DEPDC5

DEPDC5
Identifiers
Gene ontology
Molecular function	protein-containing complex binding; GTPase activator activity;
Cellular component	cytoplasm; perinuclear region of cytoplasm; GATOR1 complex; cytosol; lysosome; lysosomal membrane; membrane; Cul3-RING ubiquitin ligase complex; intracellular anatomical structure;
Biological process	negative regulation of TOR signaling; cellular response to amino acid starvation; intracellular signal transduction; positive regulation of GTPase activity; negative regulation of TORC1 signaling; regulation of autophagy;
	Sources:Amigo / QuickGO

Ensembl


ENSG00000100150


ENSMUSG00000037426

UniProt


O75140


P61460

RefSeq (mRNA)

NM_001007188 NM_001136029 NM_001242896 NM_001242897 NM_014662
NM_001363852 NM_001363854 NM_001364318 NM_001364319 NM_001364320 NM_001369901 NM_001369902 NM_001369903


NM_001025426 NM_001170567 NM_177786 NM_001360014

RefSeq (protein)

NP_001007189 NP_001129501 NP_001229825 NP_001229826 NP_055477
NP_001350781 NP_001350783 NP_001351247 NP_001351248 NP_001351249 NP_001356830 NP_001356831 NP_001356832

NP_001020597 NP_001164038 NP_808454 NP_001346943 NP_001391242
NP_001391243 NP_001391244 NP_001391245 NP_001391246 NP_001391247 NP_001391248 NP_001391249 NP_001391261 NP_001391262 NP_001391263 NP_001391264 NP_001391265

Location (UCSC)

Chr 22: 31.75 – 31.91 Mb

Chr 5: 33.02 – 33.15 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

DEPDC5 (or DEP domain-containing 5) is a human protein of poorly understood function but has been associated with cancer in several studies.^[5]^[6] It is encoded by a gene of the same name, located on chromosome 22.

Function

The function of DEPDC5 is not yet known, but it has been implicated in intracellular signal transduction based on homology between the DEP domains of DEPDC5 and Dishevelled-1 (DVL1).^[7]

Mutations in this gene have been associated to cases of

focal epilepsy

(doi:10.1038/ng.2601).

Gene

In

SNP (rs1012068) that has been associated with a 2-fold hepatocellular carcinoma-risk increase.^[5]

Structure

Domains

DEP

The
alpha helices contained within the domain.^[9]

While its exact function is not known, the DEPDC5 DEP domain has the highest structural similarity to the DEP domain of DVL1 when performing a
plasma membrane as part of the Wnt signaling pathway.^[11]

DUF 3608

The DUF 3608 domain sits 99 amino acids from the N-terminus and itself spans 280 amino acids. PELE predicts at least one beta sheet and two alpha helices within this domain.^[12] It also contains 26 highly conserved residues and several post-translation modifications. Both occurrences are addressed later in this article.
Evidence for the function of DUF 3608 has been uncovered in the yeast homolog Iml1p. Imlp1's DUF 3608 is thought to aid in binding to two protein partners, Npr2 and Npr3. Together, these three proteins form the Iml1-Npr2-Npr3 complex and are involved in "non-nitrogen starvation" autophagy regulation. The researchers who uncovered this propose renaming DUF 3608 to RANS (Required for Autophagy induced under Non-nitrogen Starvation conditions).^[13]

Secondary Structure

Based on unanimous consensus by the secondary structure prediction tool PELE, DEPDC5 contains at least ten alpha helices and nine beta sheets. The locations of these secondary structures are illustrated in the image below: red highlights are alpha helices and blue highlights are beta sheets.

Homology

Orthologs

chimpanzees.^[14]

The following table summarizes an analysis of 20 proteins orthologous to human DEPDC5.

Species Common Name NCBI Accession # NCBI Name Length Sequence Identity Sequence Similarity Years Since Divergence from Human (mya)^[15]

Pan troglodytes
Chimpanzee XP_003317262 DEPDC5 1572 aa 99% 99% 6.4

Nomascus leucogenys
Gibbon XP_003258163 DEPDC5 1602 aa 99% 99% 20.4

Mus musculus
Mouse NP_001164038 DEPDC5 1591 aa 94% 96% 92.4

Bos Taurus
Cow XP_002694678 DEPDC5 1593 aa 94% 96% 94.4

Sorex araneus
Shrew ACE77702 DEPDC5 1570 aa 94% 96% 94.4

Monodelphis domestica
Possum XP_001378772 DEPDC5 1522 aa 89% 93% 163.9

Gallus gallus
Chicken XP_415249 DEPDC5 1592 aa 88% 93% 301.7

Meleagris gallopavo
Turkey XP_003211073 DEPDC5 1592 aa 88% 93% 301.7

Taeniopygia guttata
Zebra finch XP_002199825 DEPDC5 1572 aa 87% 92% 301.7

Xenopus tropicalis
Frog XP_002931964 DEPDC5-like 1574 aa 79% 86% 371.2

Danio rerio
Zebra fish XP_691450 DEPDC5-like 1590 aa 75% 84% 400.1

Oreochromis niloticus
Cichlid XP_003459226 DEPDC5 1577 aa 74% 82% 400.1

Strongylocentrotus purpuratus Sea urchin XP_794020 similar to DEPDC5 1608 aa 43% 57% 742.9

Drosophila melanogaster Drosophila NP_647618 GC12090 1471 aa 41% 57% 782.7

Pediculus humanus corporis
Louse XP_002429401 DEPDC, putative 1538 aa 38% 53% 782.7

Anopheles gambiae Mosquito XP_308760 AGAP007010-PA 1640 aa 36% 51% 782.7

Ascaris suum Ascaris ADY40551 DEPDCp5 1359 aa 31% 51% 937.5

Ustilago maydis
Corn smut XP_757759 vacuolar-associated protein Iml1 1867 aa 23% 52% 1215.8

Saccharomyces cerevisiae Yeast NP_012672 Iml1p 1584 aa 20% 50% 1215.8

Albugo laibachii White rust CCA27519 vacuolar membrane-associated protein putative 1591 aa 20% 46% 1362

30 residues have been conserved since animals and fungi diverged, with 26 of these located in the DUF 3608 domain.
clades
are aligned to the human DUF 3608 with completely conserved residues colored green.

Paralogs

There are no known human DEPDC5
paralogs,^[14] but there are 64 human proteins containing a homologous DEP domain.^[17] There are also no identified paralogs for the yeast protein Iml1, the most distantly related ortholog of human DEPDC5.^[14]

Expression

DEPDC5 expression has been characterized as ubiquitous in human tissue by
RT-PCR analysis^[18] and in DNA microarray studies as displayed in the chart below.^[19]

One study on patients with hepatocellular carcinoma found higher DEPDC5 expression in
cell line^[20] and low expression in P116 (ZAP70 negative) cell line.^[21]

Post-translational Modifications

The following
ExPASy^[22] and PhosphoSite Plus^[23]
for the human DEPDC5 protein.

Post-translational Modification Number/Loci Source

Phosphorylation 133/(Ser: 87 Thr: 23 Tyr: 23) NetPhos

6/S579, S582, S1499, Y1515, Y1519, Y1543 PhosphoSite Plus

Glycation 29/5, 8, 13, 14, 28, 34, 56, 59, 64, 93, 131, 147, 229, 247, 256, 319, 436, 528, 609, 710, 862, 878, 1008, 1185, 1233, 1387, 1408, 1499, 1567, 1597 NetGlycate

N-glycosylation
site 9/N201, N298, N311, N384, N684, N1157, N1377, N1444, N1529 NetNGlyc

Sulfation 3/Y397, Y459, Y462 Sulfinator

Sumoylation
2/K59, K147 SUMOsp Archived 2013-05-10 at the Wayback Machine

Propeptide cleavage 2/R1004-M1005, R1528-N1529 ProP

O-glycosylation
0 NetOGlyc

C-mannosylation 0 NetCGlyc

Myristoylation 0 Myristoylation

Prenylation 0 PrePS Archived 2012-02-08 at the Wayback Machine

Acetylation 0 NetAcet

Interaction

DEPDC5 may possibly interact with the
coimmunoprecipitation^[24] and the transcription factor MYC.^[25] DEPDC5 is in the "GATOR1" complex with NPRL2 and NPRL3.^[26]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000100150 – Ensembl, May 2017

^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000037426 – Ensembl, May 2017

^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

^
S2CID 205357903
.

^
S2CID 45003453
.

^ ^a ^b "GeneCards: DEP domain containing 5".

^ "AceView: Homo sapiens complex locus DEPDC5, encoding DEP domain containing 5".

^ "SWISS-MODEL".

^ "NCBI: CBLAST".

PMID 15353129
.

^ "Biology Workbench: PELE".

PMID 21900499
.

^ ^a ^b ^c "NCBI".

^ "TimeTree".

^ "Biology Workbench: ClustalW".

S2CID 45722575
.

PMID 9734811
.

S2CID 10007258
.

PMID 17159920
.

PMID 14624253.

^ "ExPASy Proteomic Tools: Post-translational modification prediction". Archived from the original on 2012-04-24. Retrieved 2012-05-08.

^ "PhosphoSite Plus: DEPDC5".

PMID 16713569
.

PMID 17093053
.

PMID 23723238
.

Retrieved from "https://en.wikipedia.org/w/index.php?title=DEPDC5&oldid=1212924927"

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000100150 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000037426 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[one-5] 
S2CID 205357903
.

[two-6] 
S2CID 45003453
.

[five-7] "GeneCards: DEP domain containing 5".

[three-8] "AceView: Homo sapiens complex locus DEPDC5, encoding DEP domain containing 5".

[9] "SWISS-MODEL".

[10] "NCBI: CBLAST".

[11] PMID 15353129
.

[12] "Biology Workbench: PELE".

[13] PMID 21900499
.

[four-14] "NCBI".

[15] "TimeTree".

[seven-16] "Biology Workbench: ClustalW".

[eight-17] S2CID 45722575
.

[18] PMID 9734811
.

[19] S2CID 10007258
.

[20] PMID 17159920
.

[21] PMID 14624253.

[22] "ExPASy Proteomic Tools: Post-translational modification prediction". Archived from the original on 2012-04-24. Retrieved 2012-05-08.

[23] "PhosphoSite Plus: DEPDC5".

[24] PMID 16713569
.

[25] PMID 17093053
.

[26] PMID 23723238
.

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