Huntingtin-interacting protein 1-related protein (IPR030555)

Short name: HIP1R

Overlapping homologous superfamilies


Family relationships

  • Sla2 family (IPR030224)
    • Huntingtin-interacting protein 1-related protein (IPR030555)


Huntingtin-interacting protein 1-related protein (HIP1R, also known as HIP-12) belongs to the Sla2 family. HIP1R is the only known mammalian relative of huntingtin-interacting protein 1 (HIP1) [PMID: 14732715]. HIP1R may have a role in actin regulation during endocytosis and is shown to promote clathrin assembly. It may also be involved in the apoptotic pathway through its interaction with a member of the Bcl-2 pro-apoptotic family [PMID: 19255499].

The Sla2 family, also known as Sla2p/HIP1/HIP1R family, including Sla2p from budding yeasts [PMID: 14704157], End4 from fission yeasts [PMID: 15827087], Huntingtin-interacting protein 1 (HIP1) and HIP1-related (HIP1R) from humans and mice [PMID: 14732715]. They are adaptor proteins that link actin to clathrin and endocytosis in the clathrin-mediated endocytosis (CME) pathway. They contain the ENTH and ANTH (E/ANTH) domain that binds both inositol phospholipids and proteins that contribute to the nucleation and formation of clathrin coats on membranes [PMID: 14657269]. They also contain an I/LWEQ (talin-like) domain, which is an actin-binding domain found in proteins that serve as linkers between the actin cytoskeleton and cellular compartments [PMID: 20074057]. The talin-like domains of Sla2p and HIP1R have been shown to bind F-actin (filamentous actin), however, the same level of actin binding has not been observed with HIP1 [PMID: 20074057]. The central domain of the Sla2p/HIP1/HIP1R proteins contains a coiled-coil domain and several consensus sequences enabling protein-protein interactions [PMID: 20074057]. Yeast Sla2p has been extensively studied: Sla2p arrives at existing endocytic patches with a ~25 seconds delay relative to clathrin and dissociates simultaneously with clathrin upon recruitment of actin-related proteins [PMID: 15059611, PMID: 9362070]. It serves as a bridge, connecting the endocytic patch to the cortical actin cytoskeleton [PMID: 20074057].

GO terms

Biological Process

GO:0006915 apoptotic process
GO:2000369 regulation of clathrin-dependent endocytosis

Molecular Function

GO:0003779 actin binding
GO:0030276 clathrin binding
GO:0035091 phosphatidylinositol binding

Cellular Component

GO:0005905 clathrin-coated pit
GO:0030136 clathrin-coated vesicle

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.