SII-SWORD/CoKE huggingface dataset:
Aminopyrrolnitrin oxygenase PrnD, Rieske domain (PrnD_Rieske)
Type: Domain

This entry represents the N-terminal Rieske domain of the oxygenase alpha subunit of aminopyrrolnitrin oxygenase (PrnD). PrnD is a novel Rieske N-oxygenase that catalyzes the final step in the pyrrolnitrin biosynthetic pathway, the oxidation of the amino group in aminopyrrolnitrin to a nitro group, forming the antibiotic pyrrolnitrin. The biosynthesis of pyrrolnitrin is one of the best examples of enzyme-catalyzed arylamine oxidation. Although arylamine oxygenases are widely distributed within the microbial world and used in a variety of metabolic reactions, PrnD represents one of only two known examples of arylamine oxygenases or N-oxygenases involved in arylnitro group formation, the other being AurF involved in aureothin biosynthesis .
Cytidine monophosphate-N-acetylneuraminic acid hydroxylase, Rieske domain (CMP-Neu5Ac_hydroxylase_Rieske)
Type: Domain

This entry represents the N-terminal Rieske domain of cytidine monophosphate-N-acetylneuraminic acid (CMP Neu5Ac). The Rieske domain is a [2Fe-2S] cluster binding domain involved in electron transfer . CMP Neu5Ac hydroxylase is the key enzyme for the synthesis of N-glycolylneuraminic acid (NeuGc) from N-acetylneuraminic acid (Neu5Ac), NeuGc and Neu5Ac are members of a family of cell surface sugars called sialic acids . All mammals except humans have both NeuGc variants on their cell surfaces. In humans, the gene encoding CMP Neu5Ac hydroxylase has a mutation within its coding region that abolishes NeuGc production .
SSB2, SOCS box domain (SSB2_SOCS)
Type: Domain

This entry represents the SOCS (suppressors of cytokine signaling) box of SSB2 (SPRY domain-containing SOCS box proteins). SSB proteins contain a central SPRY domain and a C-terminal SOCS. SSB2 has been shown to interact with c-Met, the hepatocyte growth factor receptor . It also regulates inducible nitric oxide synthase (iNOS) by targeting it for proteasomal degradation .

The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions .
SOCS4, SOCS box domain (SOCS4_SOCS)
Type: Domain

This entry represents the SOCS box domain of SOCS4.

SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS4 (Suppressor of cytokine signalling 4) is the substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins . SOCS4 and SOCS5 regulate epidermal growth factor receptor signaling .

The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions .
SOCS5, SOCS box domain (SOCS5_SOCS)
Type: Domain

This entry represents the SOCS box domain of SOCS5.

Suppressor of cytokine signalling (SOCS) proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS5 inhibits the IL4 signaling pathway, which promotes the Th (helper T) 2 cell development . SOCS5 and SOCS4 regulate epidermal growth factor receptor signaling .

The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions .
SOCS6, SOCS box domain (SOCS6_SOCS)
Type: Domain

This entry represents the SOCS box domain of SOCS6.

Suppressor of cytokine signaling (SOCS) family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. However, SOCS6 does not interact with cytokine signaling intermediate molecules or inhibit cytokine receptor signaling. SOCS6 can interact with c-KIT, a receptor tyrosine kinase that mediates the cellular response to stem cell factor (SCF). SOCS6 has ubiquitin ligase activity toward c-KIT and regulates c-KIT protein turnover in cells, suppressing c-KIT-dependent pathways . SOCS6 negatively regulates receptor tyrosine kinase Flt3 activation, the downstream Erk signaling pathway, and cell proliferation .

The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions .
SOCS7, SOCS box domain (SOCS7_SOCS)
Type: Domain

This entry represents the SOCS box domain of SOCS7.

SOCS7 is a member of the suppressor of cytokine signaling family of proteins. SOCS7 functions in insulin signaling and glucose homeostasis through IRS1 ubiquitination and subsequent proteasomal degradation . SOCS7 inhibits also prolactin, growth hormone and leptin signaling by preventing STAT3 and STAT5 activation, sequestering them in the cytoplasm and reducing their binding to DNA .

The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions .
MJ0144, FMN-binding domain (MJ0144_FMN)
Type: Domain

This entry represents the FMN-binding domain found in Archeal protein MJ0144. Proteins containing this domain are part of the NAD(P)H-dependent flavin oxidoreductase (oxidored) FMN-binding family that reduce a range of alternative electron acceptors. Most of them use FAD/FMN as a cofactor and NAD(P)H as electron donor. Some members contain 4Fe-4S cluster to transfer electron from FAD to FMN. The specific function of this group is unknown.
TMADH/DMDH, FMN-binding domain (TMADH/DMDH_FMN-bd)
Type: Domain

This entry represents the FMN-binding domain found in trimethylamine dehydrogenase (TMADH) and histamine dehydrogenase (HD). TMADH is an iron-sulfur flavoprotein that catalyzes the oxidative demethylation of trimethylamine to form dimethylamine and formaldehyde. The protein forms a symmetrical dimer with each subunit containing one 4Fe-4S cluster and one FMN cofactor . It contains a unique flavin, in the form of a 6-S-cysteinyl FMN which is bent by ~25 degrees along the N5-N10 axis of the flavin isoalloxazine ring. This modification of the conformation of the flavin is thought to facilitate catalysis . The closely related histamine dehydrogenase catalyzes oxidative deamination of histamine .
Lactate 2-monooxygenase, FMN-binding domain (LMO_FMN)
Type: Domain

Lactate 2-monooxygenase (LMO) is a FMN-containing enzyme that catalyzes the conversion of L-lactate and oxygen to acetate, carbon dioxide, and water. LMO is a member of the family of alpha-hydroxy acid oxidases. It is thought to be a homooctamer with two- and four- fold axes in the centre of the octamer .
COMM domain-containing protein 1 (Murr1)
Type: Family

COMM domain-containing protein 1, also called Murr1, is involved in copper homeostasis . It has been identified as a regulator of the human delta epithelial sodium channel . It has been shown to directly link to early endosomes through its interaction with a protein complex containing CCDC22, CCDC93, and C16orf62 .

The COMM domain is found at the C terminus of a variety of proteins; presumably all COMM domain-containing proteins are located in the nucleus and the COMM domain plays a role in protein-protein interactions. Several family members have been shown to bind and inhibit NF-kappaB .
Histone methyltransferase complex subunit ASH2 (ASH2)
Type: Family

The trithorax-group (trxG) protein Ash2 from C. elegans (or ASH2L in mammals) is a component of the Set1/Ash2 histone methyltransferase (HMT) complex that methylates 'Lys-4' of histone H3, a mark associated with epigenetic transcriptional activation . Mammals posses several SET1 family proteins (MLL1-4, SET1A, and SET1B). ASH2L is a core component of all the resulting mammalian histone H3K4 methyltransferase complexes, including mixed lineage leukemia (MLL) complexes .

S. cerevisiae Bre2 and Aspergillus fumigatus CclA are homologous to Ash2 . TRAUCO (TRO) is the homologue from Arabidopsis, which is required for early embryogenesis .
COMM domain-containing protein 2 (Commd2)
Type: Family

COMMD2 is a member of the COMMD family defined by the presence of a conserved and unique motif termed the COMM (copper metabolism gene MURR1) domain, which functions as an interface for protein-protein interactions . Several family members have been shown to bind and inhibit NF-kappaB .
COMM domain-containing protein 3 (COMMD3)
Type: Family

COMMD3 is a member of the COMMD family defined by the presence of a conserved and unique motif termed the COMM (copper metabolism gene MURR1) domain, which functions as an interface for protein-protein interactions . COMMD3 modulates Na+ transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits .
COMM domain-containing protein 4 (COMMD4)
Type: Family

COMMD4 is a member of the COMMD family defined by the presence of a conserved and unique motif termed the COMM (copper metabolism gene MURR1) domain, which functions as an interface for protein-protein interactions .
COMM domain-containing protein 5 (COMMD5)
Type: Family

COMMD5 (also known as HCaRG) is a member of the COMMD family defined by the presence of a conserved and unique motif termed the COMM (copper metabolism gene MURR1) domain, which functions as an interface for protein-protein interactions . It is a nuclear protein involved in the regulation of cell proliferation . It is also a regulator of renal epithelial cell growth and differentiation causing G(2)M cell cycle arrest .
COMM domain-containing protein 7 (COMMD7)
Type: Family

COMMD7 is a member of the COMMD family defined by the presence of a conserved and unique motif termed the COMM (copper metabolism gene MURR1) domain, which functions as an interface for protein-protein interactions .
Heparan sulfate sulfotransferase (NST/OST)
Type: Family

Seven 3-O-sulfotransferase isoforms in the human genome are involved in the biosynthesis of 3-O-sulfated heparan sulfate . These enzymes catalyze the transfer of a sulfo group from the sulfo donor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS), to the 3-OH position of a glucosamine unit of heparin sulfate (HS). 3-O-sulfation is critically important for anticoagulant activity . The key control of anticoagulant HS synthesis is regulation of the expression of 3-O-sulfotransferase isoforms 1 and 5 (3-OST-1 and 3-OST-5). 3-O-sulfation is also involved in the regulation of neural development .

3-OST proteins exhibit similarity with the heparan biosynthetic enzyme NST (bifunctional HS N-deacetylase/N-sulfotransferase). It appears that a common sulfotransferase structure is shared by these two types of heparan biosynthetic enzyme . The bifunctional enzyme catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in HS .
COMM domain-containing protein 9 (COMMD9)
Type: Family

COMM9 is a member of the COMMD family defined by the presence of a conserved and unique motif termed the COMM (copper metabolism gene MURR1) domain, which functions as an interface for protein-protein interactions . COMM9 modulates Na+ transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits .
COMM domain-containing protein 10 (COMMD10)
Type: Family

COMM10 is a member of the COMMD family defined by the presence of a conserved and unique motif termed the COMM (copper metabolism gene MURR1) domain, which functions as an interface for protein-protein interactions . In Drosophila, COMM10 may have an accessory function in the survival motor neuron (SMN) complex . In human, it may modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes . It may also down-regulate activation of NF-kappa-B .
CAS family (CAS_fam)
Type: Family

The CAS (Crk-Associated Substrate) protein family is a group of scaffolding proteins that play important modulatory roles in both normal and pathological cell growth regulation. They contain an N-terminal Src homology 3 (SH3) domain and a substrate domain (SD). The SD contains a large number of YxxP motifs, which when phosphorylated by Src-family kinases provide canonical binding sites for proteins containing SH2 domains such as Crk, Crk-L, CRKII .
Sec13/Seh1 family (Sec13/Seh1_fam)
Type: Family

Seh1 and Sec13 are WD40 repeat containing proteins. They are subunits of the Nup84 (Nup107-160 complex in higher eukaryotes) nuclear pore subcomplex and the the SEA complex (GATOR1 complex in higher eukaryotes) .
Protein transport protein Sec23 (Sec23)
Type: Family

Vesicular carriers mediate a continuous flux of proteins and lipids between endoplasmic reticulum (ER) and the Golgi. Anterograde and retrograde transport is mediated by distinct sets of cytosolic coat proteins, the COPI and COPII coats, respectively, which act on the membrane to capture cargo proteins into nascent vesicles .

Sec23 is a component of the coat protein complex II (COPII). Polymerization of the coat requires the recruitment of the Sec13/Sec31 complex (coat outer shell) by the Sec23/Sec24 complex. The Sec23/Sec24 coat complex then sorts the fusion machinery (SNAREs) into vesicles as they bud from the ER. Sec23 has been shown to interact in a sequential manner with other proteins (Sar1, TRAPPI and Hrr25) to control the direction of anterograde membrane flow .

This entry also includes the budding yeast Sec23 paralogue, Nel1 (YHR035W). It is a GTPase-activating protein for Sar1 and does not function as a subunit of the coat protein complex II (COPII) coat .
Slowmo/Ups family (Slowmo/Ups)
Type: Family

Protein slowmo (Slmo) is a mitochondrial protein from Drosophila involved in development of the nervous system and germline proliferation . Slmo contains a conserved PRELI/MSF1 domain, found in proteins from a wide variety of eukaryotic organisms . Slmo is a homologue of yeast UPS proteins Ups1, Ups2, and Ups3, that control phospholipid metabolism in the mitochondrial intermembrane space. Humans possess four principal homologues of the Ups family, namely PRELID1 (also known as PRELI), PRELID2, SLMO1 and SLMO2 (also termed PRELID3a and PRELID3b) .

The Ups family is evolutionary conserved from yeast to man, and together with its mitochondrial chaperones (TRIAP1/Mdm35), represent a unique heterodimeric lipid transfer system. In yeast mitochondria, Ups1 and Ups2 form tight complexes with Mdm35 and together they regulate the subsequent biosynthesis of cardiolipin and phosphatidylethanolamine .
PREX2, DEP domain 1 (Rex2_DEP_1)
Type: Domain

PREX2 functions as a RAC1 guanine nucleotide exchange factor (GEF), activating Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein . It contains an N-terminal RhoGEF domain, two DEP and PDZ domains.

This entry represents the first DEP domain of PREX2.
Integral membrane protein GPR155, DEP domain (GPR155_DEP)
Type: Domain

GRP155-like proteins, also known as PGR22, contain an N-terminal permease domain, a central transmembrane region and a C-terminal DEP domain. They are orphan receptors of the class B G protein-coupled receptors . Their function is unknown.
Pleckstrin-2, DEP domain (PLEK2_DEP)
Type: Domain

Pleckstrin 2 is found in a wide variety of cell types, which suggest a more general role in signaling than pleckstrin 1 . Pleckstrin-like proteins contain a central DEP domain, flanked by 2 PH (pleckstrin homology) domains.
Pleckstrin (Pleckstrin)
Type: Family

Pleckstrin-like proteins contain a central DEP domain, flanked by 2 PH (pleckstrin homology) domains. This entry includes pleckstrin (also known as pleckstrin-1) and pleckstrin-2.

Pleckstrin 1 plays a role in cell spreading and reorganization of actin cytoskeleton in platelets and leukocytes. Its activity is highly regulated by phosphorylation, mainly by protein kinase C .
Pleckstrin, DEP domain (PLEK_DEP)
Type: Domain

Pleckstrin (PLEK) plays a role in cell spreading and reorganization of actin cytoskeleton in platelets and leukocytes. Its activity is highly regulated by phosphorylation, mainly by protein kinase C . Pleckstrin-like proteins contain a central DEP domain, flanked by 2 PH (pleckstrin homology) domains.
Tripartite motif-containing protein 66, B-box type 1 zinc finger (TRIM66_Bbox1_Znf)
Type: Domain

Tripartite motif-containing protein 66 (TRIM66, also known as transcriptional intermediary factor 1 delta, TIF1delta) binds to HP1 (heterochromatin protein 1) and is expressed by elongating spermatids. It displays a potent trichostatin A (TSA)-sensitive repression function; TSA is a specific inhibitor of histone deacetylases. Moreover, TRIM66 plays an important role in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis . It functions as a negative regulator of postmeiotic genes acting through HP1 isotype gamma (HP1gamma) complex formation and centromere association. TRIM66 belongs to an unclassified TRIM (tripartite motif) family of proteins that do not have RING fingers and thus lack the characteristic tripartite (RING (R), B-box, and coiled coil (CC)) RBCC motif.
Transcription intermediary factor 1-beta, PHD domain (KAP1)
Type: Domain

TIF1-beta, also known as Kruppel-associated Box (KRAB)-associated protein 1 (KAP-1), belongs to the C-VI subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a plant homeodomain (PHD), and a bromodomain (Bromo) positioned C-terminal to the RBCC domain. It acts as a nuclear co-repressor that plays a role in transcription and in the DNA damage response .

Upon DNA damage, the phosphorylation of KAP-1 on serine 824 by the ataxia telangiectasia-mutated (ATM) kinase enhances cell survival and facilitates chromatin relaxation and heterochromatic DNA repair . It also regulates CHD3 nucleosome remodelling during the DNA double-strand break (DSB) response . Meanwhile, KAP-1 can be dephosphorylated by protein phosphatase PP4C in the DNA damage response . Moreover, KAP-1 is a co-activator of the orphan nuclear receptor NGFI-B (or Nur77) and is involved in NGFI-B-dependent transcription . It is also a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase . The N-terminal RBCC domains of TIF1-beta are responsible for the interaction with KRAB zinc finger proteins (KRAB-ZFPs), MDM2, MM1, C/EBPbeta, and the regulation of homo- and heterodimerization . The C-terminal PHD/Bromo domains are involved in interacting with SETDB1, Mi-2alpha and other proteins to form complexes with histone deacetylase or methyltransferase activity .

This entry represents the PHD zinc finger from TIF1-beta, which is involved in interacting with SETDB1, Mi-2alpha and other proteins to form complexes with histone deacetylase or methyltransferase activity.
BAZ2A/BAZ2B, bromodomain (BAZ2A/B_Bromo)
Type: Domain

Bromo adjacent to zinc finger 2A (BAZ2A) and 2B (BAZ2B) were identified as a novel human bromodomain genes by cDNA library screening . They may play roles in transcriptional regulation. Human BAZ2A (also known as Tip5) is part of a complex termed NoRC (nucleolar remodeling complex), which induces nucleosome sliding and may play a role in the regulation of the rDNA locus . Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine .
Tyrosine-protein kinase BAZ1B, bromodomain (BAZ1B_Bromo)
Type: Domain

This entry represents the plant bromodomain of BAZ1B.

BAZ1B (also known as Williams-Beuren syndrome transcription factor, WSTF) is a multifunctional protein implicated in several nuclear processes, including replication, transcription, and the DNA damage response. It is a component of the WICH complex (WSTF-ISWI ATP-dependent chromatin-remodelling complex). It has intrinsic tyrosine kinase activity by means of a domain that shares no sequence homology to any known kinase fold. It has been shown to phosphorylate Tyr 142 of H2A . It is involved in chromatin assembly, RNA polymerase I and III gene regulation, vitamin D metabolism, and DNA repair .
Putative transcription factor GTE, bromodomain (GTE_bromo)
Type: Domain

This entry represents the bromodomain found in a group of plant putative transcription factors, known as GLOBAL TRANSCRIPTION FACTOR GROUP E (GTE). GTE1 (also known as IMB1) regulates ABA- and phyA-mediated responses of germination in Arabidopsis .
PIKfyve, DEP domain (PIKfyve_DEP)
Type: Domain

PIKfyve catalyzes the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 3,5-bisphosphate . It is part of the PI(3,5)P2 regulatory complex that regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) . PIKfyve contains N-terminal Fyve finger and DEP domains, a central chaperonin-like domain and a C-terminal PIPK (phosphatidylinositol phosphate kinase) domain.
WDR74/Nsa1 (WDR74/Nsa1)
Type: Family

Yeast Nsa1 is a ribosomal assembly factor that is functionally linked to type II AAA-ATPase Rix7. Rix7 associates with Nsa1-containing nucleolar pre-60S particles and is required for the maturation of the large ribosomal subunit. The mammalian homologue of Nsa1 is the nucleolar protein WDR74 (WD-repeat containing 74), which has been shown to associate with NVL2 (Rix7 homologue) in the presence of the nuclear Mtr4 exosome complex .

WDR74/Nsa1 is composed of an N-terminal seven-bladed WD40 domain followed by a lysine-rich C terminus that is required for nucleolar localization. The WD40 domain of WDR74 serves as a platform for recruitment of NVL2 to pre-60S particles .
DALR anticodon-binding domain-containing protein 3 (DALRD3)
Type: Family

The function of DALRD3 is not known; it has been associated to estrogen receptor alpha-positive tumours .
E3 ubiquitin-protein ligase RFWD3 (RFWD3)
Type: Family

RFWD3 is a RING-type E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage .

During ICL repair, single-stranded DNA (ssDNA) is generated. The trimeric ssDNA binding protein complex RPA coats the ssDNA. Subsequently, RAD51 is loaded onto RPA-bound ssDNA and catalyzes the critical activity in homologous recombination (HR). RFWD3 polyubiquitinates both RPA and RAD5, which increases their local turnover in DNA damage-induced foci to facilitate HR . RFWD3-mediated ubiquitination of RPA has been shown to be essential for HR .