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Protein

AT-rich interactive domain-containing protein 4A

Gene

ARID4A

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

Functioni

DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor) (By similarity). May function as part of an mSin3A repressor complex (PubMed:14581478). Has no intrinsic transcriptional activity (By similarity). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4B (By similarity). Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier (By similarity). Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (By similarity).By similarity1 Publication

GO - Molecular functioni

  • DNA binding Source: GDB
  • DNA-binding transcription factor activity Source: ProtInc
  • DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
  • histone deacetylase activity Source: Reactome
  • transcription regulatory region DNA binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, DNA-binding
Biological processDifferentiation, Spermatogenesis, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-3214815 HDACs deacetylate histones
SIGNORiP29374

Names & Taxonomyi

Protein namesi
Recommended name:
AT-rich interactive domain-containing protein 4A
Short name:
ARID domain-containing protein 4A
Alternative name(s):
Retinoblastoma-binding protein 1
Short name:
RBBP-1
Gene namesi
Name:ARID4A
Synonyms:RBBP1, RBP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000032219.18
HGNCiHGNC:9885 ARID4A
MIMi180201 gene
neXtProtiNX_P29374

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi583Y → A: No effect on binding to trimethylated lysines. 1 Publication1
Mutagenesisi592Y → A: Significantly reduces affinity for trimethylated lysines. 1 Publication1
Mutagenesisi612Y → A: Abolishes binding to trimethylated lysines. 1 Publication1
Mutagenesisi615W → A: Abolishes binding to trimethylated lysines. 1 Publication1
Mutagenesisi619Y → A: Abolishes binding to trimethylated lysines. 1 Publication1

Organism-specific databases

DisGeNETi5926
OpenTargetsiENSG00000032219
PharmGKBiPA34249

Chemistry databases

ChEMBLiCHEMBL3709855

Polymorphism and mutation databases

BioMutaiARID4A
DMDMi206729929

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002005801 – 1257AT-rich interactive domain-containing protein 4AAdd BLAST1257

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki481Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki513Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei676PhosphoserineCombined sources1
Modified residuei716PhosphoserineCombined sources1
Cross-linki718Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki738Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki759Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei864PhosphoserineCombined sources1
Modified residuei1109PhosphoserineCombined sources1
Modified residuei1145PhosphoserineCombined sources1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP29374
MaxQBiP29374
PaxDbiP29374
PeptideAtlasiP29374
PRIDEiP29374
ProteomicsDBi54556
54557 [P29374-2]
54558 [P29374-3]

PTM databases

iPTMnetiP29374
PhosphoSitePlusiP29374

Expressioni

Gene expression databases

BgeeiENSG00000032219 Expressed in 221 organ(s), highest expression level in frontal cortex
CleanExiHS_ARID4A
HS_RBP1
ExpressionAtlasiP29374 baseline and differential
GenevisibleiP29374 HS

Organism-specific databases

HPAiHPA048899

Interactioni

Subunit structurei

Identified in mSin3A corepressor complexes together with SIN3A, SIN3B, RBBP4, RBBP7, SAP30, BRMS1, HDAC1 and HDAC2 (PubMed:14581478). Interacts with BRMS1 (PubMed:14581478). Interacts with RB1 (PubMed:8414517, PubMed:8455946). Interacts with ARID4B (PubMed:17043311). Interacts with AR (PubMed:23487765).5 Publications

Protein-protein interaction databases

BioGridi111861, 32 interactors
ComplexPortaliCPX-3321 SIN3A histone deacetylase complex
CPX-3322 SIN3B histone deacetylase complex
CPX-3323 SIN3A histone deacetylase complex, ES cell-specific variant
CORUMiP29374
DIPiDIP-463N
IntActiP29374, 9 interactors
MINTiP29374
STRINGi9606.ENSP00000347602

Structurei

Secondary structure

11257
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP29374
SMRiP29374
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP29374

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini309 – 401ARIDPROSITE-ProRule annotationAdd BLAST93

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni4 – 121DNA-binding1 PublicationAdd BLAST118
Regioni568 – 635Chromodomain-like2 PublicationsAdd BLAST68
Regioni951 – 964Retinoblastoma protein bindingSequence analysisAdd BLAST14

Domaini

The function of the chromodomain-like region is uncertain (PubMed:22247551, PubMed:29408527). One study suggests that it mediates binding to lysine-methylated histone tails, with strongest affinity for H4K20me3 and H3K36me3 (PubMed:22247551). However, another study failed to find any interaction between this domain and histone H4K20me3 peptide (PubMed:29408527).2 Publications

Phylogenomic databases

eggNOGiKOG2744 Eukaryota
KOG3001 Eukaryota
ENOG410Y2AP LUCA
GeneTreeiENSGT00900000140901
HOGENOMiHOG000015398
HOVERGENiHBG058247
InParanoidiP29374
KOiK19194
OMAiDQCAKEK
OrthoDBiEOG091G0EG4
PhylomeDBiP29374
TreeFamiTF106427

Family and domain databases

CDDicd00024 CHROMO, 1 hit
Gene3Di1.10.150.60, 1 hit
InterProiView protein in InterPro
IPR001606 ARID_dom
IPR036431 ARID_dom_sf
IPR016197 Chromo-like_dom_sf
IPR000953 Chromo/chromo_shadow_dom
IPR012603 RBB1NT
IPR002999 Tudor
IPR025995 Tudor-knot
PfamiView protein in Pfam
PF01388 ARID, 1 hit
PF08169 RBB1NT, 1 hit
PF11717 Tudor-knot, 1 hit
SMARTiView protein in SMART
SM00501 BRIGHT, 1 hit
SM00298 CHROMO, 1 hit
SM00333 TUDOR, 1 hit
SUPFAMiSSF46774 SSF46774, 1 hit
SSF54160 SSF54160, 1 hit
PROSITEiView protein in PROSITE
PS51011 ARID, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform I (identifier: P29374-1) [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
MKAADEPAYL TVGTDVSAKY RGAFCEAKIK TVKRLVKVKV LLKQDNTTQL
60 70 80 90 100
VQDDQVKGPL RVGAIVETRT SDGSFQEAII SKLTDASWYT VVFDDGDERT
110 120 130 140 150
LRRTSLCLKG ERHFAESETL DQLPLTNPEH FGTPVIAKKT NRGRRSSLPV
160 170 180 190 200
TEDEKEEESS EEEDEDKRRL NDELLGKVVS VVSATERTEW YPALVISPSC
210 220 230 240 250
NDDITVKKDQ CLVRSFIDSK FYSIARKDIK EVDILNLPES ELSTKPGLQK
260 270 280 290 300
ASIFLKTRVV PDNWKMDISE ILESSSSDDE DGPAEENDEE KEKEAKKTEE
310 320 330 340 350
EVPEEELDPE ERDNFLQQLY KFMEDRGTPI NKPPVLGYKD LNLFKLFRLV
360 370 380 390 400
YHQGGCDNID SGAVWKQIYM DLGIPILNSA ASYNVKTAYR KYLYGFEEYC
410 420 430 440 450
RSANIQFRTV HHHEPKVKEE KKDLEESMEE ALKLDQEMPL TEVKSEPEEN
460 470 480 490 500
IDSNSESERE EIELKSPRGR RRIARDVNSI KKEIEEEKTE DKLKDNDTEN
510 520 530 540 550
KDVDDDYETA EKKENELLLG RKNTPKQKEK KIKKQEDSDK DSDEEEEKSQ
560 570 580 590 600
EREETESKCD SEGEEDEEDM EPCLTGTKVK VKYGRGKTQK IYEASIKSTE
610 620 630 640 650
IDDGEVLYLV HYYGWNVRYD EWVKADRIIW PLDKGGPKKK QKKKAKNKED
660 670 680 690 700
SEKDEKRDEE RQKSKRGRPP LKSTLSSNMP YGLSKTANSE GKSDSCSSDS
710 720 730 740 750
ETEDALEKNL INEELSLKDE LEKNENLNDD KLDEENPKIS AHILKENDRT
760 770 780 790 800
QMQPLETLKL EVGENEQIVQ IFGNKMEKTE EVKKEAEKSP KGKGRRSKTK
810 820 830 840 850
DLSLEIIKIS SFGQNEAGSE PHIEAHSLEL SSLDNKNFSS ATEDEIDQCV
860 870 880 890 900
KEKKLKRKIL GQSSPEKKIR IENGMEMTNT VSQERTSDCI GSEGMKNLNF
910 920 930 940 950
EQHFERENEG MPSLIAESNQ CIQQLTSERF DSPAEETVNI PLKEDEDAMP
960 970 980 990 1000
LIGPETLVCH EVDLDDLDEK DKTSIEDVAV ESSESNSLVS IPPALPPVVQ
1010 1020 1030 1040 1050
HNFSVASPLT LSQDESRSVK SESDITIEVD SIAEESQEGL CERESANGFE
1060 1070 1080 1090 1100
TNVASGTCSI IVQERESREK GQKRPSDGNS GLMAKKQKRT PKRTSAAAKN
1110 1120 1130 1140 1150
EKNGTGQSSD SEDLPVLDNS SKCTPVKHLN VSKPQKLARS PARISPHIKD
1160 1170 1180 1190 1200
GEKDKHREKH PNSSPRTYKW SFQLNELDNM NSTERISFLQ EKLQEIRKYY
1210 1220 1230 1240 1250
MSLKSEVATI DRRRKRLKKK DREVSHAGAS MSSASSDTGM SPSSSSPPQN

VLAVECR
Length:1,257
Mass (Da):142,752
Last modified:September 23, 2008 - v3
Checksum:i5B3F6A5AFB7588CF
GO
Isoform II (identifier: P29374-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1121-1174: Missing.

Show »
Length:1,203
Mass (Da):136,495
Checksum:iB2A06AA7071AAAE2
GO
Isoform III (identifier: P29374-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1106-1174: Missing.
     1175-1175: N → D

Show »
Length:1,188
Mass (Da):134,951
Checksum:i0576FA849F761B54
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C485H7C485_HUMAN
AT-rich interactive domain-containi...
ARID4A
748Annotation score:
C9J1W3C9J1W3_HUMAN
AT-rich interactive domain-containi...
ARID4A
265Annotation score:
C9JIF4C9JIF4_HUMAN
AT-rich interactive domain-containi...
ARID4A
54Annotation score:
F8WAR5F8WAR5_HUMAN
AT-rich interactive domain-containi...
ARID4A
40Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti385V → L in AAB28543 (PubMed:8414517).Curated1
Sequence conflicti618R → S in AAB28543 (PubMed:8414517).Curated1
Sequence conflicti653K → V in AAB25833 (PubMed:8455946).Curated1
Sequence conflicti653K → V in AAB25834 (PubMed:8455946).Curated1
Sequence conflicti653K → V in AAB25835 (PubMed:8455946).Curated1
Sequence conflicti1178D → S no nucleotide entry (PubMed:1857421).Curated1
Sequence conflicti1196 – 1201IRKYYM → SENIICL no nucleotide entry (PubMed:1857421).Curated6

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_031566412H → P. Corresponds to variant dbSNP:rs34982206Ensembl.1
Natural variantiVAR_031567724N → S. Corresponds to variant dbSNP:rs2230098Ensembl.1
Natural variantiVAR_031568779T → A1 PublicationCorresponds to variant dbSNP:rs1051858Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0043711106 – 1174Missing in isoform III. 1 PublicationAdd BLAST69
Alternative sequenceiVSP_0043731121 – 1174Missing in isoform II. 1 PublicationAdd BLAST54
Alternative sequenceiVSP_0043721175N → D in isoform III. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S66427 mRNA Translation: AAB28543.1
AL132989 Genomic DNA No translation available.
AL139021 Genomic DNA No translation available.
S57153 mRNA Translation: AAB25833.1
S57160 mRNA Translation: AAB25834.1
S57162 mRNA Translation: AAB25835.2
CCDSiCCDS45114.1 [P29374-2]
CCDS9732.1 [P29374-1]
CCDS9733.1 [P29374-3]
PIRiI58383
RefSeqiNP_002883.3, NM_002892.3 [P29374-1]
NP_075376.2, NM_023000.2 [P29374-2]
NP_075377.2, NM_023001.2 [P29374-3]
UniGeneiHs.161000

Genome annotation databases

EnsembliENST00000348476; ENSP00000344556; ENSG00000032219 [P29374-3]
ENST00000355431; ENSP00000347602; ENSG00000032219 [P29374-1]
ENST00000395168; ENSP00000378597; ENSG00000032219 [P29374-2]
ENST00000431317; ENSP00000397368; ENSG00000032219 [P29374-3]
GeneIDi5926
KEGGihsa:5926
UCSCiuc001xdo.4 human [P29374-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S66427 mRNA Translation: AAB28543.1
AL132989 Genomic DNA No translation available.
AL139021 Genomic DNA No translation available.
S57153 mRNA Translation: AAB25833.1
S57160 mRNA Translation: AAB25834.1
S57162 mRNA Translation: AAB25835.2
CCDSiCCDS45114.1 [P29374-2]
CCDS9732.1 [P29374-1]
CCDS9733.1 [P29374-3]
PIRiI58383
RefSeqiNP_002883.3, NM_002892.3 [P29374-1]
NP_075376.2, NM_023000.2 [P29374-2]
NP_075377.2, NM_023001.2 [P29374-3]
UniGeneiHs.161000

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LCCNMR-A568-635[»]
2MAMNMR-A4-121[»]
2YRVNMR-A170-273[»]
6BPHX-ray1.85A568-635[»]
ProteinModelPortaliP29374
SMRiP29374
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111861, 32 interactors
ComplexPortaliCPX-3321 SIN3A histone deacetylase complex
CPX-3322 SIN3B histone deacetylase complex
CPX-3323 SIN3A histone deacetylase complex, ES cell-specific variant
CORUMiP29374
DIPiDIP-463N
IntActiP29374, 9 interactors
MINTiP29374
STRINGi9606.ENSP00000347602

Chemistry databases

ChEMBLiCHEMBL3709855

PTM databases

iPTMnetiP29374
PhosphoSitePlusiP29374

Polymorphism and mutation databases

BioMutaiARID4A
DMDMi206729929

Proteomic databases

EPDiP29374
MaxQBiP29374
PaxDbiP29374
PeptideAtlasiP29374
PRIDEiP29374
ProteomicsDBi54556
54557 [P29374-2]
54558 [P29374-3]

Protocols and materials databases

DNASUi5926
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000348476; ENSP00000344556; ENSG00000032219 [P29374-3]
ENST00000355431; ENSP00000347602; ENSG00000032219 [P29374-1]
ENST00000395168; ENSP00000378597; ENSG00000032219 [P29374-2]
ENST00000431317; ENSP00000397368; ENSG00000032219 [P29374-3]
GeneIDi5926
KEGGihsa:5926
UCSCiuc001xdo.4 human [P29374-1]

Organism-specific databases

CTDi5926
DisGeNETi5926
EuPathDBiHostDB:ENSG00000032219.18
GeneCardsiARID4A
H-InvDBiHIX0037655
HGNCiHGNC:9885 ARID4A
HPAiHPA048899
MIMi180201 gene
neXtProtiNX_P29374
OpenTargetsiENSG00000032219
PharmGKBiPA34249
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2744 Eukaryota
KOG3001 Eukaryota
ENOG410Y2AP LUCA
GeneTreeiENSGT00900000140901
HOGENOMiHOG000015398
HOVERGENiHBG058247
InParanoidiP29374
KOiK19194
OMAiDQCAKEK
OrthoDBiEOG091G0EG4
PhylomeDBiP29374
TreeFamiTF106427

Enzyme and pathway databases

ReactomeiR-HSA-3214815 HDACs deacetylate histones
SIGNORiP29374

Miscellaneous databases

ChiTaRSiARID4A human
EvolutionaryTraceiP29374
GeneWikiiARID4A
GenomeRNAii5926
PROiPR:P29374
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000032219 Expressed in 221 organ(s), highest expression level in frontal cortex
CleanExiHS_ARID4A
HS_RBP1
ExpressionAtlasiP29374 baseline and differential
GenevisibleiP29374 HS

Family and domain databases

CDDicd00024 CHROMO, 1 hit
Gene3Di1.10.150.60, 1 hit
InterProiView protein in InterPro
IPR001606 ARID_dom
IPR036431 ARID_dom_sf
IPR016197 Chromo-like_dom_sf
IPR000953 Chromo/chromo_shadow_dom
IPR012603 RBB1NT
IPR002999 Tudor
IPR025995 Tudor-knot
PfamiView protein in Pfam
PF01388 ARID, 1 hit
PF08169 RBB1NT, 1 hit
PF11717 Tudor-knot, 1 hit
SMARTiView protein in SMART
SM00501 BRIGHT, 1 hit
SM00298 CHROMO, 1 hit
SM00333 TUDOR, 1 hit
SUPFAMiSSF46774 SSF46774, 1 hit
SSF54160 SSF54160, 1 hit
PROSITEiView protein in PROSITE
PS51011 ARID, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiARI4A_HUMAN
AccessioniPrimary (citable) accession number: P29374
Secondary accession number(s): Q15991, Q15992, Q15993
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: September 23, 2008
Last modified: November 7, 2018
This is version 173 of the entry and version 3 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
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