SII-SWORD/CoKE huggingface dataset:
Protein translocase subunit SecY (SecY)
Type: Family

This entry represents protein translocase subunit SecY.

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component . From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.

The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral membrane complex (SecY, SecE and SecG), and two additional membrane proteins that promote the release of the mature peptide into the periplasm (SecD and SecF) . The chaperone protein SecB is a highly acidic homotetrameric protein that exists as a "dimer of dimers" in the bacterial cytoplasm. SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane protein ATPase SecA for secretion . The structure of the Escherichia coli SecYEG assembly revealed a sandwich of two membranes interacting through the extensive cytoplasmic domains . Each membrane is composed of dimers of SecYEG. The monomeric complex contains 15 transmembrane helices.
Domain of unknown function, CHP04279 (CHP04279)
Type: Domain

This domain, with length just over 300 amino acids, occurs in predicted extracellular proteins in a number of methanogens, in one to three proteins per genome. The aromatic residue tyrosine, comprising about five percent of the amino acid composition, is overrepresented among the most highly conserved columns of the multiple sequence alignment. The three members containing this domain in Methanosarcina barkeri occur all within a six-gene region.
Bifunctional enzyme IspD/IspF (IspD/F)
Type: Family

This entry represents bifunctional enzyme that catalyses the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from CTP and 2-C-methyl-D-erythritol 4-phosphate (MEP) (IspD), and converts 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate into 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MECDP) and CMP (IspF) .
Hypoxanthine/guanine phosphoribosyltransferase-like (HGPRTase-like)
Type: Family

This entry consists of the hypoxanthine/guanine phosphoribosyltransferase (HPRT) and HPRT-like proteins. HPRT catalyses a salvage reaction resulting in the formation of IMP that is energically less costly than de novo synthesis . HPRT-like proteins may catalyse a purine salvage reaction, the substrate is unknown.
GMP synthase subunit B (GMP_synthase_B)
Type: Family

This entry represents the GMP synthase subunit B. It catalyses the synthesis of GMP from XMP (xanthosine 5'-phosphate).

The amidotransferase family of enzymes utilises the ammonia derived from the hydrolysis of glutamine for a subsequent chemical reaction catalyzed by the same enzyme. The ammonia intermediate does not dissociate into solution during the chemical transformations . GMP synthetase is a glutamine amidotransferase from the
de novo
purine biosynthetic pathway. The C-terminal domain is specific to the GMP synthases

. In prokaryotes this domain mediates dimerisation. Eukaryotic GMP synthases are monomers. This domain in eukaryotes includes several large insertions that may form globular domains .
DMRT family (DMRT)
Type: Family

The DMRT family contains putative transcription factors related to the sexual regulators doublesex (Drosophila melanogaster) and mab-3 (Caenorhabditis elegans). Its members are involved in sex determination/differentiation .

Mab-3 promotes male-specific development of two tissues. In the peripheral nervous system, it directs differentiation of sensory ray neuroblasts into peripheral sense organs. In the intestine, It causes repression of vitellogenin gene transcription. It binds the DNA motif 5'-[CGA][TCA][TA]ACAATGT[AT][TGA]C-3', probably as a monomer .
Opalin (Opalin)
Type: Family

Opalin (oligodendrocytic myelin paranodal and inner loop protein) is a brain specific, single-pass type I membrane protein . Its function is not clear. In mouse, it is expressed specifically in oligodendrocytes of the brain . It is induced by leukemia inhibitory factor (LIF) and cAMP analogs. It is suppressed in the presence of astrocytic or neural-stem-like differentiation factors such as bone morphotic protein (BMP) and fetal calf serum .
3'-RNA ribose 2'-O-methyltransferase, Hen1 (Hen1)
Type: Family

This entry consists of the eukaryal and bacterial 3'-RNA ribose 2'-O-methyltransferase, Hen1. Eukaryal Hen1 is a methyltransferase that adds a 2'-O-methyl group at the 3'-end small RNAs to protects the 3'-end of sRNAs from uridylation activity and subsequent degradation . In bacetria, Hen1 catalyses the same chemical reaction, but forms Pnkp/Hen1 heterotetramer and is involved in RNA repair .
Serine/threonine-protein kinase MRCK alpha, catalytic domain (MRCK_alpha_cat)
Type: Domain

Serine/threonine-protein kinase MRCK (myotonic dystrophy kinase-related CDC42-binding kinase) is an serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in actin-myosin regulation and activities including cell adhesion, motility and invasion . Three isoforms have been described in mammals: alpha, beta and gamma .

This entry represent the N-terminal catalytic domain of Serine/threonine-protein kinase MRCK alpha.
Receptor for retinol uptake STRA6-like (STRA6-like)
Type: Family

Receptor for retinol uptake STRA6 (also known as "stimulated by retinoic acid gene 6 protein") is a multitransmembrane domain protein, which acts as a retinol transporter for the complex retinol-retinol binding protein (RBP/RBP4). It acts by removing retinol (vitamin A) from RBP/RBP4 and transports it across the plasma membrane, where it can be metabolised. This mechanism does not depend on endocytosis .

Vitamin A and its derivatives are essential for vision and many other biological processes. In humans, defects in STRA6 are the cause of microphthalmia syndromic type 9 (MCOPS9); also called Matthew-Wood syndrome or Spear syndrome. Microphthalmia is a clinically heterogeneous disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS9 is a rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia .

In addition to serving as a retinol transporter, STRA6 is a ligand-activated cell surface signalling receptor that activates JAK/STAT signalling upon binding to the retinol-RBP complex .
Angiopoietin-like protein 8 (ANGPTL8)
Type: Family

Angiopoietin-like protein 8 (ANGPTL8), also known as betatrophin or lipasin, is a regulator of lipid metabolism .
Testis-expressed sequence 15 protein (TEX15)
Type: Family

Testis-expressed sequence 15 protein (TEXT15), also known as cancer/testis antigen 42, is a testis-specific protein. It is also expressed in several cancers . TEXT15 is essential for DNA double-strand break repair and chromosomal synapsis during male meiosis .
Transmembrane and coiled-coil domain-containing protein 2/5 (SMCO2/5)
Type: Family

Proteins in this family are single-pass membrane proteins. Their function is unknown.
M-phase-specific PLK1-interacting protein-like, vertebrate (MPLKIP-like_vertebrate)
Type: Family

This entry represents M-phase-specific PLK1-interacting protein and related uncharacterised sequences from vertebrates.

M-phase-specific PLK1-interacting protein (also known as TTD non-photosensitive 1 protein, TTDN1) may play a role in maintenance of cell cycle integrity by regulating mitosis or cytokinesis . Its The subcellular location is regulated during cell cycle. During interphase, it is located in the nucleus. During mitosis, it is located at the centrosome and dispersed in the cytoplasm. During telophase, it is located in the midbody. It colocalizes with PLK1 at the centrosome in M phase . It is phosphorylated during mitosis in the cell cycle probably by CDK1 .
Centrosomal protein of 95kDa (CEP95)
Type: Family

Centrosomal protein of 95kDa is localised to the centrosome and the spindle pole . Its function is not clear. It is phosphorylated upon DNA damage, probably by ATM or ATR .
Transmembrane protein 177 (TMEM177)
Type: Family

Complex IV (CIV) is a copper-heme oxidase that couples electron transfer from cytochrome c to oxygen with proton extrusion across the inner membrane to contribute to the proton gradient required for ATP generation. Human CIV is formed by three catalytic core subunits (COX1/2/3). TMEM177 is a mitochondrial protein involved in the COX2 biogenesis pathway .
Immortalization up-regulated protein (IMUP)
Type: Family

Immortalization up-regulated protein is upregulated in SV40-immortalized human fibroblasts. It is localised in nucleus .
Matrix-remodeling-associated protein 7 (Mxra7)
Type: Family

This family consists of matrix-remodeling-associated protein 7 (also known as transmembrane anchor protein 1). It is a single-pass membrane protein with unknown function.
Mucin-like protein 3 (MUCL3)
Type: Family

Mucin-like protein 3 (MUCL3; also known as diffuse panbronchiolitis critical region protein 1) is a single-pass type I membrane protein of unknown function. It is expressed in numerous tissues, with most-abundant expression in lung, kidney, and testis .
Cat eye syndrome critical region protein 6 (CECR6)
Type: Family

This entry represents the human Cat eye syndrome critical region protein 6 (also known as transmembrane protein 121B) and its homologues . Cat Eye Syndrome (CES) is characterised clinically by the combination of coloboma of the iris and anal atresia with fistula. CES is a rare condition caused by the duplication of a 2 Mb region of human 22q11.2 resulting in four copies of the region rather than the usual two copies .
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 (NDUFA3)
Type: Family

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 is a accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I), that is believed not to be involved in catalysis . Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone .
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, animal type (NDUFB2_animal)
Type: Family

This entry represent NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2 mostly from animals.

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2 is an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone .
Protein-tyrosine sulfotransferase-like (TPST-like)
Type: Family

Protein-tyrosine sulfotransferase catalyses the O-sulfation of tyrosine residues within acidic motifs of polypeptides, a common post-translational modification in eukaryotes . Mammals possess two protein-tyrosine sulfotransferases, designated TPST-1 and TPST-2 .

This family also includes NoeE from Sinorhizobium fredii, which is required for the formation of sulfated nod factor.
Protein-lysine N-methyltransferase Efm4/METTL10 (Efm4/METTL10)
Type: Family

Saccharomyces cerevisiae
Efm4 (also known as See1) is a lysine methyltransferase that dimethylates eukaryotic elongation factor 1A (eEF1A1) at lysine residues . It may also play a role in intracellular transport . This entry also includes methyltransferase-like protein 10 (METTL10; EEF1A lysine methyltransferase 2) from fish and mammals, which catalyzes the trimethylation of EEF1A at 'Lys-318' .
M-phase phosphoprotein 9 (MPHOSPH9)
Type: Family

This is a family of proteins phosphorylated in the M (mitotic) phase, known as M-phase phosphoprotein 9 (MPHOSPH9 or MPP9) . MPHOSPH9 appears to localise to the distal and proximal end of centriole pairs in duplicated centrosomes. Following centrosome splitting it is no longer visible, suggesting a role in the early steps of the centrosome cycle. In ciliated cells, it localises to the distal and proximal end of daughter centriole and proximal but not distal end of the mother centriole, suggesting that it may have a role in ciliogenesis .
Nuclear receptor coactivator 6 (NCOA6)
Type: Family

Nuclear receptor coactivator 6 (NCOA6, also known as ASC-2, TRBP and RAP250) is a general coactivator . It is involved in the coactivation of different nuclear receptors, such as steroid receptors (GR and ERs), retinoid receptors (RARs and RXRs), thyroid hormone receptors (TRs), vitamin D3 receptor (VDR) and prostanoid receptors (PPARs) . NCOA6 possesses an LXXLL sequence motif, which mediates its interaction with nuclear receptors . Altered expression of NCOA6 may contribute to the development of certain cancers .
Glucocorticoid-induced transcript 1/FAM117 (Glcci1/FAM117)
Type: Family

This family includes glucocorticoid-induced transcript 1 protein, a protein of unkown function that is expressed at specific stages of T-cell and sperm maturation , and uncharacterised proteins FAM117A and FAM117B.
CAMPATH-1 antigen (CD52) (CAMPATH-1)
Type: Family

CAMPATH-1 antigen (also known as CD52) is a very small glycosylphosphatidylinositol (GPI)-anchored glycoprotein present in lymphocytes , male reproductive tracts and female cumulus cells . CD52 on the lymphocyte membrane surface induces regulatory T cells with immunosuppressive activities . In the male reproductive tract, CD52 may protect sperm function from complement attack if antisperm antibody is generated in the female reproductive tracts . It has also been suggested that CD52 has some functional roles around fertilisation in females as well as in males .
Dermatopontin (Dermatopontin)
Type: Family

This family includes dermatopontin, millepora cytotoxin-1 and hemagglutinin/amebocyte aggregation factor.

Dermatopontin is a small molecular weight protein in the extracellular matrix, which has been reported to be involved in different functions . It seems to mediate adhesion by cell surface integrin binding . It interacts with transforming growth factor beta . A role of this protein in cell proliferation and collagen fibrillogenesis has also been reported.
G protein-regulated inducer of neurite outgrowth (GPRIN2-like/GPRIN3)
Type: Family

This entry consists of the G protein-regulated inducer of neurite outgrowth 2 (GPRIN2), GPRIN2-like and GPRIN3 proteins. They may be involved in neurite outgrowth .
Nuclear receptor-interacting protein 1 (NRIP1)
Type: Family

Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 . It also modulates transcriptional repression by nuclear hormone receptors .
Centrosomal protein of 128kDa (CEP128)
Type: Family

Centrosomal protein of 128kDa (CEP128) associates with the mother centriole . It is phosphorylated upon DNA damage, probably by ATM or ATR .
Variably charged protein VCX/VCY1 (VCX/VCY1)
Type: Family

This family includes variable charge X-linked proteins (VCX1, VCX2 and VCX3) and basic protein Y1 or variable charge Y1 (VCY1). Their function is unknown, but they may mediate a process in spermatogenesis or may play a role in sex ratio distortion. It's worth noting that the VCX/Y family has members on both the X and Y chromosome, but all appear to be expressed exclusively in male germ cells .
Proline/serine-rich coiled-coil protein 1/G2 and S phase-expressed protein 1 (DDA3/GTSE-1)
Type: Family

This is a family of phosphoproteins which includes proline/serine-rich coiled-coil protein 1 (PSRC1, also known as DDA3) and G2 and S phase-expressed protein 1 (GTSE1).

DDA3 is a microtubule-destabilising protein that controls spindle dynamics and mitotic progression by regulating microtubule depolymerases, such as Kif2a and MCAK . Deletion of DDA3 causes spindle hyper-stabilisation, inter-kinectochore tension loss, chromosome congression defects. This leads to unaligned chromosomes at metaphase and the accumulation of CENP-E (a plus end-motor protein) at kinectochore in these chromosomes . It has also been suggested that DDA3 may participate in p53/TP53-regulated growth suppression .
Phosphoribosyl-AMP cyclohydrolase (PRA-CH)
Type: Family

This entry represents phosphoribosyl-AMP cyclohydrolase (PRA-CH,

) which catalyses hydrolysis of phosphoribosyl-AMP, the third step in the histidine biosynthetic pathway . It also includes a number of histidine biosynthesis bifunctional proteins.
NADH-quinone oxidoreductase subunit CD (NDH-1_subunit_CD)
Type: Family

NADH dehydrogenase I (NDH-1) shuttles electrons from NADH, via FMN and iron-sulfur (Fe-S) centres, to quinones in the respiratory chain. It is composed of a number of different subunits. Subunits NuoB, CD, E, F, and G constitute the peripheral sector of the complex.
Stereocilin-related (Stereocilin-rel)
Type: Family

Members of this family includes stereocilin, mesothelin, mesothelin-like protein and otoancorin. They are predicted to have superhelical structures with ARM-type repeats which suggests that they may act as superhelical lectins to bind the carbohydrate moieties of extracellular glycoproteins .
Arsenite methyltransferase-like (Arsenite_MeTrfase-like)
Type: Family

Methylation is an important reaction in the biotransformation of arsenic. Arsenite methyltransferase catalyses the transfer of a methyl group from AdoMet to trivalent arsenicals producing methylated and dimethylated arsenicals .
SPEC3/Stum (SPEC3/Stum)
Type: Family

Proteins in this family are multi-pass membrane proteins including SPEC3 and Stum. The Stum protein was identified in Drosophila and has orthologues in animals ranging from nematodes to mammals. It is required for transduction of mechanical stimuli .

Purple sea urchin SPEC3 was found at the cilia and Golgi complexes of embryonic ectoderm cells. It has been suggested that this protein involves in ectodermal ciliogenesis .
Flagellum-associated coiled-coil domain-containing protein 1 (FLACC1)
Type: Family

Juvenile amyotrophic lateral sclerosis (ALS) is a form of chronic motor neuron disease characterised by combined upper and lower motor neuron symptoms. Amyotrophic lateral sclerosis 2 (ALS2) is an autosomal recessive form of juvenile ALS and has been mapped to human chromosome 2q33 . Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 12 protein (ALS2CR12), also known as FLACC1, is a putative GTPase regulator and its mutation is linked to the familial amyotrophic lateral sclerosis 2 .
Synaptonemal complex central element protein 1 (SYCE1)
Type: Family

Synaptonemal complex central element protein 1 is a major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. It requires the transverse filament protein-SYCP1 in order to be incorporated into the central element. It may have a role in the synaptonemal complex assembly, stabilisation and recombination .
Spermatogenesis-associated protein 31G1-like (Spata31g1-like)
Type: Family

This entry represents a family of mammalian proteins, including mouse Spermatogenesis-associated protein 31G1 (Spata31g1, also known as C9orf131), which has been reported to be dispensable for normal development and fertility .
INO80 complex subunit E (INO80E)
Type: Family

Proteins in this family are INO80 complex subunit E, a metazoan-specific subunit . Subunit E is a putative regulatory component of the chromatin remodeling INO80 complex, which is involved in transcriptional regulation, DNA replication and probably DNA repair .
Microtubule-associated protein 10, C-terminal (MAP10_C-term)
Type: Domain

This entry represents a C-terminal domain found in microtubule-associated protein 10.

Microtubule-associated protein 10 (MAP10, also known as MTR120/KIAA1383) localises to stabilised MTs during interphase and to the mitotic apparatus during mitosis. It may promote microtubule stability and ensures normal progress of cytokinesis .
Coiled-coil domain-containing protein 137 (CCDC137)
Type: Family

This entry represents the coiled-coil domain-containing protein 137. Its function is not clear.
Proline-rich AKT1 substrate 1 protein (AKT1S1)
Type: Family

Proline-rich AKT1 substrate 1 protein (AKT1S1, PRAS40) is part of the mammalian target of rapamycin complex 1 (mTORC1, contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR), which regulates cell growth and survival in response to nutrient and hormonal signals . Within mTORC1, AKT1S1 negatively regulates mTOR activity in a manner that is dependent on its phosphorylation state and binding to 14-3-3 proteins. AKT1S1 is a substrate for AKT1 phosphorylation, but can also be activated by AKT1-independent mechanisms. It may also play a role in nerve growth factor-mediated neuroprotection .
Serine/threonine-protein kinase TOR, catalytic domain (TOR_cat)
Type: Domain

This entry represents the catalytic domain of Serine/threonine-protein kinase TOR (target of rapamycin), which was first identified by mutations in yeast that confer resistance to the growth inhibitory properties of rapamycin . TOR proteins are structurally and functionally conserved in all eukaryotes examined. However, yeasts contain two Tor proteins (Tor1 and Tor2), while higher eukaryotes such as humans possess a single TOR protein . They are central regulators of cellular metabolism, growth and survival in response environmental signals . The catalytic domain is similar to that of phosphoinositide 3-kinase (PI3K) .

In budding yeast, the Tor2 protein exists in two distinct multi-component complexes, TORC1 and TORC2. TORC1 regulates cell growth by regulating many growth-related processes and is rapamycin sensitive, while TORC2 regulates the cell cytoskeleton and is rapamycin insensitive. Budding yeast TORC1 consists of either Tor1 or Tor2 in complex with Kog1, Lst8 and Tco89, while TORC2 is composed of Avo1, Avo2, Tsc11, Lst8, Bit61, Slm, Slm2 and Tor2 . In both yeast and mammals, FKBP12-rapamycin binds to Tor (Tor1, Tor2, or mTOR) in TORC1, but not to Tor (Tor2 or mTOR) in TORC2. It has been suggested that the architecture of TORC2 or its unique composition might be responsible for the observed rapamycin resistance .
Heat shock 70kDa protein 12A, nucleotide-binding domain (HSPA12A_NBD)
Type: Domain

Heat shock 70kDa protein 12A (HS12A) is an adapter protein for the amyloid precursor protein receptor SorLA . As a member of the heat shock protein 70 (HSP70) family of chaperones, HS12A shows a nucleotide-binding domain (NBD, represented in this entry) and a substrate-binding domain (SBD). The nucleotide sits in a deep cleft formed between the two lobes of the NBD. It is predominantly expressed in neuronal cells. and may play a role in the atherosclerotic process . Mutations in this protein have been related to both schizophrenia and bipolar affective disorder .
UPF0708 protein C6orf162 (UPF0708)
Type: Family

This entry consists of uncharacterised, single-pass membrane proteins.
Coiled-coil domain-containing protein 181 (CCDC181)
Type: Family

CCDC181 is a microtubule-binding protein that may play a role in mediating ciliary motility .
Zinc finger CCCH-type antiviral protein 1-like (Zc3hav1-like)
Type: Family

Proteins in this family contain C3H1-type zinc fingers. However, despite their name, they do not contain a canonical C3H1-type zinc-finger. Their function is not clear.
Protein CUSTOS (CUSTOS)
Type: Family

Custos regulates Wnt signaling pathway during early development. It plays a role in anterior head development in zebrafish .
Coiled-coil domain-containing protein 71/71L (Ccdc71/71L)
Type: Family

This family consists of coiled-coil domain-containing protein 71 and 71L. Their function is not clear.