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

Double-strand-break repair protein rad21 homolog

Gene

RAD21

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

Functioni

Cleavable component of the cohesin complex, involved in chromosome cohesion during cell cycle, in DNA repair, and in apoptosis. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At metaphase-anaphase transition, this protein is cleaved by separase/ESPL1 and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. Also plays a role in apoptosis, via its cleavage by caspase-3/CASP3 or caspase-7/CASP7 during early steps of apoptosis: the C-terminal 64 kDa cleavage product may act as a nuclear signal to initiate cytoplasmic events involved in the apoptotic pathway.2 Publications

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell division Source: UniProtKB-KW
  • DNA recombination Source: ProtInc
  • double-strand break repair Source: ProtInc
  • meiotic sister chromatid cohesion, centromeric Source: GO_Central
  • mitotic sister chromatid cohesion Source: GO_Central
  • positive regulation of sister chromatid cohesion Source: UniProtKB
  • protein localization to chromatin Source: UniProtKB
  • protein sumoylation Source: Reactome
  • reciprocal meiotic recombination Source: ProtInc
  • regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • sister chromatid cohesion Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Apoptosis, Cell cycle, Cell division, Chromosome partition, DNA damage, DNA repair, Mitosis

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000164754-MONOMER.
ZFISH:ENSG00000164754-MONOMER.
ReactomeiR-HSA-1221632. Meiotic synapsis.
R-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2468052. Establishment of Sister Chromatid Cohesion.
R-HSA-2470946. Cohesin Loading onto Chromatin.
R-HSA-2500257. Resolution of Sister Chromatid Cohesion.
R-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
SIGNORiO60216.

Names & Taxonomyi

Protein namesi
Recommended name:
Double-strand-break repair protein rad21 homolog
Short name:
hHR21
Alternative name(s):
Nuclear matrix protein 1
Short name:
NXP-1
SCC1 homolog
Gene namesi
Name:RAD21
Synonyms:HR21, KIAA0078, NXP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:9811. RAD21.

Subcellular locationi

  • Nucleus 1 Publication
  • Chromosome 1 Publication
  • Chromosomecentromere 1 Publication

  • Note: Associates with chromatin. Before prophase it is scattered along chromosome arms. During prophase, most of cohesin complexes dissociate from chromatin probably because of phosphorylation by PLK, except at centromeres, where cohesin complexes remain. At anaphase, it is cleaved by separase/ESPL1, leading to the dissociation of the complex from chromosomes, allowing chromosome separation. Once cleaved by caspase-3, the C-terminal 64 kDa cleavage product translocates to the cytoplasm, where it may trigger apoptosis.1 Publication

GO - Cellular componenti

  • chromatin Source: Ensembl
  • chromosome Source: Reactome
  • chromosome, centromeric region Source: Reactome
  • cohesin complex Source: BHF-UCL
  • cytosol Source: Reactome
  • membrane Source: UniProtKB
  • nuclear meiotic cohesin complex Source: GO_Central
  • nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

Cornelia de Lange syndrome 4 (CDLS4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies.
See also OMIM:614701
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068691376P → R in CDLS4. 1 PublicationCorresponds to variant rs387907212dbSNPEnsembl.1
Natural variantiVAR_068692585C → R in CDLS4. 1 PublicationCorresponds to variant rs387907213dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi172R → A: Abolishes first cleavage by ESPL1. 1 Publication1
Mutagenesisi279D → A: Abolishes cleavage by caspase-3. 2 Publications1
Mutagenesisi450R → A: Abolishes second cleavage by ESPL1. 1 Publication1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi5885.
MalaCardsiRAD21.
MIMi614701. phenotype.
OpenTargetsiENSG00000164754.
Orphaneti199. Cornelia de Lange syndrome.
PharmGKBiPA34170.

Polymorphism and mutation databases

BioMutaiRAD21.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000978721 – 631Double-strand-break repair protein rad21 homologAdd BLAST631

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei46PhosphoserineCombined sources1
Modified residuei153PhosphoserineCombined sources1
Modified residuei175PhosphoserineCombined sources1
Modified residuei249PhosphoserineCombined sources1
Modified residuei394PhosphothreonineCombined sources1
Modified residuei454PhosphoserineCombined sources1
Modified residuei545PhosphoserineCombined sources1
Modified residuei623PhosphothreonineCombined sources1

Post-translational modificationi

Cleaved by separase/ESPL1 at the onset of anaphase. Cleaved by caspase-3 and caspase-7 at the beginning of apoptosis. The cleavage by ESPL1 and caspase-3 take place at different sites.3 Publications
Phosphorylated; becomes hyperphosphorylated in M phase of cell cycle. The large dissociation of cohesin from chromosome arms during prophase may be partly due to its phosphorylation by PLK.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei172 – 173Cleavage; by ESPL12
Sitei279 – 280Cleavage; by caspase-3 or caspase-72
Sitei450 – 451Cleavage; by ESPL12

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO60216.
MaxQBiO60216.
PaxDbiO60216.
PeptideAtlasiO60216.
PRIDEiO60216.

PTM databases

iPTMnetiO60216.
PhosphoSitePlusiO60216.
SwissPalmiO60216.

Miscellaneous databases

PMAP-CutDBO60216.

Expressioni

Gene expression databases

BgeeiENSG00000164754.
CleanExiHS_RAD21.
ExpressionAtlasiO60216. baseline and differential.
GenevisibleiO60216. HS.

Organism-specific databases

HPAiCAB022065.
HPA020044.

Interactioni

Subunit structurei

Cohesin complexes are composed of the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer attached via their hinge domain, RAD21 which link them, and one STAG protein (STAG1, STAG2 or STAG3), which interacts with RAD21 (PubMed:11590136, PubMed:19696148). Found in a complex with SMC1A, SMC3, CDCA5, PDS5A/SCC-112 and PDS5B/APRIN (PubMed:15837422). Interacts with PDS5B and WAPL; the interaction is direct (PubMed:19696148). Interacts with SMC1A and SMC3 (By similarity). Interacts with DDX11 (PubMed:17105772).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FHL3Q136433EBI-80739,EBI-741101
PDS5AQ29RF74EBI-80739,EBI-1175454
PDS5BQ9NTI54EBI-80739,EBI-1175604
SMC3Q9UQE712EBI-80739,EBI-80718
SSU72Q9NP779EBI-80739,EBI-2515416
WAPLQ7Z5K213EBI-80739,EBI-1022242

Protein-protein interaction databases

BioGridi111822. 267 interactors.
DIPiDIP-29201N.
IntActiO60216. 32 interactors.
MINTiMINT-2999858.
STRINGi9606.ENSP00000297338.

Structurei

Secondary structure

1631
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi334 – 342Combined sources9
Helixi345 – 347Combined sources3
Helixi358 – 366Combined sources9
Helixi369 – 372Combined sources4
Helixi383 – 390Combined sources8
Turni391 – 393Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4PJUX-ray3.05B281-420[»]
4PJWX-ray2.85B281-420[»]
4PK7X-ray2.95B281-420[»]
ProteinModelPortaliO60216.
SMRiO60216.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni287 – 403Interaction with WAPL and PDS5B1 PublicationAdd BLAST117
Regioni362 – 403Interaction with STAG11 PublicationAdd BLAST42

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi469 – 510Pro-richAdd BLAST42

Domaini

The C-terminal part associates with the head of SMC1A, while the N-terminal part binds to the head of SMC3.By similarity

Sequence similaritiesi

Belongs to the rad21 family.Curated

Phylogenomic databases

eggNOGiKOG1213. Eukaryota.
ENOG410XRB4. LUCA.
GeneTreeiENSGT00390000011606.
HOGENOMiHOG000233800.
HOVERGENiHBG059956.
InParanoidiO60216.
KOiK06670.
OMAiDEPIMEE.
OrthoDBiEOG091G03QW.
PhylomeDBiO60216.
TreeFamiTF101215.

Family and domain databases

Gene3Di1.10.10.580. 1 hit.
InterProiIPR023093. Rad21/Rec8_C.
IPR006909. Rad21/Rec8_C_eu.
IPR006910. Rad21_Rec8_N.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF04824. Rad21_Rec8. 1 hit.
PF04825. Rad21_Rec8_N. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.

Sequencei

Sequence statusi: Complete.

O60216-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFYAHFVLSK RGPLAKIWLA AHWDKKLTKA HVFECNLESS VESIISPKVK
60 70 80 90 100
MALRTSGHLL LGVVRIYHRK AKYLLADCNE AFIKIKMAFR PGVVDLPEEN
110 120 130 140 150
REAAYNAITL PEEFHDFDQP LPDLDDIDVA QQFSLNQSRV EEITMREEVG
160 170 180 190 200
NISILQENDF GDFGMDDREI MREGSAFEDD DMLVSTTTSN LLLESEQSTS
210 220 230 240 250
NLNEKINHLE YEDQYKDDNF GEGNDGGILD DKLISNNDGG IFDDPPALSE
260 270 280 290 300
AGVMLPEQPA HDDMDEDDNV SMGGPDSPDS VDPVEPMPTM TDQTTLVPNE
310 320 330 340 350
EEAFALEPID ITVKETKAKR KRKLIVDSVK ELDSKTIRAQ LSDYSDIVTT
360 370 380 390 400
LDLAPPTKKL MMWKETGGVE KLFSLPAQPL WNNRLLKLFT RCLTPLVPED
410 420 430 440 450
LRKRRKGGEA DNLDEFLKEF ENPEVPREDQ QQQHQQRDVI DEPIIEEPSR
460 470 480 490 500
LQESVMEASR TNIDESAMPP PPPQGVKRKA GQIDPEPVMP PQQVEQMEIP
510 520 530 540 550
PVELPPEEPP NICQLIPELE LLPEKEKEKE KEKEDDEEEE DEDASGGDQD
560 570 580 590 600
QEERRWNKRT QQMLHGLQRA LAKTGAESIS LLELCRNTNR KQAAAKFYSF
610 620 630
LVLKKQQAIE LTQEEPYSDI IATPGPRFHI I
Length:631
Mass (Da):71,690
Last modified:November 15, 2002 - v2
Checksum:i7D4A6EA6392BE73D
GO

Sequence cautioni

The sequence BAA07554 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti136N → I in CAA66940 (PubMed:8812457).Curated1

Polymorphismi

Some radiosensitive cancer patients seem to have Arg-481 instead of the conserved Gly-481. It may be that this mutation could contribute to radiosensitivity.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068691376P → R in CDLS4. 1 PublicationCorresponds to variant rs387907212dbSNPEnsembl.1
Natural variantiVAR_014281481G → R.1 PublicationCorresponds to variant rs755168088dbSNPEnsembl.1
Natural variantiVAR_068692585C → R in CDLS4. 1 PublicationCorresponds to variant rs387907213dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X98294 mRNA. Translation: CAA66940.1.
D38551 mRNA. Translation: BAA07554.2. Different initiation.
AY675320 Genomic DNA. Translation: AAT70725.1.
AK289505 mRNA. Translation: BAF82194.1.
CH471060 Genomic DNA. Translation: EAW91963.1.
BC050381 mRNA. Translation: AAH50381.1.
CCDSiCCDS6321.1.
RefSeqiNP_006256.1. NM_006265.2.
UniGeneiHs.81848.

Genome annotation databases

EnsembliENST00000297338; ENSP00000297338; ENSG00000164754.
GeneIDi5885.
KEGGihsa:5885.
UCSCiuc003yod.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X98294 mRNA. Translation: CAA66940.1.
D38551 mRNA. Translation: BAA07554.2. Different initiation.
AY675320 Genomic DNA. Translation: AAT70725.1.
AK289505 mRNA. Translation: BAF82194.1.
CH471060 Genomic DNA. Translation: EAW91963.1.
BC050381 mRNA. Translation: AAH50381.1.
CCDSiCCDS6321.1.
RefSeqiNP_006256.1. NM_006265.2.
UniGeneiHs.81848.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4PJUX-ray3.05B281-420[»]
4PJWX-ray2.85B281-420[»]
4PK7X-ray2.95B281-420[»]
ProteinModelPortaliO60216.
SMRiO60216.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111822. 267 interactors.
DIPiDIP-29201N.
IntActiO60216. 32 interactors.
MINTiMINT-2999858.
STRINGi9606.ENSP00000297338.

PTM databases

iPTMnetiO60216.
PhosphoSitePlusiO60216.
SwissPalmiO60216.

Polymorphism and mutation databases

BioMutaiRAD21.

Proteomic databases

EPDiO60216.
MaxQBiO60216.
PaxDbiO60216.
PeptideAtlasiO60216.
PRIDEiO60216.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000297338; ENSP00000297338; ENSG00000164754.
GeneIDi5885.
KEGGihsa:5885.
UCSCiuc003yod.4. human.

Organism-specific databases

CTDi5885.
DisGeNETi5885.
GeneCardsiRAD21.
GeneReviewsiRAD21.
HGNCiHGNC:9811. RAD21.
HPAiCAB022065.
HPA020044.
MalaCardsiRAD21.
MIMi606462. gene.
614701. phenotype.
neXtProtiNX_O60216.
OpenTargetsiENSG00000164754.
Orphaneti199. Cornelia de Lange syndrome.
PharmGKBiPA34170.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1213. Eukaryota.
ENOG410XRB4. LUCA.
GeneTreeiENSGT00390000011606.
HOGENOMiHOG000233800.
HOVERGENiHBG059956.
InParanoidiO60216.
KOiK06670.
OMAiDEPIMEE.
OrthoDBiEOG091G03QW.
PhylomeDBiO60216.
TreeFamiTF101215.

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000164754-MONOMER.
ZFISH:ENSG00000164754-MONOMER.
ReactomeiR-HSA-1221632. Meiotic synapsis.
R-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2468052. Establishment of Sister Chromatid Cohesion.
R-HSA-2470946. Cohesin Loading onto Chromatin.
R-HSA-2500257. Resolution of Sister Chromatid Cohesion.
R-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
SIGNORiO60216.

Miscellaneous databases

ChiTaRSiRAD21. human.
GeneWikiiRAD21.
GenomeRNAii5885.
PMAP-CutDBO60216.
PROiO60216.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164754.
CleanExiHS_RAD21.
ExpressionAtlasiO60216. baseline and differential.
GenevisibleiO60216. HS.

Family and domain databases

Gene3Di1.10.10.580. 1 hit.
InterProiIPR023093. Rad21/Rec8_C.
IPR006909. Rad21/Rec8_C_eu.
IPR006910. Rad21_Rec8_N.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF04824. Rad21_Rec8. 1 hit.
PF04825. Rad21_Rec8_N. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiRAD21_HUMAN
AccessioniPrimary (citable) accession number: O60216
Secondary accession number(s): A8K0E0, Q15001, Q99568
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: November 15, 2002
Last modified: November 30, 2016
This is version 158 of the entry and version 2 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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, 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. 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.