Harmonizome 3.0

non-SMC element 2, MMS21 homolog (S. cerevisiae)

This gene encodes a member of a family of E3 small ubiquitin-related modifier (SUMO) ligases that mediates the attachment of a SUMO protein to proteins involved in nuclear transport, transcription, chromosome segregation and DNA repair. The encoded protein is part of the structural maintenance of chromosomes (SMC) 5/6 complex which plays a key role genome maintenance, facilitating chromosome segregation and suppressing mitotic recombination. A knockout of the orthologous mouse gene is lethal prior to embryonic day 10.5. Naturally occurring mutations in this gene, that abolish the SUMO ligase activity, are associated with primordial dwarfism and extreme insulin resistance. [provided by RefSeq, Mar 2017]

SUMO-interacting motifs containing 1

Enables SUMO polymer binding activity and peptidase inhibitor activity. Located in PML body and sarcomere. [provided by Alliance of Genome Resources, Mar 2025]

SUMO-interacting motifs containing 1 pseudogene

SUMO/sentrin specific peptidase family member 8

This gene encodes a cysteine protease that is a member of the sentrin-specific protease family. The encoded protein is involved in processing and deconjugation of the ubiquitin-like protein termed, neural precursor cell expressed developmentally downregulated 8. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

succinate-CoA ligase, ADP-forming, beta subunit pseudogene

glutamate-ammonia ligase

The protein encoded by this gene belongs to the glutamine synthetase family. It catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP-dependent reaction. This protein plays a role in ammonia and glutamate detoxification, acid-base homeostasis, cell signaling, and cell proliferation. Glutamine is an abundant amino acid, and is important to the biosynthesis of several amino acids, pyrimidines, and purines. Mutations in this gene are associated with congenital glutamine deficiency, and overexpression of this gene was observed in some primary liver cancer samples. There are six pseudogenes of this gene found on chromosomes 2, 5, 9, 11, and 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

succinate-CoA ligase, ADP-forming, beta subunit pseudogene

succinate-CoA ligase, ADP-forming, beta subunit pseudogene

tubulin tyrosine ligase-like family member 11

Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule cytoskeleton organization. Predicted to act upstream of or within microtubule severing and protein polyglutamylation. Predicted to be located in cytosol. Predicted to be active in ciliary basal body. [provided by Alliance of Genome Resources, Mar 2025]

tubulin tyrosine ligase-like family member 10

Predicted to enable protein-glycine ligase activity, elongating. Predicted to be involved in protein polyglycylation. Predicted to be located in axoneme and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Mar 2025]

tubulin tyrosine ligase-like family member 12

Enables H4K20me3 modified histone binding activity and tubulin binding activity. Involved in negative regulation of type I interferon-mediated signaling pathway and regulation of mitotic cell cycle. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Mar 2025]

ligase IV, DNA, ATP-dependent

The protein encoded by this gene is a DNA ligase that joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. This protein is essential for V(D)J recombination and DNA double-strand break (DSB) repair through nonhomologous end joining (NHEJ). This protein forms a complex with the X-ray repair cross complementing protein 4 (XRCC4), and further interacts with the DNA-dependent protein kinase (DNA-PK). Both XRCC4 and DNA-PK are known to be required for NHEJ. The crystal structure of the complex formed by this protein and XRCC4 has been resolved. Defects in this gene are the cause of LIG4 syndrome. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

ligase I, DNA, ATP-dependent

This gene encodes a member of the ATP-dependent DNA ligase protein family. The encoded protein functions in DNA replication, recombination, and the base excision repair process. Mutations in this gene that lead to DNA ligase I deficiency result in immunodeficiency and increased sensitivity to DNA-damaging agents. Disruption of this gene may also be associated with a variety of cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ligase III, DNA, ATP-dependent

This gene is a member of the DNA ligase family. Each member of this family encodes a protein that catalyzes the joining of DNA ends but they each have a distinct role in DNA metabolism. The protein encoded by this gene is involved in excision repair and is located in both the mitochondria and nucleus, with translation initiation from the upstream start codon allowing for transport to the mitochondria and translation initiation from a downstream start codon allowing for transport to the nucleus. Additionally, alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

succinate-CoA ligase, ADP-forming, beta subunit pseudogene 1

succinate-CoA ligase, ADP-forming, beta subunit pseudogene 2

succinate-CoA ligase, ADP-forming, beta subunit pseudogene 3

tubulin tyrosine ligase-like family member 13, pseudogene

Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule bundle formation. Predicted to be located in cytosol. Predicted to be active in ciliary basal body. [provided by Alliance of Genome Resources, Mar 2025]

phosphopantothenate--cysteine ligase pseudogene

succinate-CoA ligase, ADP-forming, beta subunit pseudogene

succinate-CoA ligase, ADP-forming, beta subunit pseudogene

5,10-methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclo-ligase)

The protein encoded by this gene is an enzyme that catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate, a precursor of reduced folates involved in 1-carbon metabolism. An increased activity of the encoded protein can result in an increased folate turnover rate and folate depletion. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

tubulin tyrosine ligase-like family member 5

This gene encodes a member of the tubulin tyrosine ligase like protein family. This protein interacts with two glucocorticoid receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. This protein may function as a coregulator of glucocorticoid receptor mediated gene induction and repression. This protein may also function as an alpha tubulin polyglutamylase.[provided by RefSeq, Feb 2010]

tubulin tyrosine ligase-like family member 4

Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule cytoskeleton organization and protein polyglutamylation. Predicted to act upstream of or within regulation of blastocyst development. Predicted to be located in cytosol. Predicted to be active in ciliary basal body. [provided by Alliance of Genome Resources, Mar 2025]

tubulin tyrosine ligase-like family member 7

Enables alpha-tubulin binding activity; beta-tubulin binding activity; and tubulin-glutamic acid ligase activity. Involved in protein polyglutamylation. Predicted to be located in 9+0 non-motile cilium. Predicted to be active in ciliary basal body. [provided by Alliance of Genome Resources, Mar 2025]

tubulin tyrosine ligase-like family member 6

Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule bundle formation; protein polyglutamylation; and regulation of cilium beat frequency involved in ciliary motility. Predicted to act upstream of or within microtubule severing and positive regulation of cilium movement. Located in ciliary basal body. [provided by Alliance of Genome Resources, Mar 2025]

tubulin tyrosine ligase-like family member 1

Enables tubulin-glutamic acid ligase activity. Involved in microtubule cytoskeleton organization. Is active in microtubule. [provided by Alliance of Genome Resources, Mar 2025]

tubulin tyrosine ligase-like family member 3

Enables protein-glycine ligase activity. Predicted to be involved in several processes, including axoneme assembly; flagellated sperm motility; and protein polyglycylation. Predicted to be located in cilium. Predicted to be active in axoneme; microtubule cytoskeleton; and sperm flagellum. [provided by Alliance of Genome Resources, Mar 2025]

tubulin tyrosine ligase-like family member 2

Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule cytoskeleton organization. Predicted to be active in ciliary basal body. [provided by Alliance of Genome Resources, Mar 2025]

tubulin tyrosine ligase-like family member 9

Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in flagellated sperm motility and microtubule cytoskeleton organization. Predicted to act upstream of or within protein polyglutamylation. Predicted to be located in cytoplasm; microtubule; and motile cilium. Predicted to be active in ciliary basal body. [provided by Alliance of Genome Resources, Mar 2025]

tubulin tyrosine ligase-like family member 8

Predicted to enable protein-glycine ligase activity, initiating. Predicted to be involved in several processes, including axoneme assembly; flagellated sperm motility; and protein polyglycylation. Predicted to act upstream of or within cilium assembly. Predicted to be located in cilium. Predicted to be active in axoneme; microtubule cytoskeleton; and sperm flagellum. [provided by Alliance of Genome Resources, Mar 2025]

succinate-CoA ligase, ADP-forming, beta subunit pseudogene

deltex 3 like, E3 ubiquitin ligase

Enables several functions, including STAT family protein binding activity; histone H4K91 ubiquitin ligase activity; and protein ADP-ribosyltransferase-substrate adaptor activity. Involved in several processes, including positive regulation of protein localization; protein ubiquitination; and regulation of macromolecule metabolic process. Located in several cellular components, including early endosome; lysosome; and nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Mar 2025]

tubulin tyrosine ligase

TTL is a cytosolic enzyme involved in the posttranslational modification of alpha-tubulin (see MIM 602529). Alpha-tubulin within assembled microtubules is detyrosinated over time at the C terminus. After microtubule disassembly, TTL restores the tyrosine residues and consequently participates in a cycle of tubulin detyrosination and tyrosination (Erck et al., 2003 [PubMed 14571137]).[supplied by OMIM, Mar 2008]

glutamate-cysteine ligase, modifier subunit

Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase, is the first rate limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. Gamma glutamylcysteine synthetase deficiency has been implicated in some forms of hemolytic anemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

glutamate-cysteine ligase, catalytic subunit

Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase is the first rate-limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. This locus encodes the catalytic subunit, while the regulatory subunit is derived from a different gene located on chromosome 1p22-p21. Mutations at this locus have been associated with hemolytic anemia due to deficiency of gamma-glutamylcysteine synthetase and susceptibility to myocardial infarction.[provided by RefSeq, Oct 2010]

succinate-CoA ligase, ADP-forming, beta subunit

Succinyl-CoA synthetase (SCS) is a mitochondrial matrix enzyme that acts as a heterodimer, being composed of an invariant alpha subunit and a substrate-specific beta subunit. The protein encoded by this gene is an ATP-specific SCS beta subunit that dimerizes with the SCS alpha subunit to form SCS-A, an essential component of the tricarboxylic acid cycle. SCS-A hydrolyzes ATP to convert succinate to succinyl-CoA. Defects in this gene are a cause of myopathic mitochondrial DNA depletion syndrome. A pseudogene of this gene has been found on chromosome 6. [provided by RefSeq, Jul 2008]

holocarboxylase synthetase (biotin-(proprionyl-CoA-carboxylase (ATP-hydrolysing)) ligase)

This gene encodes an enzyme that catalyzes the binding of biotin to carboxylases and histones. The protein plays an important role in gluconeogenesis, fatty acid synthesis and branched chain amino acid catabolism. Defects in this gene are the cause of holocarboxylase synthetase deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jun 2011]

RNA 2',3'-cyclic phosphate and 5'-OH ligase

Enables RNA ligase (GTP) activity and vinculin binding activity. Involved in tRNA splicing, via endonucleolytic cleavage and ligation. Located in cytosol and nucleoplasm. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Mar 2025]

deltex 4, E3 ubiquitin ligase

Enables ubiquitin protein ligase activity. Involved in negative regulation of innate immune response; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein K48-linked ubiquitination. Is active in centrosome. [provided by Alliance of Genome Resources, Mar 2025]

deltex 1, E3 ubiquitin ligase

Studies in Drosophila have identified this gene as encoding a positive regulator of the Notch-signaling pathway. The human gene encodes a protein of unknown function; however, it may play a role in basic helix-loop-helix transcription factor activity. [provided by RefSeq, Jul 2008]

deltex 2, E3 ubiquitin ligase

DTX2 functions as an E3 ubiquitin ligase (Takeyama et al., 2003 [PubMed 12670957]).[supplied by OMIM, Nov 2009]

deltex 3, E3 ubiquitin ligase

DTX3 functions as an E3 ubiquitin ligase (Takeyama et al., 2003 [PubMed 12670957]).[supplied by OMIM, Nov 2009]

succinate-CoA ligase, GDP-forming, beta subunit pseudogene 4

succinate-CoA ligase, GDP-forming, beta subunit pseudogene 2

succinate-CoA ligase, GDP-forming, beta subunit pseudogene 3

succinate-CoA ligase, GDP-forming, beta subunit pseudogene 1

glutamate-ammonia ligase (glutamine synthetase) pseudogene 1

glutamate-ammonia ligase (glutamine synthetase) pseudogene 2

glutamate-ammonia ligase (glutamine synthetase) pseudogene 3

glutamate-ammonia ligase (glutamine synthetase) pseudogene 4

glutamate-ammonia ligase (glutamine synthetase) pseudogene 5

glutamate-ammonia ligase (glutamine synthetase) pseudogene 6

succinate-CoA ligase, ADP-forming, beta subunit pseudogene

succinate-CoA ligase, ADP-forming, beta subunit pseudogene

succinate-CoA ligase, ADP-forming, beta subunit pseudogene

succinate-CoA ligase, ADP-forming, beta subunit pseudogene

UFM1-specific ligase 1

Enables UFM1 ligase activity and protein kinase binding activity. Involved in several processes, including positive regulation of reticulophagy; regulation of intracellular signal transduction; and regulation of primary metabolic process. Acts upstream of or within several processes, including positive regulation of cell population proliferation; regulation of proteasomal ubiquitin-dependent protein catabolic process; and response to endoplasmic reticulum stress. Located in cytoplasm; nucleus; and site of double-strand break. Part of protein-containing complex. Is active in endoplasmic reticulum membrane and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Mar 2025]

succinate-CoA ligase, GDP-forming, beta subunit

This gene encodes a GTP-specific beta subunit of succinyl-CoA synthetase. Succinyl-CoA synthetase catalyzes the reversible reaction involving the formation of succinyl-CoA and succinate. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 5 and 12. [provided by RefSeq, Apr 2010]

succinate-CoA ligase, alpha subunit

This gene encodes the alpha subunit of the heterodimeric enzyme succinate coenzyme A ligase. This enzyme is targeted to the mitochondria and catalyzes the conversion of succinyl CoA and ADP or GDP to succinate and ATP or GTP. Mutations in this gene are the cause of the metabolic disorder fatal infantile lactic acidosis and mitochondrial DNA depletion. [provided by RefSeq, Feb 2010]

tubulin tyrosine ligase like 13

Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule bundle formation. Predicted to be located in cytosol. Predicted to be active in ciliary basal body. [provided by Alliance of Genome Resources, Mar 2025]

ORC ubiquitin ligase 1

Enables chromatin binding activity and ubiquitin-protein transferase activity. Involved in protein autoubiquitination; protein monoubiquitination; and regulation of DNA replication. Located in chromatin. [provided by Alliance of Genome Resources, Mar 2025]

COP1 E3 ubiquitin ligase

Enables ubiquitin protein ligase activity. Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process; proteasome-mediated ubiquitin-dependent protein catabolic process; and response to ionizing radiation. Part of Cul4A-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Mar 2025]

RNA 5'-phosphate and 3'-OH ligase 1

Enables RNA ligase (ATP) activity. Involved in response to reactive oxygen species. [provided by Alliance of Genome Resources, Mar 2025]

arkadia (RNF111) C-terminal like ring finger ubiquitin ligase 2C

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in motor neuron axon guidance and positive regulation of BMP signaling pathway. Predicted to act upstream of or within several processes, including forelimb morphogenesis; nervous system development; and protein polyubiquitination. Predicted to be part of protein-containing complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Mar 2025]

tRNA splicing ligase complex subunit 1

Predicted to enable metal ion binding activity. Involved in tRNA splicing, via endonucleolytic cleavage and ligation. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Mar 2025]

tRNA splicing ligase complex subunit 3B

Enables identical protein binding activity and protein methyltransferase activity. Involved in positive regulation of cell population proliferation; positive regulation of gene expression; and protein methylation. Located in cytoplasm and nucleoplasm. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Mar 2025]

tRNA splicing ligase complex subunit 2

Predicted to be involved in tRNA splicing, via endonucleolytic cleavage and ligation. Located in nucleoplasm. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Mar 2025]

tRNA splicing ligase complex subunit 3C

Predicted to be part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Mar 2025]

tRNA splicing ligase complex subunit 3A

Enables protein methyltransferase activity. Involved in positive regulation of cell population proliferation; positive regulation of gene expression; and protein methylation. Predicted to be part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Mar 2025]