UniProtKB - F8VPQ2 (ARI4A_MOUSE)
Protein
AT-rich interactive domain-containing protein 4A
Gene
Arid4a
Organism
Mus musculus (Mouse)
Status
Functioni
DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor) (PubMed:17043311, PubMed:23487765). May function as part of an mSin3A repressor complex (By similarity). Has no intrinsic transcriptional activity (PubMed:23487765). 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 (PubMed:17043311). Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation (PubMed:23487765). Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier (PubMed:23487765). 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 (PubMed:18728284). May function as a leukemia suppressor (PubMed:18728284).By similarity3 Publications
GO - Molecular functioni
- DNA binding Source: MGI
- transcription regulatory region DNA binding Source: GO_Central
GO - Biological processi
- erythrocyte development Source: MGI
- establishment of Sertoli cell barrier Source: MGI
- histone H3-K4 trimethylation Source: MGI
- histone H3-K9 trimethylation Source: MGI
- histone H4-K20 trimethylation Source: MGI
- negative regulation of transcription, DNA-templated Source: MGI
- positive regulation of transcription by RNA polymerase II Source: MGI
- regulation of gene expression by genetic imprinting Source: MGI
- regulation of transcription by RNA polymerase II Source: GO_Central
- spermatogenesis Source: MGI
Keywordsi
Molecular function | Chromatin regulator, DNA-binding |
Biological process | Differentiation, Spermatogenesis, Transcription, Transcription regulation |
Enzyme and pathway databases
Reactomei | R-MMU-3214815 HDACs deacetylate histones |
Names & Taxonomyi
Protein namesi | Recommended name: AT-rich interactive domain-containing protein 4A1 PublicationImportedShort name: ARID domain-containing protein 4A Alternative name(s): Retinoblastoma-binding protein 11 Publication |
Gene namesi | |
Organismi | Mus musculus (Mouse)Imported |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2444354 Arid4a |
Subcellular locationi
Nucleus
- Nucleus SAAS annotation2 Publications
Cytosol
- cytosol Source: MGI
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: GO_Central
Plasma Membrane
- plasma membrane Source: MGI
Other locations
- transcriptional repressor complex Source: MGI
Keywords - Cellular componenti
NucleusPathology & Biotechi
Disruption phenotypei
Viable and fertile, although females have reduced fertility (PubMed:17043311, PubMed:18728284). At two months of age, animals show abnormal blood cell production accompanied by mild anemia, leukopenia and thrombocytopenia. Hematologic abnormalities become progressively more severe with age (PubMed:18728284). Monocytosis is observed at 5 months onwards, along with splenomegaly and hepatomegaly (PubMed:18728284). Approximately 12% of animals develop acute myeloid leukemia (AML) and/or myeloid sarcoma (PubMed:18728284). Mortality increases rapidly from age 6 months onwards, with no survival past 22 months (PubMed:18728284). Expansion of hematopoietic stem cell and common myeloid progenitor cell populations, and their downstream lineage, is observed in bone marrow and spleen; the effect is most significant in spleen (PubMed:18728284). Bone marrow cells show altered patterns of histone methylation and significantly increased levels of both H3K4me3 and H3K9me3 (PubMed:18728284). Expression of HOXB3, HOXB5, HOXB6, HOXB8 and PITX2 in bone marrow cells is reduced (PubMed:18728284). No effect on histone methlyation at the PWS/AS imprinting center (PubMed:17043311). Double knockouts with ARID4B heterozygotes show a more severe hematologic phenotype with 83% of animals progressing to AML, and with earlier age of onset (PubMed:18728284). In bone marrow cells, expression of FOXP3 is significantly reduced (PubMed:18728284). Males show progressive reduction in fertility from 2 months of age onwards, with reduced testis size and variable defects in seminal vesicle formation (PubMed:23487765). Spermatogenesis is partially blocked from the meiois II stage onwards leading to reduced numbers of mature spermatozoa (PubMed:23487765). Expression in testis of CLDN3, an androgen receptor-regulated gene, is significantly reduced (PubMed:23487765). Expression of PTGDS is also reduced, whereas expression of INHA and EMB is moderately increased (PubMed:23487765). Maternal-specific trimethylation of H4K20 and H3K9 at the PWS/AS imprinting center is significantly reduced (PubMed:17043311).3 Publications
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000444995 | 1 – 1261 | AT-rich interactive domain-containing protein 4AAdd BLAST | 1261 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 481 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 679 | PhosphoserineBy similarity | 1 | |
Modified residuei | 719 | PhosphoserineBy similarity | 1 | |
Cross-linki | 723 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Cross-linki | 743 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 867 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1113 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1149 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | F8VPQ2 |
MaxQBi | F8VPQ2 |
PaxDbi | F8VPQ2 |
PRIDEi | F8VPQ2 |
PTM databases
iPTMneti | F8VPQ2 |
PhosphoSitePlusi | F8VPQ2 |
Expressioni
Tissue specificityi
Expressed in Sertoli cells of the testis.1 Publication
Gene expression databases
Bgeei | ENSMUSG00000048118 Expressed in 235 organ(s), highest expression level in pineal body |
ExpressionAtlasi | F8VPQ2 baseline and differential |
Genevisiblei | F8VPQ2 MM |
Interactioni
Subunit structurei
Identified in mSin3A corepressor complexes together with SIN3A, SIN3B, RBBP4, RBBP7, SAP30, BRMS1, HDAC1 and HDAC2 (By similarity). Interacts with BRMS1 (By similarity). Interacts with RB1 (By similarity). Interacts with ARID4B (PubMed:17043311). Interacts with AR (PubMed:23487765).By similarity2 Publications
Protein-protein interaction databases
ComplexPortali | CPX-3441 SIN3A histone deacetylase complex, ES cell-specific variant CPX-3443 SIN3A histone deacetylase complex CPX-3444 SIN3B histone deacetylase complex |
STRINGi | 10090.ENSMUSP00000035512 |
Structurei
3D structure databases
ProteinModelPortali | F8VPQ2 |
SMRi | F8VPQ2 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 309 – 401 | ARIDPROSITE-ProRule annotationAdd BLAST | 93 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 4 – 121 | DNA-bindingBy similarityAdd BLAST | 118 | |
Regioni | 571 – 638 | Chromodomain-likeBy similarityAdd BLAST | 68 | |
Regioni | 955 – 968 | Retinoblastoma protein bindingBy similarityAdd BLAST | 14 |
Domaini
The function of the chromodomain-like region is uncertain. One study suggests that it mediates binding to lysine-methlyated histone tails, with strongest affinity for H4K20me3 and H3K36me3. However, another study failed to find any interaction between this domain and histone H4K20me3 peptide.By similarity
Phylogenomic databases
eggNOGi | KOG2744 Eukaryota KOG3001 Eukaryota ENOG410Y2AP LUCA |
GeneTreei | ENSGT00940000156159 |
HOGENOMi | HOG000015398 |
HOVERGENi | HBG058248 |
InParanoidi | F8VPQ2 |
KOi | K19194 |
OMAi | DQCAKEK |
OrthoDBi | 329541at2759 |
TreeFami | TF106427 |
Family and domain databases
CDDi | cd00024 CHROMO, 1 hit |
Gene3Di | 1.10.150.60, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF01388 ARID, 1 hit PF08169 RBB1NT, 1 hit PF11717 Tudor-knot, 1 hit |
SMARTi | View protein in SMART SM00501 BRIGHT, 1 hit SM00298 CHROMO, 1 hit SM00333 TUDOR, 1 hit |
SUPFAMi | SSF46774 SSF46774, 1 hit SSF54160 SSF54160, 1 hit |
PROSITEi | View protein in PROSITE PS51011 ARID, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
F8VPQ2-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MKAADEPAYL TVGTDVSAKY RGAFCEAKIK TVKRLVKVKV LLKQDNTTQL
60 70 80 90 100
VQDDQVKGPL RVGAIVETRT SDGSIQEAII SKLTDASWYT VVFDDGDERT
110 120 130 140 150
LRRTSLCLKG ERHFAESETL DQLPLTNPEH FGTPVIAKKT NRGRRSSLPI
160 170 180 190 200
TEDEKEEESS EEEDEDKRRL NDELLGKVVS VASTAESTGW YPALVVSPSC
210 220 230 240 250
NDDVTVKKDQ CLVRSFIDSK FYSIARKDIK ELDILTLPES ELCARPGLRR
260 270 280 290 300
ASVFLKGRIV PDNWKMDISE ILESSSSDDE ECPAEEHEEE KEKEAKKEEE
310 320 330 340 350
ELPEEELDPE ERDNFLQQLY KFMEDRGTPI NKPPVLGYKD LNLFKLFRLV
360 370 380 390 400
YHQGGCGNID SGAVWKQIYM DLGIPILNSA ASYNVKTAYR KYLYGFEEYC
410 420 430 440 450
RSANIQFRTI HHHEPKVKEE KKDFEDSMDE ALKEAPEMPL LDVKSEPEEN
460 470 480 490 500
TDSNSESDRE DTELKSPRGR RKIVRDANCI KKEIEEEKIE DKFLRDDLEN
510 520 530 540 550
KDAGDDDDDG DPAAKREHEL LFGRKSTPKN KEKKIKKPED SERDSDEEEE
560 570 580 590 600
KSQEREETES RCDSEGEDEE DDTEPCLTGT KVKVKYGRGK TQKIYEASIK
610 620 630 640 650
STEMDDGEIL YLVHYYGWNV RYDEWVKADR IIWPLDKGGP KKKQKKKVKN
660 670 680 690 700
KEDSEKDEKR DEERQKSKRG RPPLKSTFSP NMPYSLSKTS NSEGKSDSCS
710 720 730 740 750
SDSEADDQLE KSSGGEDLSP DVKEELEKNE NAHDDKLDEE NPKIVHISKE
760 770 780 790 800
NDRTQAQPSD TLTVEAGDSD QIVHIFGDKV DQVEEFKKQV EKSPKGKGRR
810 820 830 840 850
SKTKDLSLEL IKISPFGQEE AGSEAHGDVH SLEFSSLECK NFSSTEDDID
860 870 880 890 900
PYEKEKKLKR KILGQQSPEK KLRLDNGMEM TTGVSQERSD DGAGAEGMKG
910 920 930 940 950
AHVEQHFETE GEGMPSLTAE PDQGLQELTS EKSDSPAEEE PVHTPLKEEE
960 970 980 990 1000
DAMPLIGPET LVCHEVDLDD LDEKDKTSIE DVVVEGSESN SLASVPPALP
1010 1020 1030 1040 1050
PVAQHNFSVA SPLTLSQDES RSIKSESDIT IEVDSIAEES QEGLCERESA
1060 1070 1080 1090 1100
NGFEASVASG ACSIIAHERE SREKGQKRPS DGNSGLIAKK QKRTPKRTSA
1110 1120 1130 1140 1150
AAKTEKNGAG QSSDSEDLPA MDSSSNCTPV KRLTLPKSQK LPRSPARTSP
1160 1170 1180 1190 1200
HIKDAEKEKH REKHPNSSPR TYKWSFQLNE LDNMNSTERI SFLQEKLQEI
1210 1220 1230 1240 1250
RKYYMSLKSE VATIDRRRKR LKKKDREVSH AGASMSSASS DTGMSPSSSS
1260
PPQNVLAVEC R
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9Q9V1 | E9Q9V1_MOUSE | AT-rich interactive domain-containi... | Arid4a | 531 | Annotation score: | ||
Q8BY40 | Q8BY40_MOUSE | AT-rich interactive domain-containi... | Arid4a | 295 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 419 – 420 | EE → KK in AAH25436 (PubMed:15489334).Curated | 2 | |
Sequence conflicti | 491 | D → E in AAI58110 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 534 | Missing in AAI57976 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 535 | I → K in AAH58209 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 732 | A → G in AAI57976 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 786 | F → L in AAI57976 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 1134 | T → S in AAI57976 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 1138 | S → P in AAI57976 (PubMed:15489334).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC112794 Genomic DNA No translation available. AC132325 Genomic DNA No translation available. BC025436 mRNA Translation: AAH25436.1 BC058209 mRNA Translation: AAH58209.1 BC157975 mRNA Translation: AAI57976.1 BC158109 mRNA Translation: AAI58110.1 |
CCDSi | CCDS36471.1 |
RefSeqi | NP_001074664.1, NM_001081195.1 XP_017170546.1, XM_017315057.1 |
UniGenei | Mm.241601 |
Genome annotation databases
Ensembli | ENSMUST00000046305; ENSMUSP00000035512; ENSMUSG00000048118 |
GeneIDi | 238247 |
KEGGi | mmu:238247 |
UCSCi | uc007nud.1 mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC112794 Genomic DNA No translation available. AC132325 Genomic DNA No translation available. BC025436 mRNA Translation: AAH25436.1 BC058209 mRNA Translation: AAH58209.1 BC157975 mRNA Translation: AAI57976.1 BC158109 mRNA Translation: AAI58110.1 |
CCDSi | CCDS36471.1 |
RefSeqi | NP_001074664.1, NM_001081195.1 XP_017170546.1, XM_017315057.1 |
UniGenei | Mm.241601 |
3D structure databases
ProteinModelPortali | F8VPQ2 |
SMRi | F8VPQ2 |
ModBasei | Search... |
MobiDBi | Search... |
Protein-protein interaction databases
ComplexPortali | CPX-3441 SIN3A histone deacetylase complex, ES cell-specific variant CPX-3443 SIN3A histone deacetylase complex CPX-3444 SIN3B histone deacetylase complex |
STRINGi | 10090.ENSMUSP00000035512 |
PTM databases
iPTMneti | F8VPQ2 |
PhosphoSitePlusi | F8VPQ2 |
Proteomic databases
jPOSTi | F8VPQ2 |
MaxQBi | F8VPQ2 |
PaxDbi | F8VPQ2 |
PRIDEi | F8VPQ2 |
Protocols and materials databases
DNASUi | 238247 |
Structural Biology Knowledgebase | Search... |
Genome annotation databases
Ensembli | ENSMUST00000046305; ENSMUSP00000035512; ENSMUSG00000048118 |
GeneIDi | 238247 |
KEGGi | mmu:238247 |
UCSCi | uc007nud.1 mouse |
Organism-specific databases
CTDi | 5926 |
MGIi | MGI:2444354 Arid4a |
Phylogenomic databases
eggNOGi | KOG2744 Eukaryota KOG3001 Eukaryota ENOG410Y2AP LUCA |
GeneTreei | ENSGT00940000156159 |
HOGENOMi | HOG000015398 |
HOVERGENi | HBG058248 |
InParanoidi | F8VPQ2 |
KOi | K19194 |
OMAi | DQCAKEK |
OrthoDBi | 329541at2759 |
TreeFami | TF106427 |
Enzyme and pathway databases
Reactomei | R-MMU-3214815 HDACs deacetylate histones |
Miscellaneous databases
ChiTaRSi | Arid4a mouse |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000048118 Expressed in 235 organ(s), highest expression level in pineal body |
ExpressionAtlasi | F8VPQ2 baseline and differential |
Genevisiblei | F8VPQ2 MM |
Family and domain databases
CDDi | cd00024 CHROMO, 1 hit |
Gene3Di | 1.10.150.60, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF01388 ARID, 1 hit PF08169 RBB1NT, 1 hit PF11717 Tudor-knot, 1 hit |
SMARTi | View protein in SMART SM00501 BRIGHT, 1 hit SM00298 CHROMO, 1 hit SM00333 TUDOR, 1 hit |
SUPFAMi | SSF46774 SSF46774, 1 hit SSF54160 SSF54160, 1 hit |
PROSITEi | View protein in PROSITE PS51011 ARID, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | ARI4A_MOUSE | |
Accessioni | F8VPQ2Primary (citable) accession number: F8VPQ2 Secondary accession number(s): B2RXT8 Q6PE90 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 12, 2018 |
Last sequence update: | September 21, 2011 | |
Last modified: | January 16, 2019 | |
This is version 65 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot