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Protein

Microcephalin

Gene

MCPH1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Implicated in chromosome condensation and DNA damage induced cellular responses. May play a role in neurogenesis and regulation of the size of the cerebral cortex.3 Publications

GO - Biological processi

  • cerebral cortex development Source: InterPro
  • mitotic cell cycle arrest Source: CACAO
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-2299718. Condensation of Prophase Chromosomes.
SignaLinkiQ8NEM0.

Names & Taxonomyi

Protein namesi
Recommended name:
Microcephalin
Gene namesi
Name:MCPH1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:6954. MCPH1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

Microcephaly 1, primary, autosomal recessive (MCPH1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals are mentally retarded. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder. Some MCHP1 patients also present growth retardation, short stature, and misregulated chromosome condensation as indicated by a high number of prophase-like cells detected in routine cytogenetic preparations and poor-quality metaphase G-banding.
See also OMIM:251200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04674527T → R in MCPH1; mild phenotype. 1 Publication1

Keywords - Diseasei

Mental retardation, Primary microcephaly

Organism-specific databases

DisGeNETi79648.
MalaCardsiMCPH1.
MIMi251200. phenotype.
OpenTargetsiENSG00000147316.
Orphaneti2512. Autosomal recessive primary microcephaly.
52183. Premature chromosome condensation with microcephaly and intellectual disability.
PharmGKBiPA30701.

Polymorphism and mutation databases

BioMutaiMCPH1.
DMDMi296439305.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000962961 – 835MicrocephalinAdd BLAST835

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei279PhosphoserineCombined sources1
Modified residuei287PhosphoserineCombined sources1
Modified residuei296PhosphoserineBy similarity1
Modified residuei333PhosphoserineCombined sources1
Modified residuei335PhosphothreonineCombined sources1
Modified residuei548PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8NEM0.
MaxQBiQ8NEM0.
PaxDbiQ8NEM0.
PeptideAtlasiQ8NEM0.
PRIDEiQ8NEM0.

PTM databases

iPTMnetiQ8NEM0.
PhosphoSitePlusiQ8NEM0.

Expressioni

Tissue specificityi

Expressed in fetal brain, liver and kidney.1 Publication

Gene expression databases

BgeeiENSG00000147316.
CleanExiHS_MCPH1.
ExpressionAtlasiQ8NEM0. baseline and differential.
GenevisibleiQ8NEM0. HS.

Organism-specific databases

HPAiCAB012177.
HPA008238.

Interactioni

Subunit structurei

Interacts with CDC27 and maybe other components of the APC/C complex. Interacts with histone variant H2AFX under DNA damage conditions.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-1565483,EBI-1565483
E2F1Q010946EBI-1565483,EBI-448924

Protein-protein interaction databases

BioGridi122776. 27 interactors.
DIPiDIP-39802N.
IntActiQ8NEM0. 7 interactors.
STRINGi9606.ENSP00000342924.

Structurei

Secondary structure

1835
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni5 – 8Combined sources4
Beta strandi10 – 16Combined sources7
Helixi25 – 34Combined sources10
Beta strandi49 – 54Combined sources6
Helixi57 – 66Combined sources10
Beta strandi69 – 71Combined sources3
Helixi73 – 82Combined sources10
Helixi88 – 90Combined sources3
Turni96 – 99Combined sources4
Beta strandi649 – 654Combined sources6
Helixi657 – 670Combined sources14
Beta strandi674 – 678Combined sources5
Beta strandi683 – 690Combined sources8
Helixi695 – 702Combined sources8
Beta strandi706 – 709Combined sources4
Helixi711 – 719Combined sources9
Helixi726 – 728Combined sources3
Turni731 – 733Combined sources3
Helixi736 – 746Combined sources11
Beta strandi748 – 750Combined sources3
Turni755 – 758Combined sources4
Beta strandi762 – 764Combined sources3
Helixi772 – 781Combined sources10
Beta strandi786 – 789Combined sources4
Helixi790 – 792Combined sources3
Beta strandi794 – 798Combined sources5
Beta strandi809 – 811Combined sources3
Helixi813 – 822Combined sources10
Helixi828 – 831Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WT8X-ray1.60A/B/C/D1-95[»]
3KTFX-ray1.60A/B/C1-101[»]
3PA6X-ray1.50A/B/C1-105[»]
3SHTX-ray1.95A/B/C639-835[»]
3SHVX-ray2.10A/B639-835[»]
3SZMX-ray2.63A/B/C/D/E/F/G/H640-835[»]
3T1NX-ray2.60A/B640-835[»]
3U3ZX-ray1.50A640-835[»]
ProteinModelPortaliQ8NEM0.
SMRiQ8NEM0.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8NEM0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 93BRCT 1PROSITE-ProRule annotationAdd BLAST93
Domaini640 – 730BRCT 2PROSITE-ProRule annotationAdd BLAST91
Domaini751 – 833BRCT 3PROSITE-ProRule annotationAdd BLAST83

Domaini

BRCT domain 1 is required to prevent abnormal chromosome condensation. It binds directly to the SWI-SNF chromatin remodeling complex (PubMed:19925808).1 Publication
BRCT domains 2 and 3 recognize phosphoserine/phosphothreonine marks on proteins with high selectivity, and mediate interaction with phosphorylated CDC27. They also mediate the dual recognition of phosphoserine and phosphotyrosine in the C-terminal tail of histone H2AFX (PubMed:22139841, PubMed:22908299 and PubMed:22908299).

Sequence similaritiesi

Contains 3 BRCT domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG4362. Eukaryota.
ENOG41120NI. LUCA.
GeneTreeiENSGT00390000018842.
HOGENOMiHOG000113501.
HOVERGENiHBG052433.
InParanoidiQ8NEM0.
KOiK19403.
PhylomeDBiQ8NEM0.
TreeFamiTF332942.

Family and domain databases

CDDicd00027. BRCT. 3 hits.
Gene3Di3.40.50.10190. 3 hits.
InterProiIPR001357. BRCT_dom.
IPR022047. Microcephalin-like.
IPR029504. Microcephalin_mammal.
[Graphical view]
PANTHERiPTHR14625. PTHR14625. 1 hit.
PfamiPF16589. BRCT_2. 1 hit.
PF12258. Microcephalin. 1 hit.
PF12738. PTCB-BRCT. 1 hit.
[Graphical view]
SMARTiSM00292. BRCT. 3 hits.
[Graphical view]
SUPFAMiSSF52113. SSF52113. 3 hits.
PROSITEiPS50172. BRCT. 3 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8NEM0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAPILKDVV AYVEVWSSNG TENYSKTFTT QLVDMGAKVS KTFNKQVTHV
60 70 80 90 100
IFKDGYQSTW DKAQKRGVKL VSVLWVEKCR TAGAHIDESL FPAANMNEHL
110 120 130 140 150
SSLIKKKRKC MQPKDFNFKT PENDKRFQKK FEKMAKELQR QKTNLDDDVP
160 170 180 190 200
ILLFESNGSL IYTPTIEINS RHHSAMEKRL QEMKEKRENL SPTSSQMIQQ
210 220 230 240 250
SHDNPSNSLC EAPLNISRDT LCSDEYFAGG LHSSFDDLCG NSGCGNQERK
260 270 280 290 300
LEGSINDIKS DVCISSLVLK ANNIHSSPSF THLDKSSPQK FLSNLSKEEI
310 320 330 340 350
NLQRNIAGKV VTPDQKQAAG MSQETFEEKY RLSPTLSSTK GHLLIHSRPR
360 370 380 390 400
SSSVKRKRVS HGSHSPPKEK CKRKRSTRRS IMPRLQLCRS EDRLQHVAGP
410 420 430 440 450
ALEALSCGES SYDDYFSPDN LKERYSENLP PESQLPSSPA QLSCRSLSKK
460 470 480 490 500
ERTSIFEMSD FSCVGKKTRT VDITNFTAKT ISSPRKTGNG EGRATSSCVT
510 520 530 540 550
SAPEEALRCC RQAGKEDACP EGNGFSYTIE DPALPKGHDD DLTPLEGSLE
560 570 580 590 600
EMKEAVGLKS TQNKGTTSKI SNSSEGEAQS EHEPCFIVDC NMETSTEEKE
610 620 630 640 650
NLPGGYSGSV KNRPTRHDVL DDSCDGFKDL IKPHEELKKS GRGKKPTRTL
660 670 680 690 700
VMTSMPSEKQ NVVIQVVDKL KGFSIAPDVC ETTTHVLSGK PLRTLNVLLG
710 720 730 740 750
IARGCWVLSY DWVLWSLELG HWISEEPFEL SHHFPAAPLC RSECHLSAGP
760 770 780 790 800
YRGTLFADQP VMFVSPASSP PVAKLCELVH LCGGRVSQVP RQASIVIGPY
810 820 830
SGKKKATVKY LSEKWVLDSI TQHKVCAPEN YLLSQ
Length:835
Mass (Da):92,877
Last modified:May 18, 2010 - v3
Checksum:iD1797320C5D0D928
GO
Isoform 2 (identifier: Q8NEM0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     146-194: DDDVPILLFESNGSLIYTPTIEINSRHHSAMEKRLQEMKEKRENLSPTS → A
     610-610: V → M
     611-835: Missing.

Note: No experimental confirmation available.
Show »
Length:562
Mass (Da):62,333
Checksum:iFEF23EDAC81BBF8E
GO
Isoform 3 (identifier: Q8NEM0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     610-610: V → M
     611-835: Missing.

Show »
Length:610
Mass (Da):67,915
Checksum:i615DA760A3F01C09
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04674527T → R in MCPH1; mild phenotype. 1 Publication1
Natural variantiVAR_046746171R → S.4 PublicationsCorresponds to variant rs2442513dbSNPEnsembl.1
Natural variantiVAR_046747212A → T.Corresponds to variant rs2922828dbSNPEnsembl.1
Natural variantiVAR_046748264I → V.Corresponds to variant rs34121009dbSNPEnsembl.1
Natural variantiVAR_046749288P → H.Corresponds to variant rs35590577dbSNPEnsembl.1
Natural variantiVAR_046750304R → I.Corresponds to variant rs2083914dbSNPEnsembl.1
Natural variantiVAR_046751314D → H.4 PublicationsCorresponds to variant rs930557dbSNPEnsembl.1
Natural variantiVAR_046752392D → G.4 PublicationsCorresponds to variant rs2515569dbSNPEnsembl.1
Natural variantiVAR_046753580S → G.Corresponds to variant rs17076894dbSNPEnsembl.1
Natural variantiVAR_046754602L → F.Corresponds to variant rs34418490dbSNPEnsembl.1
Natural variantiVAR_046755682T → N.Corresponds to variant rs12674488dbSNPEnsembl.1
Natural variantiVAR_046756761V → A May be associated with cranial volume variation in males in a Chinese population. 1 PublicationCorresponds to variant rs1057090dbSNPEnsembl.1
Natural variantiVAR_046757828P → S.1 PublicationCorresponds to variant rs1057091dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_046135146 – 194DDDVP…LSPTS → A in isoform 2. 2 PublicationsAdd BLAST49
Alternative sequenceiVSP_046136610V → M in isoform 2 and isoform 3. 2 Publications1
Alternative sequenceiVSP_046137611 – 835Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST225

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AX087870 mRNA. Translation: CAC34661.1.
AK022909 mRNA. Translation: BAB14304.1.
AK301702 mRNA. Translation: BAG63174.1.
AC016065 Genomic DNA. No translation available.
AC018398 Genomic DNA. No translation available.
AF287957 Genomic DNA. No translation available.
BC030702 mRNA. Translation: AAH30702.2.
BK004076 mRNA. Translation: DAA04567.1.
CCDSiCCDS43689.1. [Q8NEM0-1]
CCDS55190.1. [Q8NEM0-3]
CCDS55191.1. [Q8NEM0-2]
RefSeqiNP_001166045.1. NM_001172574.1.
NP_001166046.1. NM_001172575.1. [Q8NEM0-2]
NP_001308971.1. NM_001322042.1.
NP_001308972.1. NM_001322043.1.
NP_001308974.1. NM_001322045.1.
NP_078872.2. NM_024596.4.
UniGeneiHs.593807.
Hs.656769.
Hs.708770.

Genome annotation databases

EnsembliENST00000519480; ENSP00000430962; ENSG00000147316. [Q8NEM0-3]
ENST00000522905; ENSP00000430768; ENSG00000147316. [Q8NEM0-2]
GeneIDi79648.
KEGGihsa:79648.
UCSCiuc003wqh.4. human. [Q8NEM0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Protein Spotlight

A grey matter - Issue 64 of November 2005

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AX087870 mRNA. Translation: CAC34661.1.
AK022909 mRNA. Translation: BAB14304.1.
AK301702 mRNA. Translation: BAG63174.1.
AC016065 Genomic DNA. No translation available.
AC018398 Genomic DNA. No translation available.
AF287957 Genomic DNA. No translation available.
BC030702 mRNA. Translation: AAH30702.2.
BK004076 mRNA. Translation: DAA04567.1.
CCDSiCCDS43689.1. [Q8NEM0-1]
CCDS55190.1. [Q8NEM0-3]
CCDS55191.1. [Q8NEM0-2]
RefSeqiNP_001166045.1. NM_001172574.1.
NP_001166046.1. NM_001172575.1. [Q8NEM0-2]
NP_001308971.1. NM_001322042.1.
NP_001308972.1. NM_001322043.1.
NP_001308974.1. NM_001322045.1.
NP_078872.2. NM_024596.4.
UniGeneiHs.593807.
Hs.656769.
Hs.708770.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WT8X-ray1.60A/B/C/D1-95[»]
3KTFX-ray1.60A/B/C1-101[»]
3PA6X-ray1.50A/B/C1-105[»]
3SHTX-ray1.95A/B/C639-835[»]
3SHVX-ray2.10A/B639-835[»]
3SZMX-ray2.63A/B/C/D/E/F/G/H640-835[»]
3T1NX-ray2.60A/B640-835[»]
3U3ZX-ray1.50A640-835[»]
ProteinModelPortaliQ8NEM0.
SMRiQ8NEM0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122776. 27 interactors.
DIPiDIP-39802N.
IntActiQ8NEM0. 7 interactors.
STRINGi9606.ENSP00000342924.

PTM databases

iPTMnetiQ8NEM0.
PhosphoSitePlusiQ8NEM0.

Polymorphism and mutation databases

BioMutaiMCPH1.
DMDMi296439305.

Proteomic databases

EPDiQ8NEM0.
MaxQBiQ8NEM0.
PaxDbiQ8NEM0.
PeptideAtlasiQ8NEM0.
PRIDEiQ8NEM0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000519480; ENSP00000430962; ENSG00000147316. [Q8NEM0-3]
ENST00000522905; ENSP00000430768; ENSG00000147316. [Q8NEM0-2]
GeneIDi79648.
KEGGihsa:79648.
UCSCiuc003wqh.4. human. [Q8NEM0-1]

Organism-specific databases

CTDi79648.
DisGeNETi79648.
GeneCardsiMCPH1.
GeneReviewsiMCPH1.
HGNCiHGNC:6954. MCPH1.
HPAiCAB012177.
HPA008238.
MalaCardsiMCPH1.
MIMi251200. phenotype.
607117. gene.
neXtProtiNX_Q8NEM0.
OpenTargetsiENSG00000147316.
Orphaneti2512. Autosomal recessive primary microcephaly.
52183. Premature chromosome condensation with microcephaly and intellectual disability.
PharmGKBiPA30701.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4362. Eukaryota.
ENOG41120NI. LUCA.
GeneTreeiENSGT00390000018842.
HOGENOMiHOG000113501.
HOVERGENiHBG052433.
InParanoidiQ8NEM0.
KOiK19403.
PhylomeDBiQ8NEM0.
TreeFamiTF332942.

Enzyme and pathway databases

ReactomeiR-HSA-2299718. Condensation of Prophase Chromosomes.
SignaLinkiQ8NEM0.

Miscellaneous databases

ChiTaRSiMCPH1. human.
EvolutionaryTraceiQ8NEM0.
GenomeRNAii79648.
PROiQ8NEM0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147316.
CleanExiHS_MCPH1.
ExpressionAtlasiQ8NEM0. baseline and differential.
GenevisibleiQ8NEM0. HS.

Family and domain databases

CDDicd00027. BRCT. 3 hits.
Gene3Di3.40.50.10190. 3 hits.
InterProiIPR001357. BRCT_dom.
IPR022047. Microcephalin-like.
IPR029504. Microcephalin_mammal.
[Graphical view]
PANTHERiPTHR14625. PTHR14625. 1 hit.
PfamiPF16589. BRCT_2. 1 hit.
PF12258. Microcephalin. 1 hit.
PF12738. PTCB-BRCT. 1 hit.
[Graphical view]
SMARTiSM00292. BRCT. 3 hits.
[Graphical view]
SUPFAMiSSF52113. SSF52113. 3 hits.
PROSITEiPS50172. BRCT. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMCPH1_HUMAN
AccessioniPrimary (citable) accession number: Q8NEM0
Secondary accession number(s): B4DWW2
, E9PGU5, E9PH63, Q66GU1, Q9H9C7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 18, 2010
Last modified: November 30, 2016
This is version 132 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

MCPH1 deficient cells exhibit a delay in post-mitotic chromosome decondensation.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.