Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Microcephalin

Gene

MCPH1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

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

GO - Molecular functioni

  • identical protein binding Source: IntAct

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-2299718 Condensation of Prophase Chromosomes
SignaLinkiQ8NEM0
SIGNORiQ8NEM0

Names & Taxonomyi

Protein namesi
Recommended name:
Microcephalin1 Publication
Gene namesi
Name:MCPH1Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000147316.12
HGNCiHGNC:6954 MCPH1
MIMi607117 gene
neXtProtiNX_Q8NEM0

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 PublicationCorresponds to variant dbSNP:rs199422124EnsemblClinVar.1

Keywords - Diseasei

Mental retardation, Primary microcephaly

Organism-specific databases

DisGeNETi79648
GeneReviewsiMCPH1
MalaCardsiMCPH1
MIMi251200 phenotype
OpenTargetsiENSG00000147316
Orphaneti2512 Autosomal recessive primary microcephaly
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
PaxDbiQ8NEM0
PeptideAtlasiQ8NEM0
PRIDEiQ8NEM0
ProteomicsDBi73178

PTM databases

iPTMnetiQ8NEM0
PhosphoSitePlusiQ8NEM0

Expressioni

Tissue specificityi

Expressed in fetal brain, liver and kidney.1 Publication

Gene expression databases

BgeeiENSG00000147316 Expressed in 172 organ(s), highest expression level in skeletal muscle tissue
CleanExiHS_MCPH1
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122776, 89 interactors
DIPiDIP-39802N
IntActiQ8NEM0, 10 interactors
MINTiQ8NEM0
STRINGi9606.ENSP00000342924

Structurei

Secondary structure

1835
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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).

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG4362 Eukaryota
ENOG41120NI LUCA
GeneTreeiENSGT00390000018842
HOGENOMiHOG000113501
HOVERGENiHBG052433
InParanoidiQ8NEM0
KOiK19403
OMAiTQHKVCA
OrthoDBiEOG091G037P
PhylomeDBiQ8NEM0
TreeFamiTF332942

Family and domain databases

CDDicd00027 BRCT, 3 hits
Gene3Di3.40.50.10190, 3 hits
InterProiView protein in InterPro
IPR001357 BRCT_dom
IPR036420 BRCT_dom_sf
IPR022047 Microcephalin-like
IPR029504 Microcephalin_mammal
PANTHERiPTHR14625 PTHR14625, 1 hit
PfamiView protein in Pfam
PF16589 BRCT_2, 1 hit
PF12258 Microcephalin, 1 hit
PF12738 PTCB-BRCT, 1 hit
SMARTiView protein in SMART
SM00292 BRCT, 3 hits
SUPFAMiSSF52113 SSF52113, 3 hits
PROSITEiView protein in PROSITE
PS50172 BRCT, 3 hits

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 AMFVSPASSP PVAKLCELVH LCGGRVSQVP RQASIVIGPY
810 820 830
SGKKKATVKY LSEKWVLDSI TQHKVCAPEN YLLSQ
Length:835
Mass (Da):92,849
Last modified:May 10, 2017 - v4
Checksum:iD17961B94EC240A3
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 PublicationCorresponds to variant dbSNP:rs199422124EnsemblClinVar.1
Natural variantiVAR_046746171R → S4 PublicationsCorresponds to variant dbSNP:rs2442513Ensembl.1
Natural variantiVAR_046747212A → T. Corresponds to variant dbSNP:rs2922828EnsemblClinVar.1
Natural variantiVAR_046748264I → V. Corresponds to variant dbSNP:rs34121009EnsemblClinVar.1
Natural variantiVAR_046749288P → H. Corresponds to variant dbSNP:rs35590577EnsemblClinVar.1
Natural variantiVAR_046750304R → I. Corresponds to variant dbSNP:rs2083914EnsemblClinVar.1
Natural variantiVAR_046751314D → H4 PublicationsCorresponds to variant dbSNP:rs930557EnsemblClinVar.1
Natural variantiVAR_046752392D → G4 PublicationsCorresponds to variant dbSNP:rs2515569EnsemblClinVar.1
Natural variantiVAR_046753580S → G. Corresponds to variant dbSNP:rs17076894EnsemblClinVar.1
Natural variantiVAR_046754602L → F. Corresponds to variant dbSNP:rs34418490EnsemblClinVar.1
Natural variantiVAR_046755682T → N. Corresponds to variant dbSNP:rs12674488EnsemblClinVar.1
Natural variantiVAR_046756761A → V1 PublicationCorresponds to variant dbSNP:rs1057090EnsemblClinVar.1
Natural variantiVAR_046757828P → S1 PublicationCorresponds to variant dbSNP:rs1057091EnsemblClinVar.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.
KC877206 Genomic DNA No translation available.
KC877207 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

EnsembliENST00000344683; ENSP00000342924; ENSG00000147316 [Q8NEM0-1]
ENST00000519480; ENSP00000430962; ENSG00000147316 [Q8NEM0-3]
ENST00000522905; ENSP00000430768; ENSG00000147316 [Q8NEM0-2]
ENST00000643429; ENSP00000496505; ENSG00000285262 [Q8NEM0-3]
ENST00000646478; ENSP00000494584; ENSG00000285262 [Q8NEM0-2]
ENST00000647051; ENSP00000493874; ENSG00000285262 [Q8NEM0-1]
GeneIDi79648
KEGGihsa:79648
UCSCiuc003wqh.4 human [Q8NEM0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

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.
KC877206 Genomic DNA No translation available.
KC877207 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, 89 interactors
DIPiDIP-39802N
IntActiQ8NEM0, 10 interactors
MINTiQ8NEM0
STRINGi9606.ENSP00000342924

PTM databases

iPTMnetiQ8NEM0
PhosphoSitePlusiQ8NEM0

Polymorphism and mutation databases

BioMutaiMCPH1
DMDMi296439305

Proteomic databases

EPDiQ8NEM0
PaxDbiQ8NEM0
PeptideAtlasiQ8NEM0
PRIDEiQ8NEM0
ProteomicsDBi73178

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344683; ENSP00000342924; ENSG00000147316 [Q8NEM0-1]
ENST00000519480; ENSP00000430962; ENSG00000147316 [Q8NEM0-3]
ENST00000522905; ENSP00000430768; ENSG00000147316 [Q8NEM0-2]
ENST00000643429; ENSP00000496505; ENSG00000285262 [Q8NEM0-3]
ENST00000646478; ENSP00000494584; ENSG00000285262 [Q8NEM0-2]
ENST00000647051; ENSP00000493874; ENSG00000285262 [Q8NEM0-1]
GeneIDi79648
KEGGihsa:79648
UCSCiuc003wqh.4 human [Q8NEM0-1]

Organism-specific databases

CTDi79648
DisGeNETi79648
EuPathDBiHostDB:ENSG00000147316.12
GeneCardsiMCPH1
GeneReviewsiMCPH1
HGNCiHGNC:6954 MCPH1
HPAiCAB012177
HPA008238
MalaCardsiMCPH1
MIMi251200 phenotype
607117 gene
neXtProtiNX_Q8NEM0
OpenTargetsiENSG00000147316
Orphaneti2512 Autosomal recessive primary microcephaly
PharmGKBiPA30701
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4362 Eukaryota
ENOG41120NI LUCA
GeneTreeiENSGT00390000018842
HOGENOMiHOG000113501
HOVERGENiHBG052433
InParanoidiQ8NEM0
KOiK19403
OMAiTQHKVCA
OrthoDBiEOG091G037P
PhylomeDBiQ8NEM0
TreeFamiTF332942

Enzyme and pathway databases

ReactomeiR-HSA-2299718 Condensation of Prophase Chromosomes
SignaLinkiQ8NEM0
SIGNORiQ8NEM0

Miscellaneous databases

ChiTaRSiMCPH1 human
EvolutionaryTraceiQ8NEM0
GenomeRNAii79648
PROiPR:Q8NEM0
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147316 Expressed in 172 organ(s), highest expression level in skeletal muscle tissue
CleanExiHS_MCPH1
GenevisibleiQ8NEM0 HS

Family and domain databases

CDDicd00027 BRCT, 3 hits
Gene3Di3.40.50.10190, 3 hits
InterProiView protein in InterPro
IPR001357 BRCT_dom
IPR036420 BRCT_dom_sf
IPR022047 Microcephalin-like
IPR029504 Microcephalin_mammal
PANTHERiPTHR14625 PTHR14625, 1 hit
PfamiView protein in Pfam
PF16589 BRCT_2, 1 hit
PF12258 Microcephalin, 1 hit
PF12738 PTCB-BRCT, 1 hit
SMARTiView protein in SMART
SM00292 BRCT, 3 hits
SUPFAMiSSF52113 SSF52113, 3 hits
PROSITEiView protein in PROSITE
PS50172 BRCT, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiMCPH1_HUMAN
AccessioniPrimary (citable) accession number: Q8NEM0
Secondary accession number(s): A0A075B6F8
, B4DWW2, E9PGU5, E9PH63, Q66GU1, Q9H9C7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 10, 2017
Last modified: November 7, 2018
This is version 151 of the entry and version 4 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again