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Protein

Protein DDI1 homolog 2

Gene

DDI2

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

Functioni

Aspartic protease that mediates the cleavage of NFE2L1/NRF1 at 'Leu-104', thereby promoting release of NFE2L1/NRF1 from the endoplasmic reticulum membrane (PubMed:27676298, PubMed:27528193). Ubiquitination of NFE2L1/NRF1 is a prerequisite for cleavage, suggesting that DDI2 specifically recognizes and binds ubiquitinated NFE2L1/NRF1 (PubMed:27528193).2 Publications

Caution

The protein was initially thought to be catalytically inactive (PubMed:27461074). It was later shown that it has aspartyl protease activity and mediates cleavage of NFE2L1/NRF1 (PubMed:27676298).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei2521 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAspartyl protease, Hydrolase, Protease

Protein family/group databases

MEROPSiA28.003

Names & Taxonomyi

Protein namesi
Recommended name:
Protein DDI1 homolog 2Curated (EC:3.4.23.-1 Publication)
Gene namesi
Name:DDI2Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000197312.11
HGNCiHGNC:24578 DDI2
neXtProtiNX_Q5TDH0

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi252D → N: Abolishes aspartic protease activity. 1 Publication1

Organism-specific databases

DisGeNETi84301
OpenTargetsiENSG00000197312
PharmGKBiPA142672004

Polymorphism and mutation databases

BioMutaiDDI2
DMDMi74746201

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002870901 – 399Protein DDI1 homolog 2Add BLAST399

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei104PhosphothreonineCombined sources1
Modified residuei106PhosphoserineCombined sources1
Modified residuei121PhosphoserineCombined sources1
Modified residuei128PhosphoserineCombined sources1
Modified residuei150PhosphoserineCombined sources1
Modified residuei194PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ5TDH0
MaxQBiQ5TDH0
PaxDbiQ5TDH0
PeptideAtlasiQ5TDH0
PRIDEiQ5TDH0
ProteomicsDBi65023
65024 [Q5TDH0-2]
65025 [Q5TDH0-3]

PTM databases

iPTMnetiQ5TDH0
PhosphoSitePlusiQ5TDH0

Expressioni

Gene expression databases

BgeeiENSG00000197312 Expressed in 201 organ(s), highest expression level in liver
CleanExiHS_DDI2
ExpressionAtlasiQ5TDH0 baseline and differential
GenevisibleiQ5TDH0 HS

Organism-specific databases

HPAiHPA043119
HPA043225

Interactioni

Subunit structurei

Homodimer.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi124027, 30 interactors
STRINGi9606.ENSP00000417748

Structurei

Secondary structure

1399
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ5TDH0
SMRiQ5TDH0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 81Ubiquitin-likePROSITE-ProRule annotationAdd BLAST81

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi376 – 395Ubiquitin-binding1 PublicationAdd BLAST20

Sequence similaritiesi

Belongs to the DDI1 family.Curated

Phylogenomic databases

eggNOGiKOG0012 Eukaryota
ENOG410XPA0 LUCA
GeneTreeiENSGT00510000047125
HOGENOMiHOG000234736
HOVERGENiHBG058638
InParanoidiQ5TDH0
KOiK11885
OMAiCAERCHI
OrthoDBiEOG091G0CIP
PhylomeDBiQ5TDH0
TreeFamiTF333421

Family and domain databases

CDDicd01796 DDI1_N, 1 hit
cd05479 RP_DDI, 1 hit
Gene3Di2.40.70.10, 1 hit
InterProiView protein in InterPro
IPR033322 DDI1
IPR033882 DDI1_N
IPR019103 Peptidase_aspartic_DDI1-type
IPR021109 Peptidase_aspartic_dom_sf
IPR029071 Ubiquitin-like_domsf
IPR000626 Ubiquitin_dom
PANTHERiPTHR12917 PTHR12917, 1 hit
PfamiView protein in Pfam
PF09668 Asp_protease, 1 hit
PF00240 ubiquitin, 1 hit
SUPFAMiSSF50630 SSF50630, 1 hit
SSF54236 SSF54236, 1 hit
PROSITEiView protein in PROSITE
PS50053 UBIQUITIN_2, 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 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q5TDH0-1) [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
MLLTVYCVRR DLSEVTFSLQ VDADFELHNF RALCELESGI PAAESQIVYA
60 70 80 90 100
ERPLTDNHRS LASYGLKDGD VVILRQKENA DPRPPVQFPN LPRIDFSSIA
110 120 130 140 150
VPGTSSPRQR QPPGTQQSHS SPGEITSSPQ GLDNPALLRD MLLANPHELS
160 170 180 190 200
LLKERNPPLA EALLSGDLEK FSRVLVEQQQ DRARREQERI RLFSADPFDL
210 220 230 240 250
EAQAKIEEDI RQQNIEENMT IAMEEAPESF GQVVMLYINC KVNGHPVKAF
260 270 280 290 300
VDSGAQMTIM SQACAERCNI MRLVDRRWAG IAKGVGTQKI IGRVHLAQVQ
310 320 330 340 350
IEGDFLPCSF SILEEQPMDM LLGLDMLKRH QCSIDLKKNV LVIGTTGSQT
360 370 380 390
TFLPEGELPE CARLAYGAGR EDVRPEEIAD QELAEALQKS AEDAERQKP
Length:399
Mass (Da):44,523
Last modified:December 21, 2004 - v1
Checksum:iD04FCA9ECECCD1D8
GO
Isoform 2 (identifier: Q5TDH0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     212-399: Missing.

Note: No experimental confirmation available.
Show »
Length:211
Mass (Da):23,721
Checksum:i6B1027CC287835C6
GO
Isoform 3 (identifier: Q5TDH0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     395-399: ERQKP → GIWDGQTLQYLLLMGKPGKCGLQKG

Show »
Length:419
Mass (Da):46,571
Checksum:iECD977FFB8DD56C9
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YI90H0YI90_HUMAN
Protein DDI1 homolog 2
DDI2
103Annotation score:
H0YII4H0YII4_HUMAN
Protein DDI1 homolog 2
DDI2
99Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_025297212 – 399Missing in isoform 2. 1 PublicationAdd BLAST188
Alternative sequenceiVSP_025298395 – 399ERQKP → GIWDGQTLQYLLLMGKPGKC GLQKG in isoform 3. Curated5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK293006 mRNA Translation: BAF85695.1
AL121992 Genomic DNA No translation available.
CH471167 Genomic DNA Translation: EAW51743.1
BC006011 mRNA Translation: AAH06011.1
BN000122 mRNA Translation: CAD67552.1
CCDSiCCDS30607.1 [Q5TDH0-1]
RefSeqiNP_115717.3, NM_032341.4 [Q5TDH0-1]
UniGeneiHs.718857

Genome annotation databases

EnsembliENST00000480945; ENSP00000417748; ENSG00000197312 [Q5TDH0-1]
GeneIDi84301
KEGGihsa:84301
UCSCiuc001awz.4 human [Q5TDH0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK293006 mRNA Translation: BAF85695.1
AL121992 Genomic DNA No translation available.
CH471167 Genomic DNA Translation: EAW51743.1
BC006011 mRNA Translation: AAH06011.1
BN000122 mRNA Translation: CAD67552.1
CCDSiCCDS30607.1 [Q5TDH0-1]
RefSeqiNP_115717.3, NM_032341.4 [Q5TDH0-1]
UniGeneiHs.718857

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N7DNMR-A1-76[»]
4RGHX-ray1.90A/B212-360[»]
5K57NMR-A116-212[»]
ProteinModelPortaliQ5TDH0
SMRiQ5TDH0
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124027, 30 interactors
STRINGi9606.ENSP00000417748

Protein family/group databases

MEROPSiA28.003

PTM databases

iPTMnetiQ5TDH0
PhosphoSitePlusiQ5TDH0

Polymorphism and mutation databases

BioMutaiDDI2
DMDMi74746201

Proteomic databases

EPDiQ5TDH0
MaxQBiQ5TDH0
PaxDbiQ5TDH0
PeptideAtlasiQ5TDH0
PRIDEiQ5TDH0
ProteomicsDBi65023
65024 [Q5TDH0-2]
65025 [Q5TDH0-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000480945; ENSP00000417748; ENSG00000197312 [Q5TDH0-1]
GeneIDi84301
KEGGihsa:84301
UCSCiuc001awz.4 human [Q5TDH0-1]

Organism-specific databases

CTDi84301
DisGeNETi84301
EuPathDBiHostDB:ENSG00000197312.11
GeneCardsiDDI2
HGNCiHGNC:24578 DDI2
HPAiHPA043119
HPA043225
neXtProtiNX_Q5TDH0
OpenTargetsiENSG00000197312
PharmGKBiPA142672004
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0012 Eukaryota
ENOG410XPA0 LUCA
GeneTreeiENSGT00510000047125
HOGENOMiHOG000234736
HOVERGENiHBG058638
InParanoidiQ5TDH0
KOiK11885
OMAiCAERCHI
OrthoDBiEOG091G0CIP
PhylomeDBiQ5TDH0
TreeFamiTF333421

Miscellaneous databases

ChiTaRSiDDI2 human
GenomeRNAii84301
PROiPR:Q5TDH0

Gene expression databases

BgeeiENSG00000197312 Expressed in 201 organ(s), highest expression level in liver
CleanExiHS_DDI2
ExpressionAtlasiQ5TDH0 baseline and differential
GenevisibleiQ5TDH0 HS

Family and domain databases

CDDicd01796 DDI1_N, 1 hit
cd05479 RP_DDI, 1 hit
Gene3Di2.40.70.10, 1 hit
InterProiView protein in InterPro
IPR033322 DDI1
IPR033882 DDI1_N
IPR019103 Peptidase_aspartic_DDI1-type
IPR021109 Peptidase_aspartic_dom_sf
IPR029071 Ubiquitin-like_domsf
IPR000626 Ubiquitin_dom
PANTHERiPTHR12917 PTHR12917, 1 hit
PfamiView protein in Pfam
PF09668 Asp_protease, 1 hit
PF00240 ubiquitin, 1 hit
SUPFAMiSSF50630 SSF50630, 1 hit
SSF54236 SSF54236, 1 hit
PROSITEiView protein in PROSITE
PS50053 UBIQUITIN_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDDI2_HUMAN
AccessioniPrimary (citable) accession number: Q5TDH0
Secondary accession number(s): A8KAE1, Q7RTZ0, Q9BRT1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: December 21, 2004
Last modified: October 10, 2018
This is version 125 of the entry and version 1 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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