The FAM83 family of proteins: from pseudo-PLDs to anchors for CK1 isoforms

Polyxeni Bozatzi, Gopal Sapkota (Lead / Corresponding author)

Research output: Contribution to journalReview article

7 Citations (Scopus)
86 Downloads (Pure)

Abstract

The eight members of the FAM83 (FAMily with sequence similarity 83) family of poorly characterised proteins are only present in vertebrates and are defined by the presence of the conserved DUF1669 domain of unknown function at their N-termini. The DUF1669 domain consists of a conserved phospholipase D (PLD)-like catalytic motif. However, the FAM83 proteins display no PLD catalytic (PLDc) activity, and the pseudo-PLDc motif present in each FAM83 member lacks the crucial elements of the native PLDc motif. In the absence of catalytic activity, it is likely that the DUF1669 domain has evolved to espouse novel function(s) in biology. Recent studies have indicated that the DUF1669 domain mediates the interaction with different isoforms of the CK1 (casein kinase 1) family of Ser/Thr protein kinases. In turn, different FAM83 proteins, which exhibit unique amino acid sequences outside the DUF1669 domain, deliver CK1 isoforms to unique subcellular compartments. One of the first protein kinases to be discovered, the CK1 isoforms are thought to be constitutively active and are known to control a plethora of biological processes. Yet, their regulation of kinase activity, substrate selectivity and subcellular localisation has remained a mystery. The emerging evidence now supports a central role for the DUF1669 domain, and the FAM83 proteins, in the regulation of CK1 biology.
Original languageEnglish
Pages (from-to)761-771
Number of pages11
JournalBiochemical Society Transactions
Volume46
Issue number3
DOIs
Publication statusPublished - 5 Jun 2018

Fingerprint

Casein Kinase I
Anchors
Protein Isoforms
Phospholipase D
Protein Kinases
Catalyst activity
Proteins
Biological Phenomena
Vertebrates
Amino Acid Sequence
Phosphotransferases
Amino Acids
1-dodecylpyridoxal
Substrates

Keywords

  • Animals
  • Humans
  • Neoplasm Proteins/metabolism
  • Protein Isoforms/metabolism

Cite this

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title = "The FAM83 family of proteins: from pseudo-PLDs to anchors for CK1 isoforms",
abstract = "The eight members of the FAM83 (FAMily with sequence similarity 83) family of poorly characterised proteins are only present in vertebrates and are defined by the presence of the conserved DUF1669 domain of unknown function at their N-termini. The DUF1669 domain consists of a conserved phospholipase D (PLD)-like catalytic motif. However, the FAM83 proteins display no PLD catalytic (PLDc) activity, and the pseudo-PLDc motif present in each FAM83 member lacks the crucial elements of the native PLDc motif. In the absence of catalytic activity, it is likely that the DUF1669 domain has evolved to espouse novel function(s) in biology. Recent studies have indicated that the DUF1669 domain mediates the interaction with different isoforms of the CK1 (casein kinase 1) family of Ser/Thr protein kinases. In turn, different FAM83 proteins, which exhibit unique amino acid sequences outside the DUF1669 domain, deliver CK1 isoforms to unique subcellular compartments. One of the first protein kinases to be discovered, the CK1 isoforms are thought to be constitutively active and are known to control a plethora of biological processes. Yet, their regulation of kinase activity, substrate selectivity and subcellular localisation has remained a mystery. The emerging evidence now supports a central role for the DUF1669 domain, and the FAM83 proteins, in the regulation of CK1 biology.",
keywords = "Animals, Humans, Neoplasm Proteins/metabolism, Protein Isoforms/metabolism",
author = "Polyxeni Bozatzi and Gopal Sapkota",
note = "P.B. ias supported by the U.K. MRC Prize PhD studentship. G.P.S. is supported by the U.K. Medical Research Council [MC_UU_12016/3] and the pharmaceutical companies supporting the DSTT (Boehringer-Ingelheim, GlaxoSmithKline and Merck-Serono).",
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The FAM83 family of proteins : from pseudo-PLDs to anchors for CK1 isoforms. / Bozatzi, Polyxeni; Sapkota, Gopal (Lead / Corresponding author).

In: Biochemical Society Transactions, Vol. 46, No. 3, 05.06.2018, p. 761-771.

Research output: Contribution to journalReview article

TY - JOUR

T1 - The FAM83 family of proteins

T2 - from pseudo-PLDs to anchors for CK1 isoforms

AU - Bozatzi, Polyxeni

AU - Sapkota, Gopal

N1 - P.B. ias supported by the U.K. MRC Prize PhD studentship. G.P.S. is supported by the U.K. Medical Research Council [MC_UU_12016/3] and the pharmaceutical companies supporting the DSTT (Boehringer-Ingelheim, GlaxoSmithKline and Merck-Serono).

PY - 2018/6/5

Y1 - 2018/6/5

N2 - The eight members of the FAM83 (FAMily with sequence similarity 83) family of poorly characterised proteins are only present in vertebrates and are defined by the presence of the conserved DUF1669 domain of unknown function at their N-termini. The DUF1669 domain consists of a conserved phospholipase D (PLD)-like catalytic motif. However, the FAM83 proteins display no PLD catalytic (PLDc) activity, and the pseudo-PLDc motif present in each FAM83 member lacks the crucial elements of the native PLDc motif. In the absence of catalytic activity, it is likely that the DUF1669 domain has evolved to espouse novel function(s) in biology. Recent studies have indicated that the DUF1669 domain mediates the interaction with different isoforms of the CK1 (casein kinase 1) family of Ser/Thr protein kinases. In turn, different FAM83 proteins, which exhibit unique amino acid sequences outside the DUF1669 domain, deliver CK1 isoforms to unique subcellular compartments. One of the first protein kinases to be discovered, the CK1 isoforms are thought to be constitutively active and are known to control a plethora of biological processes. Yet, their regulation of kinase activity, substrate selectivity and subcellular localisation has remained a mystery. The emerging evidence now supports a central role for the DUF1669 domain, and the FAM83 proteins, in the regulation of CK1 biology.

AB - The eight members of the FAM83 (FAMily with sequence similarity 83) family of poorly characterised proteins are only present in vertebrates and are defined by the presence of the conserved DUF1669 domain of unknown function at their N-termini. The DUF1669 domain consists of a conserved phospholipase D (PLD)-like catalytic motif. However, the FAM83 proteins display no PLD catalytic (PLDc) activity, and the pseudo-PLDc motif present in each FAM83 member lacks the crucial elements of the native PLDc motif. In the absence of catalytic activity, it is likely that the DUF1669 domain has evolved to espouse novel function(s) in biology. Recent studies have indicated that the DUF1669 domain mediates the interaction with different isoforms of the CK1 (casein kinase 1) family of Ser/Thr protein kinases. In turn, different FAM83 proteins, which exhibit unique amino acid sequences outside the DUF1669 domain, deliver CK1 isoforms to unique subcellular compartments. One of the first protein kinases to be discovered, the CK1 isoforms are thought to be constitutively active and are known to control a plethora of biological processes. Yet, their regulation of kinase activity, substrate selectivity and subcellular localisation has remained a mystery. The emerging evidence now supports a central role for the DUF1669 domain, and the FAM83 proteins, in the regulation of CK1 biology.

KW - Animals

KW - Humans

KW - Neoplasm Proteins/metabolism

KW - Protein Isoforms/metabolism

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DO - 10.1042/BST20160277

M3 - Review article

C2 - 29871876

VL - 46

SP - 761

EP - 771

JO - Biochemical Society Transactions

JF - Biochemical Society Transactions

SN - 0300-5127

IS - 3

ER -