem. 286:23234-23246(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.89 ANGSTROMS) OF 173-245 IN COMPLEX WITH GMNN,
RP FUNCTION, COILED-COIL DOMAIN, AND SUBUNIT.
RX PubMed=24064211; DOI=10.1074/jbc.m113.491928;
RA Caillat C., Pefani E.D., Gillespie P.J., Taraviras S., Blow J.J.,
RA Lygerou Z., Perrakis A.;
RT "The Geminin and Idas coiled coils preferentially form a heterodimer that
RT inhibits Geminin function in DNA replication licensing.";
RL J. Biol. Chem. 288:31624-31634(2013).
RN [4]
RP INVOLVEMENT IN CILD42, VARIANTS CILD42 147-CYS--SER-385 DEL; ASP-366 AND
RP HIS-381, CHARACTERIZATION OF VARIANTS CILD42 147-CYS--SER-385 DEL; ASP-366
RP AND HIS-381, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=25048963; DOI=10.1038/ncomms5418;
RA Boon M., Wallmeier J., Ma L., Loges N.T., Jaspers M., Olbrich H.,
RA Dougherty G.W., Raidt J., Werner C., Amirav I., Hevroni A., Abitbul R.,
RA Avital A., Soferman R., Wessels M., O'Callaghan C., Chung E.M., Rutman A.,
RA Hirst R.A., Moya E., Mitchison H.M., Van Daele S., De Boeck K.,
RA Jorissen M., Kintner C., Cuppens H., Omran H.;
RT "MCIDAS mutations result in a mucociliary clearance disorder with reduced
RT generation of multiple motile cilia.";
RL Nat. Commun. 5:4418-4418(2014).
CC -!- FUNCTION: Transcription regulator specifically required for
CC multiciliate cell differentiation (PubMed:25048963). Acts in a
CC multiprotein complex containing E2F4 and E2F5 that binds and activates
CC genes required for centriole biogenesis. Required for the deuterosome-
CC mediated acentriolar pathway (PubMed:25048963). Plays a role in mitotic
CC cell cycle progression by promoting cell cycle exit. Modulates GMNN
CC activity by reducing its affinity for CDT1 (PubMed:21543332,
CC PubMed:24064211). {ECO:0000250|UniProtKB:Q08B36,
CC ECO:0000269|PubMed:21543332, ECO:0000269|PubMed:24064211,
CC ECO:0000269|PubMed:25048963}.
CC -!- SUBUNIT: Heterodimer (via coiled-coil domain) with GMNN (via coiled-
CC coil domain); targets GMNN to the nucleus. Can form homodimers (in
CC vitro, via coiled-coil domain), but these are much less stable than the
CC heterodimer formed with GMNN. {ECO:0000269|PubMed:21543332,
CC ECO:0000269|PubMed:24064211}.
CC -!- INTERACTION:
CC D6RGH6; Q13895: BYSL; NbExp=3; IntAct=EBI-3954372, EBI-358049;
CC D6RGH6; O75496: GMNN; NbExp=8; IntAct=EBI-3954372, EBI-371669;
CC D6RGH6; D6RGH6: MCIDAS; NbExp=2; IntAct=EBI-3954372, EBI-3954372;
CC D6RGH6; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-3954372, EBI-11955057;
CC D6RGH6; O43167: ZBTB24; NbExp=3; IntAct=EBI-3954372, EBI-744471;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21543332,
CC ECO:0000269|PubMed:25048963}. Note=Excluded from the nucleolus.
CC {ECO:0000269|PubMed:21543332}.
CC -!- DEVELOPMENTAL STAGE: Probable target of the anaphase promoting
CC complex/cyclosome (APC/C) which regulates its level in the cell during
CC the mitotic cell cycle. Highly expressed during interphase and early
CC mitosis. Expression decreases during anaphase to become undetectable
CC during telophase and cytokinesis. Expressed in cells destined for
CC multiciliated cell differentiation, its expression is very weak in
CC fully differentiated ciliated respiratory cells (PubMed:25048963).
CC {ECO:0000269|PubMed:21543332, ECO:0000269|PubMed:25048963}.
CC -!- DISEASE: Ciliary dyskinesia, primary, 42 (CILD42) [MIM:618695]: A form
CC of primary ciliary dyskinesia, a disorder characterized by
CC abnormalities of motile cilia. Respiratory infections leading to
CC chronic inflammation and bronchiectasis are recurrent, due to defects
CC in the respiratory cilia. Other more variable features may include
CC infertility and mild hydrocephalus. Patients with this form of the
CC disorder do not have situs abnormalities. CILD42 inheritance is
CC autosomal recessive. {ECO:0000269|PubMed:25048963}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Was named Idas in reference to the cousin of the Gemini
CC in ancient Greek mythology. {ECO:0000305|PubMed:21543332}.
CC -!- SIMILARITY: Belongs to the geminin family. {ECO:0000305}.
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DR EMBL; FR854393; CCA89438.1; -; mRNA.
DR EMBL; AC091977; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS54853.1; -.
DR RefSeq; NP_001177716.1; NM_001190787.1.
DR PDB; 4BRY; X-ray; 2.89 A; B=173-245.
DR PDBsum; 4BRY; -.
DR AlphaFoldDB; D6RGH6; -.
DR SMR; D6RGH6; -.
DR BioGRID; 131360; 7.
DR ComplexPortal; CPX-661; IDAS-Geminin complex.
DR CORUM; D6RGH6; -.
DR IntAct; D6RGH6; 5.
DR STRING; 9606.ENSP00000426359; -.
DR iPTMnet; D6RGH6; -.
DR PhosphoSitePlus; D6RGH6; -.
DR BioMuta; MCIDAS; -.
DR jPOST; D6RGH6; -.
DR MassIVE; D6RGH6; -.
DR PaxDb; D6RGH6; -.
DR PeptideAtlas; D6RGH6; -.
DR PRIDE; D6RGH6; -.
DR Antibodypedia; 62363; 107 antibodies from 17 providers.
DR DNASU; 345643; -.
DR Ensembl; ENST00000513312.3; ENSP00000426359.1; ENSG00000234602.9.
DR GeneID; 345643; -.
DR KEGG; hsa:345643; -.
DR MANE-Select; ENST00000513312.3; ENSP00000426359.1; NM_001190787.3; NP_001177716.1.
DR UCSC; uc021xyp.2; human.
DR CTD; 345643; -.
DR DisGeNET; 345643; -.
DR GeneCards; MCIDAS; -.
DR GeneReviews; MCIDAS; -.
DR HGNC; HGNC:40050; MCIDAS.
DR HPA; ENSG00000234602; Tissue enhanced (parathyroid).
DR MalaCards; MCIDAS; -.
DR MIM; 614086; gene.
DR MIM; 618695; phenotype.
DR neXtProt; NX_D6RGH6; -.
DR OpenTargets; ENSG00000234602; -.
DR Orphanet; 244; Primary ciliary dyskinesia.
DR VEuPathDB; HostDB:ENSG00000234602; -.
DR eggNOG; ENOG502R4B5; Eukaryota.
DR GeneTree; ENSGT00940000153270; -.
DR HOGENOM; CLU_063884_0_0_1; -.
DR InParanoid; D6RGH6; -.
DR OMA; ITQSRDC; -.
DR OrthoDB; 935155at2759; -.
DR PhylomeDB; D6RGH6; -.
DR PathwayCommons; D6RGH6; -.
DR SignaLink; D6RGH6; -.
DR BioGRID-ORCS; 345643; 18 hits in 1066 CRISPR screens.
DR GenomeRNAi; 345643; -.
DR Pharos; D6RGH6; Tbio.
DR PRO; PR:D6RGH6; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; D6RGH6; protein.
DR Bgee; ENSG00000234602; Expressed in olfactory segment of nasal mucosa and 34 other tissues.
DR ExpressionAtlas; D6RGH6; baseline and differential.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003713; F:transcription coactivator activity; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0098534; P:centriole assembly; ISS:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0044458; P:motile cilium assembly; IMP:UniProtKB.
DR GO; GO:1903251; P:multi-ciliated epithelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; IBA:GO_Central.
DR GO; GO:0008156; P:negative regulation of DNA replication; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:1902017; P:regulation of cilium assembly; IMP:UniProtKB.
DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; IDA:ComplexPortal.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IDA:ComplexPortal.
DR InterPro; IPR022786; Geminin/Multicilin.
DR InterPro; IPR029699; Multicilin/Idas.
DR PANTHER; PTHR13372:SF3; PTHR13372:SF3; 1.
DR Pfam; PF07412; Geminin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cell cycle; Ciliopathy;
KW Cilium biogenesis/degradation; Coiled coil; Disease variant; Nucleus;
KW Primary ciliary dyskinesia; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..385
FT /note="Multicilin"
FT /id="PRO_0000411076"
FT REGION 1..130
FT /note="Necessary and sufficient for its degradation during
FT the cell cycle"
FT REGION 86..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..385
FT /note="Necessary and sufficient for proper nuclear
FT localization"
FT REGION 173..245
FT /note="Necessary and sufficient for interaction with GMNN
FT and sufficient for homodimerization"
FT /evidence="ECO:0000269|PubMed:21543332"
FT REGION 294..319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 179..227
FT /evidence="ECO:0000269|PubMed:24064211"
FT COMPBIAS 294..308
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 147..385
FT /note="Missing (in CILD42; reduced number of cilia and
FT basal bodies)"
FT /evidence="ECO:0000269|PubMed:25048963"
FT /id="VAR_083455"
FT VARIANT 366
FT /note="G -> D (in CILD42; reduced number of cilia and basal
FT bodies; dbSNP:rs797045151)"
FT /evidence="ECO:0000269|PubMed:25048963"
FT /id="VAR_071800"
FT VARIANT 381
FT /note="R -> H (in CILD42; reduced expression; reduced
FT number of cilia and basal bodies; dbSNP:rs797045152)"
FT /evidence="ECO:0000269|PubMed:25048963"
FT /id="VAR_071801"
FT HELIX 178..225
FT /evidence="ECO:0007829|PDB:4BRY"
FT HELIX 227..241
FT /evidence="ECO:0007829|PDB:4BRY"
SQ SEQUENCE 385 AA; 41720 MW; D52A35B926E75723 CRC64;
MQACGGGAAG RRAFDSICPN RMLALPGRAL LCKPGKPERK FAPPRKFFPG CTGGSPVSVY
EDPPDAEPTA LPALTTIDLQ DLADCSSLLG SDAPPGGDLA ASQNHSHQTE ADFNLQDFRD
TVDDLISDSS SMMSPTLASG DFPFSPCDIS PFGPCLSPPL DPRALQSPPL RPPDVPPPEQ
YWKEVADQNQ RALGDALVEN NQLHVTLTQK QEEIASLKER NVQLKELASR TRHLASVLDK
LMITQSRDCG AAAEPFLLKA KAKRSLEELV SAAGQDCAEV DAILREISER CDEALQSRDP
KRPRLLPEPA NTDTRPGNLH GAFRGLRTDC SRSALNLSHS ELEEGGSFST RIRSHSTIRT
LAFPQGNAFT IRTANGGYKF RWVPS
