HHIP binds Hedgehog

Stable Identifier
Reaction [binding]
Homo sapiens
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HHIP is a Hh-binding transmembrane protein that antagonizes Hh signaling by sequestering the ligand away from PTCH. HHIP is also a downstream target gene of Hh signaling, establishing a negative feedback loop that limits the extent of signaling (Chuang et al, 1999; Chuang et al, 2003; Bosanac et al, 2009; Bishop et al, 2009: Holtz et al, 2013). HHIP binds to all three Hh ligands, and also exists in a secreted form, which also sequesters ligand (Chuang et al, 1999; Coulombe et al, 2004). HHIP expression is altered in some cancers that show upregulated Hh signaling (Olsen et al, 2004; Tada et al, 2008; Tojo et al, 2002).
Literature References
PubMed ID Title Journal Year
11841368 Expression of a sonic hedgehog signal transducer, hedgehog-interacting protein, by human basal cell carcinoma

Iwatsuki, K, Kaneko, F, Tojo, M, Kiyosawa, H

Br. J. Dermatol. 2002
15019948 Hedgehog interacting protein in the mature brain: membrane-associated and soluble forms

Faure, H, Coulombe, J, Traiffort, E, Ruat, M, Loulier, K

Mol. Cell. Neurosci. 2004
23900540 Essential role for ligand-dependent feedback antagonism of vertebrate hedgehog signaling by PTCH1, PTCH2 and HHIP1 during neural patterning

Charron, F, Song, JY, Nishi, Y, Morin, S, Allen, BL, McMahon, AP, Holtz, AM, Peterson, KA

Development 2013
15294024 Hedgehog-interacting protein is highly expressed in endothelial cells but down-regulated during angiogenesis and in several human tumors

Hsu, PP, Rubanyi, GM, Glienke, J, Olsen, CL, Brooks, AR

BMC Cancer 2004
12569124 Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung

Chuang, PT, Kawcak, T, McMahon, AP

Genes Dev. 2003
18559595 Down-regulation of hedgehog-interacting protein through genetic and epigenetic alterations in human hepatocellular carcinoma

Tanaka, Y, Asaoka, Y, Seto, M, Muroyama, R, Ohta, M, Tateishi, K, Kawabe, T, Yokosuka, O, Imazeki, F, Omata, M, Tada, M, Fukai, K, Kanai, F

Clin. Cancer Res. 2008
10050855 Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein

McMahon, AP, Chuang, PT

Nature 1999
19561611 Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP

O'Callaghan, CA, Aricescu, AR, Bishop, B, Jones, EY, Harlos, K, Siebold, C

Nat. Struct. Mol. Biol. 2009
19561609 The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling

Scales, SJ, Hymowitz, SG, Wen, X, Bosanac, I, Lingel, A, de Sauvage, FJ, Maun, HR, Lazarus, RA, Bazan, JF

Nat. Struct. Mol. Biol. 2009
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