TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
9.B.278.1.1









The Adaptor Protein Complex, AP1 with subunits β1 (AP1B1, 949 aas), γ1 (AP1G1, 822 aas), μ1 (AP1M1; 423 aas) and σ1 (AP1S1, 158 aas).  Subunits of clathrin-associated adaptor protein complex 1 form a complex that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules (Guardia et al. 2018). These complexes therefore play a role in protein insertion into organellar membranes.  There is one isoform of β1, two of γ1, two of
μ1, and three of σ1. Only one iso-form of each is included here.  Although there are 5 such complexes in humans (AP-1 - 5), and many eukaryotic organisms have one of more of them, only AP1 of humans is tabulated in TCDB (Guardia et al. 2018). Parts of subunits β1 and γ1 are homologous, and parts of subunits μ1 and σ1 show significant sequence similarity, suggestiong homology. Subunits β and γ are homologous as are subunits sigma and mu.

Eukaryota
Metazoa
AP1 complex of Homo sapiens
β1
γ1
μ1
σ1
9.B.278.1.2









Golgi/endosome-localizing monomeric clathrin adaptors, GGAs.  GGA1 is of 639 aas and is a gamma-adaptin ear-containing, ADP ribosylation factor [Arf]-binding protein. The family is  ubiquitously expressed Arf-dependent monomeric clathrin adaptor proteins that are conserved from yeast to humans. Mammals have three GGAs (GGA1-3) that work not only at the trans-Golgi network, but also in endosomes to sort transmembrane cargo proteins such as mannose 6-phosphate receptors, sortilin, beta-site amyloid precursor protein cleaving enzyme 1, and epidermal growth factor receptor (Uemura and Waguri 2019).

Eukaryota
Metazoa
GGA1 of Homo sapiens
9.B.278.1.3









GGA3, a paralog of GGA1 (TC# 9.B.278.1.2) of 723 aas with 50% identity with GGA1 (Uemura and Waguri 2019).  It plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes and mediates the ARF-dependent recruitment of clathrin to the TGN.  It binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (DXXLL) motif (PubMed Puertollano et al. 2001). It also mediates export of the GPCR receptor ADRA2B to the cell surface (Zhang et al. 2016). It is involved in BACE1 transport and sorting as well as regulation of BACE1 protein levels (Tesco et al. 2007, He et al. 2005, Kang et al. 2010). Finally it regulates retrograde transport of BACE1 from endosomes to the trans-Golgi network via interaction through the VHS motif, dependent of BACE1 phosphorylation (He et al. 2005). The N-terminal 200 residue region resembles (e-6) that of ESCRT-III family protein P38753 in TC# 3.A.31.1.1.

Eukaryota
Metazoa
GGA3 of Homo sapiens
9.B.278.1.4









AP2 clathrin adaptor complex, AP2A1, A2, B1, M1, S1.  Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways and are vesicle coat components that appear to be involved in cargo selection and vesicle formation (Nakatsu and Ohno 2003). AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome (Owen et al. 2004). The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components; AP2 directly regulates PAR1 trafficking, (Paing et al. 2006). Clathrin-associated adaptor protein (AP) complexes, which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes, are considered to be the major clathrin adaptors contributing to CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis and seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway (Lau and Chou 2008). During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (Marcello et al. 2013). The AP-2 mu subunit binds to transmembrane cargo proteins and recognizes the Y-X-X-Phi motifs. The surface region interacting with the Y-X-X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at 'Tyr-156' in membrane-associated AP-2 (Partlow et al. 2019). Subunits α1, α2 and β appear to be homologous.

Eukaryota
Metazoa
AP2 clathrin adaptor protein complex of Homo sapiens
AP2A1 (α-1)
AP2A2 (α-2)
AP2B1 (β)
AP2M1 (μ)
AP2S1 (σ)
9.B.278.1.5









AP4 complex with 5 subunits, alpha-1, beta-1, epsilon-1, mu-1 and Tepsin. The FTS-Hook-FHIP (FHF) complex interacts With the AP-4 complex to mediate perinuclear distribution of AP-4 and its cargo, ATG9A (Mattera et al. 2020).

Eukaryota
Metazoa
AP4 complex of Homo sapiens

Sigma-1 or AP4S1 of 144 aas (Q9Y587)
Beta-1 or AP4B1 of 737 aas (Q9Y6B7)
Mu-1 or AP4M1 of 453 aas (O00189)
Epsilon-1 or AP4E1 of 1137 aas (Q9UPM8)
Tepsin or Enthd2 or 525 aas and 1 TMS (Q96N21)
9.B.278.1.6









The target of Myp protein 1, TOM1 of 492 aas and    TMSs. Lysosomal degradation of ubiquitinated transmembrane protein receptors (cargo) relies on the function of Endosomal Sorting Complex Required for Transport (ESCRT; TC# #.A.31) protein complexes. The ESCRT machinery is comprised of five unique oligomeric complexes with distinct functions. The target of Myb1 (TOM1) is an ESCRT protein involved in the initial steps of endosomal cargo sorting. To exert its function, TOM1 associates with ubiquitin moieties on the cargo via its VHS and GAT domains. Several ESCRT proteins, including TOLLIP, Endofin, and Hrs, have been reported to form a complex with TOM1 at early endosomal membrane surfaces, which may potentiate the role of TOM1 in cargo sorting. TOM1 is involved in other physiological processes, including autophagy, immune responses, and neuroinflammation, which crosstalk with its endosomal cargo sorting function. Alteration of TOM1 function has emerged as a phosphoinositide-dependent survival mechanism for bacterial infections and cancer progression. Based on current knowledge of TOM1-dependent cellular processes, Roach et al. 2021 reviewed how TOM1 functions in coordination with an array of protein partners under physiological and pathological scenarios.

Eukaryota
Opisthokonta