{PDOC52086}
{PS52086; PITP_LIKE}
{BEGIN}
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* PITP-like domain profile *
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Phosphatidylinositol transfer  proteins  (PITPs) constitute a highly conserved
family of  proteins found in many organisms, including mammals, Caenorhabditis
elegans (worms), Drosophila melanogaster (flies), and Dictyostelium discoideum
(slime molds),  but not in yeasts or plants. The PITP family is one of the two
families of  phosphoinositide transfer proteins that can bind and exchange one
molecule of  either phosphatidylinositol or phosphatidylcholine and facilitate
the transfer  of  these  lipids  between  different membrane compartments; the
other is   the  structurally  unrelated  Sec14p  family.  PITPs  are  critical
regulators of  phosphoinositides  in several cellular compartments, where they
participate in  signal  transduction  and  in  membrane traffic. To transfer a
phospholipid, PITP  must  first bind to the membrane, exchange its bound lipid
for a  membrane  lipid,  and  then dissociate from the membrane. The PITP-like
domain is  required  to  facilitate  the  exchange of phosphatidylinositol and
phosphatidic acid at their associated membranes [1,2,3].

Three subfamilies can be defined and all isoforms have an amino-terminal PITP-
like domain  comprising ~260 amino acids. All three types occur in humans: the
first comprises   the  small  PITPalpha  and  PITPbeta  proteins;  the  second
comprises the  large rdgBalpha (also called M-RdgB1, Nir2 and PITPnm) and Nir3
(also called  M-RdgB2)  proteins;  and  the  third type comprises the rdgBbeta
protein, which  is  intermediate  in  size  and  was identified by homology to
rdgBalpha. The  rdgB  acronym  is  derived  from a retinal degeneration mutant
phenotype (type  B)  in  Drosophila,  and  the  Nir  acronym is derived from a
reported interaction  with  the  amino-terminal  domain  of  the Pyk2 tyrosine
kinase (Pyk2  N-terminal domain-interacting receptor). A third protein, termed
Nir1, was also identified, but this lacks a PITP domain [1,2].

The amino  acid  sequence  of  the PITP-like domain is highly conserved in all
isoforms and no characteristic short sequence motifs have been identified. The
prominent structural  features  of  PITP-like  domains include a large concave
beta-sheet and  several  long  helices  (see  <PDB:1T27>).  The amino-terminal
lipid-binding region  contains the most highly conserved residues. It contains
an eight-stranded,  concave,  mostly  antiparallel beta-sheet and two helices,
which encircle  the  bound  lipid and are structurally homologous to the START
family of  lipid-binding  proteins  (see  <PDOC50848>).  A lipid exchange loop
which contains  a  small  helix  acts  as a lid to the lipid-binding cavity. A
regulatory loop  is  likely  required for the association of PITP-like domains
with a  wide  variety  of  lipid-  and protein-modifying enzymes. The carboxy-
terminal helical  region  of  the  PITP-like  domain  shows  greatest sequence
variation and may play an important role in membrane binding [2,3,4,5].

The profile we developed covers the entire PITP-like domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: December 2025 / First entry.

[ 1] Hsuan J., Cockcroft S.
     "The PITP family of phosphatidylinositol transfer proteins."
     Genome Biol 2:REVIEWS3011-REVIEWS3011(2001).
     PubMed=11574064; DOI=10.1186/gb-2001-2-9-reviews3011
[ 2] Yoder M.D., Thomas L.M., Tremblay J.M., Oliver R.L., Yarbrough L.R.,
     Helmkamp G.M. Jr.
     "Structure of a multifunctional protein. Mammalian
     phosphatidylinositol transfer  protein complexed with
     phosphatidylcholine."
     J. Biol. Chem. 276:9246-9252(2001).
     PubMed=11104777; DOI=10.1074/jbc.M010131200
[ 3] Kim D., Lee S., Jun Y., Lee C.
     "Nir2 crystal structures reveal a phosphatidic acid-sensing mechanism
     at ER-PM  contact sites."
     Proc. Natl. Acad. Sci. U. S. A. 122:E2516849122-E2516849122(2025).
     PubMed=41129229; DOI=10.1073/pnas.2516849122
[ 4] Schouten A., Agianian B., Westerman J., Kroon J., Wirtz K.W.A., Gros P.
     "Structure of apo-phosphatidylinositol transfer protein alpha provides
     insight  into membrane association."
     EMBO. J. 21:2117-2121(2002).
     PubMed=11980708; DOI=10.1093/emboj/21.9.2117
[ 5] Vordtriede P.B., Doan C.N., Tremblay J.M., Helmkamp G.M. Jr.,
     Yoder M.D.
     "Structure of PITPbeta in complex with phosphatidylcholine: comparison
     of  structure and lipid transfer to other PITP isoforms."
     Biochemistry 44:14760-14771(2005).
     PubMed=16274224; DOI=10.1021/bi051191r

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