UniProtKB - Q6P5D8 (SMHD1_MOUSE)
Protein
Structural maintenance of chromosomes flexible hinge domain-containing protein 1
Gene
Smchd1
Organism
Mus musculus (Mouse)
Status
Functioni
Non-canonical member of the structural maintenance of chromosomes (SMC) protein family that plays a key role in epigenetic silencing by regulating chromatin architecture (PubMed:26091879, PubMed:29887375). Promotes heterochromatin formation in both autosomes and chromosome X, probably by mediating the merge of chromatin compartments (PubMed:23754746, PubMed:23819640, PubMed:26391951, PubMed:28587678, PubMed:29887375). Plays a key role in chromosome X inactivation in females by promoting the spreading of heterochromatin (PubMed:18425126, PubMed:22841499, PubMed:26391951, PubMed:29887375). Recruited to inactivated chromosome X by Xist RNA and acts by mediating the merge of chromatin compartments: promotes random chromatin interactions that span the boundaries of existing structures, leading to create a compartment-less architecture typical of inactivated chromosome X (PubMed:29887375). Required to facilitate Xist RNA spreading (PubMed:29887375). Also required for silencing of a subset of clustered autosomal loci in somatic cells, such as the DUX4 locus (PubMed:23754746, PubMed:23819640, PubMed:28587678). Has ATPase activity; may participate in structural manipulation of chromatin in an ATP-dependent manner as part of its role in gene expression regulation (PubMed:26391951, PubMed:27059856). Also plays a role in DNA repair: localizes to sites of DNA double-strand breaks in response to DNA damage to promote the repair of DNA double-strand breaks (By similarity). Acts by promoting non-homologous end joining (NHEJ) and inhibiting homologous recombination (HR) repair (By similarity). Required during preimplantation development, probably acts by regulating chromatin architecture (PubMed:29900695).By similarity10 Publications
Catalytic activityi
GO - Molecular functioni
- ATPase activity Source: UniProtKB
- ATP binding Source: InterPro
- DNA binding Source: UniProtKB-KW
- protein homodimerization activity Source: UniProtKB
GO - Biological processi
- dosage compensation by inactivation of X chromosome Source: MGI
- double-strand break repair Source: InterPro
- heterochromatin organization involved in chromatin silencing Source: UniProtKB
- inactivation of X chromosome by DNA methylation Source: MGI
- inactivation of X chromosome by heterochromatin assembly Source: UniProtKB
- negative regulation of double-strand break repair via homologous recombination Source: UniProtKB
- nose development Source: UniProtKB
- positive regulation of DNA repair Source: UniProtKB
- positive regulation of double-strand break repair via nonhomologous end joining Source: UniProtKB
Keywordsi
Molecular function | Chromatin regulator, DNA-binding, Hydrolase, Repressor |
Biological process | DNA damage, DNA repair |
Names & Taxonomyi
Protein namesi | Recommended name: Structural maintenance of chromosomes flexible hinge domain-containing protein 11 Publication (EC:3.6.1.-2 Publications)Short name: SMC hinge domain-containing protein 11 Publication |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1921605, Smchd1 |
Subcellular locationi
Other locations
- Chromosome 3 Publications
Note: Recruited to inactivated chromosome X in females by Xist RNA (PubMed:29887375). Localizes at sites of DNA damage at double-strand breaks (DSBs) (By similarity).By similarity1 Publication
Nucleus
- Barr body Source: UniProtKB
Other locations
- chromosome, telomeric region Source: Ensembl
- site of double-strand break Source: UniProtKB
Keywords - Cellular componenti
ChromosomePathology & Biotechi
Disruption phenotypei
Defects in Smchd1 are the cause of the MommeD1 (modifier of murine metastable epialleles) phenotype, a semi-dominant suppressor of variegation (PubMed:18425126, PubMed:21553025). Mice display female-specific mid-gestation lethality and hypomethylation of the X-linked gene Hprt1, due to defects in X inactivation (PubMed:18425126, PubMed:21553025, PubMed:23754746). Mice do not show defects on telomeres length (PubMed:18425126, PubMed:21553025). Male mice are less affected, with some surviving to become fertile adults on the FVB/n genetic background (PubMed:18425126). On other genetic backgrounds, all males lacking die perinatally (PubMed:18425126). A subset of clustered autosomal loci display hypomethylation and derepression (PubMed:23754746, PubMed:23819640, PubMed:28587678).5 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 147 | E → A: Abolishes ATPase activity. 1 Publication | 1 | |
Mutagenesisi | 1867 | R → G: Abolishes ability to bind DNA without altering the ability of the SMC hinge domain to mediate homodimerization. 2 Publications | 1 | |
Mutagenesisi | 1872 – 1876 | GKFGG → AKFAA: Abolishes homodimerization. 1 Publication | 5 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000332145 | 2 – 2007 | Structural maintenance of chromosomes flexible hinge domain-containing protein 1Add BLAST | 2006 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineBy similarity | 1 | |
Modified residuei | 833 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1350 | N6-acetyllysineBy similarity | 1 | |
Cross-linki | 1375 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 1500 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 1803 | N6-succinyllysineCombined sources | 1 | |
Modified residuei | 1975 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Sumoylated with SUMO1.1 Publication
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q6P5D8 |
jPOSTi | Q6P5D8 |
MaxQBi | Q6P5D8 |
PaxDbi | Q6P5D8 |
PeptideAtlasi | Q6P5D8 |
PRIDEi | Q6P5D8 |
ProteomicsDBi | 261270 |
PTM databases
iPTMneti | Q6P5D8 |
PhosphoSitePlusi | Q6P5D8 |
Expressioni
Tissue specificityi
During embryogenesis, specifically expressed in immature olfactory sensory neurons.1 Publication
Developmental stagei
Expressed in the nasal placodes and optic vesicles at day 9.5 dpc and in the nasal epithelium at 12.5 dpc (PubMed:28067911). Expressed in the nasal cavity in 14.5 dpc animals (PubMed:28067911).1 Publication
Inductioni
Expression is repressed by CDX2.1 Publication
Gene expression databases
Bgeei | ENSMUSG00000024054, Expressed in pes and 264 other tissues |
ExpressionAtlasi | Q6P5D8, baseline and differential |
Genevisiblei | Q6P5D8, MM |
Interactioni
Subunit structurei
GO - Molecular functioni
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 216686, 24 interactors |
IntActi | Q6P5D8, 21 interactors |
MINTi | Q6P5D8 |
STRINGi | 10090.ENSMUSP00000121835 |
Miscellaneous databases
RNActi | Q6P5D8, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q6P5D8 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1721 – 1848 | SMC hingeSequence analysisAdd BLAST | 128 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 111 – 702 | ATPase activity domain1 PublicationAdd BLAST | 592 |
Domaini
Atypical member of the structural maintenance of chromosomes (SMC) protein family (PubMed:26733688, PubMed:27059856). Like other members of the SMC family, has ATPase activity, which is probably necessary for its engagement with chromatin, and a SMC hinge domain (PubMed:26733688, PubMed:27059856). However, the SMC hinge domain adopts an unconventional homodimeric arrangement augmented by an intermolecular coiled coil formed between the two monomers. This suggests that protein may assemble as a head-to-head parallel dimer without adopting a hairpin shape at the hinge domain, unlike the dimeric arrangement conventionally found in other members of the SMC protein family (PubMed:26733688). The SMC hinge domain binds DNA and RNA (PubMed:26091879).3 Publications
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502QREW, Eukaryota |
GeneTreei | ENSGT00390000006950 |
HOGENOMi | CLU_002288_1_0_1 |
InParanoidi | Q6P5D8 |
OMAi | WPELKEC |
OrthoDBi | 34310at2759 |
PhylomeDBi | Q6P5D8 |
TreeFami | TF329426 |
Family and domain databases
Gene3Di | 3.30.565.10, 1 hit |
InterProi | View protein in InterPro IPR036890, HATPase_C_sf IPR010935, SMC_hinge IPR036277, SMC_hinge_sf IPR038892, SMCHD1 |
PANTHERi | PTHR22640, PTHR22640, 1 hit |
Pfami | View protein in Pfam PF06470, SMC_hinge, 1 hit |
SMARTi | View protein in SMART SM00968, SMC_hinge, 1 hit |
SUPFAMi | SSF55874, SSF55874, 1 hit SSF75553, SSF75553, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
Q6P5D8-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAAEGASDPA GLSEGSGRDG AVDGCRTVYL FDRRGKDSEL GDRALQVSEH
60 70 80 90 100
ADYAGFRASV CQTIGISSEE KFVITTTSRK EITCNNFDHT VKDGVTLYLL
110 120 130 140 150
QSVDQSLLTA TKERIDFLPH YDTLVKSGMY EYYASEGQNP LPFALAELID
160 170 180 190 200
NSLSATSRNN GVRRIQIKLL FDETQGKPAV AVVDNGRGMT SKQLNNWAVY
210 220 230 240 250
RLSKFTRQGD FESDHSGYVR PLPVPRSLNS DISYFGVGGK QAVFFVGQSA
260 270 280 290 300
RMISKPIDSK DVHELVLSKE DFEKKEKNKE AIYSGYIRNR KPADSAHITN
310 320 330 340 350
DDERFLHNLI EEEKEKDSFT AVVITGVQPE HIQYLKNYLH LWTRQLTHIY
360 370 380 390 400
HYYIHGPKGN EISTAKAIGP FNNIDIEISL FEKGKTPKII NLREIQDDMQ
410 420 430 440 450
TLYINTASDS FEFKAHVEGD GVVEGVIRYH PFLYDRETFP DDPCFPSKLK
460 470 480 490 500
DEDDDDDCFI SEKAARGKRP IFECFWNGRL IPYTSVGDFD WCAPPKKRGL
510 520 530 540 550
VPIECFNRIS GALFTNDKFQ VSTNKLTFMD LELKLKDKNT LFTRILNGQE
560 570 580 590 600
QRMKIDREFA LWLKDCHEKH DKQIKFTLFK GIITRPDLPT KKQGPWATFS
610 620 630 640 650
AIEWDGKIYK AGQLVKTIKT LPLCYGSIVR FFLHGDHDGE VYATGGEVQI
660 670 680 690 700
AMEPQALYDE IKTVPIAKLD RTVAEKTIRK YVEDEMARLP DRLSVTWPEG
710 720 730 740 750
DELLPNEVRP AGTPIGALRI EILNKKGEAM QKLPGTSHGG SKKLLVELKV
760 770 780 790 800
ILHTSSGNKE IISHISQHGG KWPYWFKKME NIQKLGNYTL KLQVVLNESN
810 820 830 840 850
ADTYAGRSLP SKVIKFSVKE GKPEKFSFGL LDSPFRVGVP FNIPLELQDE
860 870 880 890 900
FGHTTQLLSD IEPVLEASGL SLHYEGITKG PNCVIQGVVA KGPVNSCQGK
910 920 930 940 950
NFNLKVILPG LKEDSQILKI RLLPGPPHQL KVKPDSEVLV IENGTAFPFQ
960 970 980 990 1000
VEVVDESDNI TAQPKLIVHC KFLGAPNLPV YTVDCSSSGT SILTGSPIQV
1010 1020 1030 1040 1050
QNIKKDQKTL TARIEIPSCK DVSPVEKTIK LLPSSHAACL QIFSVEEQKA
1060 1070 1080 1090 1100
IQIKHQDEVT WVAGDVIRNL IFQMYDEGER EINITPSLAE KIKVNWTPEV
1110 1120 1130 1140 1150
NKEHLVQGLL PDVQVPTSVK DVRYCHVSFQ DDHVCLESAF TVRPLPDDPK
1160 1170 1180 1190 1200
HLKCELKGGK TVQMGQELQG EIVVIIADQY GNQISSFSPD SLSTLSITGD
1210 1220 1230 1240 1250
GLDSSNLKIT LEANSQSVSV QGIRFTPGPP GPKDLCFTWR EFSDFLRVQL
1260 1270 1280 1290 1300
VSGPPTKLLL MDWPELKESI PVINGRQLEN PLIVQLCDQW DNPALVPNVK
1310 1320 1330 1340 1350
ICLIKASSLR LLPSNQQHKT DDKGRANLGV FTVCAPRGEH TVQVKGVYNK
1360 1370 1380 1390 1400
STIEGPTIKL TILPDPEKPI RLNVKYDQDA SFIAGDIFTD FMVSVISESG
1410 1420 1430 1440 1450
SVIKNINPTR ISMKMWKLSS GMSRPPANAE TFSCNKIKGN DKEDGCFYFR
1460 1470 1480 1490 1500
EKTIPNKVGA YCIQFDFMID KTNILSSQQV IVDVLPNQPM KLVPDSQPAT
1510 1520 1530 1540 1550
PAVSNVRSIA SRTLVKDLRL SITDNYGNHT GMDLVGTVVA TIKGFNEEDT
1560 1570 1580 1590 1600
DTPLFIGKVR TLEFPFVKGS AEITTLVLAE NSPGRDSTEY FIIFEPRLST
1610 1620 1630 1640 1650
VSGTLESYSL PFMFYNDVKK QQQMAALTKE KDELSKSITM YRSLFDANKQ
1660 1670 1680 1690 1700
LVDEMKCQAE EAKLKETQLR NELKAYNIDI PATQQTTHIE ALLEKKITEQ
1710 1720 1730 1740 1750
NELKKRPRRL CTLPNYTKRS GDILGKIAHL AQIEDDRAAM VISWHLASDM
1760 1770 1780 1790 1800
DCVVTLTTDA ARAIYDETQG RQQVLPLDSI YRKTLPDWKR PLPHFRNGKL
1810 1820 1830 1840 1850
HFKPFGNPVF ARDLLTFPDN IEHCETVFGM LLGDTIILDN LDAANHYRKE
1860 1870 1880 1890 1900
VVKITHCPTL LTRDGDRIRS NGKFGGLQNK APPMDKLRGM VFGAPVPKQC
1910 1920 1930 1940 1950
VVLGKQIDLI QQYRTALYRL SSVNEDLDNQ LQYLHTPDMK KKKQELDEQE
1960 1970 1980 1990 2000
KSLKRIEQKL GMTPVRRCNE SLCHSPKIEV TECPIPTKRM RRESTRQNRR
PKGDVPN
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A3B2W494 | A0A3B2W494_MOUSE | Structural maintenance of chromosom... | Smchd1 | 119 | Annotation score: | ||
A0A3B2WD81 | A0A3B2WD81_MOUSE | Structural maintenance of chromosom... | Smchd1 | 87 | Annotation score: |
Sequence cautioni
The sequence AAH44905 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence BAB30222 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 1120 | K → E in BAB30222 (PubMed:19468303).Curated | 1 | |
Sequence conflicti | 1611 | P → S in BAC97991 (PubMed:14621295).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC107664 Genomic DNA No translation available. AC126942 Genomic DNA No translation available. AK016419 mRNA Translation: BAB30222.1 Frameshift. AK078494 mRNA Translation: BAC37307.1 BC044905 mRNA Translation: AAH44905.1 Different initiation. BC058205 mRNA Translation: AAH58205.1 BC058618 mRNA Translation: AAH58618.1 BC062946 mRNA Translation: AAH62946.1 AK129181 mRNA Translation: BAC97991.1 |
CCDSi | CCDS28958.2 |
RefSeqi | NP_083163.3, NM_028887.3 |
Genome annotation databases
Ensembli | ENSMUST00000127430; ENSMUSP00000121835; ENSMUSG00000024054 |
GeneIDi | 74355 |
KEGGi | mmu:74355 |
UCSCi | uc008dmh.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC107664 Genomic DNA No translation available. AC126942 Genomic DNA No translation available. AK016419 mRNA Translation: BAB30222.1 Frameshift. AK078494 mRNA Translation: BAC37307.1 BC044905 mRNA Translation: AAH44905.1 Different initiation. BC058205 mRNA Translation: AAH58205.1 BC058618 mRNA Translation: AAH58618.1 BC062946 mRNA Translation: AAH62946.1 AK129181 mRNA Translation: BAC97991.1 |
CCDSi | CCDS28958.2 |
RefSeqi | NP_083163.3, NM_028887.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6N64 | X-ray | 3.30 | A/B/C/D/E/F | 1683-1899 | [»] | |
SMRi | Q6P5D8 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 216686, 24 interactors |
IntActi | Q6P5D8, 21 interactors |
MINTi | Q6P5D8 |
STRINGi | 10090.ENSMUSP00000121835 |
PTM databases
iPTMneti | Q6P5D8 |
PhosphoSitePlusi | Q6P5D8 |
Proteomic databases
EPDi | Q6P5D8 |
jPOSTi | Q6P5D8 |
MaxQBi | Q6P5D8 |
PaxDbi | Q6P5D8 |
PeptideAtlasi | Q6P5D8 |
PRIDEi | Q6P5D8 |
ProteomicsDBi | 261270 |
Protocols and materials databases
Antibodypediai | 49899, 74 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000127430; ENSMUSP00000121835; ENSMUSG00000024054 |
GeneIDi | 74355 |
KEGGi | mmu:74355 |
UCSCi | uc008dmh.2, mouse |
Organism-specific databases
CTDi | 23347 |
MGIi | MGI:1921605, Smchd1 |
Rougei | Search... |
Phylogenomic databases
eggNOGi | ENOG502QREW, Eukaryota |
GeneTreei | ENSGT00390000006950 |
HOGENOMi | CLU_002288_1_0_1 |
InParanoidi | Q6P5D8 |
OMAi | WPELKEC |
OrthoDBi | 34310at2759 |
PhylomeDBi | Q6P5D8 |
TreeFami | TF329426 |
Miscellaneous databases
BioGRID-ORCSi | 74355, 0 hits in 47 CRISPR screens |
ChiTaRSi | Smchd1, mouse |
PROi | PR:Q6P5D8 |
RNActi | Q6P5D8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000024054, Expressed in pes and 264 other tissues |
ExpressionAtlasi | Q6P5D8, baseline and differential |
Genevisiblei | Q6P5D8, MM |
Family and domain databases
Gene3Di | 3.30.565.10, 1 hit |
InterProi | View protein in InterPro IPR036890, HATPase_C_sf IPR010935, SMC_hinge IPR036277, SMC_hinge_sf IPR038892, SMCHD1 |
PANTHERi | PTHR22640, PTHR22640, 1 hit |
Pfami | View protein in Pfam PF06470, SMC_hinge, 1 hit |
SMARTi | View protein in SMART SM00968, SMC_hinge, 1 hit |
SUPFAMi | SSF55874, SSF55874, 1 hit SSF75553, SSF75553, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SMHD1_MOUSE | |
Accessioni | Q6P5D8Primary (citable) accession number: Q6P5D8 Secondary accession number(s): Q6PDM8 Q9D4M7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 29, 2008 |
Last sequence update: | April 29, 2008 | |
Last modified: | April 7, 2021 | |
This is version 124 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families