SDF4

Last update 08 May 2025

Basic Info

Synonyms

45 kDa calcium-binding protein, Cab45, SDF-4

+ [3]

Introduction

Isoform 5 may be involved in the exocytosis of zymogens by pancreatic acini. May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment.

100 Clinical Results associated with SDF4

100 Translational Medicine associated with SDF4

0 Patents (Medical) associated with SDF4

Literatures (Medical) associated with SDF4

25 Feb 2025·Proceedings of the National Academy of Sciences

PSKH1 kinase activity is differentially modulated via allosteric binding of Ca ²⁺ sensor proteins

Article

Author: Mather, Lucy J. ; Cadell, Antonia L. ; Yousef, Jumana ; Byrne, Dominic P. ; McAloon, Luke M. ; Johnson, Jared L. ; Multari, Dylan H. ; Febbraio, Mark A. ; Huntsman, Emily M. ; Dite, Toby A. ; Yaron-Barir, Tomer M. ; Tanzer, Maria C. ; Horne, Christopher R. ; Scott, John W. ; Murphy, James M. ; Means, Anthony R. ; Croucher, David R. ; Manning, Gerard ; Eyers, Claire E. ; Young, Samuel N. ; Eyers, Patrick A. ; Daly, Leonard A. ; Shen, Lianju ; Cantley, Lewis C. ; Dagley, Laura F. ; Ng, Boaz H.

Protein Serine Kinase H1 (PSKH1) was recently identified as a crucial factor in kidney development and is overexpressed in prostate, lung, and kidney cancers. However, little is known about PSKH1 regulatory mechanisms, leading to its classification as a “dark” kinase. Here, we used biochemistry and mass spectrometry to define PSKH1’s consensus substrate motif, protein interactors, and how interactors, including Ca 2+ sensor proteins, promote or suppress activity. Intriguingly, despite the absence of a canonical Calmodulin binding motif, Ca 2+ -Calmodulin activated PSKH1 while, in contrast, the ER-resident Ca 2+ sensor of the Cab45, Reticulocalbin, Erc55, Calumenin (CREC) family, Reticulocalbin-3, suppressed PSKH1 catalytic activity. In addition to antagonistic regulation of the PSKH1 kinase domain by Ca 2+ sensing proteins, we identified UNC119B as a protein interactor that activates PSKH1 via direct engagement of the kinase domain. Our findings identify complementary allosteric mechanisms by which regulatory proteins tune PSKH1’s catalytic activity and raise the possibility that different Ca 2+ sensors may act more broadly to tune kinase activities by detecting and decoding extremes of intracellular Ca 2+ concentrations.

06 Jan 2025·Journal of Cell Biology

ER export via SURF4 uses diverse mechanisms of both client and coat engagement

Article

Author: Gomez-Navarro, Natalia ; Li, Xiao-Han ; Robertson, Evan G. ; Miller, Elizabeth A. ; Maldutyte, Julija

Protein secretion is an essential process that drives cell growth and communication. Enrichment of soluble secretory proteins into ER-derived transport carriers occurs via transmembrane cargo receptors that connect lumenal cargo to the cytosolic COPII coat. Here, we find that the cargo receptor, SURF4, recruits different SEC24 cargo adaptor paralogs of the COPII coat to export different cargoes. The secreted protease, PCSK9, requires both SURF4 and a co-receptor, TMED10, for export via SEC24A. In contrast, secretion of Cab45 and NUCB1 requires SEC24C/D. We further show that ER export signals of Cab45 and NUCB1 bind co-translationally to SURF4 via a lumenal pocket, contrasting prevailing models of receptor engagement only upon protein folding/maturation. Bioinformatics analyses suggest that strong SURF4-binding motifs are features of proteases, receptor-binding ligands, and Ca2+-binding proteins. We propose that certain classes of proteins are fast-tracked for rapid export to protect the health of the ER lumen.

01 Apr 2024·Molecular Biology of the Cell

Calcium flow at ER-TGN contact sites facilitates secretory cargo export

Article

Author: Kumar, Abhishek ; Schwartz, Martin A ; Luini, Alberto ; Kim, Yeongho ; Parchure, Anup ; Griesbeck, Oliver ; von Blume, Julia ; Di Martino, Rosaria ; Chung, Minhwan ; Ramazanov, Bulat R

Ca2+ influx into the trans-Golgi Network (TGN) promotes secretory cargo sorting by the Ca2+-ATPase SPCA1 and the luminal Ca2+ binding protein Cab45. Cab45 oligomerizes upon local Ca2+ influx, and Cab45 oligomers sequester and separate soluble secretory cargo from the bulk flow of proteins in the TGN. However, how this Ca2+ flux into the lumen of the TGN is achieved remains mysterious, as the cytosol has a nanomolar steady-state Ca2+ concentration. The TGN forms membrane contact sites (MCS) with the Endoplasmic Reticulum (ER), allowing protein-mediated exchange of molecular species such as lipids. Here, we show that the TGN export of secretory proteins requires the integrity of ER-TGN MCS and inositol 3 phosphate receptor (IP3R)-dependent Ca2+ fluxes in the MCS, suggesting Ca2+ transfer between these organelles. Using an MCS-targeted Ca2+ FRET sensor module, we measure the Ca2+ flow in these sites in real time. These data show that ER-TGN MCS facilitates the Ca2+ transfer required for Ca2+-dependent cargo sorting and export from the TGN, thus solving a fundamental question in cell biology.

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