ID MCPH1_HUMAN Reviewed; 835 AA.
AC Q8NEM0; A0A075B6F8; B4DWW2; E9PGU5; E9PH63; Q66GU1; Q9H9C7;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2017, sequence version 4.
DT 27-MAR-2024, entry version 182.
DE RecName: Full=Microcephalin {ECO:0000303|PubMed:12046007};
GN Name=MCPH1 {ECO:0000312|HGNC:HGNC:6954};
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), AND VARIANTS SER-171 AND GLY-392.
RA Barry C., Chumakov I., Blumenfeld M.;
RT "Prostate cancer-related gene 3 (pg3) and biallelic markers thereof.";
RL Patent number WO0114550, 01-MAR-2001.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 96-835, AND VARIANTS SER-171; HIS-314 AND GLY-392.
RC TISSUE=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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS SER-171;
RP HIS-314 AND GLY-392.
RC TISSUE=Testis;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 96-835 (ISOFORM 1), AND VARIANTS SER-171;
RP HIS-314 AND GLY-392.
RA Lin S.-Y., Elledge S.J.;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND INVOLVEMENT IN MCPH1.
RX PubMed=12046007; DOI=10.1086/341283;
RA Jackson A.P., Eastwood H., Bell S.M., Toomes C., Adu J., Carr I.M.,
RA Roberts E., Hampshire D.J., Crow Y.J., Mighell A.J., Karbani G., Jafri H.,
RA Rashid Y., Mueller R.F., Markham A.F., Woods C.G.;
RT "Identification of microcephalin, a protein implicated in determining the
RT size of the human brain.";
RL Am. J. Hum. Genet. 71:136-142(2002).
RN [7]
RP FUNCTION, AND INVOLVEMENT IN MCPH1.
RX PubMed=15199523; DOI=10.1086/422855;
RA Trimborn M., Bell S.M., Felix C., Rashid Y., Jafri H., Griffiths P.D.,
RA Neumann L.M., Krebs A., Reis A., Sperling K., Neitzel H., Jackson A.P.;
RT "Mutations in microcephalin cause aberrant regulation of chromosome
RT condensation.";
RL Am. J. Hum. Genet. 75:261-266(2004).
RN [8]
RP FUNCTION.
RX PubMed=15220350; DOI=10.1074/jbc.c400139200;
RA Xu X., Lee J., Stern D.F.;
RT "Microcephalin is a DNA damage response protein involved in regulation of
RT CHK1 and BRCA1.";
RL J. Biol. Chem. 279:34091-34094(2004).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=16479174; DOI=10.4161/cc.5.4.2481;
RA Zhong X., Pfeifer G.P., Xu X.;
RT "Microcephalin encodes a centrosomal protein.";
RL Cell Cycle 5:457-458(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, AND IDENTIFICATION BY
RP 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-279; SER-287; THR-335 AND
RP SER-548, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-95.
RX PubMed=19925808; DOI=10.1016/j.jmb.2009.11.029;
RA Richards M.W., Leung J.W., Roe S.M., Li K., Chen J., Bayliss R.;
RT "A pocket on the surface of the N-terminal BRCT domain of Mcph1 is required
RT to prevent abnormal chromosome condensation.";
RL J. Mol. Biol. 395:908-915(2010).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 640-835 IN COMPLEX WITH
RP PHOSPHORYLATED CDC27 PEPTIDE.
RX PubMed=22139841; DOI=10.1074/jbc.m111.307868;
RA Singh N., Wiltshire T.D., Thompson J.R., Mer G., Couch F.J.;
RT "Molecular basis for the association of microcephalin (MCPH1) protein with
RT the cell division cycle protein 27 (Cdc27) subunit of the anaphase-
RT promoting complex.";
RL J. Biol. Chem. 287:2854-2862(2012).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 639-835 OF MUTANT ALA-761 ALONE
RP AND IN COMPLEX WITH H2FAX PEPTIDE.
RX PubMed=22154951; DOI=10.1016/j.jsb.2011.11.022;
RA Shao Z., Li F., Sy S.M., Yan W., Zhang Z., Gong D., Wen B., Huen M.S.,
RA Gong Q., Wu J., Shi Y.;
RT "Specific recognition of phosphorylated tail of H2AX by the tandem BRCT
RT domains of MCPH1 revealed by complex structure.";
RL J. Struct. Biol. 177:459-468(2012).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 640-835.
RX PubMed=22908299; DOI=10.1073/pnas.1212366109;
RA Singh N., Basnet H., Wiltshire T.D., Mohammad D.H., Thompson J.R.,
RA Heroux A., Botuyan M.V., Yaffe M.B., Couch F.J., Rosenfeld M.G., Mer G.;
RT "Dual recognition of phosphoserine and phosphotyrosine in histone variant
RT H2A.X by DNA damage response protein MCPH1.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:14381-14386(2012).
RN [16]
RP VARIANT MCPH1 ARG-27.
RX PubMed=16211557; DOI=10.1002/humu.9382;
RA Trimborn M., Richter R., Sternberg N., Gavvovidis I., Schindler D.,
RA Jackson A.P., Prott E.-C., Sperling K., Gillessen-Kaesbach G., Neitzel H.;
RT "The first missense alteration in the MCPH1 gene causes autosomal recessive
RT microcephaly with an extremely mild cellular and clinical phenotype.";
RL Hum. Mutat. 26:496-496(2005).
RN [17]
RP VARIANTS HIS-314; VAL-761 AND SER-828.
RX PubMed=18204051; DOI=10.1093/hmg/ddn021;
RA Wang J.-K., Li Y., Su B.;
RT "A common SNP of MCPH1 is associated with cranial volume variation in
RT Chinese population.";
RL Hum. Mol. Genet. 17:1329-1335(2008).
CC -!- FUNCTION: Implicated in chromosome condensation and DNA damage induced
CC cellular responses. May play a role in neurogenesis and regulation of
CC the size of the cerebral cortex. {ECO:0000269|PubMed:12046007,
CC ECO:0000269|PubMed:15199523, ECO:0000269|PubMed:15220350}.
CC -!- SUBUNIT: Interacts with CDC27 and maybe other components of the APC/C
CC complex. Interacts with histone variant H2AX under DNA damage
CC conditions. {ECO:0000269|PubMed:22139841, ECO:0000269|PubMed:22154951}.
CC -!- INTERACTION:
CC Q8NEM0; Q01094: E2F1; NbExp=6; IntAct=EBI-1565483, EBI-448924;
CC Q8NEM0; Q8NEM0: MCPH1; NbExp=2; IntAct=EBI-1565483, EBI-1565483;
CC Q8NEM0; Q15554: TERF2; NbExp=5; IntAct=EBI-1565483, EBI-706637;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000269|PubMed:16479174}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8NEM0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NEM0-2; Sequence=VSP_046135, VSP_046136, VSP_046137;
CC Name=3;
CC IsoId=Q8NEM0-3; Sequence=VSP_046136, VSP_046137;
CC -!- TISSUE SPECIFICITY: Expressed in fetal brain, liver and kidney.
CC {ECO:0000269|PubMed:12046007}.
CC -!- DOMAIN: BRCT domain 1 is required to prevent abnormal chromosome
CC condensation. It binds directly to the SWI-SNF chromatin remodeling
CC complex (PubMed:19925808). {ECO:0000269|PubMed:19925808}.
CC -!- DOMAIN: BRCT domains 2 and 3 recognize phosphoserine/phosphothreonine
CC marks on proteins with high selectivity, and mediate interaction with
CC phosphorylated CDC27. They also mediate the dual recognition of
CC phosphoserine and phosphotyrosine in the C-terminal tail of histone
CC H2AX (PubMed:22139841, PubMed:22908299, PubMed:22908299).
CC -!- DISEASE: Microcephaly 1, primary, autosomal recessive (MCPH1)
CC [MIM:251200]: A disease defined as a head circumference more than 3
CC standard deviations below the age-related mean. Brain weight is
CC markedly reduced and the cerebral cortex is disproportionately small.
CC Despite this marked reduction in size, the gyral pattern is relatively
CC well preserved, with no major abnormality in cortical architecture.
CC Affected individuals are mentally retarded. Primary microcephaly is
CC further defined by the absence of other syndromic features or
CC significant neurological deficits due to degenerative brain disorder.
CC Some MCHP1 patients also present growth retardation, short stature, and
CC misregulated chromosome condensation as indicated by a high number of
CC prophase-like cells detected in routine cytogenetic preparations and
CC poor-quality metaphase G-banding. {ECO:0000269|PubMed:12046007,
CC ECO:0000269|PubMed:15199523, ECO:0000269|PubMed:16211557}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: MCPH1 deficient cells exhibit a delay in post-mitotic
CC chromosome decondensation.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=A grey matter - Issue 64 of
CC November 2005;
CC URL="https://web.expasy.org/spotlight/back_issues/064";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/44370/MCPH1";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AX087870; CAC34661.1; -; mRNA.
DR EMBL; AK022909; BAB14304.1; -; mRNA.
DR EMBL; AK301702; BAG63174.1; -; mRNA.
DR EMBL; AC016065; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC018398; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF287957; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KC877206; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KC877207; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC030702; AAH30702.2; -; mRNA.
DR EMBL; BK004076; DAA04567.1; -; mRNA.
DR CCDS; CCDS43689.1; -. [Q8NEM0-1]
DR CCDS; CCDS55190.1; -. [Q8NEM0-3]
DR CCDS; CCDS55191.1; -. [Q8NEM0-2]
DR RefSeq; NP_001166045.1; NM_001172574.1. [Q8NEM0-3]
DR RefSeq; NP_001166046.1; NM_001172575.1. [Q8NEM0-2]
DR RefSeq; NP_001308971.1; NM_001322042.1.
DR RefSeq; NP_001308972.1; NM_001322043.1.
DR RefSeq; NP_001308974.1; NM_001322045.1.
DR RefSeq; NP_078872.2; NM_024596.4. [Q8NEM0-1]
DR PDB; 2WT8; X-ray; 1.60 A; A/B/C/D=1-95.
DR PDB; 3KTF; X-ray; 1.60 A; A/B/C=1-101.
DR PDB; 3PA6; X-ray; 1.50 A; A/B/C=1-105.
DR PDB; 3SHT; X-ray; 1.95 A; A/B/C=639-835.
DR PDB; 3SHV; X-ray; 2.10 A; A/B=639-835.
DR PDB; 3SZM; X-ray; 2.63 A; A/B/C/D/E/F/G/H=640-835.
DR PDB; 3T1N; X-ray; 2.60 A; A/B=640-835.
DR PDB; 3U3Z; X-ray; 1.50 A; A=640-835.
DR PDB; 7C5D; X-ray; 2.15 A; C/D=322-342.
DR PDBsum; 2WT8; -.
DR PDBsum; 3KTF; -.
DR PDBsum; 3PA6; -.
DR PDBsum; 3SHT; -.
DR PDBsum; 3SHV; -.
DR PDBsum; 3SZM; -.
DR PDBsum; 3T1N; -.
DR PDBsum; 3U3Z; -.
DR PDBsum; 7C5D; -.
DR AlphaFoldDB; Q8NEM0; -.
DR SMR; Q8NEM0; -.
DR BioGRID; 122776; 100.
DR DIP; DIP-39802N; -.
DR IntAct; Q8NEM0; 13.
DR MINT; Q8NEM0; -.
DR STRING; 9606.ENSP00000342924; -.
DR iPTMnet; Q8NEM0; -.
DR PhosphoSitePlus; Q8NEM0; -.
DR BioMuta; MCPH1; -.
DR DMDM; 296439305; -.
DR EPD; Q8NEM0; -.
DR jPOST; Q8NEM0; -.
DR MassIVE; Q8NEM0; -.
DR MaxQB; Q8NEM0; -.
DR PaxDb; 9606-ENSP00000342924; -.
DR PeptideAtlas; Q8NEM0; -.
DR ProteomicsDB; 20396; -.
DR ProteomicsDB; 20465; -.
DR ProteomicsDB; 73178; -. [Q8NEM0-1]
DR Antibodypedia; 2158; 423 antibodies from 32 providers.
DR DNASU; 79648; -.
DR Ensembl; ENST00000344683.10; ENSP00000342924.5; ENSG00000147316.15. [Q8NEM0-1]
DR Ensembl; ENST00000519480.6; ENSP00000430962.1; ENSG00000147316.15. [Q8NEM0-3]
DR Ensembl; ENST00000522905.1; ENSP00000430768.1; ENSG00000147316.15. [Q8NEM0-2]
DR GeneID; 79648; -.
DR KEGG; hsa:79648; -.
DR MANE-Select; ENST00000344683.10; ENSP00000342924.5; NM_024596.5; NP_078872.3.
DR UCSC; uc003wqh.4; human. [Q8NEM0-1]
DR AGR; HGNC:6954; -.
DR CTD; 79648; -.
DR DisGeNET; 79648; -.
DR GeneCards; MCPH1; -.
DR HGNC; HGNC:6954; MCPH1.
DR HPA; ENSG00000147316; Low tissue specificity.
DR MalaCards; MCPH1; -.
DR MIM; 251200; phenotype.
DR MIM; 607117; gene.
DR neXtProt; NX_Q8NEM0; -.
DR OpenTargets; ENSG00000147316; -.
DR Orphanet; 2512; Autosomal recessive primary microcephaly.
DR PharmGKB; PA30701; -.
DR VEuPathDB; HostDB:ENSG00000147316; -.
DR eggNOG; KOG4362; Eukaryota.
DR GeneTree; ENSGT00390000018842; -.
DR InParanoid; Q8NEM0; -.
DR OMA; QIQVIHK; -.
DR OrthoDB; 76720at2759; -.
DR PhylomeDB; Q8NEM0; -.
DR TreeFam; TF332942; -.
DR PathwayCommons; Q8NEM0; -.
DR Reactome; R-HSA-2299718; Condensation of Prophase Chromosomes.
DR SignaLink; Q8NEM0; -.
DR SIGNOR; Q8NEM0; -.
DR BioGRID-ORCS; 79648; 182 hits in 1156 CRISPR screens.
DR ChiTaRS; MCPH1; human.
DR EvolutionaryTrace; Q8NEM0; -.
DR GenomeRNAi; 79648; -.
DR Pharos; Q8NEM0; Tbio.
DR PRO; PR:Q8NEM0; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q8NEM0; Protein.
DR Bgee; ENSG00000147316; Expressed in secondary oocyte and 137 other cell types or tissues.
DR Genevisible; Q8NEM0; HS.
DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0060348; P:bone development; IEA:Ensembl.
DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IEA:Ensembl.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0071539; P:protein localization to centrosome; IEA:Ensembl.
DR GO; GO:0046605; P:regulation of centrosome cycle; IEA:Ensembl.
DR GO; GO:0060623; P:regulation of chromosome condensation; IEA:Ensembl.
DR GO; GO:0050727; P:regulation of inflammatory response; IEA:Ensembl.
DR CDD; cd17716; BRCT_microcephalin_rpt1; 1.
DR CDD; cd17736; BRCT_microcephalin_rpt2; 1.
DR CDD; cd17751; BRCT_microcephalin_rpt3; 1.
DR Gene3D; 3.40.50.10190; BRCT domain; 3.
DR IDEAL; IID00516; -.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR022047; Microcephalin-like.
DR InterPro; IPR029504; Microcephalin_mammal.
DR PANTHER; PTHR14625; MICROCEPHALIN; 1.
DR PANTHER; PTHR14625:SF3; MICROCEPHALIN; 1.
DR Pfam; PF12258; Microcephalin; 1.
DR Pfam; PF12738; PTCB-BRCT; 1.
DR SMART; SM00292; BRCT; 3.
DR SUPFAM; SSF52113; BRCT domain; 3.
DR PROSITE; PS50172; BRCT; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Cytoskeleton;
KW Intellectual disability; Phosphoprotein; Primary microcephaly;
KW Reference proteome; Repeat.
FT CHAIN 1..835
FT /note="Microcephalin"
FT /id="PRO_0000096296"
FT DOMAIN 1..93
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 640..730
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 751..833
FT /note="BRCT 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT REGION 313..381
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 419..443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 555..584
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 316..346
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 349..380
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 559..579
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 279
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 296
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TT79"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 335
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 146..194
FT /note="DDDVPILLFESNGSLIYTPTIEINSRHHSAMEKRLQEMKEKRENLSPTS ->
FT A (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_046135"
FT VAR_SEQ 610
FT /note="V -> M (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_046136"
FT VAR_SEQ 611..835
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_046137"
FT VARIANT 27
FT /note="T -> R (in MCPH1; mild phenotype;
FT dbSNP:rs199422124)"
FT /evidence="ECO:0000269|PubMed:16211557"
FT /id="VAR_046745"
FT VARIANT 171
FT /note="R -> S (in dbSNP:rs2442513)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.1,
FT ECO:0000269|Ref.5"
FT /id="VAR_046746"
FT VARIANT 212
FT /note="A -> T (in dbSNP:rs2922828)"
FT /id="VAR_046747"
FT VARIANT 264
FT /note="I -> V (in dbSNP:rs34121009)"
FT /id="VAR_046748"
FT VARIANT 288
FT /note="P -> H (in dbSNP:rs35590577)"
FT /id="VAR_046749"
FT VARIANT 304
FT /note="R -> I (in dbSNP:rs2083914)"
FT /id="VAR_046750"
FT VARIANT 314
FT /note="D -> H (in dbSNP:rs930557)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:18204051,
FT ECO:0000269|Ref.5"
FT /id="VAR_046751"
FT VARIANT 392
FT /note="D -> G (in dbSNP:rs2515569)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.1,
FT ECO:0000269|Ref.5"
FT /id="VAR_046752"
FT VARIANT 580
FT /note="S -> G (in dbSNP:rs17076894)"
FT /id="VAR_046753"
FT VARIANT 602
FT /note="L -> F (in dbSNP:rs34418490)"
FT /id="VAR_046754"
FT VARIANT 682
FT /note="T -> N (in dbSNP:rs12674488)"
FT /id="VAR_046755"
FT VARIANT 761
FT /note="A -> V (in dbSNP:rs1057090)"
FT /evidence="ECO:0000269|PubMed:18204051"
FT /id="VAR_046756"
FT VARIANT 828
FT /note="P -> S (in dbSNP:rs1057091)"
FT /evidence="ECO:0000269|PubMed:18204051"
FT /id="VAR_046757"
FT TURN 5..8
FT /evidence="ECO:0007829|PDB:3PA6"
FT STRAND 10..16
FT /evidence="ECO:0007829|PDB:3PA6"
FT HELIX 25..34
FT /evidence="ECO:0007829|PDB:3PA6"
FT STRAND 49..54
FT /evidence="ECO:0007829|PDB:3PA6"
FT HELIX 57..66
FT /evidence="ECO:0007829|PDB:3PA6"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:3PA6"
FT HELIX 73..82
FT /evidence="ECO:0007829|PDB:3PA6"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:3PA6"
FT TURN 96..99
FT /evidence="ECO:0007829|PDB:3PA6"
FT HELIX 326..329
FT /evidence="ECO:0007829|PDB:7C5D"
FT STRAND 649..654
FT /evidence="ECO:0007829|PDB:3U3Z"
FT HELIX 657..670
FT /evidence="ECO:0007829|PDB:3U3Z"
FT STRAND 674..678
FT /evidence="ECO:0007829|PDB:3U3Z"
FT STRAND 683..690
FT /evidence="ECO:0007829|PDB:3U3Z"
FT HELIX 695..702
FT /evidence="ECO:0007829|PDB:3U3Z"
FT STRAND 706..709
FT /evidence="ECO:0007829|PDB:3U3Z"
FT HELIX 711..719
FT /evidence="ECO:0007829|PDB:3U3Z"
FT HELIX 726..728
FT /evidence="ECO:0007829|PDB:3U3Z"
FT TURN 731..733
FT /evidence="ECO:0007829|PDB:3U3Z"
FT HELIX 736..746
FT /evidence="ECO:0007829|PDB:3U3Z"
FT STRAND 748..750
FT /evidence="ECO:0007829|PDB:3U3Z"
FT TURN 755..758
FT /evidence="ECO:0007829|PDB:3U3Z"
FT STRAND 762..764
FT /evidence="ECO:0007829|PDB:3U3Z"
FT HELIX 772..781
FT /evidence="ECO:0007829|PDB:3U3Z"
FT STRAND 786..789
FT /evidence="ECO:0007829|PDB:3SHV"
FT HELIX 790..792
FT /evidence="ECO:0007829|PDB:3U3Z"
FT STRAND 794..798
FT /evidence="ECO:0007829|PDB:3U3Z"
FT STRAND 809..811
FT /evidence="ECO:0007829|PDB:3U3Z"
FT HELIX 813..822
FT /evidence="ECO:0007829|PDB:3U3Z"
FT HELIX 828..831
FT /evidence="ECO:0007829|PDB:3U3Z"
SQ SEQUENCE 835 AA; 92849 MW; D17961B94EC240A3 CRC64;
MAAPILKDVV AYVEVWSSNG TENYSKTFTT QLVDMGAKVS KTFNKQVTHV IFKDGYQSTW
DKAQKRGVKL VSVLWVEKCR TAGAHIDESL FPAANMNEHL SSLIKKKRKC MQPKDFNFKT
PENDKRFQKK FEKMAKELQR QKTNLDDDVP ILLFESNGSL IYTPTIEINS RHHSAMEKRL
QEMKEKRENL SPTSSQMIQQ SHDNPSNSLC EAPLNISRDT LCSDEYFAGG LHSSFDDLCG
NSGCGNQERK LEGSINDIKS DVCISSLVLK ANNIHSSPSF THLDKSSPQK FLSNLSKEEI
NLQRNIAGKV VTPDQKQAAG MSQETFEEKY RLSPTLSSTK GHLLIHSRPR SSSVKRKRVS
HGSHSPPKEK CKRKRSTRRS IMPRLQLCRS EDRLQHVAGP ALEALSCGES SYDDYFSPDN
LKERYSENLP PESQLPSSPA QLSCRSLSKK ERTSIFEMSD FSCVGKKTRT VDITNFTAKT
ISSPRKTGNG EGRATSSCVT SAPEEALRCC RQAGKEDACP EGNGFSYTIE DPALPKGHDD
DLTPLEGSLE EMKEAVGLKS TQNKGTTSKI SNSSEGEAQS EHEPCFIVDC NMETSTEEKE
NLPGGYSGSV KNRPTRHDVL DDSCDGFKDL IKPHEELKKS GRGKKPTRTL VMTSMPSEKQ
NVVIQVVDKL KGFSIAPDVC ETTTHVLSGK PLRTLNVLLG IARGCWVLSY DWVLWSLELG
HWISEEPFEL SHHFPAAPLC RSECHLSAGP YRGTLFADQP AMFVSPASSP PVAKLCELVH
LCGGRVSQVP RQASIVIGPY SGKKKATVKY LSEKWVLDSI TQHKVCAPEN YLLSQ
//
