PMID- 10428856
OWN - NLM
STAT- MEDLINE
DCOM- 19990902
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 32
DP  - 1999 Aug 6
TI  - OB-BP1/Siglec-6. a leptin- and sialic acid-binding protein of the immunoglobulin 
      superfamily.
PG  - 22729-38
AB  - We report the expression cloning of a novel leptin-binding protein of the
      immunoglobulin superfamily (OB-BP1) and a cross-hybridizing clone (OB-BP2) that
      is identical to a recently described sialic acid-binding I-type lectin called
      Siglec-5. Comparisons to other known Siglec family members (CD22, CD33,
      myelin-associated glycoprotein, and sialoadhesin) show that OB-BP1,
      OB-BP2/Siglec-5, and CD33/Siglec-3 constitute a unique related subgroup with a
      high level of overall amino acid identity: OB-BP1 versus Siglec-5 (59%), OB-BP1
      versus CD33 (63%), and OB-BP2/Siglec-5 versus CD33 (56%). The cytoplasmic domains
      are not as highly conserved, but display novel motifs which are putative sites of
      tyrosine phosphorylation, including an immunoreceptor tyrosine kinase inhibitory 
      motif and a motif found in SLAM and SLAM-like proteins. Human tissues showed high
      levels of OB-BP1 mRNA in placenta and moderate expression in spleen, peripheral
      blood leukocytes, and small intestine. OB-BP2/Siglec-5 mRNA was detected in
      peripheral blood leukocytes, lung, spleen, and placenta. A monoclonal antibody
      specific for OB-BP1 confirmed high expression in the cyto- and
      syncytiotrophoblasts of the placenta. Using this antibody on peripheral blood
      leukocytes showed an almost exclusive expression pattern on B cells. Recombinant 
      forms of the extracellular domains of OB-BP1, OB-BP2/Siglec-5, and CD33/Siglec-3 
      were assayed for specific binding of leptin. While OB-BP1 exhibited tight binding
      (K(d) 91 nM), the other two showed weak binding with K(d) values in the 1-2
      microM range. Studies with sialylated ligands indicated that OB-BP1 selectively
      bound Neu5Acalpha2-6GalNAcalpha (sialyl-Tn) allowing its formal designation as
      Siglec-6. The identification of OB-BP1/Siglec-6 as a Siglec family member,
      coupled with its restricted expression pattern, suggests that it may mediate
      cell-cell recognition events by interacting with sialylated glycoprotein ligands 
      expressed on specific cell populations. We also propose a role for OB-BP1 in
      leptin physiology, as a molecular sink to regulate leptin serum levels.
FAU - Patel, N
AU  - Patel N
AD  - Molecular Biology Department, DNAX Research Institute, Palo Alto, California
      94304, USA.
FAU - Brinkman-Van der Linden, E C
AU  - Brinkman-Van der Linden EC
FAU - Altmann, S W
AU  - Altmann SW
FAU - Gish, K
AU  - Gish K
FAU - Balasubramanian, S
AU  - Balasubramanian S
FAU - Timans, J C
AU  - Timans JC
FAU - Peterson, D
AU  - Peterson D
FAU - Bell, M P
AU  - Bell MP
FAU - Bazan, J F
AU  - Bazan JF
FAU - Varki, A
AU  - Varki A
FAU - Kastelein, R A
AU  - Kastelein RA
LA  - eng
SI  - GENBANK/U71382
SI  - GENBANK/U71383
GR  - R01 GM32373/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD33 protein, human)
RN  - 0 (DNA, Complementary)
RN  - 0 (Immunoglobulins)
RN  - 0 (Lectins)
RN  - 0 (Leptin)
RN  - 0 (Ligands)
RN  - 0 (Proteins)
RN  - 0 (SIGLEC6 protein, human)
RN  - 0 (Sialic Acid Binding Ig-like Lectin 3)
RN  - GZP2782OP0 (N-Acetylneuraminic Acid)
SB  - IM
EIN - J Biol Chem 1999 Sep 24;274(39):28058
MH  - Amino Acid Sequence
MH  - Antigens, CD/genetics/isolation & purification/*metabolism
MH  - Antigens, Differentiation, Myelomonocytic/genetics/isolation &
      purification/*metabolism
MH  - Cloning, Molecular
MH  - DNA, Complementary/genetics
MH  - Evolution, Molecular
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Immunoglobulins/*genetics
MH  - *Lectins
MH  - Leptin
MH  - Ligands
MH  - Molecular Sequence Data
MH  - *Multigene Family
MH  - N-Acetylneuraminic Acid/*metabolism
MH  - Placenta/chemistry
MH  - Pregnancy
MH  - Protein Binding
MH  - Proteins/*metabolism
MH  - Sequence Analysis, DNA
MH  - Sequence Homology, Amino Acid
MH  - Sialic Acid Binding Ig-like Lectin 3
MH  - Tissue Distribution
EDAT- 1999/07/31 00:00
MHDA- 1999/07/31 00:01
CRDT- 1999/07/31 00:00
PHST- 1999/07/31 00:00 [pubmed]
PHST- 1999/07/31 00:01 [medline]
PHST- 1999/07/31 00:00 [entrez]
AID - 10.1074/jbc.274.32.22729 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 6;274(32):22729-38. doi: 10.1074/jbc.274.32.22729.