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Protein

Double-strand-break repair protein rad21 homolog

Gene

RAD21

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • chromosome segregation Source: UniProtKB-KW
  • DNA recombination Source: ProtInc
  • double-strand break repair Source: ProtInc
  • negative regulation of G2/M transition of mitotic cell cycle Source: Ensembl
  • negative regulation of mitotic metaphase/anaphase transition Source: Ensembl
  • positive regulation of sister chromatid cohesion Source: UniProtKB
  • protein localization to chromatin Source: UniProtKB
  • reciprocal meiotic recombination Source: ProtInc
  • regulation of transcription by RNA polymerase II Source: BHF-UCL

Keywordsi

Biological processApoptosis, Cell cycle, Cell division, Chromosome partition, DNA damage, DNA repair, Mitosis

Enzyme and pathway databases

BioCyciMetaCyc: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
R-HSA-9018519 Estrogen-dependent gene expression
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, SCC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000164754.12
HGNCiHGNC:9811 RAD21
MIMi606462 gene
neXtProtiNX_O60216

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

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 dbSNP:rs387907212EnsemblClinVar.1
Natural variantiVAR_068692585C → R in CDLS4. 1 PublicationCorresponds to variant dbSNP:rs387907213EnsemblClinVar.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
GeneReviewsiRAD21
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
Cross-linki48Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei153PhosphoserineCombined sources1
Modified residuei175PhosphoserineCombined sources1
Cross-linki216Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei249PhosphoserineCombined sources1
Modified residuei394PhosphothreonineCombined sources1
Cross-linki418Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
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

Isopeptide bond, Phosphoprotein, Ubl conjugation

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). 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). Found in a cohesin complex with SMC1A, SMC3 and STAG1 (PubMed:22628566).By similarity5 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi111822, 278 interactors
CORUMiO60216
DIPiDIP-29201N
ELMiO60216
IntActiO60216, 36 interactors
MINTiO60216
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
OMAiKRLMHWK
OrthoDBiEOG091G03QW
PhylomeDBiO60216
TreeFamiTF101215

Family and domain databases

InterProiView protein in InterPro
IPR006909 Rad21/Rec8_C_eu
IPR006910 Rad21_Rec8_N
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF04824 Rad21_Rec8, 1 hit
PF04825 Rad21_Rec8_N, 1 hit
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 dbSNP:rs387907212EnsemblClinVar.1
Natural variantiVAR_014281481G → R1 PublicationCorresponds to variant dbSNP:rs755168088Ensembl.1
Natural variantiVAR_068692585C → R in CDLS4. 1 PublicationCorresponds to variant dbSNP:rs387907213EnsemblClinVar.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

Similar proteinsi

Entry informationi

Entry nameiRAD21_HUMAN
AccessioniPrimary (citable) accession number: O60216
Secondary accession number(s): A8K0E0, Q15001, Q99568
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: November 15, 2002
Last modified: May 23, 2018
This is version 171 of the entry and version 2 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, Direct protein sequencing, Reference proteome

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