SII-SWORD/CoKE huggingface dataset:
Transcription initiation factor TFIID subunit 8 (TAF8)
Type: Family

Transcription initiation factor TFIID subunit 8 (TAF8 or TAF(II)65) is a component of the general purpose transcription factor complex TFIID . TAF8 contains a histone fold domain . This entry includes TAF8 from animals, plants and fungi.

The DNA-binding general transcription factor complex TFIID is central to the initiation of DNA-dependent RNA polymerase II transcription. TFIID is the only general transcription initiation factor that bind to the TATA box. The binding of TFIID to the TATA-box is the first step in the formation of a complex able to initiate transcription . TFIID consists of the TATA binding protein (TBP) and 14 TBP-associated factors (TAFs). One copy of each TAF1, TAF2, TAF3, TAF7, TAF8, TAF11, TAF13, two copies of each TAF4, TAF5, TAF6, TAF9, TAF10, TAF12, and three copies of TAF14 .
ARHGEF28, PH domain (ARHGEF28_PH)
Type: Domain

ARHGEF28 (also called RIP2 or p190RhoGEF) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. In addition to the Dbl homology (DH)-PH domain, p190RhoGEF contains an N-terminal C1 (Protein kinase C conserved region 1) domain. The DH-PH domains bind and catalyze the exchange of GDP for GTP on RhoA .
NdvB, GH94N domain 1 (GH94N_NdvB)
Type: Domain

Cyclic beta 1-2 glucan synthetases, known as NdvB in Agrobacterium tumefaciens and ChvB in Rhizobium meliloti, belong to the glycoside hydrolase family 94 (previously known as glycosyltransferase family 36) . NdvB is required for the synthesis of cyclic beta-(1,2)-glucans, which play a role in interactions between bacteria and plants .

This is the first of the two tandemly repeated GH94-N-terminal-like domains in these enzymes.
Syntaxin-binding protein 6, PH domain (STXBP6_PH)
Type: Domain

Syntaxin binding protein 6 (STXBP6, also called Amisyn) contains, beside the N-terminal PH-like domain, a C-terminal R-SNARE-like domain, which allows it to assemble into SNARE complexes, which in turn makes the complexes inactive and inhibits exocytosis . SNARE complexes mediate membrane fusion, important for trafficking of newly synthesized proteins, recycling of pre-existing proteins and organelle formation. SNARE proteins are classified into four groups, Qa-, Qb-, Qc- and R-SNAREs, with STXBP6 being a R-SNARE .

This entry represents the PH domain of STXBP6.
STXBP6, SNARE domain (STXBP6_SNARE)
Type: Domain

Syntaxin binding protein 6 (STXBP6, also called Amisyn) contains, beside the N-terminal PH-like domain, a C-terminal R-SNARE-like domain, which allows it to assemble into SNARE complexes, which in turn makes the complexes inactive and inhibits exocytosis . SNARE complexes mediate membrane fusion, important for trafficking of newly synthesized proteins, recycling of pre-existing proteins and organelle formation. SNARE proteins are classified into four groups, Qa-, Qb-, Qc- and R-SNAREs, with STXBP6 being a R-SNARE .

This entry represents the SNARE domain of STXBP6.
Myotubularin-related protein 13, PH-GRAM domain (MTMR13_PH-GRAM)
Type: Domain

Myotubularin-related protein 13 (MTMR13), also known as SET-binding factor 2 (SBF2), belongs to the myotubularin family. It may function as a guanine nucleotide exchange factor (GEF) that activates Rab28 (a Rab GTPase) . Loss of MTMR13 leads to the Charcot-Marie-Tooth 4B (CMT4B) peripheral neuropathy, which is a recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system .

The family of myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, which contain inactivating substitutions in the phosphatase domain. MTMR13 is one of them. MTMR13 exists in cells independently as a homodimer, as well as in complex with a homodimer of MTMR2. Association with MTMR2 dramatically increases MTMR2 enzymatic activity .

MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. This entry represents the PH-GRAM domain of MTMR13.
NdvB, GH94N domain 2 (GH94N_2_NdvB)
Type: Domain

Cyclic beta 1-2 glucan synthetases, known as NdvB in Agrobacterium tumefaciens and ChvB in Rhizobium meliloti, belong to the glycoside hydrolase family 94 (previously known as glycosyltransferase family 36) . NdvB is required for the synthesis of cyclic beta-(1,2)-glucans, which play a role in interactions between bacteria and plants .

This is the second of the two tandemly repeated GH94-N-terminal-like domains in these enzymes.
Cellobiose phosphorylase, N-terminal (GH94N_CBP)
Type: Domain

Cellobiose phosphorylase (

) or cellobiose:phosphate alpha-D-glucosyltransferase, or CepA belongs to the glycoside hydrolase family 94 (previously known as glycosyltransferase family 36). This N-terminal domain is involved in oligomerisation and may play a role in catalysis, but it is separate from the catalytic domain - an (α/α)(6) barrel. Cellobiose phosphorylase participates in the degradation of cellulose, it catalyses the phosphate dependent hydrolysis of cellobiose into alpha-D-glucose-1-phosphate and D-glucose, a reversible reaction .
SNX27, atypical FERM-like domain (SNX27_FERM-like_dom)
Type: Domain

Sorting nexin-27 (SNX27) belongs to the sorting nexin family, which contains a conserved PX (phox homology) domain that may be responsible for binding to specific phosphoinositides . SNX27 also possesses an PDZ (DHR) domain, a Ras-associating domain and a FERM-like domain with an atypical tertiary structure .

SNX27 is a core component of the SNX27-retromer, a multiprotein complex composed of SNX27, the WASH complex and the retromer complex. It specifically binds and directs sorting of a subset of transmembrane proteins containing a PDZ-binding motif at the C terminus . Its PDZ domain mediates binding to the retromer complex via direct interaction with VPS26 (VPS26A or VPS26B) , while its PX domain mediates binding to phosphatidylinositol 3-phosphate (PtdIns(3P)) and localization to early endosome membranes .

This entry represents the FERM-like domain of SNX27. This domain binds PtdInsPs in a manner that is distinct to that of distantly related FERM, pleckstrin homology (PH) and phosphotyrosine-binding (PTB) domains .
N,N'-diacetylchitobiose phosphorylase, N-terminal (GH94N_ChBP)
Type: Domain

Chitobiose phosphorylase belongs to the glycoside hydrolase family 94 (previously known as glycosyltransferase family 36). This N-terminal domain is involved in oligomerization and may play a role in catalysis, but it is separate from the catalytic domain - an (α/α)(6) barrel]. Chitobiose phosphorylase catalyzes the reversible phosphate dependent hydrolysis of chitobiose [(GlcNAc)2] into alpha-GlcNAc-1-phosphate and GlcNAc. In some organisms, ChBP may be involved in the production of GlcNac-6-phosphate in intracellular pathways .
ZZ-type zinc finger-containing protein 3 (ZZZ3)
Type: Family

ZZ-type zinc finger-containing protein 3 (ZZZ3) is a component of the ATAC complex . ZZZ3 contains an HTH myb-type domain (PDB:2YUM) and a ZZ-type zinc-finger (PDB:2FC7).

The human ADA2A-containing complex (ATAC) is a histone acetyltransferase acting on histones H3 and H4 that is similar to but distinct from a similar complex initially identified in Drosophila melanogaster. The ATAC complex is composed of KAT14, KAT2A, TADA2L, TADA3L, ZZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 .
Vav, PH domain (PH_Vav)
Type: Domain

Vav acts as a guanosine nucleotide exchange factor (GEF) for Rho/Rac proteins. They control processes including T cell activation, phagocytosis, and migration of cells. The Vav subgroup of Dbl GEFs consists of three family members (Vav1, Vav2, and Vav3) in mammals . Vav1 is preferentially expressed in the hematopoietic system, while Vav2 and Vav3 are described by broader expression patterns . Mammalian Vav proteins consist of a calponin homology (CH) domain, an acidic region, a catalytic Dbl homology (DH) domain, a PH domain, a zinc finger cysteine rich domain (C1/CRD), and an SH2 domain, flanked by two SH3 domains. In invertebrates such as Drosophila and C. elegans, Vav is missing the N-terminal SH3 domain. The DH domain is involved in RhoGTPase recognition and selectivity and stimulates the reorganization of the switch regions for GDP/GTP exchange . The PH domain is implicated in directing membrane localization, allosteric regulation of guanine nucleotide exchange activity, and as a phospholipid-dependent regulator of GEF activity . Vavs bind RhoGTPases including Rac1, RhoA, and RhoG, while other members of the GEF family are specific for a single RhoGTPase. This promiscuity is thought to be a result of its CRD .

PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner . They share little sequence conservation, but all have a common fold, which is electrostatically polarised. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity . PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane . A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signalling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes .
SNX27, PX domain (SNX27_PX)
Type: Domain

Sorting nexin-27 (SNX27) belongs to the sorting nexin family, which contains a conserved PX (phox homology) domain that may be responsible for binding to specific phosphoinositides . SNX27 also possesses an PDZ (DHR) domain, a Ras-associating domain and a FERM-like domain with an atypical tertiary structure .

SNX27 is a core component of the SNX27-retromer, a multiprotein complex composed of SNX27, the WASH complex and the retromer complex. It specifically binds and directs sorting of a subset of transmembrane proteins containing a PDZ-binding motif at the C terminus . Its PDZ domain mediates binding to the retromer complex via direct interaction with VPS26 (VPS26A or VPS26B) , while its PX domain mediates binding to phosphatidylinositol 3-phosphate (PtdIns(3P)) and localization to early endosome membranes .

This entry represents the PX domain of SNX27. The SNX27 PX domain preferentially binds to phosphatidylinositol-3-phosphate (PI3P) and is important for targeting to the early endosome .
SNX27, RA domain (SNX27_RA)
Type: Domain

Sorting nexin-27 (SNX27) belongs to the sorting nexin family, which contains a conserved PX (phox homology) domain that may be responsible for binding to specific phosphoinositides . SNX27 also possesses an PDZ (DHR) domain, a Ras-associating domain and a FERM-like domain with an atypical tertiary structure .

SNX27 is a core component of the SNX27-retromer, a multiprotein complex composed of SNX27, the WASH complex and the retromer complex. It specifically binds and directs sorting of a subset of transmembrane proteins containing a PDZ-binding motif at the C terminus . Its PDZ domain mediates binding to the retromer complex via direct interaction with VPS26 (VPS26A or VPS26B) , while its PX domain mediates binding to phosphatidylinositol 3-phosphate (PtdIns(3P)) and localization to early endosome membranes .

This entry represents the RAS-associated (RA) domain of SNX27.
SNX17, atypical FERM-like domain (SNX17_FERM-like_dom)
Type: Domain

SNX17 is a critical regulator of endosomal recycling of numerous receptors, channels, and other transmembrane proteins. It binds to Asn-Pro-Xaa-Tyr (NPxY) sequences in the cytoplasmic tails of cargo such as LDL receptors and the amyloid precursor protein .

SNX17 contains a defining PtdInsP-binding PX domain, and a C-terminal 4.1, ezrin, radixin, moesin (FERM) domain with an atypical tertiary structure. This entry represents the FERM-like domain of SNX17. SNX17 binds Ras GTPase through its FERM-like domains .
Kindlin/fermitin, PH domain (PH_Kindlin/fermitin)
Type: Domain

Fermitin, also known as Unc-112-related protein , functions as a mediator of integrin inside-out signalling. The recruitment of Fermitin proteins and Talin to the membrane mediates the terminal event of integrin signalling, via interaction with integrin beta subunits . Fermatin has a FERM domain interrupted with a pleckstrin homology (PH) domain . Fermitin family homologues (Fermt1, 2, and 3, also known as Kindlins) are each encoded by a different gene. In mammalian studies, Fermt1 is generally expressed in epithelial cells, Fermt2 is expressed in muscle tissues, and Fermt3 is expressed in hematopoietic lineages. Specifically Fermt2 is expressed in smooth and striated muscle tissues in mice and in the somites (a trunk muscle precursor) and neural crest in Xenopus embryos. As such it has been proposed that Fermt2 plays a role in cardiomyocyte and neural crest differentiation. Expression of mammalian Fermt3 is associated with hematopoietic lineages: the anterior ventral blood islands, vitelline veins, and early myeloid cells. In Xenopus embryos this expression, also include the notochord and cement gland .

This entry represents the PH domain of fermitins.
JAK2, FERM domain C-lobe (JAK2_FERM_C-lobe)
Type: Domain

Janus kinases (JAKs) are tyrosine kinases that function in membrane-proximal signalling events initiated by a variety of extracellular factors binding to cell surface receptors . Many type I and II cytokine receptors lack a protein tyrosine kinase domain and rely on JAKs to initiate the cytoplasmic signal transduction cascade. Ligand binding induces oligomerisation of the receptors, which then activates the cytoplasmic receptor-associated JAKs. These subsequently phosphorylate tyrosine residues along the receptor chains with which they are associated. The phosphotyrosine residues are a target for a variety of SH2 domain-containing transducer proteins. Amongst these are the signal transducers and activators of transcription (STAT) proteins, which, after binding to the receptor chains, are phosphorylated by the JAK proteins. Phosphorylation enables the STAT proteins to dimerise and translocate into the nucleus, where they alter the expression of cytokine-regulated genes. This system is known as the JAK-STAT pathway.

Four mammalian JAK family members have been identified: JAK1, JAK2, JAK3, and TYK2. They are relatively large kinases of approximately 1150 amino acids, with molecular weights of ~120-130kDa. Their amino acid sequences are characterised by the presence of 7 highly conserved domains, termed JAK homology (JH) domains. The C-terminal domain (JH1) is responsible for the tyrosine kinase function. The next domain in the sequence (JH2) is known as the tyrosine kinase-like domain, as its sequence shows high similarity to functional kinases but does not possess any catalytic activity. Although the function of this domain is not well established, there is some evidence for a regulatory role on the JH1 domain, thus modulating catalytic activity. The N-terminal portion of the JAKs (spanning JH7 to JH3) is important for receptor association and non-catalytic activity, and consists of JH3-JH4, which is homologous to the SH2 domain, and lastly JH5-JH7, which is a FERM domain.

The FERM domain has a cloverleaf tripart structure composed of A-lobe or F1, B-lobe or F2, and C-lobe or F3 . This entry represents the C-lobe/F3 of the FERM domain of JAK2.
PLEKHN1, PH domain (PLEKHN1_PH)
Type: Domain

PLEKHN1 (also known as CLPABP) is a cardiolipin phosphatidic acid binding protein that associates with microtubules and accumulates in RNA granules, which contain cytochrome-c mRNA . It binds to Bid (a pro-apoptotic protein), removes Bid from transient Bid-Bax complexes, and promotes apoptosis . This entry represents the PH domain of PLEKHN1.

PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner . They share little sequence conservation, but all have a common fold, which is electrostatically polarised. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity . PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane . A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signalling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes .
Anillin, PH domain (PH_Anillin)
Type: Domain

Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci .

This entry represents the PH domain.
Histone-lysine N-methyltransferase SETD1A/B-like, SET domain (SET_SETD1A/B)
Type: Domain

In animals, SETD1A/B are histone methyltransferases that produce mono-, di-, and trimethylated histone H3 at 'Lys-4. However, if 'Lys-9' residue is already methylated, 'Lys-4' will not be. The 'Lys-4' methylation is a tag for epigenetic transcriptional activation . The animal COMPASS complex is composed of at least the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 .

ATXR7, the Arabidopsis homologue to Set1, is required for the expression of the flowering repressors FLC and MADS-box genes of the MAF family . ATXR7 is also involved in the control of seed dormancy and germination .

This entry represents the SET domain found in SETD1A/B and its homologues.
Kindlin/fermitin (Kindlin/fermitin)
Type: Family

Fermitin, also known as Unc-112-related protein , functions as a mediator of integrin inside-out signalling. The recruitment of Fermitin proteins and Talin to the membrane mediates the terminal event of integrin signalling, via interaction with integrin beta subunits . Fermatin has a FERM domain interrupted with a pleckstrin homology (PH) domain . Fermitin family homologues (Fermt1, 2, and 3, also known as Kindlins) are each encoded by a different gene. In mammalian studies, Fermt1 is generally expressed in epithelial cells, Fermt2 is expressed in muscle tissues, and Fermt3 is expressed in hematopoietic lineages. Specifically Fermt2 is expressed in smooth and striated muscle tissues in mice and in the somites (a trunk muscle precursor) and neural crest in Xenopus embryos. As such it has been proposed that Fermt2 plays a role in cardiomyocyte and neural crest differentiation. Expression of mammalian Fermt3 is associated with hematopoietic lineages: the anterior ventral blood islands, vitelline veins, and early myeloid cells. In Xenopus embryos this expression, also include the notochord and cement gland .
ASAP, PH domain (PH_ASAP)
Type: Domain

This entry represents the PH domain of Arf-GAP with SH3 domain, ANK repeat and PH domain-containing proteins (ASAPs). ASAPs (ASAP1, ASAP2, and ASAP3) function as Arf-specific GTPase-activating proteins (GAPs), participate in rhodopsin trafficking, are associated with tumour cell metastasis, modulate phagocytosis, promote cell proliferation, facilitate vesicle budding, Golgi exocytosis, and regulate vesicle coat assembly via a Bin/Amphiphysin/Rvs domain . Each member has a BAR, PH, Arf GAP, Ank repeat and proline rich domains. ASAP1 and ASAP2 also have a SH3 domain at the C terminus . The ASAP family is named for the first identified member, ASAP1 .

PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner . They share little sequence conservation, but all have a common fold, which is electrostatically polarised. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity . PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane . A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signalling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes .
GRAMDC4, PH-GRAM domain (GRAMDC4_PH-GRAM)
Type: Domain

GRAMDC4, also known as DIP, is a pro-apoptotic protein that mimics p53 and mediates the apoptotic function of p73 at mitochondria . It contains a single PH-GRAM domain at its C terminus. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold .
GRAM domain-containing protein 4 (GRAMDC4)
Type: Family

GRAMDC4, also known as DIP, is a pro-apoptotic protein that mimics p53 and mediates the apoptotic function of p73 at mitochondria .
GEM-like protein (GEM-like)
Type: Family

This entry represents the GEM and GEM-like (GER 1-8) proteins from plants. They contain a GRAM domain. GEM binds to phospholipids and its expression can be regulated by ABA . GER5 has been shown to be involved in seed development and inflorescence architecture .
ADAP, PH domain 1 (PH1_ADAP)
Type: Domain

ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate . Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity .

This entry contains the first PH domain repeat.
Retinoblastoma-binding protein 5/Swd1 (RBBP5/Swd1)
Type: Family

This entry includes RBBP5 from animals, RBL from plants and Swd1 from yeasts.