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Protein

TSC22 domain family protein 3

Gene

TSC22D3

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

Functioni

Protects T-cells from IL2 deprivation-induced apoptosis through the inhibition of FOXO3A transcriptional activity that leads to the down-regulation of the pro-apoptotic factor BCL2L11. In macrophages, plays a role in the anti-inflammatory and immunosuppressive effects of glucocorticoids and IL10. In T-cells, inhibits anti-CD3-induced NFKB1 nuclear translocation. In vitro, suppresses AP1 and NFKB1 DNA-binding activities (By similarity). Isoform 1 inhibits myogenic differentiation and mediates anti-myogenic effects of glucocorticoids by binding and regulating MYOD1 and HDAC1 transcriptional activity resulting in reduced expression of MYOG (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels
SIGNORiQ99576

Names & Taxonomyi

Protein namesi
Recommended name:
TSC22 domain family protein 3
Alternative name(s):
DSIP-immunoreactive peptide
Short name:
Protein DIP
Short name:
hDIP
Delta sleep-inducing peptide immunoreactor
Glucocorticoid-induced leucine zipper protein
Short name:
GILZ
TSC-22-like protein
TSC-22-related protein
Short name:
TSC-22R
Gene namesi
Name:TSC22D3
Synonyms:DSIPI, GILZ
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000157514.16
HGNCiHGNC:3051 TSC22D3
MIMi300506 gene
neXtProtiNX_Q99576

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

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi1831
OpenTargetsiENSG00000157514
PharmGKBiPA27504

Polymorphism and mutation databases

BioMutaiTSC22D3
DMDMi14195584

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002193701 – 134TSC22 domain family protein 3Add BLAST134

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei102PhosphoserineCombined sources1
Isoform 2 (identifier: Q99576-3)
Modified residuei42PhosphoserineCombined sources1
Modified residuei73PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ99576
MaxQBiQ99576
PaxDbiQ99576
PeptideAtlasiQ99576
PRIDEiQ99576
ProteomicsDBi78335
78336 [Q99576-3]
78337 [Q99576-4]

PTM databases

iPTMnetiQ99576
PhosphoSitePlusiQ99576

Expressioni

Tissue specificityi

Expressed in brain, lung, spleen and skeletal muscle. Lower levels detected in heart and kidney. Not detected in the pancreas. In non-lymphoid tissues, in the absence of inflammation, the major source of constitutive expression is the macrophage lineage. Also expressed in cells from different hemopoietic cell lineages, including bone marrow cells, CD34+ stem cells, mature B- and T-cells, monocytes and granulocytes. Down-regulated in activated macrophages from inflammatory lesions of delayed-type hypersensitivity (DTH) reactions, such as in tuberculosis and in Crohn disease, whereas in Burkitt lymphoma, persists in macrophages involved in the phagocytosis of apoptotic malignant cells.2 Publications

Inductioni

By glucocorticoids in lymphoid cells and upon IL4, IL10, IL13 or glucocorticoid treatment in monocyte/macrophage cells. Transiently induced by IL2 deprivation in T-cells. Isoform 1 expression is up-regulated by synthetic glucocorticoid dexamethasone in differentiating myoblasts (By similarity).By similarity

Gene expression databases

BgeeiENSG00000157514
CleanExiHS_TSC22D3
ExpressionAtlasiQ99576 baseline and differential
GenevisibleiQ99576 HS

Organism-specific databases

HPAiCAB034364
HPA001916

Interactioni

Subunit structurei

Can form homodimers, however it is likely to function as a monomer. Interacts with AP1 (By similarity). Interacts with NFKB1. Isoform 1 interacts with MYOD1 (By similarity). Isoform 1 interacts with HDAC1; this interaction affects HDAC1 activity on MYOG promoter and thus inhibits MYOD1 transcriptional activity (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108165, 48 interactors
IntActiQ99576, 11 interactors
STRINGi9606.ENSP00000314655

Structurei

3D structure databases

ProteinModelPortaliQ99576
SMRiQ99576
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 60AP1-bindingBy similarityAdd BLAST60
Regioni76 – 97Leucine-zipperAdd BLAST22

Domaini

The leucine-zipper is involved in homodimerization.By similarity

Sequence similaritiesi

Belongs to the TSC-22/Dip/Bun family.Curated

Phylogenomic databases

eggNOGiENOG410IRR1 Eukaryota
ENOG410YAFT LUCA
GeneTreeiENSGT00530000063062
HOVERGENiHBG056226
InParanoidiQ99576
OMAiSTEMFAK
OrthoDBiEOG091G06PM
PhylomeDBiQ99576
TreeFamiTF329224

Family and domain databases

InterProiView protein in InterPro
IPR000580 TSC-22_Dip_Bun
PANTHERiPTHR12348 PTHR12348, 1 hit
PfamiView protein in Pfam
PF01166 TSC22, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD007152 TSC-22_Dip_Bun, 1 hit
PROSITEiView protein in PROSITE
PS01289 TSC22, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q99576-1) [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
MNTEMYQTPM EVAVYQLHNF SISFFSSLLG GDVVSVKLDN SASGASVVAI
60 70 80 90 100
DNKIEQAMDL VKNHLMYAVR EEVEILKEQI RELVEKNSQL ERENTLLKTL
110 120 130
ASPEQLEKFQ SCLSPEEPAP ESPQVPEAPG GSAV
Length:134
Mass (Da):14,810
Last modified:June 1, 2001 - v2
Checksum:i77B1024969FA8687
GO
Isoform 2 (identifier: Q99576-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-40: MNTEMYQTPM...GDVVSVKLDN → MAQSKLDCRS...TMLSILLFFH

Show »
Length:200
Mass (Da):22,213
Checksum:i5CBFE801E1700C8C
GO
Isoform 3 (identifier: Q99576-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-41: MNTEMYQTPMEVAVYQLHNFSISFFSSLLGGDVVSVKLDNS → GGWPSAVRAWEKAGSLPAEKEFLASFRAG

Note: Incomplete sequence. No experimental confirmation available.
Show »
Length:122
Mass (Da):13,286
Checksum:i3FA577D9052EDB7C
GO

Sequence cautioni

The sequence AAH18148 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA90644 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAB53669 differs from that shown. Reason: Frameshift at position 4.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti54I → F in CAA90644 (PubMed:8982256).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0207321 – 41MNTEM…KLDNS → GGWPSAVRAWEKAGSLPAEK EFLASFRAG in isoform 3. 2 PublicationsAdd BLAST41
Alternative sequenceiVSP_0126891 – 40MNTEM…VKLDN → MAQSKLDCRSPVGLDCCNCC LDLAHRSGLQRGSSGENNNP GSPTVSNFRQLQEKLVFENL NTDKLNSIMRQDSLEPVLRD PCYLINEGICNRNIDQTMLS ILLFFH in isoform 2. 1 PublicationAdd BLAST40

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z50781 mRNA Translation: CAA90644.1 Different initiation.
AF228339 mRNA Translation: AAG12456.1
AF183393 mRNA Translation: AAD56234.1
AB025432 mRNA Translation: BAB18680.1
AF153603 mRNA Translation: AAD41085.1
AL110191 mRNA Translation: CAB53669.1 Frameshift.
AK092645 mRNA Translation: BAC03934.1
AK092669 mRNA Translation: BAG52587.1
AL590423 Genomic DNA No translation available.
CH471120 Genomic DNA Translation: EAX02704.1
CH471120 Genomic DNA Translation: EAX02705.1
CH471120 Genomic DNA Translation: EAX02706.1
CR933650 mRNA Translation: CAI45951.1
BC018148 mRNA Translation: AAH18148.3 Different initiation.
BC072446 mRNA Translation: AAH72446.1
CR533450 mRNA Translation: CAG38481.1
CCDSiCCDS14530.1 [Q99576-3]
CCDS14531.1 [Q99576-1]
PIRiT14749
RefSeqiNP_001015881.1, NM_001015881.1
NP_001305397.1, NM_001318468.1 [Q99576-3]
NP_001305399.1, NM_001318470.1 [Q99576-3]
NP_004080.2, NM_004089.3 [Q99576-1]
NP_932174.1, NM_198057.2 [Q99576-3]
XP_005262156.1, XM_005262099.1 [Q99576-3]
XP_005262157.1, XM_005262100.1 [Q99576-3]
XP_005262159.1, XM_005262102.1 [Q99576-3]
XP_005262160.1, XM_005262103.3 [Q99576-3]
XP_011529186.1, XM_011530884.1 [Q99576-3]
XP_016884824.1, XM_017029335.1 [Q99576-3]
UniGeneiHs.522074

Genome annotation databases

EnsembliENST00000315660; ENSP00000314655; ENSG00000157514 [Q99576-3]
ENST00000372383; ENSP00000361458; ENSG00000157514 [Q99576-3]
ENST00000372384; ENSP00000361459; ENSG00000157514 [Q99576-3]
ENST00000372397; ENSP00000361474; ENSG00000157514 [Q99576-1]
ENST00000506081; ENSP00000427427; ENSG00000157514 [Q99576-3]
GeneIDi1831
KEGGihsa:1831
UCSCiuc004eng.4 human [Q99576-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiT22D3_HUMAN
AccessioniPrimary (citable) accession number: Q99576
Secondary accession number(s): Q5H9S3
, Q5JRI9, Q6FIH6, Q8NAI1, Q8WVB9, Q9UBN5, Q9UG13
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: June 1, 2001
Last modified: June 20, 2018
This is version 168 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

Complete proteome, Reference proteome

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