SII-SWORD/CoKE huggingface dataset:
LIPIN family (LIPIN)
Type: Family

Lipin family consists of lipin proteins, which are magnesium-dependent phosphatidate phosphatase enzymes that provide diacylglycerol for synthesis of triacylglycerol and phospholipids. Mammalian lipin proteins also exhibit transcriptional coactivator activity .

Common polymorphisms in human LPIN1 and LPIN2 genes are associated with traits underlying common metabolic diseases, including increased adiposity, hypertension, insulin sensitivity, and response to commonly used antidiabetic drugs .
Rab3GAP regulatory subunit (Rab3GAP2)
Type: Family

This family represents the regulatory subunit of the Rab3GAP complex, also known as Rab3GAP2.

Small G proteins of the Rab family are regulators of intracellular vesicle traffic. Their rate of GTP hydrolysis is enhanced by specific GTPase-activating proteins (GAPs) that switch G proteins to their inactive form . Rab3GAP1 (catalytic subunit) has been shown to form a heterodimeric complex with Rab3GAP2 (the regulatory subunit), and this complex acts as a guanosine nucleotide exchange factor for Rab3 subfamily (RAB3A, RAB3B, RAB3C and RAB3D). Rab3GAP complex may participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters . It also activates Rab18 and promotes autolysosome maturation through the Vps34 Complex I .

Mutations in the Rab3GAP1/2 gene cause Warburg micro syndrome (WMS), a hereditary autosomal neuromuscular disorder .
Associate of Myc 1 (AMY1)
Type: Family

AMY1 (associate of Myc1) family consists of the c-Myc-binding proteins that stimulate c-Myc transcription activity .
Terminal deoxynucleotidyltransferase-interacting factor 1 (TdIF1)
Type: Family

Terminal deoxynucleotidyltransferase (TdT) interacting factor 1 has been shown to bind and enhance TdT activity in vitro .
SIN3-HDAC complex-associated factor (FAM60A)
Type: Family

SIN3-HDAC complex-associated factor (also known as FAM60A) is found in eukaryotes. It has been shown to be a subunit of the Sin3 deacetylase complex (Sin3/HDAC), important for the repression of genes involved in the TGF-beta signaling pathway .
Headcase (Headcase)
Type: Family

The functions of this group of proteins are unclear. Drosophila headcase(hdc) protein is involved in dendrite pruning and is a branching inhibitor during tracheal development . It also promotes cell survival and niche maintenance in the Drosophila testis . The human headcase protein may be part of the regulatory mechanism in the development of epithelial tube networks such as the circulatory system and lungs and may play an important role in some human cancers .
Fuzzy protein (Fuzzy)
Type: Family

Drosophila Fuzzy protein plays a role in the organisation of cell polarity via a planar cell polarity (PCP) cascade. It is involved in the development of the hairs on the wings .
Glycosyl hydrolase family 99 (Glyco_Hydrolase_99)
Type: Family

This family contains endomannosidases and endomannosidase-like proteins. Glycoprotein endo-alpha-1,2-mannosidase hydrolyses the terminal alpha-D-glucosyl-(1,3)-D-mannosyl unit from the GlcMan9(GlcNAc)2 oligosaccharide component of the glycoprotein produced in the Golgi membrane .
Lck-interacting transmembrane adapter 1 (Lime1)
Type: Family

Lime is involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and TCR (T-cell antigen receptor)-mediated T-cell signaling in T-cells. It couples activation of these receptors and their associated kinases with distal intracellular events such as calcium mobilisation or MAPK activation through the recruitment of PLCG2, GRB2, GRAP2, and other signaling molecules .
Gametogenetin-binding protein 2 (GGNBP2)
Type: Family

Mouse gametogenetin binding protein 2 (GGNBP2) was found to interact with gametogenetin protein 1 (GGN1), which is the product of a testicular germ cell-specific gene specifically expressed from late pachytene spermatocytes through round spermatids. Therefore, GGNBP2 was suggested to be involved in spermatogenesis .
Microtubule associated protein 1 (MAP1)
Type: Family

MAP1-family proteins are microtubule-associated proteins (MAPs) that bind along the microtubule lattice. Mammalian genomes usually contain three family members, MAP1A, MAP1B and MAP1S. Only one family member, Futsch, is found in Drosophila.

Human MAP1A and MAP1B, are predominantly expressed in neurons, where they are thought to be important in the formation and development of axons and dendrites . Human MAP1A and MAP1B stabilise microtubules and interact with other cellular components, including filamentous actin and signaling proteins. The activity of MAP1A and MAP1B is controlled by upstream signaling mechanisms, including the MAP kinase and glycogen synthase kinase-3 beta pathways .
Late cornified envelope-like proline-rich protein 1 (Lelp1)
Type: Family

Lelp1 is a novel small proline rich protein (SPRR) still uncharacterised .
Protamine-P3 (PRMP3)
Type: Family

Protamine-P3 family consists of protamine 3 (PRM3) proteins. PRM3 proteins localize in the elongated spermatid cytoplasm (but not in mature sperm) and have been shown to affect sperm mobility . Despite their name, protamine, PRM3 proteins might not share the same function such as replacing somatic histones during spermiogenesis with other protamines .
Cerebellar degeneration-related protein 2 (CDR2)
Type: Family

Cerebellar degeneration-related protein 2 is a tumour antigen, which is aberrantly expressed in breast and ovarian tumors . It is also an important tumor antigen for papillary renal cell carcinoma .
Disrupted in schizophrenia 1 (DISC1)
Type: Family

Disrupted-In-Schizophrenia 1 (DISC1) was identified as a novel gene disrupted by a (1;11)(q42.1;q14.3) translocation segregating with schizophrenia, bipolar disorder and other major mental illnesses in a Scottish family .
ABC transporter A (ABCA)
Type: Family

ATP-binding cassette transporters (ABC) are multipass transmembrane proteins that use the energy of ATP hydrolysis to transport substrates across membrane bilayers. Members of ABC transporter subfamily A are full-length transporters , which consist of a single long polypeptide chain organised into two tandemly arranged halves. Each half contains a membrane-spanning domain (MSD) followed by a cytoplasmic nucleotide binding domain (NBD) . Several members of this group have been shown to mediate the transport of a variety of physiologic lipid compounds, such as sterols, phospholipids and bile acids .

ABCA7 plays a role in clearance of apoptotic cells by affecting their phagocytosis . In the human visual cycle, ABCA4 acts as an inward-directed retinoid flipase, retinoid substrates imported by ABCA4 from the extracellular or intradiscal (rod) membrane surfaces to the cytoplasmic membrane surface are all-trans-retinaldehyde (ATR) and N-retinyl-phosphatidyl-ethanolamine (NR-PE). Once transported to the cytoplasmic surface, ATR is reduced to vitamin A by trans-retinol dehydrogenase (tRDH) and then transferred to the retinal pigment epithelium (RPE) where it is converted to 11-cis-retinal. ABCA4 may also play a role in photoresponse, removing ATR/NR-PE from the extracellular photoreceptor surfaces during bleach recovery . It has been suggested that ABCA9 plays a role in monocyte differentiation and lipid homeostasis .
Activating transcription factor 7-interacting protein (ATF7-int)
Type: Family

Activating transcription factor 7-interacting protein (MCAF) family consists of MCAF1 and MCAF2 .

MCAF1 (also known as MBD1-containing chromatin-associated factor 1) is a recruiter that couples transcriptional factors to general transcription apparatus and thereby modulates transcription regulation and chromatin formation. It can both act as an activator or a repressor depending on the context .
Proline-rich protein (Pro-rich)
Type: Family

This family consists of several proline-rich proteins (PRPs). PRPs are tissue-specific expressions of salivary gland multigene families .
Corneodesmosin (Corneodesmosin)
Type: Family

Corneodesmosin (also known as S protein) is important for the epidermal barrier integrity .
Niban-like (Niban-like)
Type: Family

The Niban-like family is also known as family with sequence similarity 129 (FAM129). This family consists of Niban (FAM129A), Niban-like protein 1 (FAM129B or MINERVA) and Niban-like protein 2 (FAM129C) .

Overexpression of Niban (FAM129A) has been detected in patients with many types of cancer, including thyroid, head and neck, renal, and liver cancer. Niban is highly expressed in the early stages of cancer development and remains overexpressed throughout the cancer progression . It has been suggested that Niban might be involved in the ER stress response and can modulate cell death signaling by regulating translation .

Niban-like protein 1 was suggested to play a role in apoptosis suppression in cancer cells .
BLOC-3 complex member HPS4 (HPS4)
Type: Family

Hermansky-Pudlak syndrome (HPS) is a disorder of organelle biogenesis in which oculocutaneous albinism, bleeding and pulmonary fibrosis result from defects of melanosomes, platelet dense granules and lysosomes . HPS is common in Puerto Rico, where is mostly caused by mutations in the genes HPS1 or HPS3. Another HPS locus, HPS4 was identified by using mouse models . It was suggested that HPS4 and HPS1 proteins may function in the same pathway of organelle biogenesis .

This family represents BLOC-3 complex member HPS4, a component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into an active GTP-bound form. The BLOC-3 complex plays an important role in the control of melanin production and melanosome biogenesis and promotes the membrane localization of RAB32 and RAB38 .
Retinoic acid-induced protein 2/sine oculis-binding protein homologue (RAI2/SOBP)
Type: Family

Retinoic acid (RA) has been shown to modulate the expression of a number of proteins implicated in the control of early embryonic development. One of these is retinoic acid-induced protein 2 (RAI2), which has been isolated in mouse and humans .

Sine oculis-binding protein homologue (Jxc1, SOBP) is implicated in the development of the cochlea in the inner ear . Mutations in this gene also cause intellectual disability (ID) .
Protein MGARP (MGARP)
Type: Family

Protein MGARP, also known as HUMMR, localises to mitochondria and interacts with the mitochondrial membrane protein Miro . In response to hypoxia, it biases mitochondrial movement in the anterograde direction .
G protein pathway suppressor 2 (GPS2)
Type: Family

G protein pathway suppressor 2 is involved in G protein-mitogen-activated protein kinase (MAPK) signaling cascades. When overexpressed in mammalian cells, this protein could potently suppress a RAS- and MAPK-mediated signal and interfere with JNK activity, suggesting that the function of this protein may be signal repression . This protein is a component of the N-CoR-HDAC3 and also the SMRT corepressor complexes .
Myb/SANT-like DNA-binding domain-containing protein (Myb/SANT-like_DNA-bd_dom_prot)
Type: Family

This entry represents a family of proteins that have the Myb/SANT-like DNA-binding domain. The function of this family is unknown.
Receptor-transporting protein (R-trans_p)
Type: Family

This family consists of receptor-transporting proteins (RTP1, 2, 3, 4, 5). RTP5 is also known as CXXC-type zinc finger protein 11 (CXXC11). Mammalian RTP1 and RTP2 are accessory proteins to mammalian odorant receptors (ORs) and play significant roles in the translocation of ORs to the plasma membrane. They are expressed in the olfactory sensory neurons and facilitate OR trafficking to the cell-surface membrane and ligand-induced responses in heterologous cells . The functions of RTP3, RTP4 and RTP5 are not clear.
S100P-binding protein (S100PBP)
Type: Family

S100P-binding protein (S100PBP) interacts with S100P. S100P is a member of the S100 family of calcium-binding proteins and there have been several recent reports of its overexpression in pancreatic ductal adenocarcinoma (PDAC) .
Outer dense fibre protein 2-related (Odf2-rel)
Type: Family

This family consists of outer dense fibre protein 2 and related proteins.
Outer dense fibre protein 2 (Odf2), also known as cenexin, seems to be a major component of sperm tail outer dense fibres (ODFs). ODFs are filamentous structures located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail and may help to maintain the passive elastic structures and elastic recoil of the sperm tail. Odf2 may have a modulating influence on sperm motility. It functions as a general scaffold protein that is specifically localized at the distal/subdistal appendages of mother centrioles .
Transmembrane protein 223 (Tmem223)
Type: Family

This protein family represents an uncharacterised group of presumed integral membrane proteins that includes TMEM233.
Harbinger transposase-derived nuclease, animal (HARBI1_animal)
Type: Family

This entry represents the Harbinger transposase-derived proteins mostly from animals. Proteins in this family may have nuclease activity, but do not appear to have transposase activity .

Harbinger DNA transposons have been identified in protists, plants, insects,
worms, and vertebrates. However, mammals do not have Harbinger transposons. In human, no recognisable members of Harbinger transposase superfamily are found. Instead, a widely expressed HARBI1 gene encoding a 350-amino acid protein derived from a Harbinger transposase has been identified . The HARBI1 protein is conserved in humans, rats, mice, cows, pigs, chickens, frogs and various bony fish . Conserved motifs, which are expected to be catalytic centres of nuclease/ligase reactions necessary for transpositions, found in the Harbinger transposases, are also well preserved in the HARBI1 proteins . It was also proposed that these hypothetical HARBI1 nucleases are also characterised by a strong DNA-target specificity .
Zinc finger C2HC domain-containing protein 1C (ZNF_C2HC_dom_1C)
Type: Family

The function of zinc finger C2HC domain-containing protein 1C is not clear.
Microtubule-associated protein 9 (MAP9)
Type: Family

Human MAP9 is involved in organisation of the mitotic spindle . Besides being required for mitosis progression and cytokinesis, it may stabilise interphase microtubules . Upon DNA damage, it is phosphorylated probably by ATM or ATR .
G kinase-anchoring protein 1 (GKAP1)
Type: Family

GKAP1 is also called GKAP42. cGMP-dependent protein kinase (cGK) is a major cellular receptor of cGMP, playing important roles in cGMP-dependent signal transduction pathways . Using the yeast two-hybrid system with cGK-Ialpha as a bait, a male germ- cell-specific 42kDa protein, GKAP42 (42kDa cGMP-dependent protein kinase anchoring protein) has been identified .

The N-terminal 66 amino acids of cGK-Ialpha were shown to be sufficient for association with GKAP42, but GKAP42 did not interact with cGK-Ibeta, cGK-II or cAMP-dependent protein kinase . GKAP42 mRNA is specifically expressed in testis, where it is restricted to spermatocytes and early-round spermatids . GKAP42 is believed to function as an anchoring protein for cGK-Ialpha, and it is thought that cGK-Ialpha may participate in germ-cell development through phosphorylation of Golgi-associated proteins such as GKAP42 .

A recurring chromosomal aberration in acute myeloid leukemia (AML) is deletion of the long arm of chromosome 9, del(9q) . The Commonly Deleted Region (CDR) has been defined to less than 2.4 Mb, and found to contain 7 known genes, including GKAP42. The results of mutation and expression analyses of these genes are consistent with a model of tumour suppression mediated by haploinsufficiency of critical genes in del(9q) AML.
Lymphocyte antigen 6 complex locus protein G5c (LY6G5C)
Type: Family

Proteins in this family may have a role in hematopoietic cell differentiation .
Actin-binding Rho-activating protein (Abra)
Type: Family

Actin-binding Rho-activating protein is also known as striated muscle activator of Rho-dependent signaling (STARS) in mouse and myocyte stress 1 (MS1) in rat. STARS acts as an activator of serum response factor (SRF)-dependent transcription, possibly by inducing nuclear translocation of MKL1 or MKL2 and through a mechanism requiring Rho-actin signaling .
Amnionless (AMN)
Type: Family

Human amnionless (AMN) is necessary for efficient absorption of vitamin B12. Defects in AMN is a cause of recessive hereditary megaloblastic anemia 1 (RH-MGA1), also known as MGA1 Norwegian type or Imerslund-Grasbeck syndrome (I-GS).
tRNA N(3)-methylcytidine methyltransferase METTL2/6/8-like (METTL2/6/8-like)
Type: Family

This family includes tRNA N(3)-methylcytidine methyltransferases METTL2, 6 and 8, O-methyltransferase 3 and methyltransferase-like protein Metl from Drosophila. These proteins are S-adenosyl-L-methionine-dependent methyltransferases that mediate N3-methylcytidine modification of residue 32 of the tRNA anticodon loop of tRNA(Thr) and tRNA(Ser) .

tRNA N(3)-methylcytidine methyltransferase METTL2, 6 and 8 are part of a group of proteins known as TIPs (from tension-induced/inhibited protein) required for the recruitment of histone acetyltransferase p300 to specific promoters. TIP-6 is involved in the adipogenic cascade . O-methyltransferase 3 is up-regulated by phagocytic stimuli .
Apolipoprotein F (APOF)
Type: Family

Human apolipoprotein F (APOF) is a minor apolipoprotein that associates with LDL. It inhibits cholesteryl ester transfer protein (CETP) activity and appears to be an important regulator of cholesterol transport. It also associates to a lesser degree with VLDL, Apo-AI and Apo-AII .
Novel Amplified in Breast Cancer-1 (NABC1)
Type: Family

Human NABC1 (also denoted as breast carcinoma amplified sequence-1 (BCAS1)) is overexpressed in most breast cancer cell lines and down-regulated in some colorectal tumors . It forms detergent stable homodimer, and it is this homodimeric form that accumulates in cells that overexpress this protein .
Glycosyltransferase family 18, catalytic domain (GT18_cat)
Type: Domain

This entry represents the catalytic domain of glycosyltransferase family 18 enzymes.

The glycosyltransferase family 18 consists of alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferases. This enzyme catalyses the addition of N-acetylglucosamine in beta 1-6 linkage to the alpha-linked mannose of biantennary N-linked oligosaccharides. It is one of the most important enzymes involved in the regulation of the biosynthesis of glycoprotein oligosaccharides.

In humans, two homologues have been described, Gnt-V(A) and Gnt-VB (GnT-IX). Gnt-VB is predominantly expressed in brain and catalyses the transfer of N-acetylglucosamine (GlcNAc) to the beta 1-6 linkage of the mannose residue of GlcNAcbeta1,2-Manalpha on both the alpha1,3- and alpha1,6-linked mannose arms in the core structure of N-glycan. Gnt-VB could be responsible for the synthesis of a unique oligosaccharide structure in the brain. It plays an active role in modulating integrin and laminin-dependent adhesion and migration of neuronal cells via its activity in the O-mannosyl glycan pathway .

Caenorhabditis elegans has only one homologue .
Prostate apoptosis response 4 (Par-4)
Type: Family

Prostate apoptosis response 4 (Par-4) induced apoptosis of selective prostate cancer cells PC-3, DU-145, and TSU-Pr and caused tumor regression by inhibition of NF-kappaB activity and cell membrane trafficking of Fas and FasL that leads to the activation of the Fas-Fas-associated death domain-caspase-8 pro-death pathway . It modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1. It down-regulates the anti-apoptotic protein BCL2 via its interaction with WT1 . Par-4 also regulates the amyloid precursor protein (APP) cleavage activity of BACE1 .
Calcium-binding and spermatid-specific protein 1 (Ca-bd_spermatid)
Type: Family

Calcium-binding and spermatid-specific protein, also known as casein-like phosphoprotein, is involved in spermatogenesis .
Transmembrane protein 11 (TMEM11)
Type: Family

TMEM11 (also called PMI in Drosophila) regulates mitochondrial morphogenesis via a mechanism which is independent of mitofusins and dynamin-related protein 1 .
Helicase MOV-10/SDE3, DEXXQ/H-box helicase domain (MOV-10/SDE3_DEXXQ/H-box)
Type: Domain

MOV-10 (moloney leukemia virus 10 protein) is the human homologue of Drosophila melanogaster Armitage (armi). Human MOV-10 is a 5' to 3' RNA helicase required for RNA-mediated gene silencing by the RNA-induced silencing complex (RISC) . It has been shown to interact with fragile X messenger ribonucleoprotein 1 (FMRP) and regulates miRNA-mediated translational repression by AGO2 . Interestingly, it interacts with retrotransposons and acts as a potent inhibitor of retrotransposition in cells . This protein is required for RNA-directed transcription and replication of the human hepatitis delta virus (HDV). It interacts with small capped HDV RNAs derived from genomic hairpin structures that mark the initiation sites of RNA-dependent HDV RNA transcription .
SCL-interrupting locus protein (Sil)
Type: Family

SIL (also called STIL/TAL1 interrupting locus) is an immediate-early gene that is essential for embryonic development and is implicated in T-cell leukemia-associated translocations . Sil protein is necessary for proper mitotic spindle organisation in zebrafish and human cells and localizes to the mitotic spindle poles only during metaphase . Mouse Sil was suggested to play a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1 . In human, cell cycle-dependent phosphorylation of Sil is required for its interaction with Pin1, a regulator of mitosis .

Primary microcephaly (MCPH) is an autosomal-recessive congenital disorder characterised by smaller-than-normal brain size and mental retardation. Three different homozygous mutations in SIL were identified in patients from three of the five families linked to the MCPH7 locus; all are predicted to truncate the Sil protein .
Sperm-associated antigen 8 (Sperm-assoc_Ag8)
Type: Family

Sperm associated antigen 8 (SPAG8) is a testis-specific protein produced during male germ cell differentiation . It has been shown to interact with microtubules and to modulate microtubule assembly and/or activity .
SPAG8 has also been implicated in regulation of the cell cycle by changing the phosphorylation level of Tyr15 on cdc2, suggesting it might play a role in cell division during spermatogenesis .
BRISC and BRCA1-A complex member 1 (BABAM1)
Type: Family

BRISC and BRCA1-A complex member 1 (BABAM1, also known as MERIT40 and NBA1) was initially identified as a gene required for resistance to ionizing radiation . It is a component of the BRCA1-A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE . The BRCA1-A complex recognises 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the brca1-bard1 heterodimer to sites of DNA damage at double-strand breaks (DSBs), facilitating DNA damage repair. The BRCA1-A complex is also involved in G2/M transition DNA damage checkpoint control. BABAM1 may also play a role as a component of the BRISC complex (contains the FAM175B/ABRO1, BRCC3/BRCC36, BRE/BRCC45 and MERIT40/NBA1 proteins), a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin. In these 2 complexes, BABAM1 is probably required to maintain the stability of BRE/BRCC45 and help the 'Lys-63'-linked deubiquitinase activity mediated by BRCC3/BRCC36 component .
Neurosecretory protein VGF (VGF)
Type: Family

VGF protein is a neurosecretory protein originally identified as a product of the nerve growth factor responsive gene Vgf in rat pheochromocytoma PC12 cells . VGF may be involved in the regulation of cell-cell interactions or in synatogenesis during the maturation of the nervous system .