SII-SWORD/CoKE huggingface dataset:
Ras association domain-containing protein 1-6 (RASSF1-6)
Type: Family

The Ras association domain (RASSF) proteins are named due to the presence of a Ras association (RA) domain in their N or C terminus that can potentially interact with the Ras GTPase family of proteins. These GTPases control a variety of cellular processes, such as membrane trafficking, apoptosis, and proliferation. RASSF proteins contain several other functional domains that modulate associations with other proteins. RASSF proteins with the RA domain at the C terminus (which are termed C-terminal or classical RASSF) usually also include a Salvador-RASSF-Hippo (SARAH) domain involved in several protein-protein interactions and for homo- and heterodimerisation of RASSF isoforms. N-terminal RASSF proteins (with the RA domain in the N terminus) do not usually contain a SARAH domain .

At least 10 RASSF family members have been characterised (with multiple splice variants), many of which have been shown to play a role in tumour suppression. RASSF proteins also act as scaffolding agents in microtubule stability, regulate mitotic cell division, control cell migration and cell adhesion, and modulate NF-KB activity and the duration of inflammation. Loss of RASSF expression through promoter methylation has been shown in numerous types of cancer, including leukemia, melanoma, breast and prostate cancer .

This entry includes RASSF1-6, which contain the RA domain at the C terminus.
Protein EOLA1/EOLA2 (EOLA1/EOLA2)
Type: Family

This family consists of EOLA1/EOLA2 from human, and their homologues from vertebrates.

Endothelial-overexpressed LPS-associated factor 1 (EOLA1, also known as CXorf40A), seems to play a role as a signal transduction factor . EOLA1 interacts with metallothionein 2A (MT2A) and functions as a negative regulator for LPS (lipopolysaccharide) response by regulation of MT2A .
Bridge-like lipid transfer protein family member 1 (BLTP1)
Type: Family

Bridge-like lipid transfer protein family member 1 (BLTP1, formerly known as Tweek/KIAA1109/FSA in human) is a tube-forming lipid transport protein which provides phosphatidylethanolamine for glycosylphosphatidylinositol (GPI) anchor synthesis in the endoplasmic reticulum. It plays a role in endosomal trafficking and endosome recycling and it is also involved in the actin cytoskeleton and cilia structural dynamics . BLTP1 also acts as a regulator of phagocytosis . In humans, it has been associated with rheumatoid arthritis . Mutations of the BLTP1 gene has been associated with Alkuraya-Kucinskas syndrome (MIM 617822), a severe disorder of brain development and arthrogryposis .

Members of this entry belong to the repeating β-groove (RBG) superfamily together with VPS13, ATG2, SHIP164, BLTP2/FMP27, which are all conserved lipid transfer proteins containing long hydrophobic grooves . They all share the same structure comprising multiple repeating modules consisting of five β-sheets followed by a loop.
Ras association domain-containing protein 2, RA domain (RASSF2_RA)
Type: Domain

The Ras association domain (RASSF) proteins are named due to the presence of a Ras association (RA) domain in their N or C terminus that can potentially interact with the Ras GTPase family of proteins. These GTPases control a variety of cellular processes, such as membrane trafficking, apoptosis, and proliferation. RASSF proteins contain several other functional domains that modulate associations with other proteins. RASSF proteins with the RA domain at the C terminus (which are termed C-terminal or classical RASSF) usually also include a Salvador-RASSF-Hippo (SARAH) domain involved in several protein-protein interactions and for homo- and heterodimerisation of RASSF isoforms. N-terminal RASSF proteins (with the RA domain in the N terminus) do not usually contain a SARAH domain .

At least 10 RASSF family members have been characterised (with multiple splice variants), many of which have been shown to play a role in tumour suppression. RASSF proteins also act as scaffolding agents in microtubule stability, regulate mitotic cell division, control cell migration and cell adhesion, and modulate NF-KB activity and the duration of inflammation. Loss of RASSF expression through promoter methylation has been shown in numerous types of cancer, including leukemia, melanoma, breast and prostate cancer .

RASSF2 is one of the C-terminal (also known as classical) RASSF proteins, characterised by an RA domain and a SARAH domain (

) in the C terminus. It is primarily a nuclear protein existing in two major isoforms, A and C, which has been implicated in tumourigenesis and in regulation of cell cycle and apoptosis .

This entry represents the Ras-associating (RA) domain of RASSF2, which has a β-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases.
Small ribosomal subunit protein mS37, metazoan (Ribosomal_mS37_met)
Type: Family

This entry represents the small ribosomal subunit protein mS37 family (also know as CHCHD1 and MRPS37) found in Metazoa . These are mitochondrial ribosomal proteins with a role in mitochondrial protein synthesis .
TRAF-interacting protein with FHA domain-containing protein (TIFA)
Type: Family

TRAF-interacting protein with a forkhead-associated domain (TIFA), also called T2BP, is an adapter protein which mediates the IRAK1 and TRAF6 interaction following IL-1 stimulation, resulting in the downstream activation of NF-kappa-B and c-Jun amino-terminal kinase (JNK) . TIFA has been shown to induce the oligomerization and polyubiquitination of TRAF6, which in turn activates transforming growth factor-activated kinase (TAK1) and IkappaB kinase (IKK) . TIFA contains a phosphothreonine and phosphoserine-binding FHA domain and a consensus TRAF6-binding motif .
Ras association domain-containing protein 4, RA domain (RASSF4_RA)
Type: Domain

The Ras association domain (RASSF) proteins are named due to the presence of a Ras association (RA) domain in their N or C terminus that can potentially interact with the Ras GTPase family of proteins. These GTPases control a variety of cellular processes, such as membrane trafficking, apoptosis, and proliferation. RASSF proteins contain several other functional domains that modulate associations with other proteins. RASSF proteins with the RA domain at the C terminus (which are termed C-terminal or classical RASSF) usually also include a Salvador-RASSF-Hippo (SARAH) domain involved in several protein-protein interactions and for homo- and heterodimerisation of RASSF isoforms. N-terminal RASSF proteins (with the RA domain in the N terminus) do not usually contain a SARAH domain .

At least 10 RASSF family members have been characterised (with multiple splice variants), many of which have been shown to play a role in tumour suppression. RASSF proteins also act as scaffolding agents in microtubule stability, regulate mitotic cell division, control cell migration and cell adhesion, and modulate NF-KB activity and the duration of inflammation. Loss of RASSF expression through promoter methylation has been shown in numerous types of cancer, including leukemia, melanoma, breast and prostate cancer .

RASSF4 is one of the C-terminal (also known as classical) RASSF proteins, characterised by an RA domain and a SARAH domain (

) in the C terminus. There is conflicting evidence for the function of RASSF4. It is variously reported to have tumour suppressor characteristics , and to have a function in promoting cell proliferation .

This entry represents the Ras-associating (RA) domain of RASSF4, which has a β-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases.
Ras association domain-containing protein 5, RA domain (RASSF5_RA)
Type: Domain

The Ras association domain (RASSF) proteins are named due to the presence of a Ras association (RA) domain in their N or C terminus that can potentially interact with the Ras GTPase family of proteins. These GTPases control a variety of cellular processes, such as membrane trafficking, apoptosis, and proliferation. RASSF proteins contain several other functional domains that modulate associations with other proteins. RASSF proteins with the RA domain at the C terminus (which are termed C-terminal or classical RASSF) usually also include a Salvador-RASSF-Hippo (SARAH) domain involved in several protein-protein interactions and for homo- and heterodimerisation of RASSF isoforms. N-terminal RASSF proteins (with the RA domain in the N terminus) do not usually contain a SARAH domain .

At least 10 RASSF family members have been characterised (with multiple splice variants), many of which have been shown to play a role in tumour suppression. RASSF proteins also act as scaffolding agents in microtubule stability, regulate mitotic cell division, control cell migration and cell adhesion, and modulate NF-KB activity and the duration of inflammation. Loss of RASSF expression through promoter methylation has been shown in numerous types of cancer, including leukemia, melanoma, breast and prostate cancer .

RASSF5 is one of the C-terminal (also known as classical) RASSF proteins, characterised by an RA domain and a SARAH domain (

) in the C terminus. RASSF5 is also referred to as NORE1 or RAPL, and is known to exist as at least three transcripts. RASSF5 is primarily involved in the control of apoptosis, through involvement in a number of different apoptosis pathways , and functions as a tumour suppressor . One transcript (A) has been suggested to be involved in developing the nervous system . It has also been reported that RASSF5 is involved in the regulation of p27 localisation .

This entry represents the Ras-associating (RA) domain of RASSF5, which has a β-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases.
Class II PurE (PurE_classII)
Type: Domain

The novo purine biosynthesis proceeds by two divergent paths. In bacteria, yeasts, and plants, 5-aminoimidazole ribonucleotide (AIR) is converted to 4-carboxy-AIR (CAIR) by two enzymes: N5-carboxy-AIR (N5-CAIR) synthetase (PurK) and N5-CAIR mutase (class I PurE). In animals, the conversion of AIR to CAIR requires a single enzyme, AIR carboxylase (class II PurE) . Class I and class II PurEs are mechanistically related but bind different substrates. In yeast and plants PurE is found in PurK-class I PurE fusion proteins, known as ADE2 , while animal class II PurEs are found in PurC-PurE fusion proteins, also known as ADE2 or PAICS .

This entry represents a class II PurE domain found in ADE2 fusion proteins from animals. It is also found in some bacteria, such as Treponema denticola. This spirochete dental pathogen lacks a purK gene and contains a class II purE gene .
Ras association domain-containing protein 7, RA domain (RASSF7_RA)
Type: Domain

The Ras association domain (RASSF) proteins are named due to the presence of a Ras association (RA) domain in their N or C terminus that can potentially interact with the Ras GTPase family of proteins. These GTPases control a variety of cellular processes, such as membrane trafficking, apoptosis, and proliferation. RASSF proteins contain several other functional domains that modulate associations with other proteins. RASSF proteins with the RA domain at the C terminus (which are termed C-terminal or classical RASSF) usually also include a Salvador-RASSF-Hippo (SARAH) domain involved in several protein-protein interactions and for homo- and heterodimerisation of RASSF isoforms. N-terminal RASSF proteins (with the RA domain in the N terminus) do not usually contain a SARAH domain .

At least 10 RASSF family members have been characterised (with multiple splice variants), many of which have been shown to play a role in tumour suppression. RASSF proteins also act as scaffolding agents in microtubule stability, regulate mitotic cell division, control cell migration and cell adhesion, and modulate NF-KB activity and the duration of inflammation. Loss of RASSF expression through promoter methylation has been shown in numerous types of cancer, including leukemia, melanoma, breast and prostate cancer .

RASSF7 is one of the N-terminal RASSF proteins, characterised by an RA domain in the N terminus. It was previously known as HRC1 (HRAS1-related cluster protein 1), and is predicted to exist as at least three isoforms as a result of alternative splicing . RASSF7 has been shown to promote mitosis through the regulation of spindle formation . There is conflicting evidence on the methylation of the RASSF7 promoter, and subsequently on the status of RASSF7 as a tumour suppressor .

This entry represents the as-associating (RA) domain of RASSF7.
Ras association domain-containing protein 9, RA domain (RASSF9_RA)
Type: Domain

The Ras association domain (RASSF) proteins are named due to the presence of a Ras association (RA) domain in their N or C terminus that can potentially interact with the Ras GTPase family of proteins. These GTPases control a variety of cellular processes, such as membrane trafficking, apoptosis, and proliferation. RASSF proteins contain several other functional domains that modulate associations with other proteins. RASSF proteins with the RA domain at the C terminus (which are termed C-terminal or classical RASSF) usually also include a Salvador-RASSF-Hippo (SARAH) domain involved in several protein-protein interactions and for homo- and heterodimerisation of RASSF isoforms. N-terminal RASSF proteins (with the RA domain in the N terminus) do not usually contain a SARAH domain .

At least 10 RASSF family members have been characterised (with multiple splice variants), many of which have been shown to play a role in tumour suppression. RASSF proteins also act as scaffolding agents in microtubule stability, regulate mitotic cell division, control cell migration and cell adhesion, and modulate NF-KB activity and the duration of inflammation. Loss of RASSF expression through promoter methylation has been shown in numerous types of cancer, including leukemia, melanoma, breast and prostate cancer .

RASSF9 is one of the N-terminal RASSF proteins, characterised by an RA domain in the N terminus. It was previously called P-CIP1 (peptidylglycine alpha-amidating monooxygenase (PAM) COOH-terminal interactor protein-1), and was believed to play a role in the regulation of PAM in endosomal pathways . Very little else is known about the function of RASSF9, but it has been suggested to be involved in epidermal homeostasis .

This entry represents the as-associating (RA) domain of RASSF9.
Ras association domain-containing protein 10, RA domain (RASSF10_RA)
Type: Domain

RASSF10 is one of the N-terminal RASSF proteins, characterised by an RA domain in the N terminus. It is expressed in a range of tissues, and has been shown to function as a tumour suppressor in a number of studies .

This entry represents the as-associating (RA) domain of RASSF10.

The Ras association domain (RASSF) proteins are named due to the presence of a Ras association (RA) domain in their N or C terminus that can potentially interact with the Ras GTPase family of proteins. These GTPases control a variety of cellular processes, such as membrane trafficking, apoptosis, and proliferation. RASSF proteins contain several other functional domains that modulate associations with other proteins. RASSF proteins with the RA domain at the C terminus (which are termed C-terminal or classical RASSF) usually also include a Salvador-RASSF-Hippo (SARAH) domain involved in several protein-protein interactions and for homo- and heterodimerisation of RASSF isoforms. N-terminal RASSF proteins (with the RA domain in the N terminus) do not usually contain a SARAH domain .

At least 10 RASSF family members have been characterised (with multiple splice variants), many of which have been shown to play a role in tumour suppression. RASSF proteins also act as scaffolding agents in microtubule stability, regulate mitotic cell division, control cell migration and cell adhesion, and modulate NF-KB activity and the duration of inflammation. Loss of RASSF expression through promoter methylation has been shown in numerous types of cancer, including leukemia, melanoma, breast and prostate cancer .
Ankyrin repeat and SAM domain-containing protein 1/Caskin (ANKS1/Caskin)
Type: Family

This entry represents a family of multi-SAM containing proteins (MSCPs) predominantly found in animals, including
Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A, also known as Odin), Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B, also known as AIDA-1 or EB-1) and Caskin-1/2. Structurally, ANKS1 proteins consist of N-terminal ankyrin motifs followed by tandem sterile alpha motif (SAM) domains and a carboxyl phosphotyrosine binding (PTB) domain while Caskin-1/2 show N-terminal ankyrin repeats, an SH3 domain, two SAM domains, and an extended Proline-rich C-terminal tail .
WFIKKN1/2, immunoglobulin-like domain 3 (WFIKKN1/2_Ig-like_3)
Type: Domain

WFIKKN proteins are secreted multidomain proteins containing a WAP (whey acidic protein)-, a follistatin/Kazal-, an immunoglobulin-, two Kunitz-type protease inhibitor-domains, and an NTR (netrin) domain. They have been reported to inhibit the activity of trypsin, and to bind GDF11 (growth and differentiation factor 11) and myostatin (GDF8) . Due to the presence of multiple domains that frequently serve as protease inhibitors, WFIKKN proteins are presumed to control the action of diverse serine proteases as well as metalloproteinases .

In humans, WFIKKN1 expression is observed in pancreas, liver, thymus, kidney, testis and lung and WFIKKN2 (also known as WFIKKNRP) expression is observed in ovary, testis, pancreas, brain and lung .

This entry represents the third immunoglobulin-like domain of WFIKKN1/2.
Fatty acyl-CoA reductase, C-terminal (FAR_C)
Type: Domain

This entry represents the C-terminal domain of fatty acyl CoA reductases, a family of SDR-like proteins. SDRs or short-chain dehydrogenases/reductases are Rossmann-fold NAD(P)H-binding proteins. Many proteins with this domain may function as fatty acyl-CoA reductases (FARs), acting on medium and long chain fatty acids, and have been reported to be involved in diverse processes such as the biosynthesis of insect pheromones , plant cuticular wax production , and mammalian wax biosynthesis . In Arabidopsis thaliana, proteins with this particular architecture have also been identified as the MALE STERILITY 2 (MS2) gene product, which is implicated in male gametogenesis. Mutations in MS2 inhibit the synthesis of exine (sporopollenin), rendering plants unable to reduce pollen wall fatty acids to corresponding alcohols . The function of this C-terminal domain is unclear.
CRISPR-associated protein Cas1, type I-E (Cas1_I-E)
Type: Family

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and associated Cas proteins comprise a system for heritable host defense by prokaryotic cells against phage and other foreign DNA . Cas1 is the most universal CRISPR system protein thought to be involved in spacer integration . Cas1 is metal-dependent deoxyribonuclease , also binds RNA , and has been shown to possess a unique fold consisting of a N-terminal β-strand domain and a C-terminal α-helical domain .

This entry represents CRISPR-Cas subtype I-E. In E. coli, the CRISPR-Cas I-E system consists of up to three CRISPR-spacer arrays (i.e., CRISPR2.1, CRISPR2.2 and CRISPR2.3) made of type 2 repeats .
SH3YL1-like, SYLF domain (SYLF_SH3YL1-like)
Type: Domain

This subfamily is composed of yeast Ysc84 (also called LAS17-binding protein 4, Lsb4p) and Lsb3p proteins, vertebrate SH3YL1 (SH3 domain containing Ysc84-like 1), and similar proteins. They contain an N-terminal SYLF domain and a C-terminal SH3 domain. SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation . Ysc84p localizes to actin patches and plays an important role in actin polymerization during endocytosis . A study of the yeast SH3 domain interactome predicts that Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes . The SYLF domain of SH3YL1 binds phosphoinositides with high affinity, while the N-terminal SYLF domains of both Ysc84p and Lsb3p have been shown to bind and bundle actin filaments, as well as bind liposomes with high affinity.
Ferrochelatase, C-terminal (Ferrochelatase_C)
Type: Domain

Ferrochelatase (protoheme ferrolyase or HemH) is the terminal enzyme of the heme biosynthetic pathway. It catalyzes the insertion of ferrous iron into the protoporphyrin IX ring yielding protoheme. This enzyme is ubiquitous in nature and widely distributed in bacteria and eukaryotes. Recently, some archaeal members have been identified. The oligomeric state of these enzymes varies depending on the presence of a dimerization motif at the C terminus .

This entry represents the C-terminal domain.
VirB9/CagX/TrbG, C-terminal (VirB9/CagX/TrbG_C)
Type: Domain

VirB9 is a component of the type IV secretion system, which is employed by pathogenic bacteria to export virulence proteins directly from the bacterial cytoplasm into the host cell. Unlike the more common type III secretion system, type IV systems evolved from the conjugative apparatus, which is used to transfer DNA between cells. VirB9 was initially identified as an essential virulence gene on the Agrobacterium tumefaciens Ti plasmid. In the pilin-like conjugative structure, VirB9 appears to form a stabilizing complex in the outer membrane, by interacting with the lipoprotein VirB7. The heterodimer has been shown to stabilize other components of the type IV system .

This entry represents the C-terminal domain of VirB9. It is also found in TrbG, a probable conjugal transfer protein from Rhizobium and CagX, a component of the Helicobacter pylori cag PAI-encoded type IV secretion system .
CLU central domain (CLU-central)
Type: Domain

Mutations in the mitochondrial CLU proteins have been shown to result in clustered mitochondria . CLU proteins include Saccharomyces cerevisiae clustered mitochondria protein (Clu1p, alias translation initiation factor 31/TIF31p), Dictyostelium discoideum clustered mitochondria protein homologue (CluA), Caenorhabditis elegans clustered mitochondria protein homologue (CLUH/ Protein KIAA0664), Drosophila clueless (alias clustered mitochondria protein homologue), Arabidopsis clustered mitochondria protein (CLU, alias friendly mitochondria protein/FMT), and human clustered mitochondria protein homologue (CLUH).

Dictyostelium CluA is involved in mitochondrial dynamics and is necessary for both, mitochondrial fission and fusion . Drosophila clueless is essential for cytoplasmic localization and function of cellular mitochondria . The Drosophila clu gene interacts genetically with parkin (park, the Drosophila ortholog of a human gene responsible for many familial cases of Parkinson's disease) . Arabidopsis CLU/FMT is required for correct mitochondrial distribution and morphology . The specific role CLU proteins play in mitochondrial processes in not yet known. In an early study, S. cerevisiae Clu1/TIF31p was reported as sometimes being associated with the elF3 translation initiation factor. The authors noted, however, that its tentative assignment as a subunit of elf3 was uncertain, and to date there has been no direct evidence for a role of this protein in translation .

This entry represents a central domain in CLU proteins.
AAR2, N-terminal (Aar2_N)
Type: Domain

This entry consists of the N-terminal domain of eukaryotic Aar2 and Aar2-like proteins.

Aar2 is a U5 small nuclear ribonucleoprotein (snRNP) particle assembly factor and part of Prp8, which forms a large complex containing U5 snRNA, Snu114, and seven Sm proteins (B, D1, D2, D3, E, F and G). Upon import of the complex into the nucleus, Aar2 phosphorylation leads to its release from Prp8 and replacement by Brr2p, thus playing an important role in Brr2p regulation and possibly safeguarding against non-specific RNA binding to Prp8 . Aar2p binds directly with the RNaseH-like domain in the C-terminal region of Prp8p . In yeast, Aar2 protein is involved in splicing pre-mRNA of the a1 cistron and other genes important for cell growth .