Human Gene RAD21 (ENST00000297338.7)
  Description: Homo sapiens RAD21 cohesin complex component (RAD21), mRNA. (from RefSeq NM_006265)
RefSeq Summary (NM_006265): The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad21, a gene involved in the repair of DNA double-strand breaks, as well as in chromatid cohesion during mitosis. This protein is a nuclear phospho-protein, which becomes hyperphosphorylated in cell cycle M phase. The highly regulated association of this protein with mitotic chromatin specifically at the centromere region suggests its role in sister chromatid cohesion in mitotic cells. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000297338.7
Gencode Gene: ENSG00000164754.15
Transcript (Including UTRs)
   Position: hg38 chr8:116,845,934-116,874,776 Size: 28,843 Total Exon Count: 14 Strand: -
Coding Region
   Position: hg38 chr8:116,847,500-116,866,729 Size: 19,230 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr8:116,845,934-116,874,776)mRNA (may differ from genome)Protein (631 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: RAD21_HUMAN
DESCRIPTION: RecName: Full=Double-strand-break repair protein rad21 homolog; Short=hHR21; AltName: Full=Nuclear matrix protein 1; Short=NXP-1; AltName: Full=SCC1 homolog;
FUNCTION: 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.
SUBUNIT: 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. Found in a complex with SMC1A, SMC3, CDCA5, PDS5A/APRIN and PDS5B/SCC-112. Interacts with PDS5B and WAPAL; the interaction is direct.
INTERACTION: Q29RF7:PDS5A; NbExp=3; IntAct=EBI-80739, EBI-1175454; Q9NTI5:PDS5B; NbExp=3; IntAct=EBI-80739, EBI-1175604; Q9UQE7:SMC3; NbExp=8; IntAct=EBI-80739, EBI-80718; Q7Z5K2:WAPAL; NbExp=11; IntAct=EBI-80739, EBI-1022242;
SUBCELLULAR LOCATION: Nucleus. Chromosome. Chromosome, centromere. 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.
DOMAIN: The C-terminal part associates with the head of SMC1A, while the N-terminal part binds to the head of SMC3 (By similarity).
PTM: 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.
PTM: 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.
POLYMORPHISM: 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.
DISEASE: Defects in RAD21 are the cause of Cornelia de Lange syndrome type 4 (CDLS4) [MIM:614701]. A 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.
SIMILARITY: Belongs to the rad21 family.
SEQUENCE CAUTION: Sequence=BAA07554.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/rad21/";

-  MalaCards Disease Associations
  MalaCards Gene Search: RAD21
Diseases sorted by gene-association score: cornelia de lange syndrome 4* (1230), rad21-related cornelia de lange syndrome* (500), cornelia de lange syndrome* (179), trichorhinophalangeal syndrome, type ii (7), roberts syndrome (7), kbg syndrome (6)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 57.61 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 1389.34 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -61.60198-0.311 Picture PostScript Text
3' UTR -355.301566-0.227 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR023093 - Rad21/Rec8_C
IPR006909 - Rad21/Rec8_C_eu
IPR006910 - Rad21_Rec8_N

Pfam Domains:
PF04824 - Conserved region of Rad21 / Rec8 like protein
PF04825 - N terminus of Rad21 / Rec8 like protein

ModBase Predicted Comparative 3D Structure on O60216
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologGenome BrowserNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsemblEnsembl  
Protein SequenceProtein Sequence Protein Sequence  
AlignmentAlignment Alignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003682 chromatin binding
GO:0005515 protein binding
GO:0044877 macromolecular complex binding

Biological Process:
GO:0006281 DNA repair
GO:0006302 double-strand break repair
GO:0006310 DNA recombination
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006366 transcription from RNA polymerase II promoter
GO:0006915 apoptotic process
GO:0006974 cellular response to DNA damage stimulus
GO:0007049 cell cycle
GO:0007059 chromosome segregation
GO:0007131 reciprocal meiotic recombination
GO:0010972 negative regulation of G2/M transition of mitotic cell cycle
GO:0045841 negative regulation of mitotic metaphase/anaphase transition
GO:0045876 positive regulation of sister chromatid cohesion
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0051301 cell division
GO:0071168 protein localization to chromatin

Cellular Component:
GO:0000228 nuclear chromosome
GO:0000775 chromosome, centromeric region
GO:0000785 chromatin
GO:0000794 condensed nuclear chromosome
GO:0000798 nuclear cohesin complex
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0005829 cytosol
GO:0008278 cohesin complex
GO:0016020 membrane
GO:0016363 nuclear matrix


-  Descriptions from all associated GenBank mRNAs
  LF210267 - JP 2014500723-A/17770: Polycomb-Associated Non-Coding RNAs.
MA445844 - JP 2018138019-A/17770: Polycomb-Associated Non-Coding RNAs.
BC001229 - Homo sapiens RAD21 homolog (S. pombe), mRNA (cDNA clone IMAGE:3455406).
BC050381 - Homo sapiens RAD21 homolog (S. pombe), mRNA (cDNA clone MGC:51902 IMAGE:6044010), complete cds.
AK097915 - Homo sapiens cDNA FLJ40596 fis, clone THYMU2010831, highly similar to Double-strand-break repair protein rad21 homolog.
D38551 - Homo sapiens KIAA0078 mRNA.
JD243445 - Sequence 224469 from Patent EP1572962.
LF336421 - JP 2014500723-A/143924: Polycomb-Associated Non-Coding RNAs.
MA571998 - JP 2018138019-A/143924: Polycomb-Associated Non-Coding RNAs.
LF336422 - JP 2014500723-A/143925: Polycomb-Associated Non-Coding RNAs.
MA571999 - JP 2018138019-A/143925: Polycomb-Associated Non-Coding RNAs.
JD433696 - Sequence 414720 from Patent EP1572962.
JD533915 - Sequence 514939 from Patent EP1572962.
LF336423 - JP 2014500723-A/143926: Polycomb-Associated Non-Coding RNAs.
MA572000 - JP 2018138019-A/143926: Polycomb-Associated Non-Coding RNAs.
LF336424 - JP 2014500723-A/143927: Polycomb-Associated Non-Coding RNAs.
MA572001 - JP 2018138019-A/143927: Polycomb-Associated Non-Coding RNAs.
JD499570 - Sequence 480594 from Patent EP1572962.
JD312491 - Sequence 293515 from Patent EP1572962.
JD267208 - Sequence 248232 from Patent EP1572962.
JD174464 - Sequence 155488 from Patent EP1572962.
LF336425 - JP 2014500723-A/143928: Polycomb-Associated Non-Coding RNAs.
MA572002 - JP 2018138019-A/143928: Polycomb-Associated Non-Coding RNAs.
AK289505 - Homo sapiens cDNA FLJ76327 complete cds, highly similar to Homo sapiens RAD21 homolog (S. pombe) (RAD21), mRNA.
LF336426 - JP 2014500723-A/143929: Polycomb-Associated Non-Coding RNAs.
MA572003 - JP 2018138019-A/143929: Polycomb-Associated Non-Coding RNAs.
JD091668 - Sequence 72692 from Patent EP1572962.
JD020992 - Sequence 2016 from Patent EP1572962.
AK125620 - Homo sapiens cDNA FLJ43632 fis, clone SPLEN2031674, highly similar to H.sapiens mRNA for protein involved in DNA double-strand break repair.
JD546332 - Sequence 527356 from Patent EP1572962.
JD027663 - Sequence 8687 from Patent EP1572962.
JD440020 - Sequence 421044 from Patent EP1572962.
JD342717 - Sequence 323741 from Patent EP1572962.
AK098521 - Homo sapiens cDNA FLJ25655 fis, clone TST00286, highly similar to H.sapiens mRNA for protein involved in DNA double-strand break repair.
LF336427 - JP 2014500723-A/143930: Polycomb-Associated Non-Coding RNAs.
MA572004 - JP 2018138019-A/143930: Polycomb-Associated Non-Coding RNAs.
KJ891973 - Synthetic construct Homo sapiens clone ccsbBroadEn_01367 RAD21 gene, encodes complete protein.
AB463209 - Synthetic construct DNA, clone: pF1KA0078, Homo sapiens RAD21 gene for RAD21 homolog, without stop codon, in Flexi system.
X98294 - Homo sapiens mRNA for protein involved in DNA double-strand break repair (HR21SPA gene).
LF336428 - JP 2014500723-A/143931: Polycomb-Associated Non-Coding RNAs.
MA572005 - JP 2018138019-A/143931: Polycomb-Associated Non-Coding RNAs.
LF336429 - JP 2014500723-A/143932: Polycomb-Associated Non-Coding RNAs.
MA572006 - JP 2018138019-A/143932: Polycomb-Associated Non-Coding RNAs.
LF336430 - JP 2014500723-A/143933: Polycomb-Associated Non-Coding RNAs.
MA572007 - JP 2018138019-A/143933: Polycomb-Associated Non-Coding RNAs.
LF336431 - JP 2014500723-A/143934: Polycomb-Associated Non-Coding RNAs.
MA572008 - JP 2018138019-A/143934: Polycomb-Associated Non-Coding RNAs.
LF336433 - JP 2014500723-A/143936: Polycomb-Associated Non-Coding RNAs.
MA572010 - JP 2018138019-A/143936: Polycomb-Associated Non-Coding RNAs.
LF336434 - JP 2014500723-A/143937: Polycomb-Associated Non-Coding RNAs.
MA572011 - JP 2018138019-A/143937: Polycomb-Associated Non-Coding RNAs.
LF336436 - JP 2014500723-A/143939: Polycomb-Associated Non-Coding RNAs.
MA572013 - JP 2018138019-A/143939: Polycomb-Associated Non-Coding RNAs.
LF336437 - JP 2014500723-A/143940: Polycomb-Associated Non-Coding RNAs.
MA572014 - JP 2018138019-A/143940: Polycomb-Associated Non-Coding RNAs.
LF336438 - JP 2014500723-A/143941: Polycomb-Associated Non-Coding RNAs.
MA572015 - JP 2018138019-A/143941: Polycomb-Associated Non-Coding RNAs.
LF336439 - JP 2014500723-A/143942: Polycomb-Associated Non-Coding RNAs.
MA572016 - JP 2018138019-A/143942: Polycomb-Associated Non-Coding RNAs.
LF336440 - JP 2014500723-A/143943: Polycomb-Associated Non-Coding RNAs.
MA572017 - JP 2018138019-A/143943: Polycomb-Associated Non-Coding RNAs.
CU690658 - Synthetic construct Homo sapiens gateway clone IMAGE:100021473 5' read RAD21 mRNA.
LF336441 - JP 2014500723-A/143944: Polycomb-Associated Non-Coding RNAs.
MA572018 - JP 2018138019-A/143944: Polycomb-Associated Non-Coding RNAs.
LF336442 - JP 2014500723-A/143945: Polycomb-Associated Non-Coding RNAs.
MA572019 - JP 2018138019-A/143945: Polycomb-Associated Non-Coding RNAs.
LF336443 - JP 2014500723-A/143946: Polycomb-Associated Non-Coding RNAs.
MA572020 - JP 2018138019-A/143946: Polycomb-Associated Non-Coding RNAs.
LF336446 - JP 2014500723-A/143949: Polycomb-Associated Non-Coding RNAs.
MA572023 - JP 2018138019-A/143949: Polycomb-Associated Non-Coding RNAs.
LF336455 - JP 2014500723-A/143958: Polycomb-Associated Non-Coding RNAs.
MA572032 - JP 2018138019-A/143958: Polycomb-Associated Non-Coding RNAs.
JD191877 - Sequence 172901 from Patent EP1572962.
JD387502 - Sequence 368526 from Patent EP1572962.
JD390536 - Sequence 371560 from Patent EP1572962.
JD115861 - Sequence 96885 from Patent EP1572962.
JD389662 - Sequence 370686 from Patent EP1572962.
JD480751 - Sequence 461775 from Patent EP1572962.
HZ409095 - JP 2015528002-A/1692: CHIRAL CONTROL.
LG052429 - KR 1020150036642-A/1695: CHIRAL CONTROL.
HZ480251 - JP 2015535430-A/757: TERMINALLY MODIFIED RNA.
HZ790182 - JP 2016504050-A/1927: SIGNAL-SENSOR POLYNUCLEOTIDES FOR THE ALTERATION OF CELLULAR PHENOTYPES.
JC512914 - Sequence 3167 from Patent WO2014113089.
JE867392 - Sequence 199 from Patent WO2015128671.
LF161906 - JP 2016513950-A/1972: Oligomers with improved off-target profile.
LQ070502 - Sequence 826 from Patent EP2964234.
LX154551 - JP 2017509333-A/199: Biomarkers for Endometriosis.
MA644003 - JP 2017113010-A/1927: SIGNAL-SENSOR POLYNUCLEOTIDES FOR THE ALTERATION OF CELLULAR PHENOTYPES.
MA731887 - JP 2017140048-A/757: TERMINALLY MODIFIED RNA.
MA801056 - JP 2018183181-A/1927: SIGNAL-SENSOR POLYNUCLEOTIDES FOR THE ALTERATION OF CELLULAR PHENOTYPES.
MA822556 - WO 2019004436-A/369: Kit, device, and method for detection of lung cancer.
MA822220 - WO 2019004436-A/33: Kit, device, and method for detection of lung cancer.
MA822888 - WO 2019004436-A/701: Kit, device, and method for detection of lung cancer.
MP272132 - Sequence 80 from Patent WO2019157381.
MB485552 - WO 2019244575-A/2: BIOMARKER FOR STOMACH CANCER AND USE THEREOF.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04110 - Cell cycle

Reactome (by CSHL, EBI, and GO)

Protein O60216 (Reactome details) participates in the following event(s):

R-HSA-2545203 Deacetylation of cleaved cohesin
R-HSA-2468040 Cohesin binds PDS5 and WAPAL
R-HSA-3108212 SMC5-SMC6 Complex SUMOylates Cohesin with SUMO1
R-HSA-9011997 ESR1:ESTG, JUND:FOSB and Cohesin Complex bind distal enhancer elements in MYC gene promoter
R-HSA-2470935 Cohesin binding to decondensed chromatin is facilitated by NIPBL:MAU2
R-HSA-1638803 Phosphorylation of cohesin by PLK1 at centromeres
R-HSA-2468287 CDK1 phosphorylates CDCA5 (Sororin) at centromeres
R-HSA-2467811 Separation of sister chromatids
R-HSA-2467809 ESPL1 (Separase) cleaves centromeric cohesin
R-HSA-1638821 PP2A-B56 dephosphorylates centromeric cohesin
R-HSA-2545253 Deacetylation of cohesin
R-HSA-2467794 Resolution of sister chromatids
R-HSA-912467 BRCA1 is recruited to unsynapsed regions
R-HSA-912470 ATR phosphorylates Histone H2A.X at unsynapsed regions
R-HSA-2473152 Acetylation of SMC3 subunit of centromeric chromatin associated cohesin by ESCO1 or ESCO2
R-HSA-2468039 Acetylation of SMC3 subunit of chromosomal arm associated cohesin by ESCO1 or ESCO2
R-HSA-2473151 CDCA5 (Sororin) enables cohesion of sister centromeres
R-HSA-2468041 CDCA5 (Sororin) enables cohesion of sister chromosomal arms
R-HSA-2468293 CDK1 phosphorylates CDCA5 (Sororin) at chromosomal arms
R-HSA-2466068 Phosphorylation of cohesin by PLK1 at chromosomal arms
R-HSA-912450 ATR Kinase is recruited to unsynapsed regions
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-1221632 Meiotic synapsis
R-HSA-2470946 Cohesin Loading onto Chromatin
R-HSA-3108214 SUMOylation of DNA damage response and repair proteins
R-HSA-9018519 Estrogen-dependent gene expression
R-HSA-68882 Mitotic Anaphase
R-HSA-1500620 Meiosis
R-HSA-68884 Mitotic Telophase/Cytokinesis
R-HSA-3108232 SUMO E3 ligases SUMOylate target proteins
R-HSA-8939211 ESR-mediated signaling
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-2555396 Mitotic Metaphase and Anaphase
R-HSA-1474165 Reproduction
R-HSA-1640170 Cell Cycle
R-HSA-2468052 Establishment of Sister Chromatid Cohesion
R-HSA-68886 M Phase
R-HSA-2990846 SUMOylation
R-HSA-9006931 Signaling by Nuclear Receptors
R-HSA-68877 Mitotic Prometaphase
R-HSA-69242 S Phase
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-597592 Post-translational protein modification
R-HSA-162582 Signal Transduction
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: A8K0E0, ENST00000297338.1, ENST00000297338.2, ENST00000297338.3, ENST00000297338.4, ENST00000297338.5, ENST00000297338.6, HR21, KIAA0078, NM_006265, NXP1, O60216, Q15001, Q99568, RAD21_HUMAN, uc003yod.1, uc003yod.2, uc003yod.3, uc003yod.4, uc003yod.5
UCSC ID: ENST00000297338.7
RefSeq Accession: NM_006265
Protein: O60216 (aka RAD21_HUMAN or RA21_HUMAN)
CCDS: CCDS6321.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene RAD21:
cdls (Cornelia de Lange Syndrome)
hpe-overview (Holoprosencephaly Overview)
tps (Trichorhinophalangeal Syndrome)
cdh-ov (Congenital Diaphragmatic Hernia Overview)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.