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Protein

Replication stress response regulator SDE2

Gene

SDE2

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

Functioni

Involved in both DNA replication and cell cycle control (PubMed:27906959). Unprocessed SDE2 interacts with PCNA via its PIP-box. The interaction with PCNA prevents monoubiquitination of the latter thereby inhibiting translesion DNA synthesis. The binding of SDE2 to PCNA also leads to processing of SDE2 by an unidentified deubiquinating enzyme, cleaving off the N-terminal ubiquitin-like domain. The resulting mature SDE2 is degraded by the DCX(DTL) complex in a cell cycle- and DNA damage dependent manner (PubMed:27906959). Binding of SDE2 to PCNA is necessary to counteract damage due to ultraviolet light induced replication stress. The complete degradation of SDE2 is necessary to allow S-phase progression (PubMed:27906959).1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding
Biological processCell cycle, Cell division, DNA replication, Mitosis

Names & Taxonomyi

Protein namesi
Recommended name:
Replication stress response regulator SDE2Curated
Gene namesi
Name:SDE2
Synonyms:C1orf55
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000143751.9.
HGNCiHGNC:26643. SDE2.
neXtProtiNX_Q6IQ49.

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi47 – 48FF → AA: No binding to PCNA; no cleavage at Gly-77. 1 Publication2
Mutagenesisi76 – 77GG → AA: No cleavage at Gly-77. 1 Publication2

Organism-specific databases

OpenTargetsiENSG00000143751.
PharmGKBiPA142672506.

Polymorphism and mutation databases

BioMutaiSDE2.
DMDMi74748828.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00004425211 – 77UBL1 PublicationAdd BLAST77
ChainiPRO_000028608478 – 451Replication stress response regulator SDE2Add BLAST374

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei266PhosphoserineBy similarity1
Modified residuei274PhosphothreonineCombined sources1
Modified residuei278PhosphoserineCombined sources1
Modified residuei319PhosphothreonineCombined sources1
Modified residuei326PhosphoserineBy similarity1

Post-translational modificationi

The protein is cleaved at Gly-77 by a deubiquinating enzyme to form the active SDE2.1 Publication
Both SDE2-UBL and the mature SDE2 are polyubiquitinated.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei77 – 78Cleavage1 Publication2

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ6IQ49.
MaxQBiQ6IQ49.
PaxDbiQ6IQ49.
PeptideAtlasiQ6IQ49.
PRIDEiQ6IQ49.

PTM databases

iPTMnetiQ6IQ49.
PhosphoSitePlusiQ6IQ49.
SwissPalmiQ6IQ49.

Expressioni

Gene expression databases

BgeeiENSG00000143751.
CleanExiHS_C1orf55.
GenevisibleiQ6IQ49. HS.

Organism-specific databases

HPAiHPA028467.
HPA031255.
HPA031256.

Interactioni

Protein-protein interaction databases

BioGridi127881. 9 interactors.
IntActiQ6IQ49. 4 interactors.
STRINGi9606.ENSP00000272091.

Structurei

3D structure databases

ProteinModelPortaliQ6IQ49.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini396 – 430SAP1 PublicationAdd BLAST35

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili109 – 149Sequence analysisAdd BLAST41

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi39 – 52PIP-box1 PublicationAdd BLAST14

Domaini

The PIP-box (PCNA interacting peptide) motif mediates both the interaction with PCNA and cleavage of the SDE2 precursor by a deubiquinating enzyme.1 Publication
The SAP domain is necessary for specific binding to DNA.1 Publication
The propeptide displays a ubiquitin-like fold.1 Publication

Sequence similaritiesi

Belongs to the SDE2 family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG2827. Eukaryota.
ENOG4111WBQ. LUCA.
GeneTreeiENSGT00530000063402.
HOGENOMiHOG000013081.
HOVERGENiHBG107551.
InParanoidiQ6IQ49.
OMAiKLVEPKH.
OrthoDBiEOG091G0NOA.
PhylomeDBiQ6IQ49.
TreeFamiTF314323.

Family and domain databases

InterProiView protein in InterPro
IPR024974. Sde2_N.
PfamiView protein in Pfam
PF13019. Telomere_Sde2. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: Q6IQ49-1) [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
MAEAAALVWI RGPGFGCKAV RCASGRCTVR DFIHRHCQDQ NVPVENFFVK
60 70 80 90 100
CNGALINTSD TVQHGAVYSL EPRLCGGKGG FGSMLRALGA QIEKTTNREA
110 120 130 140 150
CRDLSGRRLR DVNHEKAMAE WVKQQAEREA EKEQKRLERL QRKLVEPKHC
160 170 180 190 200
FTSPDYQQQC HEMAERLEDS VLKGMQAASS KMVSAEISEN RKRQWPTKSQ
210 220 230 240 250
TDRGASAGKR RCFWLGMEGL ETAEGSNSES SDDDSEEAPS TSGMGFHAPK
260 270 280 290 300
IGSNGVEMAA KFPSGSQRAR VVNTDHGSPE QLQIPVTDSG RHILEDSCAE
310 320 330 340 350
LGESKEHMES RMVTETEETQ EKKAESKEPI EEEPTGAGLN KDKETEERTD
360 370 380 390 400
GERVAEVAPE ERENVAVAKL QESQPGNAVI DKETIDLLAF TSVAELELLG
410 420 430 440 450
LEKLKCELMA LGLKCGGTLQ ERAARLFSVR GLAKEQIDPA LFAKPLKGKK

K
Length:451
Mass (Da):49,742
Last modified:July 5, 2004 - v1
Checksum:iD7C19152E0051A21
GO
Isoform 2 (identifier: Q6IQ49-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     53-64: Missing.

Note: No experimental confirmation available.
Show »
Length:439
Mass (Da):48,505
Checksum:i413D6C606BC71AA5
GO
Isoform 3 (identifier: Q6IQ49-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-142: MAEAAALVWI...EQKRLERLQR → MEHSLTPVTQ...VLRLRRQPIE

Note: No experimental confirmation available.
Show »
Length:356
Mass (Da):39,367
Checksum:iF581B893396191BB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti162E → G in BAC87130 (PubMed:14702039).Curated1
Sequence conflicti229E → D in BAC03952 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032068312M → I. Corresponds to variant dbSNP:rs34348128Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0249811 – 142MAEAA…ERLQR → MEHSLTPVTQCSMELFIVWN PDFAVEKEVLDLCSEHLVLR LRRQPIE in isoform 3. 1 PublicationAdd BLAST142
Alternative sequenceiVSP_02498253 – 64Missing in isoform 2. 1 PublicationAdd BLAST12

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK092701 mRNA. Translation: BAC03952.1.
AK127780 mRNA. Translation: BAC87130.1.
AK291008 mRNA. Translation: BAF83697.1.
AL133288 Genomic DNA. No translation available.
CH471098 Genomic DNA. Translation: EAW69769.1.
BC071563 mRNA. Translation: AAH71563.1.
CCDSiCCDS41473.1. [Q6IQ49-1]
RefSeqiNP_689821.3. NM_152608.3. [Q6IQ49-1]
UniGeneiHs.520192.

Genome annotation databases

EnsembliENST00000272091; ENSP00000272091; ENSG00000143751. [Q6IQ49-1]
GeneIDi163859.
KEGGihsa:163859.
UCSCiuc001hpu.5. human. [Q6IQ49-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSDE2_HUMAN
AccessioniPrimary (citable) accession number: Q6IQ49
Secondary accession number(s): A8K4P3
, Q5TD36, Q6ZS26, Q8NAG7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: July 5, 2004
Last modified: February 28, 2018
This is version 105 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

Complete proteome, Reference proteome