POLDIP2

POLDIP2
Identifiers
Aliases	POLDIP2 , PDIP38, POLD4, p38, polymerase (DNA) delta interacting protein 2, DNA polymerase delta interacting protein 2
External IDs	OMIM: 611519 MGI: 1915061 HomoloGene: 9201 GeneCards: POLDIP2
Gene location (Human)
Chr.	Chromosome 17 (human)
End	28,357,527 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	78,413,562 bp
RNA expression pattern
	Top expressed in
	gastrocnemius muscle; ; Right adrenal gland; ; Left adrenal gland; ; right lobe of liver; ; left ventricle; ; islet of Langerhans; ; kidney; ; body of pancreas; ; rectum; ; skeletal muscle tissue;
	Top expressed in
	spermatocyte; ; spermatid; ; brown adipose tissue; ; vastus lateralis muscle; ; proximal tubule; ; tibialis anterior muscle; ; triceps brachii muscle; ; temporal muscle; ; soleus muscle; ; external carotid artery;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	DNA binding ; protein binding ;
Cellular component	mitochondrial nucleoid ; mitochondrion ; nucleus ;
Biological process	mitochondrion morphogenesis ; negative regulation of macroautophagy ; positive regulation of mitotic cell cycle ;
	Sources:Amigo / QuickGO
Orthologs
	26073
	67811
	ENSG00000004142
	ENSMUSG00000001100
	Q9Y2S7
	Q91VA6
	NM_015584 ; NM_001290145
	NM_026389
	NP_001277074 ; NP_056399
	NP_080665
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated October 14, 2022

Polymerase delta-interacting protein 2 also known as Polymerase delta-interacting protein of 38 kDa (PDIP38) is encoded by the POLDIP2 gene in humans.^[5]^[6]

This gene encodes a protein that interacts with the DNA polymerase delta p50 subunit. The encoded protein also interacts with proliferating cell nuclear antigen. Some transcripts of this gene overlap in a tail-to-tail orientation with the gene for tumor necrosis factor, alpha-induced protein 1 (TNFAIP1).^[6] POLDIP2 / PDIP38 is a moonlighting protein that has been identified in both the nucleus ^[7] and the mitochondrion ^[8]^[9]

Interactions

In the nucleus, POLDIP2 has been shown to interact with PCNA,^[5] while in the mitochondrion POLDIP2 has been shown to interact with proteins constituting the mitochondrial DNA nucleoid ^[10] and the AAA+ protease CLPXP ^[9]^[11] where it modulates both the specificity and stability of this proteolytic machine.

Related Research Articles

Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication. PCNA is a homotrimer and achieves its processivity by encircling the DNA, where it acts as a scaffold to recruit proteins involved in DNA replication, DNA repair, chromatin remodeling and epigenetics.

DnaJ homolog subfamily A member 3, mitochondrial, also known as Tumorous imaginal disc 1 (TID1), is a protein that in humans is encoded by the DNAJA3 gene on chromosome 16. This protein belongs to the DNAJ/Hsp40 protein family, which is known for binding and activating Hsp70 chaperone proteins to perform protein folding, degradation, and complex assembly. As a mitochondrial protein, it is involved in maintaining membrane potential and mitochondrial DNA (mtDNA) integrity, as well as cellular processes such as cell movement, growth, and death. Furthermore, it is associated with a broad range of diseases, including neurodegenerative diseases, inflammatory diseases, and cancers.

DNA polymerase subunit gamma is an enzyme that in humans is encoded by the POLG gene. Mitochondrial DNA polymerase is heterotrimeric, consisting of a homodimer of accessory subunits plus a catalytic subunit. The protein encoded by this gene is the catalytic subunit of mitochondrial DNA polymerase. Defects in this gene are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE).

Replication factor C subunit 4 is a protein that in humans is encoded by the RFC4 gene.

Replication factor C subunit 2 is a protein that in humans is encoded by the RFC2 gene.

Replication factor C subunit 3 is a protein that in humans is encoded by the RFC3 gene.

Replication factor C subunit 5 is a protein that in humans is encoded by the RFC5 gene.

Mitochondrial import receptor subunit TOM20 homolog is a protein that in humans is encoded by the TOMM20 gene. TOM20 is one of the receptor systems of the TOM complex in the outer mitochondrial membrane (OMM).

DNA polymerase delta subunit 2 is an enzyme that in humans is encoded by the POLD2 gene. It is a component of the DNA polymerase delta complex.

Protein reversionless 3-like (REV3L) also known as DNA polymerase zeta catalytic subunit (POLZ) is an enzyme that in humans is encoded by the REV3L gene.

Mediator of RNA polymerase II transcription subunit 31 is a protein in humans encoded by the MED31 gene. It represents subunit Med31 of the Mediator complex. The family contains the Saccharomyces cerevisiae SOH1 homologues. SOH1 is responsible for the repression of temperature sensitive growth of the HPR1 mutant and has been found to be a component of the RNA polymerase II transcription complex. SOH1 not only interacts with factors involved in DNA repair, but transcription as well. Thus, the SOH1 protein may serve to couple these two processes.

DNA polymerase delta subunit 3 is an enzyme that in humans is encoded by the POLD3 gene. It is a component of the DNA polymerase delta complex.

39S ribosomal protein L12, mitochondrial is a protein that in humans is encoded by the MRPL12 gene.

snRNA-activating protein complex subunit 1 is a protein that in humans is encoded by the SNAPC1 gene.

Polymerase delta-interacting protein 3 is an enzyme that in humans is encoded by the POLDIP3 gene.

POLRMT is a symbol of RNA polymerase mitochondrial

BTB/POZ domain-containing protein KCTD13 is a protein that in humans is encoded by the KCTD13 gene.

SEC23-interacting protein is a protein that in humans is encoded by the SEC23IP gene.

DNA polymerase delta subunit 4, also known as DNA polymerase delta subunit p12, is a protein that in humans is encoded by the POLD4 gene. It is a component of the DNA polymerase delta complex.

DNA polymerase epsilon catalytic subunit is an enzyme that in humans is encoded by the POLE gene. It is the central catalytic subunit of DNA polymerase epsilon.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000004142 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000001100 - 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.
1 2 Liu L, Rodriguez-Belmonte EM, Mazloum N, Xie B, Lee MY (March 2003). "Identification of a novel protein, PDIP38, that interacts with the p50 subunit of DNA polymerase delta and proliferating cell nuclear antigen". The Journal of Biological Chemistry. 278 (12): 10041–7. doi: 10.1074/jbc.M208694200 . PMID 12522211.
1 2 "Entrez Gene: POLDIP2 polymerase (DNA-directed), delta interacting protein 2".
↑ Wong A, Zhang S, Mordue D, Wu JM, Zhang Z, Darzynkiewicz Z, et al. (October 2013). "PDIP38 is translocated to the spliceosomes/nuclear speckles in response to UV-induced DNA damage and is required for UV-induced alternative splicing of MDM2". Cell Cycle. 12 (19): 3184–93. doi:10.4161/cc.26221. PMC 3865014 . PMID 23989611.
↑ Xie B, Li H, Wang Q, Xie S, Rahmeh A, Dai W, Lee MY (June 2005). "Further characterization of human DNA polymerase delta interacting protein 38". The Journal of Biological Chemistry. 280 (23): 22375–84. doi: 10.1074/jbc.M414597200 . PMID 15811854.
1 2 Strack PR, Brodie EJ, Zhan H, Schuenemann VJ, Valente LJ, Saiyed T, et al. (November 2020). "Polymerase delta-interacting protein 38 (PDIP38) modulates the stability and activity of the mitochondrial AAA+ protease CLPXP". Communications Biology. 3 (1): 646. doi:10.1038/s42003-020-01358-6. PMC 7647994 . PMID 33159171.
↑ Cheng X, Kanki T, Fukuoh A, Ohgaki K, Takeya R, Aoki Y, et al. (December 2005). "PDIP38 associates with proteins constituting the mitochondrial DNA nucleoid". Journal of Biochemistry. 138 (6): 673–8. doi:10.1093/jb/mvi169. PMID 16428295.
↑ Paredes F, Sheldon K, Lassègue B, Williams HC, Faidley EA, Benavides GA, et al. (February 2018). "Poldip2 is an oxygen-sensitive protein that controls PDH and αKGDH lipoylation and activation to support metabolic adaptation in hypoxia and cancer". Proceedings of the National Academy of Sciences of the United States of America. 115 (8): 1789–1794. Bibcode:2018PNAS..115.1789P. doi: 10.1073/pnas.1720693115 . PMC 5828627 . PMID 29434038.

Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, et al. (October 2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Research. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934 . PMID 11042152.
Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948 . PMID 11076863.
Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (September 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732 . PMID 11256614.
Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, et al. (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930 . PMID 15489336.
Xie B, Li H, Wang Q, Xie S, Rahmeh A, Dai W, Lee MY (June 2005). "Further characterization of human DNA polymerase delta interacting protein 38". The Journal of Biological Chemistry. 280 (23): 22375–84. doi: 10.1074/jbc.M414597200 . PMID 15811854.
Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, et al. (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. hdl: 11858/00-001M-0000-0010-8592-0 . PMID 16169070. S2CID 8235923.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, et al. (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415-8. doi:10.1093/nar/gkj139. PMC 1347501 . PMID 16381901.
Klaile E, Müller MM, Kannicht C, Otto W, Singer BB, Reutter W, et al. (September 2007). "The cell adhesion receptor carcinoembryonic antigen-related cell adhesion molecule 1 regulates nucleocytoplasmic trafficking of DNA polymerase delta-interacting protein 38". The Journal of Biological Chemistry. 282 (36): 26629–40. doi: 10.1074/jbc.M701807200 . PMID 17623671.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000004142 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000001100 - 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.

[pmid12522211-5] 1 2 Liu L, Rodriguez-Belmonte EM, Mazloum N, Xie B, Lee MY (March 2003). "Identification of a novel protein, PDIP38, that interacts with the p50 subunit of DNA polymerase delta and proliferating cell nuclear antigen". The Journal of Biological Chemistry. 278 (12): 10041–7. doi: 10.1074/jbc.M208694200 . PMID 12522211.

[entrez-6] 1 2 "Entrez Gene: POLDIP2 polymerase (DNA-directed), delta interacting protein 2".

[7] Wong A, Zhang S, Mordue D, Wu JM, Zhang Z, Darzynkiewicz Z, et al. (October 2013). "PDIP38 is translocated to the spliceosomes/nuclear speckles in response to UV-induced DNA damage and is required for UV-induced alternative splicing of MDM2". Cell Cycle. 12 (19): 3184–93. doi:10.4161/cc.26221. PMC 3865014 . PMID 23989611.

[8] Xie B, Li H, Wang Q, Xie S, Rahmeh A, Dai W, Lee MY (June 2005). "Further characterization of human DNA polymerase delta interacting protein 38". The Journal of Biological Chemistry. 280 (23): 22375–84. doi: 10.1074/jbc.M414597200 . PMID 15811854.

[:0-9] 1 2 Strack PR, Brodie EJ, Zhan H, Schuenemann VJ, Valente LJ, Saiyed T, et al. (November 2020). "Polymerase delta-interacting protein 38 (PDIP38) modulates the stability and activity of the mitochondrial AAA+ protease CLPXP". Communications Biology. 3 (1): 646. doi:10.1038/s42003-020-01358-6. PMC 7647994 . PMID 33159171.

[10] Cheng X, Kanki T, Fukuoh A, Ohgaki K, Takeya R, Aoki Y, et al. (December 2005). "PDIP38 associates with proteins constituting the mitochondrial DNA nucleoid". Journal of Biochemistry. 138 (6): 673–8. doi:10.1093/jb/mvi169. PMID 16428295.

[11] Paredes F, Sheldon K, Lassègue B, Williams HC, Faidley EA, Benavides GA, et al. (February 2018). "Poldip2 is an oxygen-sensitive protein that controls PDH and αKGDH lipoylation and activation to support metabolic adaptation in hypoxia and cancer". Proceedings of the National Academy of Sciences of the United States of America. 115 (8): 1789–1794. Bibcode:2018PNAS..115.1789P. doi: 10.1073/pnas.1720693115 . PMC 5828627 . PMID 29434038.

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POLDIP2

Contents

Interactions

Related Research Articles

References

Further reading