CD228 MF12 (antigen p97 melanoma associated), melanotransferin
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
GPI anchor
Stem Cell
Melanoma Cell
Brain Cell
Liver
Placenta
Epithelium
Muscle, Smooth
Small intestine
Umbilical cord
Sweat gland ducts
Fetal tissue
80 / 80
90 / 90

Expression
CD228 is highly expressed in stem cells, melanomas, brain cells, microglia, intestine and smooth muscle.  Expression is lower on bone marrow cells and leukocytes.  Expression is found predominantly in human melanomas and in certain fetal tissues.  There is also expression in liver, epithelium, umbilical cord, placenta and sweat gland ducts.

Structure
MOLECULAR FAMILY NAME: Belongs to the transferrin superfamily.

CD228 is a GPI-anchored melanoma-associated 738 aa glycoprotein.  It contains an extracellular domain which contains 2 nonfunctional peptidase S60 domains and has 3 potential N-linked glycosylation sites but no transmembrane domain or cytoplasmic domain.  CD228 is a sialoglycoprotein and can occur in a soluble form.  CD228 shares a sequence similarity and iron-binding properties with members of the transferrin superfamily. 

MOLECULAR MASS
Cell Type Unreduced Reduced
80-90kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.  Isoform 1 is a full length protein and isoform2 is divergent in the central coding region producing a frameshift that results in a truncated and distinct C-terminus.

POST-TRANSLATIONAL MODIFICATION

CD228 has a N-terminal aa sequencing which shows that melanotransferrin, called p97, is closely related to transferrin and lactoferrin.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD228

pro-UPA and plasminogen bind CD228.

Function
CD228 is presumed to have iron transport function.  CD228 is structurally related to members of the transferrin superfamily and involved in iron cellular uptake.  The importance of the iron binding function has not yet been determined but seems to be internalized and then recycled back to the cell membrane.  Each subunit binds a single atom of iron per subunit and high affinity and could also bind zinc.  In vitro studies have demonstrated CD228 can interact with pro-UPA and plasminogen and stimulate plasminogen activation.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD228 IN INTACT ANIMAL

CD228 is one of the 1st human tumor antigens that was characterized at the molecular level.  CD228 influences the migration capacity of endothelial cells and cell motility and invasiveness of melanoma cells.  Although CD228 is tumor associated rather than tumor specific, it suggests that it might be a useful target for immunotherapy.  CD228 is possibly involved in brain iron homeostasis.  Expression of CD228 by reactive microglia is increased five- to six-fold in Alzheimer's disease.


Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD228: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD228: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 4241P08582
Antibodies

Revised June 25, 2008


Contact us: Webmaster |  509-335-9515 | Accessibility | Copyright | Policies
College of Veterinary Medicine Washington State University, Pullman, WA, 99164-7010 USA
Copyright 1995-2003 Washington State University