TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
8.A.23.1.1









Extracellular chaperone protein precursor, Basigin (BSG; CD147). It interacts with MCT1, 3 and 4 (TC# 2.A.1.13.1, 7 and 9, respectively) (Ovens et al., 2010; Halestrap 2012).  May play a role in cancer progression (Kendrick et al. 2016). Silencing of CD147 inhibits hepatic stellate cell activation related to suppressing aerobic glycolysis via hedgehog signaling (Li et al. 2021). CD147 is an integral and potential molecule to abrogate hallmarks of cancer (Nyalali et al. 2023).

Eukaryota
Metazoa, Chordata
Basigin precursor of Homo sapiens (P35613)
8.A.23.1.2









Extracellular chaperone protein precursor, Embigin. Interacts with MCT2 (2.A.1.13.5) (Ovens et al., 2010; Halestrap 2012). Embigin facilitates monocarboxylate transporter 1 localization to the plasma membrane and its transition to a decoupling state (Xu et al. 2022).

Eukaryota
Metazoa, Chordata
Embigin of Homo sapiens (Q6PCB8)
8.A.23.1.3









Potassium channel associated protein, contactin 2, CNTN2, of 1040 aas and possibly 2 TMSs, at the N- and C-termini.  Mutations are associated with autosomal recessive cortical myoclonic tremors and epilepsy (Stogmann et al. 2013).

Eukaryota
Metazoa, Chordata
CNTN2 of Homo sapiens
8.A.23.1.4









Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110)
Eukaryota
Metazoa, Chordata
C-BAT (GP110) of Rattus norvegicus
8.A.23.1.5









Hepatocyte cell adhesion molecule (CAM) precursor of 416 aas.  Important for interactions, trafficking and function of  ClC2 (CLC-2) in several tissues including the nervious system where it influences human leukodystrophies (Capdevila-Nortes et al. 2015).

Eukaryota
Metazoa, Chordata
CAM of Homo sapiens
8.A.23.1.6









Fibroblast growth factor receptor-like protein, FGFRL1, of 504 aas and 2 TMSs, one N-terminal and one C-terminal. It is capable of inducing syncytium formation (Steinberg et al. 2010).

Eukaryota
Metazoa, Chordata
FGFRL-1 of Homo sapiens
8.A.23.1.7









Fibroblast growth factor receptor 1, FGFR1, of822 aas and 2 TMSs, one N-terminal and one central.  FGFR1 is a tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system (Haenzi and Moon 2017).

Metazoa, Chordata
FGFR1 of Homo sapiens
8.A.23.1.8









Neuroplastin NptN of 398 aas (Beesley et al. 2014).  Important for targetting of certain transporters such as Xkr8 to the plasma membrane with which it, with basigin, forms a physical complex (Suzuki et al. 2016). Neuroplastin expression is essential for hearing and hair cell PMCA (TC# 3.A.3.2.40) expression (Lin et al. 2021).

Eukaryota
Metazoa, Chordata
NptN of Homo sapiens
8.A.23.1.9









Fibroblast growth factor receptor 4, FGFR4, of 802 aas and 2 - 4 TMSs.  Serves as the receptor for FGF23 for the activation of TRP6 (TC# 1.A.4.1.5). Binding activates the TRP6 channel for inorganic cation (including Ca2+) transport (Smith et al. 2017). It also regulates Na+:phosphate co-transport together with α-Klotho (see paragraph 2 in the family description of TC# 1.A.108; Hu et al. 2018).

Eukaryota
Metazoa, Chordata
FGFR4 of Homo sapiens
8.A.23.1.10









Activated leukocyte cell adhesion molecule, ALCAM or CD166 antigen, of 583 aas and 2 TMSs, N- and C-terminal.  It is expressed on and in the cell membranes of various cells.  In the spinal cord dorsal horn (DH), the first gate for the sensory and pain transmission to the brain, ALCAM plays modulatory roles in the excitatory synaptic transmission and plasticity in the (rat) spinal DH (Park et al. 2017).

Eukaryota
Metazoa, Chordata
ALCAM of Homo sapiens
8.A.23.1.11









Interleukin 1 receptor of 569 aas and 2 TMSs, N-terminal and near the middle of the protein. It is the receptor for IL1A, IL1B and IL1RN. After binding to interleukin-1, it associates with the coreceptor IL1RAP to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B, MAPK and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. It binds ligands with comparable affinity, and binding of antagonist IL1RN prevents association with IL1RAP to form a signaling complex (Slack et al. 2000).

Eukaryota
Metazoa, Chordata
IL-1R of Homo sapiens
8.A.23.1.12









cSrc tyr kinase of 536 aas; regulates the Na+,K+-ATPase and connexin 43, probably by direct phosphorylation (Giepmans 2006).

Eukaryota
Metazoa, Chordata
cSrc of Homo sapiens
8.A.23.1.13









Epidermal growth factor receptor (EGFR) of 1426 aas and 2 or more TMSs.  Binds to four ligands: Spitz, Gurken, Vein and Argos, transducing signals through the ras-raf-MAPK pathway. Involved in a myriad of developmental decisions (Geiger et al. 2011).

Eukaryota
Metazoa, Arthropoda
EGFR of Drosophila melanogaster (Fruit fly)
8.A.23.1.14









Coxsackievirus and adenovirus receptor, CAR, of 365 aas and 2 TMSs near the N- and C-termini. It is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. It is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML, a transmembrane protein of the plasma membrane of leukocytes (Cohen et al. 2001). It's subcellular distribution has been studied (Ifie et al. 2018). The CAR in zebrafish (Q90Y50) has been discussed (Rathjen 2020).

Eukaryota
Metazoa, Chordata
CAR of Homo sapiens
8.A.23.1.15









Ephrin type-B receptor 4 (EPHB4; EC:2.7.10.1). Alternative name(s): Hepatoma transmembrane kinase; Tyrosine-protein kinase, TYRO11.  It is a receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.  It plays a role in postnatal blood vessel remodeling, morphogenesis and permeability (Erber et al. 2006; Martin-Almedina et al. 2016).

Eukaryota
Metazoa, Chordata
EPHB4 of Homo sapiens
8.A.23.1.16









Angiopoietin-1 receptor of 1072 aas, Tek, a tyrosyl protein kinase (Ward and Dumont 2002).

Eukaryota
Metazoa, Chordata
Tek of Mus musculus
8.A.23.1.17









Receptor tyrosyl protein kinase, ErbB4 (ErbB-4).  Plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis (Deng et al. 2013).

Eukaryota
Metazoa, Chordata
ErbB4 of Homo sapiens
8.A.23.1.18









Tex14 of 1497 aas and 1 or 2 TMSs.  Required both for the formation of intercellular bridges during meiosis and for kinetochore-microtubule attachment during mitosis. Intercellular bridges, called 'ring canals', probably result from nurse cell fusion with the developing oocyte.  They are evolutionarily conserved structures that connect differentiating germ cells and are required for spermatogenesis, oogenesis and male fertility. They act by promoting the conversion of midbodies into intercellular bridges via its interaction with CEP55. Interaction with CEP55 inhibits the interaction between CEP55 and PDCD6IP/ALIX and TSG101, blocking cell abscission and leading to transformation of midbodies into intercellular bridges. In spite of its PK domain, it has no protein kinase activity in vitro (Lei and Spradling 2016).

Eukaryota
Metazoa, Chordata
Tex14 of Homo sapiens
8.A.23.1.19









The Advanced glycosylation end product-specific receptor of 404 aas and 2 TMSs, N- and C-terminal, AGER or RAGE.  It is the receptor for amyloid beta peptide, and it contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons. ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space.  RAGE also has a number of other functions (Fang et al. 2010;.Jin et al. 2011). It's structure is known to 1.5 Å resolution (Park et al. 2010; Xue et al. 2011).  RAGE is a transmembrane receptor of the immunoglobulin family that can bind various endogenous and exogenous ligands, initiating the inflammatory downstream signaling pathways, including inflammaging (Dascalu et al. 2024).

;

Eukaryota
Metazoa, Chordata
RAGE of Homo sapiens
8.A.23.1.20









Polymeric immunoglobulin receptor-like protein, pIgR, of 562 aas and 2 TMSs, one N-terminal and one near the C-terminus of the protein.  It is the receptor for white spot syndrome virus (WSSV) infection (Niu et al. 2019Niu et al. 2019).

Eukaryota
Metazoa, Arthropoda
pIgR of Penaeus japonicus (Kuruma prawn) (Marsupenaeus japonicus)
8.A.23.1.21









Polymeric Ig-like receptor of 345 aas and 2 TMSs, pIgR, also called Cell adhesion molecule 4 isoform X2.

Eukaryota
Metazoa, Chordata
pIgR of Homo sapiens
8.A.23.1.22









Polymeric Ig-like receptor family protein, pIgR, of 774 aas and 1 TMS, near the C-terminus.

Eukaryota
Metazoa, Arthropoda
pIgR of Drosophila melanogaster (Fruit fly)
8.A.23.1.23









Poliovirus receptor-related protein 3-like isoform X, PVRL3, of 366 aas and 1 N-terminal TMS

Eukaryota
Metazoa, Chordata
PVRL3 of Lipotes vexillifer (Yangtze river dolphin)
8.A.23.1.24









Uncharacterized protein of 323 aas and 2 TMSs, N- and C-terminal.

Eukaryota
Metazoa, Echinodermata
UP of Strongylocentrotus purpuratus
8.A.23.1.25









T-cell surface antigen CD2 of 351 aas. CD2 interacts with lymphocyte function-associated antigen CD58 (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells,  and the cytoplasmic domain is implicated in the signaling function.

Bacteria
Bacillota
CD2 of Homo sapiens
8.A.23.1.26









Carcinoembryonic antigen-related cell adhesion molecule 1-like protein of 663 aas and 1 TMS.  This protein appears to be related to members of family 8.A.128, and these two families may comprise a superfamily.

Eukaryota
Metazoa, Chordata
Adhesin of Xenopus laevis
8.A.23.1.27









TGF-β (Tkv) receptor protein kinase of 575 aas and 1 TMS (Bartoszewski et al. 2004).

Eukaryota
Metazoa, Arthropoda
Tkv receptor of Drosophila melanogaster (Fruit fly)
8.A.23.1.28









Neural cell adhesion molecule 2-like protein of 567 aas and 2 TMSs, N- and C-terminal.

Eukaryota
Metazoa, Chordata
Adhesion protein of Astatotilapia calliptera (eastern happy)
8.A.23.1.29









Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle (Tan-Sindhunata et al. 2015). Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex (Koppel et al. 2019).

Eukaryota
Metazoa, Chordata
MUSK of Homo sapiens
8.A.23.1.30









Insulin receptor-like tyrosine kinase, DAF2, of 1846 aas and 3 putative TMSs, one near the N-terminus, and two in the C-terminal part ofthe protein. It regulates metabolism, controls longevity and prevents developmental arrest at the dauer stage (Fierro-González et al. 2011; Tiku et al. 2017; Chen et al. 2013). The nematode insulin receptor (IR), DAF-2B, modulates insulin signaling by sequestration of insulin peptides (Martinez et al. 2020).

Eukaryota
Metazoa, Nematoda
DAF2 of Caenorhabditis elegans
8.A.23.1.31









Hemicentin-1-like protein of 321 aas and 0 - 4 TMSs.

Eukaryota
Metazoa, Arthropoda
Him1 of Penaeus vannamei
8.A.23.1.32









Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family-6, SlamF6, of 351 aas and possibly 3 TMSs, two near the N-terminus, and one near the C-terminus (Togni et al. 2004). SLAM receptors, triggered by homo- or heterotypic cell-cell interactions, modulate the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune responses (Griewank et al. 2007).

Eukaryota
Metazoa, Chordata
SlamF6 of Mus musculus (Mouse)
8.A.23.1.33









Nephrin, NPHS1 of 1241 aas and two TMSs, one at the N-terminus, and one near the C-terminus of the protein.  Nephrin forms a complex with podocin (TC# 3.A.16.1.1), CD2AP (8.A.34.1.5) and TRPC6 (1.A.4.1.5) to form a macromolecular assembly that constitutes the slit-diaphragm in podocytes, a tight juntion-like complex (Mulukala et al. 2020).

 

Eukaryota
Metazoa, Chordata
Nephin of Homo sapiens
8.A.23.1.34









Signal-regulatory protein beta-1, SIRPbeta (SIRPβ) of 398 aas and 2 TMSs, N- and C-terminal.  It is an immunoglobulin-like cell surface receptor involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes, and it participates in the recruitment of tyrosine kinase SYK. It triggers activation of myeloid cells when associated with TYROBP (Dietrich et al. 2000). Positive regulation of phagocytosis by SIRPbeta has been demonstrated as part of  its signaling mechanism in macrophages (Hayashi et al. 2004).

Eukaryota
Metazoa, Chordata
SIRPβ of Homo sapiens
8.A.23.1.35









Serine/threonine-protein kinase LMTK1 (AATK) of 1374 aas and one N-terminal TMS. It plays a role in axon outgrowth and spine formation (Wei et al. 2020).

Eukaryota
Metazoa, Chordata
LMTK1 of Homo sapiens
8.A.23.1.36









CD48 antigen (BCM1; BLAST1; Sgp-60; MEM102; SLAM family member 2, SLAMF2) of 243 aas with 2 TMSs, N- and C-terminal. It is a ligand for CD2, and may facilitate interaction between activated lymphocytes. It is probably involved in regulating T-cell activation (González-Cabrero et al. 1999).

Eukaryota
Metazoa, Chordata
BCM1 of Homo sapiens
8.A.23.1.37









Platelet-derived growth factor receptor beta, PDGFRB, a tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB (Kelly et al. 1991), and plays an essential role in the regulation of embryonic development, cell proliferation, survival, Ca2+ transport, differentiation, chemotaxis and migration (Kazlauskas et al. 1991; Vanlandewijck et al. 2015). It has been associated with Primary Familial Brain Calcification (PFBC) (Monfrini et al. 2023).

Eukaryota
Metazoa, Chordata
PDGFRB of Homo sapiens
8.A.23.1.38









BDNF/NT-3 growth factors receptor, ofNKRK2 or TrkB, of 822 aas and 1 N-terminal TMS. It is a receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. It is a receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively, it can bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2 (Haniu et al. 1995, Yeo et al. 2004). Upon ligand-binding, it undergoes homodimerization, autophosphorylation and activation (Yeo et al. 2004).

Eukaryota
Metazoa, Chordata
TrkB of Homo sapiens
8.A.23.1.39









Receptor tyrosine-protein kinase ErbB-2/ErbB-3. ErbB-2 is also called ERBB2, HER2, MLN19, NEU and NGL. It is of 1255 aas and possibly 2 TMSs, one at the N-terminus, and one large hydrophobic peak in the C-terminal half of the protein. ErbB-3 is also called HER3 and is of 1342 aas with at least one TMS near residue 650, but maybe also an N-terminal TMS. These two proteins form a complex with  SorLA (TC# 9.B.87.1.17) (Al-Akhrass et al. 2021). They are parts of several cell surface receptor complexes that apparently need a coreceptor for ligand binding. They are essential components of a neuregulin-receptor complex (Ieguchi et al. 2010).

Eukaryota
Metazoa, Chordata
HER2/HER3 of Homo sapiens
8.A.23.1.40









Bone morphogenetic protein receptor type-1B, BMPR-1B or FecB, of 502 aas and one large peak of hydrophobicity at ~residue 140, as well as four smaller peaks of hydrophobicity nearer the C-terminus of the protein that could be TMSs (Lv et al. 2022).

Eukaryota
Metazoa, Chordata
fecB of Ovis aries (sheep)
8.A.23.1.41









Macrophage colony-stimulating factor 1 receptor, CSF1R or FMS of 972 aas and 2 or 3 TMSs, one at the N-terminus, one large peak of hydrophobicity at ~ residue 520, and a much smaller peak at residue 650. It is a tyrosine-protein kinase that acts as a cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. It promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. It regulates bone resorption and is required for normal bone and tooth development. It is also required for normal male and female fertility, and for normal development of milk ducts. It promotes cancer cell invasion and activates several signaling pathways in response to ligand binding, including the ERK1/2 and the JNK pathways (Wei et al. 2010, Guo et al. 2019). High expression of CSF-1R predicts poor prognosis in colon adenocarcinoma (Wang et al. 2022).

 

Eukaryota
Metazoa, Chordata
CSF1R of Homo sapiens
8.A.23.1.42









Dual leucine zipper kinase, Dlk, or mitogen-activated protein kinase kinase kinase 12, MAP3K12, of 859 aas and possibly two adjacent TMSs.  It is part of a non-canonical MAPK signaling pathway (Huang et al. 2017).

Eukaryota
Metazoa, Chordata
DLK of Homo sapiens
8.A.23.1.43









Vascular endothelial growth factor receptor 3,VGFR3, of 1363 aas and 2 TMSs, N-terminal and at residue 780.

Eukaryota
Metazoa, Chordata
VGFR3 of Homo sapiens
8.A.23.1.44









Proto-oncogene tyrosine-protein kinase receptor, Ret, of 1114 aas and 2 TMSs. N-terminal and at residue 645. The cryoEM structure is available (Cai et al. 2022).

Eukaryota
Metazoa, Chordata
RET of Homo sapiens
8.A.23.1.45









Hepatocyte growth factor receptor, Met, of 1390 aas and 2 TMSs, one N-terminal and one at residue 945. A cryoEM strucure is available (Cai et al. 2022).

 

Eukaryota
Metazoa, Chordata
MET of Homo sapiens
8.A.23.1.46









Epidermal growth factor receptor, EGFR, of 1210 aas and two TMSs, one N-terminal and one at residue 655. The CryoEM 3-d structure is available (Cai et al. 2022).  Receptor tyrosine kinase binding ligands of the EGF family activate several signaling cascades to convert extracellular cues into appropriate cellular responses (Runkle et al. 2016). Two FDA-approved EGFR inhibitor drugs (lapatinib and afatinib) inside living cells and the changes in their cellular uptake upon the addition of organic cation transporter inhibitors have been reported (Wong et al. 2024).  EGFR, a transmembrane protein commonly targeted by tyrosine kinase inhibitors (TKIs) as a front-line therapy for patients with many cancers including nonsmall cell lung cancer (NSCLC). Effective treatment requires efficient intracellular drug uptake and target binding, but despite the recent success in the development of new TKI drugs,  TKI drugs are sequestered in lysosomes.  Two Food and Drug Administration-approved EGFR inhibitory drugs (lapatinib and afatinib) inside living cells and the changes in their cellular uptake by facilitated diffusion upon the addition of organic cation transporter inhibitors has been recorded (Wong et al. 2024).

Eukaryota
Metazoa, Chordata
EGFR of Homo sapiens
8.A.23.1.47









Receptor tyrosine-protein kinase ErbB-2 or HERS of 1255 aas and one TMS at residue 350.  A 3-d cryoEM structure is available (Cai et al. 2022).

Viruses
Loebvirae, Hofneiviricota
EbrB-2 of Homo sapiens
8.A.23.1.48









Serine, threonine protein kinase B, BraF, of 766 aas and probably 0 TMSs. In thyroid cancer, BRAF V600E regulates the mitochondrial permeability transition through the pERK-pGSK-CypD pathway to resist death, providing intervention targets for BRAF V600E mutant tumours (Gao et al. 2022). Co-dependent regulation of p-BRAF and potassium channel KCNMA1 (TC# 1.A.1.3.10) levels drives glioma progression (Xie et al. 2023).

Eukaryota
Metazoa, Chordata
BraF of Homo sapiens
8.A.23.1.49









Neural cell adhesion molecule, NCAM, of 858 aas. This glycoprotein interacts with TrpC1, C4 and C5 to enhance their Ca2+ transport activities (Amores-Bonet et al. 2022)

Eukaryota
Metazoa, Chordata
NCAM proteins of Homo sapiens
8.A.23.1.50









Ser/Thr protein kinase, WNK4, of 1243 aas and possibly 2 TMSs. Plays a role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. It acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters, respectively (Hoorn and de Baaij 2022).

Eukaryota
Metazoa, Chordata
WNK4 of Homo sapiens
8.A.23.1.51









General control nonderepressible kinase 2 of 1699 aas and 0-2 TMSs. Also called eukaryotic translation initiation factor 2-alpha kinase, Gcn-2. Serine/threonine-protein kinase which phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (eIF2alpha), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis.

Eukaryota
Metazoa, Nematoda
Gcn-2 of Caenorhabditis elegans
8.A.23.1.52









Receptor-interacting serine/threonine-protein kinase 3, RIPK3 of 518 aas and probably 0 TMSs. It modulates sarcoma through immune checkpoint HAVCR2 and regulates the TMC8 channel (TC# 1.A.17.4.11).

Eukaryota
Metazoa, Chordata
RIPK3 of Homo sapiens
8.A.23.1.53









Insulin-like growth factor 1 receptor (chain F) (IGF1R) of 952 aas, possibly with 4 N-terminal TMSs. It is antagonized by viral insulin/IGF-1-like peptides (e.g., VILP of 72 aas and no TMSs (Moreau et al. 2022).

Eukaryota
Metazoa, Chordata
IGF-1 of Homo sapiens
8.A.23.1.54









Leucine-rich repeat serine/threonine-protein kinase 2, LRRK2 or PARK8, of 2527 aas. Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (Cho et al. 2014). It positively regulates autophagy through calcium-dependent activation of the CaMKK/AMPK signaling pathway (Gómez-Suaga et al. 2012).

Eukaryota
Metazoa, Chordata
LRRK2 of Homo sapiens
8.A.23.1.55









Platelet-derived growth factor receptor-like protein, DPGFRL, of 375 aas. It is a biomarker for endometriosis (EM), a common gynecological disorder that often leads to irregular menstruation and infertility (Jiang et al. 2022).

Eukaryota
Metazoa, Chordata
DPGFRL of Homo sapiens
8.A.23.1.56









V-set and transmembrane domain-containing protein 2-like (VSTM2L) of 204 aas and 2 TMSs, N- and C-terminal. It is a crucial gene closely associated with ovarian cancer metastasis, progression, and prognosis (Li et al. 2023).

Eukaryota
Metazoa, Chordata
VSTM2L of Homo sapiens
8.A.23.1.57









Translation initiation factor 2-alpha kinase 3, PERK, of 1116 aas and at least 2 TMSs, one at the N-terminus and one at about residue 530.  There are also three smaller peaks of hydrophobicity near the C-terminus of the protein that could be TMSs.  It is a metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions. It is a key activator of the integrated stress response (ISR) required for adaptation to various stresses, such as the unfolded protein response (UPR) and low amino acid availability. EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (You et al. 2021). PERK/ATF3-reduced ER stress in a high potassium environment suppresses  tumor ferroptosis (Pu et al. 2023).

Eukaryota
Metazoa, Chordata
PERK of Homo sapiens
8.A.23.1.58









Transmembrane and immunoglobulin domain-containing protein 1, TMIGD(1), isoform 2 precursor of 218 aas with 1 N-terminal TMS plus one possible TMS at about residue 120. The functions of TMIGD1 have been reviewed and include those of a tumor supressor and an adhesion receptor (Thüring et al. 2023; Mu et al. 2022). Macrophage-derived exosomes promote intestinal mucosal barrier dysfunction in inflammatory bowel disease by regulating TMIGD1 via mircroRNA-223 (Chang et al. 2023).  Decreased TMIGD1 aggravates colitis and intestinal barrier dysfunction via the BANF1-NF-kappaB pathway in Crohn's disease (Zhou et al. 2023).

Eukaryota
Metazoa, Chordata
TMIGD1 of Homo sapiens
8.A.23.1.59









Roundabout homolog 2-like protein of 1319 aas and two TMSs, one at the N-terminus and one at about residues 880.

Eukaryota
Metazoa, Arthropoda
Roundabout2 of Anopheles merus
8.A.23.1.60









Tyrosine-protein kinase transmembrane receptor, ROR1, of 937 aas and two TMSs, one at the N-terminus and one large hydrophobic peak at about residue 420.  Extracellular vesicle-associated tyrosine kinase-like orphan receptors, ROR1 and ROR2, promote breast cancer progression (Irmer et al. 2023).

Eukaryota
Metazoa, Chordata
ROR1 of Homo sapiens
8.A.23.1.61









Uncharacterized protein of 412 aas and 2 TMSs, one N-terminal and one near the C-terminus. NOTE: This family may be homologous to families 8.A.128 and 9.B.454, do these three families may conprise a Superfamily.

Eukaryota
Metazoa, Mollusca
UP of Dreissena polymorpha
8.A.23.1.62









Neural cell adhesion molecule L1, LICAM or CD171, of 1257 aas and 2 TMSs, N- and C-terminal. It is involved in the dynamics of cell adhesion and in the generation of transmembrane signals via tyrosine kinase receptors. During brain development, it is critical in multiple processes, including neuronal migration, axonal growth, fasciculation, and synaptogenesis. In the mature brain, it plays a role in the dynamics of neuronal structure and function, including synaptic plasticity (Schäfer et al. 2010).  Interaction of L1CAM with LC3 is required for L1-dependent neurite outgrowth and neuronal survival (Loers et al. 2023).

 

Eukaryota
Metazoa, Chordata
LICAM of Homo sapiens
8.A.23.1.63









Carcinoembryonic antigen-related cell adhesion molecule 6 preproprotein (CEACAM6) is of 344 aas and 1 C-terminal TMS.  Non-coding microRNAs (miRNAs) play critical roles in tumor progression and hold promise as therapeutic agents for multiple cancers. MicroRNA 29a (miR-29a) is a tumor suppressor miRNA that inhibits cancer cell growth and tumor progression in non-small cell lung cancer. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), which plays an important role in lung cancer progression, has been identified as a target of miR-29a. Delivery of miR-29a to lung adenocarcinoma cells has therapeutic potential as a unique cancer treatment approach (Son et al. 2023).

 

Eukaryota
Metazoa, Chordata
8.A.23.1.64









CD146, MCAM or MUC18 of 646 aas with 2 TMSs, N- and C-terminal.  It plays a role in cell adhesion, and in cohesion of the endothelial monolayer at intercellular junctions in vascular tissues (Anfosso et al. 2001). Its expression may allow melanoma cells to interact with cellular elements of the vascular system, thereby enhancing hematogeneous tumor spread. It could be an adhesion molecule active in neural crest cells during embryonic development. It acts as a surface receptor that triggers tyrosine phosphorylation of FYN and PTK2/FAK1, and a transient increase in the intracellular calcium concentration (Johnson et al. 1993). It is a possible drug target for pheochromocytomas and paragangliomas (PPGLs), rare neuroendocrine tumors (Vit et al. 2023).

Eukaryota
Metazoa, Chordata
CD146 of Homo sapiens
8.A.23.1.65









eIF-2-alpha kinase, GCN2, of 1648 aas and an undetermined number of putative TMSs, possibly none.  It is a metabolic-stress-sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (Lehman et al. 2015).

Eukaryota
Metazoa, Chordata
GCN2 of Mus musculus
8.A.23.1.66









Platelet-derived growth factor receptor alpha, Pdgfra, of 1089 aas and 2 TMSs, one N-terminal and one at ~ residue 530.  It is a tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development (Griffin et al. 2003). See also TC# 2.A.1.1.28 (Zhang and Xu 2023).

Eukaryota
Metazoa, Chordata
Pdgfra of Homo sapiens
8.A.23.2.1









T-cell surface glycoprotein, CD4, of 458 aas and 2 TMSs, N- and C-terminal.  It is the receptor for HIV and other viruses (see family description) (Raphael et al. 2020).

Eukaryota
Metazoa, Chordata
CD4 of Homo sapiens
8.A.23.2.2









CD4-like protein 2 of 429 aas and 2 TMSs, N- and C-terminal.

Eukaryota
Metazoa, Chordata
CD4 of Ctenopharyngodon idella (grass carp)
8.A.23.2.3









Lymphocyte activation gene 3 protein of 487 aas and 2 TMSs, one N-terminal and one C-terminal.

Eukaryota
Metazoa, Chordata
Lymphocyte activation protein of Thamnophis elegans (Western garter snake)
8.A.23.2.4









Neural cell adhesion molecule 2-like protein of 496 aas and 2 TMSs, N- and C-terminal.

Eukaryota
Metazoa, Chordata
Cell adhestion protein of Tachysurus fulvidraco (yellow cat fish)
8.A.23.2.5









Uncharacterized protein of 414 aas and 2 TMSs, N- and C-terminal.

Eukaryota
Metazoa, Chordata
UP of Colinus virginianus (northern bobwhite)
8.A.23.2.6









CD16A (FcγRIIIA, FCGR3A, FCG3, FCGR3, IGFR3) antiinflamatory protein of 254 aas and 2 TMSs, N- and C-terminal (Ben Mkaddem et al. 2014). It is a receptor for the Fc region of IgG. It binds complexed or aggregated IgG and also monomeric IgG and mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis (Ferrara et al. 2011, Mizushima et al. 2011).

Eukaryota
Metazoa, Chordata
CD16A of Homo sapiens
8.A.23.2.7









CD16B of 233 aas and 2 TMSs, N- and C-terminal. It may serve as a trap for immune complexes in the peripheral circulation which does not activate neutrophils. Microinflammation status, involving CD16, observed in chronic kidney disease patients is associated with endothelial damage (Ramirez et al. 2007). A 3-d cryoEM strcuture is available (Cai et al. 2022).

Eukaryota
Metazoa, Chordata
CD16B of Homo sapiens
8.A.23.3.1









TMEM25 of 366 aas and up to 4 TMSs, scattered throughout the protein (N-terminal, C-terminal and at residues ~150 and 250. The expression of  Tmem25 is strongly influenced by glutamate ionotropic receptor kainate type subunit 4, and it is primarily localized to late endosomes in neurons (Zhang et al. 2019). The effects of TMEM25 on neuronal excitability are likely mediated by N-methyl-D-aspartate receptors. TMEM25 affects the expression of the NR2B subunit and interacts with NR2B; both colocalize to late endosome compartments. TMEM25 induces acidification changes in lysosome compartments and accelerates the degradation of NR2B, and TMEM25 expression is decreased in brain tissues from patients with epilepsy and epileptic mice. TMEM25 overexpression attenuated the behavioral phenotypes of epileptic seizures, whereas TMEM25 downregulation exerted the opposite effect (Zhang et al. 2019). TMEM25 inhibits monomeric epidermal growth factor receptor (EGFR)-mediated STAT3 activation in the basal state to suppress triple-negative breast cancer progression (Bi et al. 2023).  In neurons, TMEM25 modulates the degradation of the NMDA receptor GRIN2B subunit. Thus, TMEM25 regulates neuronal excitability (An et al. 2023).  TMEM25 is a Par3-binding protein that attenuates claudin assembly during tight junction development (Kamakura et al. 2024).

Eukaryota
Metazoa, Chordata
TMEM25 of Homo sapiens
8.A.23.3.2









TMEM25-like protein, isoform X3 of 169 aas and 1 TMS.

Eukaryota
Metazoa, Chordata
TMEM25 of Pteropus alecto
8.A.23.3.3









TMEM25 protein of 279 aas and 1 TMS. It may be an incomplete sequence.

Eukaryota
Metazoa, Chordata
TMEM25 of Neopelma chrysocephalum (saffron-crested tyrant-manakin)
8.A.23.4.1









Intercellular adhesion molecule 1, ICAM-1 or ICAM1, of 532 aas and 2 TMSs, N- and C-terminal. During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups (Hayashi et al. 2001; van Buul et al. 2007). STAT3-dependent transcriptional regulation of ICAM-1, an endothelial transmembrane protein, regulates vascular permeability in endothelial cells (Wang et al. 2020). Martin et al. 2023 reviewed the role of ICAM-1 during both autoimmunity and islet graft rejection to understand the mechanism(s) leading to islet beta-cell death and dysfunction that results from insufficient circulating quantities of insulin to control glucose homeostasis.

 

Eukaryota
Metazoa, Chordata
ICAM1 of Homo sapiens
8.A.23.4.2









Vascular cell adhesion protein 1-like protein of 677 aas and probably two TMSs, N- and C-terminal.

Eukaryota
Metazoa, Chordata
Vascular cell adhesion protein 1 of Bufo bufo (common toad)
8.A.23.4.3









Hemicentin-1 of 590 aas and possibly two TMSs, one N-terminal and one near the C-terminus of the protein. Hemicentins are conserved extracellular matrix proteins discovered in Caenorhabditis elegans, with orthologs in all vertebrate species including humans (Vogel et al. 2006).

Eukaryota
Metazoa, Chordata
Hemicentin 1 of Sander lucioperca (pikeperch)
8.A.23.5.1









Programmed cell death 1 ligand 1, PDL1, CD274, B7H1, PDCD1L1, or PDCD1LG1, of 290 aas and 2 TMSs, one N-terminal and one C-terminal. It plays a role in induction of immune tolerance to self. It plays a critical role in induction and maintenance of immune tolerance to self (Freeman et al. 2000, Burr et al. 2017, Mezzadra et al. 2017). As a ligand for the inhibitory receptor PDCD1/PD-1, it modulates the activation threshold of T-cells and limits T-cell effector responses. Several forms of PD-L1 exist expressed on the plasma membrane (mPD-L1), at the surface of secreted cellular exosomes (exoPD-L1), in cell nuclei (nPD-L1), or as a circulating, soluble protein (sPD-L1) (Bailly et al. 2021). The membrane, exosomal and soluble forms of PD-L1 are parts of the highly dynamic PD-1/PD-L1 signaling pathway. PD-L1 translocation to the plasma membrane enables tumor immune evasion through MIB2 ubiquitination (Yu et al. 2023).

 

 

Eukaryota
Metazoa, Chordata
PD-L1 of Homo sapiens
8.A.23.5.2









V-set domain-containing T-cell activation inhibitor 1 of 282 aas and 2 TMSs, N- and C-terminal.

Eukaryota
Metazoa, Chordata
V-set domain containing protein of Pteropus giganteus (Indian flying fox)
8.A.23.5.3









Butyrophilin-like protein 2 of 487 aas and 2 TMSs, N- and C-terminal.

Eukaryota
Metazoa, Chordata
Butyrophilin of Lynx canadensis (canadian lynx)