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. 2020 Aug 24;18:132. doi: 10.1186/s12964-020-00626-6

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — The C1CR family - structures and ICD isoforms. a Structural model of the full-length human PRLR [35] in the membrane, with the ECD in light grey, the TMD in pink and a total of six ICD chains shown in blue shades to represent its disordered conformational ensemble. b Left: A representative sketch of a prototypical C1CR (blue) in a membrane (green) having a long ICD with its length given in %. Box1 and Box2 are highlighted in orange. The red shades highlight the approximate extent and position of small ICD fragments of different C1CR-ICDs having their structure solved in complex with signaling proteins. Right: Three-dimensional structures of signaling proteins (grey surfaces) in complex with C1CR-ICD fragments (red cartoon and sticks), being the FERM-SH2 domain of JAK2 in complex with EPOR-ICD_279–334 (pdb code 6E2Q) (top), SOCS2 in complex with GHR-ICD_591–603 (pdb code 6I5J, 6I5N) (middle top), the PTB domain of IRS-1 in complex with IL-4Rα_490–500 (pdb code 1IRS) (middle bottom) and the PDZ domain from syntenin in complex with IL-5Rα_417–420 (pdb code 1OBZ) (bottom). The grey arrows point to the approximate positions of the ICD fragments (red shades) on the representative ICD sketch. c The 29 receptors of the C1CR family with an ICD and their isoforms. The length of the ICDs are to scale and red indicates the length of unique sequences differing from the long-form. The receptors are divided into 5 groups according to [33].