| Structural highlights
Disease
[HIP1_HUMAN] Note=A chromosomal aberration involving HIP1 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;7)(q33;q11.2) with PDGFRB. The chimeric HIP1-PDGFRB transcript results from an in-frame fusion of the two genes. The reciprocal PDGFRB-HIP1 transcript is not expressed.
Function
[HIP1_HUMAN] Plays a role in clathrin-mediated endocytosis and trafficking. Involved in regulating AMPA receptor trafficking in the central nervous system in an NMDA-dependent manner. Enhances androgen receptor (AR)-mediated transcription. May act as a proapoptotic protein that induces cell death by acting through the intrinsic apoptosis pathway. Binds 3-phosphoinositides (via ENTH domain). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis. May play a functional role in the cell filament networks. May be required for differentiation, proliferation, and/or survival of somatic and germline progenitors.[1] [2] [3] [4] [5] [6] [7] [8]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Huntington's disease is a genetic neurological disorder that is triggered by the dissociation of the huntingtin protein (htt) from its obligate interaction partner Huntingtin-interacting protein 1 (HIP1). The release of the huntingtin protein permits HIP1 protein interactor (HIPPI) to bind to its recognition site on HIP1 to form a HIPPI/HIP1 complex that recruits procaspase-8 to begin the process of apoptosis. The interaction module between HIPPI and HIP1 was predicted to resemble a death-effector domain. Our 2.8-A crystal structure of the HIP1 371-481 subfragment that includes F432 and K474, which is important for HIPPI binding, is not a death-effector domain but is a partially opened coiled coil. The HIP1 371-481 model reveals a basic surface that we hypothesize to be suitable for binding HIPPI. There is an opened region next to the putative HIPPI site that is highly negatively charged. The acidic residues in this region are highly conserved in HIP1 and a related protein, HIP1R, from different organisms but are not conserved in the yeast homologue of HIP1, sla2p. We have modeled approximately 85% of the coiled-coil domain by joining our new HIP1 371-481 structure to the HIP1 482-586 model (Protein Data Bank code: 2NO2). Finally, the middle of this coiled-coil domain may be intrinsically flexible and suggests a new interaction model where HIPPI binds to a U-shaped HIP1 molecule.
Crystal structure at 2.8 A of Huntingtin-interacting protein 1 (HIP1) coiled-coil domain reveals a charged surface suitable for HIP1 protein interactor (HIPPI).,Niu Q, Ybe JA J Mol Biol. 2008 Feb 1;375(5):1197-205. Epub 2007 Nov 22. PMID:18155047[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wanker EE, Rovira C, Scherzinger E, Hasenbank R, Walter S, Tait D, Colicelli J, Lehrach H. HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system. Hum Mol Genet. 1997 Mar;6(3):487-95. PMID:9147654
- ↑ Hackam AS, Yassa AS, Singaraja R, Metzler M, Gutekunst CA, Gan L, Warby S, Wellington CL, Vaillancourt J, Chen N, Gervais FG, Raymond L, Nicholson DW, Hayden MR. Huntingtin interacting protein 1 induces apoptosis via a novel caspase-dependent death effector domain. J Biol Chem. 2000 Dec 29;275(52):41299-308. PMID:11007801 doi:10.1074/jbc.M008408200
- ↑ Waelter S, Scherzinger E, Hasenbank R, Nordhoff E, Lurz R, Goehler H, Gauss C, Sathasivam K, Bates GP, Lehrach H, Wanker EE. The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis. Hum Mol Genet. 2001 Aug 15;10(17):1807-17. PMID:11532990
- ↑ Mishra SK, Agostinelli NR, Brett TJ, Mizukami I, Ross TS, Traub LM. Clathrin- and AP-2-binding sites in HIP1 uncover a general assembly role for endocytic accessory proteins. J Biol Chem. 2001 Dec 7;276(49):46230-6. Epub 2001 Sep 27. PMID:11577110 doi:10.1074/jbc.M108177200
- ↑ Legendre-Guillemin V, Metzler M, Charbonneau M, Gan L, Chopra V, Philie J, Hayden MR, McPherson PS. HIP1 and HIP12 display differential binding to F-actin, AP2, and clathrin. Identification of a novel interaction with clathrin light chain. J Biol Chem. 2002 May 31;277(22):19897-904. Epub 2002 Mar 11. PMID:11889126 doi:10.1074/jbc.M112310200
- ↑ Rao DS, Hyun TS, Kumar PD, Mizukami IF, Rubin MA, Lucas PC, Sanda MG, Ross TS. Huntingtin-interacting protein 1 is overexpressed in prostate and colon cancer and is critical for cellular survival. J Clin Invest. 2002 Aug;110(3):351-60. PMID:12163454 doi:10.1172/JCI15529
- ↑ Hyun TS, Rao DS, Saint-Dic D, Michael LE, Kumar PD, Bradley SV, Mizukami IF, Oravecz-Wilson KI, Ross TS. HIP1 and HIP1r stabilize receptor tyrosine kinases and bind 3-phosphoinositides via epsin N-terminal homology domains. J Biol Chem. 2004 Apr 2;279(14):14294-306. Epub 2004 Jan 19. PMID:14732715 doi:10.1074/jbc.M312645200
- ↑ Mills IG, Gaughan L, Robson C, Ross T, McCracken S, Kelly J, Neal DE. Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors. J Cell Biol. 2005 Jul 18;170(2):191-200. PMID:16027218 doi:10.1083/jcb.200503106
- ↑ Niu Q, Ybe JA. Crystal structure at 2.8 A of Huntingtin-interacting protein 1 (HIP1) coiled-coil domain reveals a charged surface suitable for HIP1 protein interactor (HIPPI). J Mol Biol. 2008 Feb 1;375(5):1197-205. Epub 2007 Nov 22. PMID:18155047 doi:10.1016/j.jmb.2007.11.036
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