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Protein

AT-rich interactive domain-containing protein 5A

Gene

Arid5a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

DNA-binding protein that may regulate transcription and act as a repressor by binding to AT-rich stretches in the promoter region of target genes (By similarity). May positively regulate chondrocyte-specific transcription such as of COL2A1 in collaboration with SOX9 and positively regulate histone H3 acetylation at chondrocyte-specific genes. May stimulate early-stage chondrocyte differentiation and inhibit later stage differention (PubMed:21346191). Can repress ESR1-mediated transcriptional activation; proposed to act as corepressor for selective nuclear hormone receptors (By similarity). As RNA-binding protein involved in the regulation of inflammatory response by stabilizing selective inflammation-related mRNAs, such as IL6, STAT3 and TBX21. Binds to stem loop structures located in the 3'UTRs of IL6, STAT3 and TBX21 mRNAs; at least for STAT3 prevents binding of ZC3H12A to the mRNA stem loop structure thus inhibiting its degradation activity. Contributes to elevated IL6 levels possibly implicated in autoimmunity processes. IL6-dependent stabilization of STAT3 mRNA may promote differentiation of naive CD4+ T-cells into T-helper Th17 cells (PubMed:23676272, PubMed:27022145). In CD4+ T-cells may also inhibit RORC-induced Th17 cell differentiation independently of IL6 signaling (PubMed:24782182). Stabilization of TBX21 mRNA contributes to elevated interferon-gamma secretion in Th1 cells possibly implicated in the establishment of septic shock (PubMed:27671645).By similarity5 Publications

GO - Molecular functioni

GO - Biological processi

  • cellular response to estrogen stimulus Source: MGI
  • cellular response to lipopolysaccharide Source: UniProtKB
  • chondrocyte differentiation Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of histone acetylation Source: MGI
  • positive regulation of interferon-gamma secretion Source: UniProtKB
  • positive regulation of interleukin-17 secretion Source: UniProtKB
  • positive regulation of interleukin-6 secretion Source: UniProtKB
  • positive regulation of T-helper 17 type immune response Source: UniProtKB
  • positive regulation of T-helper 1 cell cytokine production Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of tumor necrosis factor secretion Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, DNA-binding, Repressor, RNA-binding
Biological processImmunity, Innate immunity, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
AT-rich interactive domain-containing protein 5A
Short name:
ARID domain-containing protein 5A
Gene namesi
Name:Arid5a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:2443039. Arid5a.

Subcellular locationi

GO - Cellular componenti

  • nucleolus Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
  • transcription factor complex Source: MGI

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi128R → A: Abolishes binding to STAT3 3'UTR stem loop structure. 1 Publication1
Mutagenesisi253S → A: Abolishes ubiquitination; largely impairs proteasomal degradation; results in overproduction of IL-6 upon overexpression; in association with A-433 and A-458. 1 Publication1
Mutagenesisi433S → A: Abolishes ubiquitination; largely impairs proteasomal degradation; results in overproduction of IL-6 upon overexpression; in association with A-253 and A-458. 1 Publication1
Mutagenesisi458S → A: Abolishes ubiquitination; largely impairs proteasomal degradation; results in overproduction of IL-6 upon overexpression; in association with A-253 and A-433. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002889311 – 590AT-rich interactive domain-containing protein 5AAdd BLAST590

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei24PhosphoserineCombined sources1
Cross-linki80Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki89Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei253Phosphoserine1 Publication1
Modified residuei283PhosphoserineCombined sources1
Modified residuei433Phosphoserine1 Publication1
Modified residuei458Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylated by MAPK14 on serine residues involving a TLR4 signaling pathway upon lipopolysaccharide (LPS) stimulation leading to its ubiquitination and proteasomal degradation.1 Publication
Ubiquitinated leading to proteasomal degradation; involving WWP1 linked to MAPK14-mediated phosphorylation upon LPS stimulation.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ3U108.
MaxQBiQ3U108.
PaxDbiQ3U108.
PRIDEiQ3U108.

PTM databases

iPTMnetiQ3U108.
PhosphoSitePlusiQ3U108.

Expressioni

Tissue specificityi

Expressed at high levels in cartilage, heart, testis and bone.1 Publication

Inductioni

In macrophages by LPS, IL1B and IL6. By IL6/STAT3 signaling in T-helper Th17 cells.2 Publications

Gene expression databases

BgeeiENSMUSG00000037447.
CleanExiMM_ARID5A.
ExpressionAtlasiQ3U108. baseline and differential.
GenevisibleiQ3U108. MM.

Interactioni

Subunit structurei

Interacts with SOX9 (PubMed:21346191). Interacts with ESR1 (By similarity). Interacts with RORC (PubMed:24782182).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000110684.

Structurei

3D structure databases

ProteinModelPortaliQ3U108.
SMRiQ3U108.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini50 – 142ARIDPROSITE-ProRule annotationAdd BLAST93

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 294Interaction with SOX91 PublicationAdd BLAST294

Phylogenomic databases

eggNOGiENOG410IQ79. Eukaryota.
ENOG4111RDB. LUCA.
GeneTreeiENSGT00880000137908.
HOVERGENiHBG062210.
InParanoidiQ3U108.
OMAiHFFHLNT.
OrthoDBiEOG091G0E6N.
TreeFamiTF324725.

Family and domain databases

InterProiView protein in InterPro
IPR001606. ARID_dom.
PfamiView protein in Pfam
PF01388. ARID. 1 hit.
SMARTiView protein in SMART
SM00501. BRIGHT. 1 hit.
SUPFAMiSSF46774. SSF46774. 1 hit.
PROSITEiView protein in PROSITE
PS51011. ARID. 1 hit.

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q3U108-1) [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
MAAPPAKGNT EQSEEGDLPQ LPVSPKPDDE QSRSQSPTQL QDSPEAGGEQ
60 70 80 90 100
EEEQAFLVSL YKFMKERHTP IERVPHLGFK QINLWKIYKA VEKLGAYELV
110 120 130 140 150
TGRRLWKNVY DELGGSPGST SAATCTRRHY ERLVLPYVRH LKGEDDKPLP
160 170 180 190 200
PTKPRKQYKM AKELRGDDGT TEKLKKAKDS EERRVEQTTP GKTKSDATGQ
210 220 230 240 250
TQLPCQGSSR DSTEQLGPVS GPSPPLTGAS SCPEAYKRLL SSFYCKGAHG
260 270 280 290 300
IMSPLAKKKL LAQVSKAEAL QCQEEGCRHG ARSPNKDIQD SPQNLRGPAE
310 320 330 340 350
NSEHQLTPRE GLQAPGGSTR MEAQVGPCPT APMFSGCFHA YPTEVLKPVS
360 370 380 390 400
QHPRDFFSGL KDRVLLGPPG KEEGPTTKES HLVWGGDANH PSAFHKGSTR
410 420 430 440 450
KRSFYPKPKA CWVSPMAKVP TERPGAPSPH PSSPGLGSKR GLEEEGFAHG
460 470 480 490 500
GKKLRAVSPF LKEVDSKETG GKPAAPGLAV SCLLGPTPGP TPPEAYRGTM
510 520 530 540 550
LRCPLNFTGS ADPLKGQASL PFSPLVIPAF PAHLLATTGS SPMAASLMHF
560 570 580 590
PPTPYDAVLR NRLGPASSAW HMPPVTTYAA PHFFHLNTKL
Length:590
Mass (Da):63,898
Last modified:October 11, 2005 - v1
Checksum:iD4C00C2F1DEBDCC3
GO
Isoform 2 (identifier: Q3U108-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-2: MA → MLKGGRPDLCVVNSLIKLQKLKLHVDAEHQT

Show »
Length:619
Mass (Da):67,163
Checksum:i45AF3962604B372A
GO
Isoform 3 (identifier: Q3U108-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     2-2: Missing.
     81-82: QI → QSASLGGGGW...DRLPCLFPSV

Show »
Length:684
Mass (Da):73,323
Checksum:i9156EB0980CD3F35
GO
Isoform 4 (identifier: Q3U108-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     42-99: Missing.

Show »
Length:532
Mass (Da):57,124
Checksum:iEC8556C8C58565C9
GO
Isoform 5 (identifier: Q3U108-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-159: Missing.

Show »
Length:431
Mass (Da):45,846
Checksum:i62191DF092B2A60E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti51E → K in BAE34133 (PubMed:16141072).Curated1
Sequence conflicti94L → Q in BAE29358 (PubMed:16141072).Curated1
Sequence conflicti540S → P in AAH27152 (PubMed:15489334).Curated1
Sequence conflicti585H → R in BAE29115 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0258381 – 159Missing in isoform 5. 2 PublicationsAdd BLAST159
Alternative sequenceiVSP_0258391 – 2MA → MLKGGRPDLCVVNSLIKLQK LKLHVDAEHQT in isoform 2. 1 Publication2
Alternative sequenceiVSP_0258402Missing in isoform 3. 1 Publication1
Alternative sequenceiVSP_02584142 – 99Missing in isoform 4. 1 PublicationAdd BLAST58
Alternative sequenceiVSP_02584281 – 82QI → QSASLGGGGWCSGRVSVGGQ QPGDVPRQDNRQGTSAKGDP GCRQPVGVACEDGASLKARG GVGFSSSWAACPVHNSGPAW ECGVTEPDRLPCLFPSV in isoform 3. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK041344 mRNA. Translation: BAC30913.1.
AK085015 mRNA. Translation: BAC39338.1.
AK149839 mRNA. Translation: BAE29115.1.
AK150170 mRNA. Translation: BAE29358.1.
AK156376 mRNA. Translation: BAE33692.1.
AK156622 mRNA. Translation: BAE33779.1.
AK156934 mRNA. Translation: BAE33904.1.
AK157607 mRNA. Translation: BAE34133.1.
BC027152 mRNA. Translation: AAH27152.1.
CCDSiCCDS14876.1. [Q3U108-4]
CCDS48239.1. [Q3U108-1]
CCDS69878.1. [Q3U108-5]
CCDS78560.1. [Q3U108-2]
RefSeqiNP_001165676.1. NM_001172205.1. [Q3U108-1]
NP_001165677.1. NM_001172206.1.
NP_001277655.1. NM_001290726.1.
NP_001277656.1. NM_001290727.1. [Q3U108-5]
NP_666108.2. NM_145996.4. [Q3U108-4]
UniGeneiMm.297482.
Mm.34316.

Genome annotation databases

EnsembliENSMUST00000115029; ENSMUSP00000110681; ENSMUSG00000037447. [Q3U108-5]
ENSMUST00000115031; ENSMUSP00000110683; ENSMUSG00000037447. [Q3U108-3]
ENSMUST00000115032; ENSMUSP00000110684; ENSMUSG00000037447. [Q3U108-1]
ENSMUST00000137906; ENSMUSP00000117810; ENSMUSG00000037447. [Q3U108-4]
GeneIDi214855.
KEGGimmu:214855.
UCSCiuc007apu.2. mouse. [Q3U108-4]
uc007apv.2. mouse. [Q3U108-1]
uc007apy.2. mouse. [Q3U108-3]

Keywords - Coding sequence diversityi

Alternative splicing

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.

Entry informationi

Entry nameiARI5A_MOUSE
AccessioniPrimary (citable) accession number: Q3U108
Secondary accession number(s): Q3TZS4
, Q3U0F0, Q3U0S2, Q3UDA3, Q3UDZ6, Q8BI45, Q8BYB5, Q8R2W1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: October 11, 2005
Last modified: July 5, 2017
This is version 95 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot