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Protein

TSC22 domain family protein 3

Gene

TSC22D3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • transcription factor activity, sequence-specific DNA binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-2672351. Stimuli-sensing channels.

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

HGNCiHGNC:3051. TSC22D3.

Subcellular locationi

Isoform 1 :
  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Localization depends on differentiation status of myoblasts. In undifferentiated myoblasts, isoform 1 localizes to the cytoplasm, but in differentiating myoblasts, isoform 1 is localized to the nucleus (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27504.

Polymorphism and mutation databases

BioMutaiTSC22D3.
DMDMi14195584.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 134134TSC22 domain family protein 3PRO_0000219370Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei102 – 1021PhosphoserineCombined sources
Isoform 2 (identifier: Q99576-3)
Modified residuei42 – 421PhosphoserineCombined sources
Modified residuei73 – 731PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ99576.
MaxQBiQ99576.
PaxDbiQ99576.
PeptideAtlasiQ99576.
PRIDEiQ99576.

PTM databases

iPTMnetiQ99576.
PhosphoSiteiQ99576.

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

HPAiHPA001916.

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

WithEntry#Exp.IntActNotes
C19orf57Q0VDD73EBI-10294415,EBI-741210
MAD1L1Q9Y6D93EBI-10294415,EBI-742610

Protein-protein interaction databases

BioGridi108165. 42 interactions.
IntActiQ99576. 9 interactions.
MINTiMINT-4715756.
STRINGi9606.ENSP00000314655.

Structurei

3D structure databases

ProteinModelPortaliQ99576.
SMRiQ99576. Positions 58-134.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 6060AP1-bindingBy similarityAdd
BLAST
Regioni76 – 9722Leucine-zipperAdd
BLAST

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

InterProiIPR000580. TSC-22_Dip_Bun.
[Graphical view]
PANTHERiPTHR12348. PTHR12348. 1 hit.
PfamiPF01166. TSC22. 1 hit.
[Graphical view]
ProDomiPD007152. TSC-22_Dip_Bun. 1 hit.
[Graphical view] [Entries sharing at least one domain]
PROSITEiPS01289. TSC22. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti54 – 541I → F in CAA90644 (PubMed:8982256).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4141MNTEM…KLDNS → GGWPSAVRAWEKAGSLPAEK EFLASFRAG in isoform 3. 2 PublicationsVSP_020732Add
BLAST
Alternative sequencei1 – 4040MNTEM…VKLDN → MAQSKLDCRSPVGLDCCNCC LDLAHRSGLQRGSSGENNNP GSPTVSNFRQLQEKLVFENL NTDKLNSIMRQDSLEPVLRD PCYLINEGICNRNIDQTMLS ILLFFH in isoform 2. 1 PublicationVSP_012689Add
BLAST

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. Translation: CAI41544.1.
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]
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

Cross-referencesi

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. Translation: CAI41544.1.
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]
UniGeneiHs.522074.

3D structure databases

ProteinModelPortaliQ99576.
SMRiQ99576. Positions 58-134.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108165. 42 interactions.
IntActiQ99576. 9 interactions.
MINTiMINT-4715756.
STRINGi9606.ENSP00000314655.

PTM databases

iPTMnetiQ99576.
PhosphoSiteiQ99576.

Polymorphism and mutation databases

BioMutaiTSC22D3.
DMDMi14195584.

Proteomic databases

EPDiQ99576.
MaxQBiQ99576.
PaxDbiQ99576.
PeptideAtlasiQ99576.
PRIDEiQ99576.

Protocols and materials databases

DNASUi1831.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi1831.
GeneCardsiTSC22D3.
HGNCiHGNC:3051. TSC22D3.
HPAiHPA001916.
MIMi300506. gene.
neXtProtiNX_Q99576.
PharmGKBiPA27504.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IRR1. Eukaryota.
ENOG410YAFT. LUCA.
GeneTreeiENSGT00530000063062.
HOVERGENiHBG056226.
InParanoidiQ99576.
OMAiSTEMFAK.
OrthoDBiEOG091G06PM.
PhylomeDBiQ99576.
TreeFamiTF329224.

Enzyme and pathway databases

ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Miscellaneous databases

ChiTaRSiTSC22D3. human.
GeneWikiiTSC22D3.
GenomeRNAii1831.
PROiQ99576.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000157514.
CleanExiHS_TSC22D3.
ExpressionAtlasiQ99576. baseline and differential.
GenevisibleiQ99576. HS.

Family and domain databases

InterProiIPR000580. TSC-22_Dip_Bun.
[Graphical view]
PANTHERiPTHR12348. PTHR12348. 1 hit.
PfamiPF01166. TSC22. 1 hit.
[Graphical view]
ProDomiPD007152. TSC-22_Dip_Bun. 1 hit.
[Graphical view] [Entries sharing at least one domain]
PROSITEiPS01289. TSC22. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiT22D3_HUMAN
AccessioniPrimary (citable) accession number: Q99576
Secondary accession number(s): Q5H9S3
, Q5JRI9, Q6FIH6, Q8NAI1, Q8WVB9, Q9UBN5, Q9UG13
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: June 1, 2001
Last modified: September 7, 2016
This is version 152 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

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.