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Protein

Centromere protein S

Gene

CENPS

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

Functioni

DNA-binding component of the Fanconi anemia (FA) core complex. Required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage (PubMed:20347428, PubMed:20347429). In complex with CENPX (MHF heterodimer), crucial cofactor for FANCM in both binding and ATP-dependent remodeling of DNA. Stabilizes FANCM (PubMed:20347428, PubMed:20347429). In complex with CENPX and FANCM (but not other FANC proteins), rapidly recruited to blocked forks and promotes gene conversion at blocked replication forks (PubMed:20347428). In complex with CENPT, CENPW and CENPX (CENP-T-W-S-X heterotetramer), involved in the formation of a functional kinetochore outer plate, which is essential for kinetochore-microtubule attachment and faithful mitotic progression (PubMed:19620631). As a component of MHF and CENP-T-W-S-X complexes, binds DNA and bends it to form a nucleosome-like structure (PubMed:20347428, PubMed:22304917). DNA-binding function is fulfilled in the presence of CENPX, with the following preference for DNA substates: Holliday junction > double-stranded > splay arm > single-stranded. Does not bind DNA on its own (PubMed:20347428, PubMed:20347429).4 Publications

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • DNA binding Source: UniProtKB

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: UniProtKB
  • CENP-A containing nucleosome assembly Source: Reactome
  • DNA repair Source: UniProtKB
  • interstrand cross-link repair Source: GO_Central
  • kinetochore assembly Source: InterPro
  • mitotic nuclear division Source: UniProtKB-KW
  • mitotic recombination Source: GO_Central
  • positive regulation of protein ubiquitination Source: UniProtKB
  • replication fork processing Source: UniProtKB
  • resolution of meiotic recombination intermediates Source: UniProtKB
  • sister chromatid cohesion Source: Reactome

Keywordsi

Molecular functionDNA-binding
Biological processCell cycle, Cell division, DNA damage, DNA repair, Mitosis

Enzyme and pathway databases

ReactomeiR-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2500257. Resolution of Sister Chromatid Cohesion.
R-HSA-5663220. RHO GTPases Activate Formins.
R-HSA-606279. Deposition of new CENPA-containing nucleosomes at the centromere.
R-HSA-6783310. Fanconi Anemia Pathway.
R-HSA-68877. Mitotic Prometaphase.

Names & Taxonomyi

Protein namesi
Recommended name:
Centromere protein S
Short name:
CENP-S
Alternative name(s):
Apoptosis-inducing TAF9-like domain-containing protein 1
FANCM-associated histone fold protein 11 Publication
FANCM-interacting histone fold protein 11 Publication
Fanconi anemia-associated polypeptide of 16 kDa
Gene namesi
Name:CENPS
Synonyms:APITD1, FAAP16, MHF12 Publications
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:23163. CENPS.

Subcellular locationi

GO - Cellular componenti

  • condensed chromosome kinetochore Source: UniProtKB-SubCell
  • cytosol Source: Reactome
  • FANCM-MHF complex Source: UniProtKB
  • Fanconi anaemia nuclear complex Source: UniProtKB
  • nucleoplasm Source: Reactome

Keywords - Cellular componenti

Centromere, Chromosome, Kinetochore, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi73 – 74KR → AA: No effect on CENPX- and FANCM-binding; loss of double-stranded DNA-binding of the MHF heterodimer and of FANCM recruitement to fork DNA; partial decrease in FA core complex activity, as shown by lower levels of FANCD2 monoubiquitination and higher frequency of sister chromatin exchanges. Complete loss of CENPX- and FANCM-binding; when associated with 87-A-A-88. 1 Publication2
Mutagenesisi87 – 88RR → AA: Partial loss of CENPX- and FANCM-binding; partial decrease in FA core complex activity, as shown by lower levels of FANCD2 monoubiquitination and higher frequency of sister chromatin exchanges. Complete loss of CENPX- and FANCM-binding; when associated with 73-A-A-74. 1 Publication2

Keywords - Diseasei

Fanconi anemia

Organism-specific databases

DisGeNETi378708.
OpenTargetsiENSG00000175279.
PharmGKBiPA134861614.

Polymorphism and mutation databases

BioMutaiAPITD1.
DMDMi74759833.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002494771 – 138Centromere protein SAdd BLAST138

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ8N2Z9.
MaxQBiQ8N2Z9.
PaxDbiQ8N2Z9.
PeptideAtlasiQ8N2Z9.
PRIDEiQ8N2Z9.

PTM databases

iPTMnetiQ8N2Z9.
PhosphoSitePlusiQ8N2Z9.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Developmental stagei

Expression varies across the cell cycle, with highest levels in G2 phase (at protein level). No statistically significant changes at the transcript level.1 Publication

Gene expression databases

BgeeiENSG00000175279.
ExpressionAtlasiQ8N2Z9. baseline and differential.
GenevisibleiQ8N2Z9. HS.

Interactioni

Subunit structurei

Heterodimer with CENPX, sometimes called MHF; this interaction stabilizes both partners (PubMed:19620631, PubMed:20347428, PubMed:20347429, PubMed:24522885). MHF heterodimers can assemble to form tetrameric structures (PubMed:22304917). MHF also coassemble with CENPT-CENPW heterodimers at centromeres to form the tetrameric CENP-T-W-S-X complex (PubMed:22304917, PubMed:24522885). Forms a discrete complex with FANCM and CENPX, called FANCM-MHF; this interaction, probably mediated by direct binding between CENPS and FANCM, leads to synergistic activation of double-stranded DNA binding and strongly stimulates FANCM-mediated DNA remodeling (PubMed:20347428, PubMed:20347429). Recruited by FANCM to the Fanconi anemia (FA) core complex, which consists of CENPS, CENPX, FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, FAAP24 and FAAP100. The FA core complex associates with Bloom syndrome (BLM) complex, which consists of at least BLM, DNA topoisomerase 3-alpha (TOP3A), RMI1/BLAP75, RPA1/RPA70 and RPA2/RPA32. The super complex between FA and BLM is called BRAFT (PubMed:20347428, PubMed:20347429). Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex is probably recruited on centromeres by the CENPA-NAC complex, composed of at least CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU (PubMed:16622419).6 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi132044. 21 interactors.
1529300. 1 interactor.
IntActiQ8N2Z9. 7 interactors.
STRINGi9606.ENSP00000308583.

Structurei

Secondary structure

1138
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi8 – 12Combined sources5
Helixi15 – 38Combined sources24
Helixi44 – 71Combined sources28
Beta strandi75 – 77Combined sources3
Helixi79 – 85Combined sources7
Turni86 – 88Combined sources3
Helixi90 – 103Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4DRAX-ray2.41A/B/C/D1-107[»]
4DRBX-ray2.63A/B/D/E/G/H1-114[»]
4E44X-ray2.10A/C1-110[»]
4E45X-ray2.00A/C/F/H/K/M1-110[»]
4NDYX-ray7.00A/C/G/I/J/K/Q/R/S/T14-105[»]
4NE1X-ray6.50A/C/G/I/J/K/Q/R/S/T/Y/a/c/e/f/g/k/l/m/n14-118[»]
4NE3X-ray1.80A14-105[»]
4NE5X-ray2.50A/C/E/G14-105[»]
4NE6X-ray2.10A/C14-105[»]
ProteinModelPortaliQ8N2Z9.
SMRiQ8N2Z9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TAF9 family. CENPS subfamily.Curated

Phylogenomic databases

eggNOGiENOG410J11U. Eukaryota.
ENOG410XX38. LUCA.
GeneTreeiENSGT00510000048007.
HOGENOMiHOG000216554.
HOVERGENiHBG080286.
InParanoidiQ8N2Z9.
KOiK11511.
OMAiEITFRQC.
OrthoDBiEOG091G19D0.
PhylomeDBiQ8N2Z9.
TreeFamiTF300253.

Family and domain databases

Gene3Di1.10.20.10. 1 hit.
InterProiView protein in InterPro
IPR029003. CENP-S/Mhf1.
IPR033554. CENPS.
IPR009072. Histone-fold.
PANTHERiPTHR22980:SF6. PTHR22980:SF6. 1 hit.
PfamiView protein in Pfam
PF15630. CENP-S. 1 hit.
SUPFAMiSSF47113. SSF47113. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q8N2Z9-1) [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
MEEEAETEEQ QRFSYQQRLK AAVHYTVGCL CEEVALDKEM QFSKQTIAAI
60 70 80 90 100
SELTFRQCEN FAKDLEMFAR HAKRTTINTE DVKLLARRSN SLLKYITDKS
110 120 130
EEIAQINLER KAQKKKKSED GSKNSRQPAE AGVVESEN
Length:138
Mass (Da):15,893
Last modified:October 1, 2002 - v1
Checksum:iCBCD22CDDE213D87
GO
Isoform 2 (identifier: Q8N2Z9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     91-138: SLLKYITDKS...AEAGVVESEN → SLHMQEAAGI...FFWKTFSSCK

Note: No experimental confirmation available.
Show »
Length:164
Mass (Da):19,048
Checksum:i389682C41252426A
GO
Isoform 3 (identifier: Q8N2Z9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     70-77: RHAKRTTI → SICRKRQE
     78-138: Missing.

Note: No experimental confirmation available.
Show »
Length:77
Mass (Da):9,074
Checksum:i447AD9A2366361C1
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02043270 – 77RHAKRTTI → SICRKRQE in isoform 3. 1 Publication8
Alternative sequenceiVSP_02043378 – 138Missing in isoform 3. 1 PublicationAdd BLAST61
Alternative sequenceiVSP_02043491 – 138SLLKY…VESEN → SLHMQEAAGIRKSSLLTFLA WWFEWTSQASAGPLIGEEAR EVARRQEGAPPQQSARRDRM PCRNFFWKTFSSCK in isoform 2. 1 PublicationAdd BLAST48

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF516753 mRNA. Translation: AAM61954.1.
AF521016 mRNA. Translation: AAM70482.1.
AL139424, AL354956 Genomic DNA. Translation: CAI95756.1.
AL354956, AL139424 Genomic DNA. Translation: CAI19200.1.
AL139424, AL354956 Genomic DNA. Translation: CAI95757.1.
AL354956, AL139424 Genomic DNA. Translation: CAI19201.1.
AL139424, AL354956 Genomic DNA. Translation: CAI95755.1.
AL354956, AL139424 Genomic DNA. Translation: CAI19199.1.
BC029430 mRNA. Translation: AAH29430.1.
CCDSiCCDS115.1. [Q8N2Z9-1]
RefSeqiNP_001257446.1. NM_001270517.1. [Q8N2Z9-1]
NP_940946.1. NM_198544.3. [Q8N2Z9-2]
NP_950171.2. NM_199006.2. [Q8N2Z9-3]
NP_954988.1. NM_199294.2. [Q8N2Z9-1]
UniGeneiHs.412311.

Genome annotation databases

EnsembliENST00000309048; ENSP00000308583; ENSG00000175279. [Q8N2Z9-1]
GeneIDi100526739.
378708.
KEGGihsa:100526739.
hsa:378708.
UCSCiuc001are.4. human. [Q8N2Z9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF516753 mRNA. Translation: AAM61954.1.
AF521016 mRNA. Translation: AAM70482.1.
AL139424, AL354956 Genomic DNA. Translation: CAI95756.1.
AL354956, AL139424 Genomic DNA. Translation: CAI19200.1.
AL139424, AL354956 Genomic DNA. Translation: CAI95757.1.
AL354956, AL139424 Genomic DNA. Translation: CAI19201.1.
AL139424, AL354956 Genomic DNA. Translation: CAI95755.1.
AL354956, AL139424 Genomic DNA. Translation: CAI19199.1.
BC029430 mRNA. Translation: AAH29430.1.
CCDSiCCDS115.1. [Q8N2Z9-1]
RefSeqiNP_001257446.1. NM_001270517.1. [Q8N2Z9-1]
NP_940946.1. NM_198544.3. [Q8N2Z9-2]
NP_950171.2. NM_199006.2. [Q8N2Z9-3]
NP_954988.1. NM_199294.2. [Q8N2Z9-1]
UniGeneiHs.412311.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4DRAX-ray2.41A/B/C/D1-107[»]
4DRBX-ray2.63A/B/D/E/G/H1-114[»]
4E44X-ray2.10A/C1-110[»]
4E45X-ray2.00A/C/F/H/K/M1-110[»]
4NDYX-ray7.00A/C/G/I/J/K/Q/R/S/T14-105[»]
4NE1X-ray6.50A/C/G/I/J/K/Q/R/S/T/Y/a/c/e/f/g/k/l/m/n14-118[»]
4NE3X-ray1.80A14-105[»]
4NE5X-ray2.50A/C/E/G14-105[»]
4NE6X-ray2.10A/C14-105[»]
ProteinModelPortaliQ8N2Z9.
SMRiQ8N2Z9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi132044. 21 interactors.
1529300. 1 interactor.
IntActiQ8N2Z9. 7 interactors.
STRINGi9606.ENSP00000308583.

PTM databases

iPTMnetiQ8N2Z9.
PhosphoSitePlusiQ8N2Z9.

Polymorphism and mutation databases

BioMutaiAPITD1.
DMDMi74759833.

Proteomic databases

EPDiQ8N2Z9.
MaxQBiQ8N2Z9.
PaxDbiQ8N2Z9.
PeptideAtlasiQ8N2Z9.
PRIDEiQ8N2Z9.

Protocols and materials databases

DNASUi378708.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000309048; ENSP00000308583; ENSG00000175279. [Q8N2Z9-1]
GeneIDi100526739.
378708.
KEGGihsa:100526739.
hsa:378708.
UCSCiuc001are.4. human. [Q8N2Z9-1]

Organism-specific databases

CTDi100526739.
378708.
DisGeNETi378708.
GeneCardsiMHF1.
HGNCiHGNC:23163. CENPS.
MIMi609130. gene.
neXtProtiNX_Q8N2Z9.
OpenTargetsiENSG00000175279.
PharmGKBiPA134861614.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J11U. Eukaryota.
ENOG410XX38. LUCA.
GeneTreeiENSGT00510000048007.
HOGENOMiHOG000216554.
HOVERGENiHBG080286.
InParanoidiQ8N2Z9.
KOiK11511.
OMAiEITFRQC.
OrthoDBiEOG091G19D0.
PhylomeDBiQ8N2Z9.
TreeFamiTF300253.

Enzyme and pathway databases

ReactomeiR-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2500257. Resolution of Sister Chromatid Cohesion.
R-HSA-5663220. RHO GTPases Activate Formins.
R-HSA-606279. Deposition of new CENPA-containing nucleosomes at the centromere.
R-HSA-6783310. Fanconi Anemia Pathway.
R-HSA-68877. Mitotic Prometaphase.

Miscellaneous databases

PROiQ8N2Z9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000175279.
ExpressionAtlasiQ8N2Z9. baseline and differential.
GenevisibleiQ8N2Z9. HS.

Family and domain databases

Gene3Di1.10.20.10. 1 hit.
InterProiView protein in InterPro
IPR029003. CENP-S/Mhf1.
IPR033554. CENPS.
IPR009072. Histone-fold.
PANTHERiPTHR22980:SF6. PTHR22980:SF6. 1 hit.
PfamiView protein in Pfam
PF15630. CENP-S. 1 hit.
SUPFAMiSSF47113. SSF47113. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCENPS_HUMAN
AccessioniPrimary (citable) accession number: Q8N2Z9
Secondary accession number(s): Q8NFE5, Q8NFG5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: October 1, 2002
Last modified: March 15, 2017
This is version 144 of the entry and version 1 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 chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.